The new england journal of medicine

clinical practice

Aortic Regurgitation
Maurice Enriquez-Sarano, M.D., and A. Jamil Tajik, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors’ clinical recommendations.

A 48-year-old woman who reports mild fatigue but no dyspnea, chest pain, or palpita-
tion is found to have a diastolic cardiac murmur. The blood pressure is 140/50 mm Hg,
and the pulses are bounding. Cardiac examination reveals decreased S1 and increased
S2 intensity, with a grade 1/6 systolic murmur and a grade 3/6 diastolic murmur along
the left sternal border. Doppler color-flow echocardiography shows a bicuspid aortic
valve with an eccentric jet of aortic regurgitation. The left ventricle is moderately en-
larged, with an end-diastolic diameter of 66 mm (or 39 mm per square meter of body-
surface area) and an end-systolic diameter of 46 mm (or 27 mm per square meter); the
ejection fraction is 51 percent, and the ascending aorta is enlarged, at 48 mm. How
should this patient be treated?

the clinical problem

The most common cause of aortic regurgitation in developing countries is rheumatic From the Division of Cardiovascular Diseas-
disease, with clinical presentation in the second or third decade of life. In Western coun- es and Internal Medicine, Mayo Clinic and
Mayo Foundation, Rochester, Minn. Ad-
tries, rheumatic disease is now rare, and severe aortic regurgitation is most frequently dress reprint requests to Dr. Enriquez-
due to diseases that are congenital (in the bicuspid valve) or degenerative (such as an- Sarano at the Mayo Clinic, 200 First St.
nuloaortic ectasia), which typically present in the fourth to sixth decades.1 In rare cas- SW, Rochester, MN 55905, or at sarano.
maurice@mayo.edu.
es, aortic regurgitation is acute, caused by endocarditis or aortic dissection.
The overall prevalence of aortic regurgitation was 4.9 percent in the Framingham N Engl J Med 2004;351:1539-46.
Heart Study2 and 10 percent in the Strong Heart Study3; the prevalence of aortic regur- Copyright © 2004 Massachusetts Medical Society.

gitation of moderate or greater severity was 0.5 percent and 2.7 percent, respectively.
These differences may reflect the difference in the distribution of racial and ethnic groups
in the cohorts (predominantly whites in the Framingham Heart Study and predominantly
Native Americans in the Strong Heart Study) or differences in the rates of rheumatic fever.
The prevalence of aortic regurgitation increases with age,2,3 and severe regurgitation is
clinically more often observed in men than in women.4,5
Aortic regurgitation is usually detected by clinical examination, manifested as a
characteristic decrescendo diastolic murmur, or incidentally by echocardiography. The
valve lesions create an orifice that allows regurgitant flow throughout diastole (measured
as the regurgitant volume), a physiologic mechanism that explains a poor tolerance to
bradycardia, given the prolonged diastolic duration. The diastolic regurgitation and
the increase in the systolic stroke volume cause increased systolic pressure, widened
pulse pressure, and bounding pulses, which are suggestive of the diagnosis. Hence,
aortic regurgitation is a unique valvular disease with both left ventricular volume over-
load (indicated by an enlarged left ventricle on echocardiography or angiography) and
pressure overload (indicated by increased end-systolic pressure). However, because left
atrial pressure increases late in the course of the disease, symptoms (including dyspnea
and angina) usually develop slowly.
Patients with severe aortic regurgitation have higher mortality than the general pop-

n engl j med 351;15 www.nejm.org october 7, 2004 1539

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

ulation, and the disorder is also associated with sub- population,5,6,10 but do have high cardiovascular-
stantial morbidity.5 Ten years after the diagnosis of event rates (i.e., death from cardiac causes, heart
severe aortic regurgitation, heart failure occurs in failure, or new symptoms) at 5 to 6 percent per year.
approximately half the patients, and most surviving
patients require aortic-valve replacement. strategies and evidence
Subgroups of patients who are at increased risk
for death from cardiovascular causes have been evaluation
identified. Patients with severe symptoms (includ- Classifying the severity of regurgitation is the first
ing dyspnea or angina with mild effort or at rest, step in evaluating patients with aortic regurgitation
categorized as New York Heart Association and Ca- (Table 1). Clinically, bounding arterial pulses, a wid-
nadian Cardiovascular Society class III or IV) are at ened pulse pressure, a loud diastolic murmur,12 and
particularly high risk, with an annual mortality of a third heart sound13 are signs of severe regurgita-
nearly 25 percent, and even those patients with mild tion but are not always specific. Doppler echocardi-
symptoms (class II) have an annual mortality rate ography has become the mainstay of the assessment
(6.3 percent) that exceeds the rate in the general of the severity of aortic regurgitation.11 Suggestive
population.5 Marked left ventricular enlargement is of severe regurgitation are signs of a broad jet width
associated with an increased risk of sudden death.6 on color-flow imaging, steep jet velocity decelera-
However, absolute left ventricular diameters (i.e., tion (reflecting equalization of aortic and ventricu-
those uncorrected for body size) underestimate the lar pressure), and prolonged diastolic flow reversal
degree of left ventricular enlargement in women; as in the aorta. The use of Doppler echocardiography
compared with men, women tend to have surgery at makes it possible to quantify the effective regur-
a later stage of the disease, have more severe symp- gitant orifice (severe if ≥0.30 cm2) and regurgitant
toms at the time of surgery, and have a higher risk of volume (severe if ≥60 ml per beat) (Fig. 1 and 2, and
death postoperatively.7 Even in the absence of symp- the video clip available with the full text of this article
toms, men and women whose end-systolic diame- at www.nejm.org).14-16 A simple, reliable measure-
ter is 25 mm per square meter or more or whose ment is the “vena contracta” — that is, the width of
ejection fraction is below 55 percent have an in- the regurgitant flow at the orifice, a surrogate mea-
creased risk of death.5 In addition, the risk of aortic surement for the size of the orifice. Measurements
dissection or rupture is clearly increased in patients that are 0.5 cm or more have a high sensitivity for
with annuloaortic ectasia and an aortic diameter of the diagnosis of severe regurgitation, and measure-
6 cm or more (close to 7 percent per year),8 and even ments that are 0.7 cm or more have a high specific-
aortic diameters between 5.5 and 6 cm are associat- ity for the diagnosis.17 On rare occasions, this ap-
ed with an increased risk.8,9 Asymptomatic patients proach is inconclusive, and either transesophageal
without left ventricular dysfunction do not have an echocardiography or angiography of the aortic root
excess risk of death, as compared with the general is necessary to determine the severity of aortic regur-
gitation. Left ventricular size and function (particu-
larly, the end-systolic diameter and ejection fraction)
Table 1. Classification of the Severity of Aortic Regurgitation.* should be routinely assessed, as should dilatation
of the ascending aorta. If transthoracic imaging is
Variable Aortic Regurgitation suboptimal for the latter, transesophageal echocar-
Mild Moderate‡ Severe diography, computed tomography, or magnetic res-
Width of vena contracta (mm)† <3.0 3.0–5.9 ≥6.0 onance imaging can be used. Exercise testing may
Ratio of width of aortic regurgitant jet <25 25–44 45–64 ≥65 be warranted in asymptomatic patients with limited
to left ventricular outflow (%) physical activity to evaluate functional limitations
Regurgitant volume (ml per beat) <30 30–44 45–59 ≥60 and may also provide information about changes of
Regurgitant fraction (%) <30 30–39 40–49 ≥50 left ventricular function with stress.10
Effective regurgitant orifice (mm2) <10 10–19 20–29 ≥30
surgical management
* The classification is from the American Society of Echocardiography.11 Surgery relieves the aortic regurgitation but is not
† The vena contracta is the regurgitant flow at the orifice on color-flow imaging. appropriate for all patients because of the small but
‡ The subdivisions of the moderate class correspond to the subcategories of
“mild to moderate” and “moderately severe.” definite risks of the procedure and because aortic
prostheses may cause complications.18 There are no

1540 n engl j med 351;15 www.nejm.org october 7 , 2004

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 clinical practice

data from randomized trials comparing surgical

management of aortic regurgitation with nonsur-
Color-flow
gical therapy, and data on the benefits and risks of velocity scale
surgery are derived only from observational studies. 0.96
These studies have demonstrated lower morbidity Right ventricle
and mortality among high-risk patients who under-
go surgery than among those who do not.4,5 A po-
tentially confounding issue is that patients who are
referred for surgery tend to be more fit than those Left ventricle
Aorta
who are not, but there is general consensus that sur-
gery is appropriate in high-risk patients who have 0.96
no surgical contraindications. The severity of regur-
gitation, the symptoms and degree of functional
impairment, the degree of left ventricular dysfunc- Aortic Flow
Vena
tion, and the degree of aortic enlargement are cen- regurgitant contracta convergence
tral to clinical decision making. jet

Symptomatic Patients
Noncoronary
The presence of severe symptoms (dyspnea or an- sinus of Valsalva
gina with mild effort or at rest, categorized as class
III or class IV in both the New York Heart Associa-
tion and the Canadian Cardiovascular Society clas-
sifications) is a definite indication for aortic-valve
surgery. Surgery in these patients results in symp- Figure 1. Example of a Jet of Aortic Regurgitation, as Shown by Color-Flow
tomatic relief,4 and long-term mortality appears to Imaging.
be considerably lower than that among patients with The three components of the regurgitant flow (flow convergence above the
severe symptoms who are treated medically.5 Al- orifice, vena contracta through the orifice, and the jet below the orifice) are
shown. The width of the vena contracta (as indicated by crosses) can be
though some practitioners have advocated using measured as a surrogate for the regurgitant orifice.
severe symptoms as the sole criterion for surgery
(e.g., in young patients with rheumatic aortic regur-
gitation),19 this strategy is associated with excess
mortality, even after successful correction of aortic companied by overt left ventricular dysfunction23;
regurgitation.4 Thus, surgery should be considered a strategy of waiting to proceed with surgery until
earlier in the course of the disease.20 Patients with this degree of deterioration is seen has been associ-
mild symptoms and those with symptoms that im- ated with increased postoperative mortality and is
proved or resolved with medical therapy remain at not advisable.
notable risk without surgery. In those patients, sur- On the basis of observational data, surgery is in-
gery relieves the symptoms and has a low risk, and dicated in patients with an end-systolic diameter of
postoperative survival is similar to the expected sur- 55 mm or more20 (or 25 mm per square meter or
vival in the general population.4 more, a measurement that applies equally to men
and women since it accounts for body-surface
Asymptomatic Patients area5,7) or an ejection fraction below 55 percent.20,24
Among asymptomatic patients with aortic insuffi- The postoperative outcome for patients with a re-
ciency, surgery is warranted if frank left ventricular duced ejection fraction depends on the magnitude
enlargement or moderate dysfunction is present.20 of the reduction.25 For patients with a preoperative
In these patients, a delay of surgery until symptoms ejection fraction below 35 percent, the 10-year post-
develop is associated with substantial postopera- operative survival rate is only 41 percent25; with an
tive risks of frank left ventricular dysfunction and ejection fraction of 35 to 49 percent, it is 56 per-
death.21,22 Extreme left ventricular dilatation (i.e., cent, and with an ejection fraction of 50 percent or
an end-diastolic diameter of 80 mm or more) is a more, it is 70 percent.25 Hence, surgery should ide-
recognized risk factor for sudden death.6 However, ally be performed in asymptomatic patients when
this degree of ventricular dilatation is generally ac- the ejection fraction is between 50 and 55 per-

n engl j med 351;15 www.nejm.org october 7, 2004 1541

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

A B
Aliasing
velocity
0.40
Left ventricle

Flow
1.2 convergence

R=0.74 cm
Aorta

Figure 2. Example of Quantitation of Aortic Regurgitation by the Convergence of the Proximal Flow.
Panel A is a color-flow image of the aortic valve; the measured radius of the proximal flow convergence (R) is 0.74 cm,
and the regurgitant flow is calculated as 138 ml per second. The “aliasing” velocity of 0.40 m per second (modified by
baseline displacement) is the blood velocity at the junction of the orange and blue flows. Panel B shows a continuous-
wave Doppler measurement of regurgitant blood velocity, at 455 cm per second (arrow). The effective regurgitant orifice
area is determined by dividing the flow by the velocity, which in this case is 0.30 cm2.

cent.22,25 However, patients with a markedly de- before surgery and a normal ejection fraction (55
creased ejection fraction should not be denied sur- percent or more), long-term postoperative survival
gery. These patients generally have an improvement is equivalent to that of the general population.4
in the ejection fraction postoperatively25 as a result For patients with ascending aortic aneurysms,
of relief of the high afterload,26 particularly if the composite graft replacement (an ascending aortic
ventricular dysfunction has lasted for less than one graft with a prosthesis) is associated with a mortal-
year,27 and they may become asymptomatic after ity of 1 to 10 percent, depending on the severity of
surgery.25 Combined correction of aortic regurgita- aortic regurgitation, ventricular dysfunction, and
tion and aortic aneurysm should be considered in clinical presentation, but the surgery appears to im-
asymptomatic patients with aneurysms of the as- prove outcome, as compared with medical manage-
cending aorta that are more than 5.5 to 6 cm in di- ment.9,25,30 In patients with mild aortic regurgita-
ameter, given the increased risk of aortic rupture or tion, a valve-sparing ascending aortic replacement
dissection.8,9 may minimize the long-term risks associated with
valvular prostheses.30
Risks of Surgery
Aortic-valve replacement is the usual intervention nonsurgical management
for aortic regurgitation and in the United States is Mild or moderate aortic regurgitation is usually
associated with a mortality of 4 percent when per- managed conservatively, unless dilatation of the as-
formed in isolation and 6.8 percent when per- cending aorta justifies surgery. A strategy of conser-
formed with coronary bypass surgery.28 The opera- vative management of severe aortic regurgitation in
tive mortality is lower in high-volume centers29 and asymptomatic patients is reasonable if the patients
among patients who have minimal or no symp- have neither marked left ventricular enlargement
toms (1 to 2 percent mortality4) or better preopera- nor left ventricular dysfunction, since several studies
tive left ventricular function (8 percent mortality have shown that asymptomatic young patients with
when the ejection fraction is 35 percent or less vs. 2 normal left ventricular function have a survival rate
percent when the ejection fraction is 50 percent or identical to that in the general population.5,6,10,31
more).25 In patients with no or minimal symptoms Vasodilator therapy may be considered for pa-

1542 n engl j med 351;15 www.nejm.org october 7 , 2004

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 clinical practice

Table 2. Guidelines for Indications for Surgery in Patients with Severe Aortic Regurgitation.

Indication Class* ACC–AHA Guidelines20 European Society of Cardiology Guidelines24†

I NYHA class III or IV symptoms Left ventricular diastolic diameter >70 mm
NYHA class II symptoms with progressive left ventricular dilata- Left ventricular systolic diameter >55 mm
tion, reduced ejection fraction, or reduced exercise tolerance or >25 mm/m2 of body-surface area
CCS class II angina Ascending aortic dilatation >55 mm
Ejection fraction 25–49%
Surgery indicated for another valve or coronary bypass
II NYHA class II symptoms isolated (IIa) Rapid increase in left ventricular diameters
Asymptomatic left ventricular dilatation >75 mm in diastole Bicuspid aortic valve or Marfan syndrome
and >55 mm in systole (IIa) with aortic diameter >50 mm
Ejection fraction <25% (IIb)
Asymptomatic left ventricular dilatation 70–75 mm in diastole
and 50–55 mm in systole (IIb)
Asymptomatic, decreased ejection fraction with exercise (IIb)

* Class I indicates that there is evidence or general agreement that the procedure is useful; class II indicates that there is conflicting evidence
or opinion. The guidelines of the American College of Cardiology and the American Heart Association (ACC–AHA) divide class II into IIa,
which indicates that the weight of evidence favors surgery, and IIb, which indicates that the efficacy of surgery is less well established. NYHA
denotes New York Heart Association, and CCS Canadian Cardiovascular Society.
† Guidelines are only for asymptomatic patients.

tients who are not candidates for surgery but have essary. Although the risk of endocarditis is low,5 all
regurgitation of a severe degree32 or possibly of a patients should receive prophylaxis for dental work
moderate degree, since studies have included pa- and surgical procedures, as recommended by the
tients who would now be classified as having mod- American Heart Association.37
erate aortic regurgitation.33-35 Controlled trials
indicate that both nifedipine35 and angiotensin- areas of uncertainty
converting–enzyme inhibitors33 reduce left ven-
tricular wall stress and volumes. In a trial compar- Although prospective studies of the natural history
ing nifedipine with digoxin, patients treated with of aortic regurgitation have been conducted,6,10,31
nifedipine were less likely to need surgery (as de- the effect of the absolute severity of regurgitation,
termined by left ventricular abnormalities or symp- as measured by regurgitant volume or orifice,14,15
toms) than those who were treated with digoxin34; on the clinical outcome is unknown. Different re-
however, the lack of a placebo group, the small gurgitant volumes (e.g., 60 ml per beat vs. 100 ml
size of the study, and the end point of surgery make per beat) may be similarly classified as severe but
the long-term benefits of nifedipine uncertain. In may have different outcomes. Furthermore, little is
a small, open-label trial, beta-blocker therapy de- known about the rate and determinants of the pro-
creased the rate of aortic enlargement among pa- gression of aortic regurgitation.38 It is not possible
tients with the Marfan syndrome.36 However, brady- to identify in advance those cases that will progress
cardia prolongs diastole and may increase aortic quickly, for which aggressive management may be
regurgitant volume, which raises a concern regard- warranted. In addition, symptoms are an imperfect
ing beta-blockade in patients with severe regurgi- measure of functional limitations.39 The value of
tation. Patients who are treated medically may sub- cardiopulmonary exercise testing in clinical decision
sequently require surgery because of progression of making is unclear.
aortic regurgitation (which occurs at a rate of 5 to Also uncertain is the optimal approach to surgi-
6 percent per year among patients with initially cal correction of aortic regurgitation. The durability
severe but asymptomatic aortic regurgitation6,10). of aortic-valve repair,40 pulmonary autografts,41 and
Therefore, with medical treatment, close follow-up homografts is imperfect, so standard valve replace-
and repeated evaluations (yearly or every six months ment is used most frequently. Progress in aortic-
in patients with severe aortic regurgitation) are nec- valve repair may expand future surgical indications.

n engl j med 351;15 www.nejm.org october 7, 2004 1543

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 The new england journal of medicine

Aortic regurgitation present on clinical assessment,

Doppler echocardiographic assessment, or both

Severe aortic regurgitation

Indeterminate No Yes

Transesophageal Regurgitation-related
echocardiography symptoms
or aortography

Indeterminate No Yes

Exercise testing

Regurgitation-related
LV alteration
(ESD ≥25 mm/m2
or EF <55%)

Indeterminate No Yes

Cardiac catherization,
radionuclide angiography

Annuloaortic
ectasia ≥5.5 to 6.0 cm

Indeterminate No Yes

CT or MRI

Medical management Surgery

Aortic regurgitation Aortic regurgitation

mild moderately severe or severe

Observation Vasodilators

Figure 3. Management Strategy for Aortic Regurgitation.

LV denotes left ventricular, ESD end-systolic diameter, and EF ejection fraction.

Despite wide agreement that left ventricular dys- have alternatively suggested that the best predictors
function or marked enlargement or both predict a of outcome are an end-diastolic diameter of 80 mm
worse outcome and are indications for surgery, spe- or more,6 an end-systolic diameter of 50 mm or
cific indexes are disputed. Natural-history studies more6 (or of 25 mm or more per square meter5), an

1544 n engl j med 351;15 www.nejm.org october 7 , 2004

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 clinical practice

ejection fraction of less than 55 percent,5 or exer- In asymptomatic patients with severe aortic re-
tional changes in the ejection fraction and wall gurgitation, such as the woman described in the vi-
stress.10 However, more research is needed to de- gnette, an ejection fraction below 55 percent or an
termine which criteria are most useful, and more end-systolic diameter of 25 mm per square meter or
data are needed to guide the decision about surgery more is an indication for surgery. Correction for
on the basis of the left ventricular function.20,25 body size with the use of body-surface area5 is par-
Finally, the effects of vasodilators in patients with ticularly important in women, in whom the severity
moderate aortic regurgitation remain unclear. of aortic regurgitation and of left ventricular en-
largement may otherwise be underestimated.7 Cor-
guidelines onary angiography is warranted before surgery in
patients who are considered at risk for coronary
Guidelines from the American Society of Echocar- disease (e.g., men over the age of 35 years, post-
diography11 underscore the importance of quanti- menopausal women, and women with coronary risk
tative measurement of aortic regurgitation (Table 1). factors). The usual operation is aortic-valve replace-
Recommendations issued by the American Heart ment with a mechanical prosthesis in young pa-
Association and the American College of Cardiolo- tients and with a bioprosthesis in older patients.
gy (Table 2) in 1998 suggested that severe symptoms Patients who have mechanical prostheses require
or left ventricular alteration (an end-diastolic diam- long-term anticoagulation (with a target interna-
eter ≥75 mm, an end-systolic diameter ≥50 mm, or tional normalized ratio of 2.5 to 3.5).42
an ejection fraction below 50 percent) were widely Regardless of the degree of regurgitation and
accepted indications for surgery (class I indications), the severity of symptoms, surgery is often indicated
whereas mild dyspnea was considered an indication for patients who have annuloaortic ectasia, a large
with limited or conflicting evidence (class II).20 The ascending aortic aneurysm, and good life expect-
2002 guidelines of the European Society of Cardi- ancy. For symptomatic patients in whom the causal
ology (Table 2), incorporating more recent data, link between symptoms and regurgitation is uncer-
underscore the importance of considering surgery tain, and for those who have advanced left ventric-
for asymptomatic patients with a left ventricular ular dysfunction (with an ejection fraction below 35
end-systolic diameter that is more than 25 mm per percent), the decision whether to operate is chal-
square meter.24 lenging. Our approach is to consider other poten-
tial causes of symptoms or ventricular dysfunction
and to quantify the regurgitation. We tend to offer
conclusions
and recommendations surgery to patients with severe regurgitation, since
marked improvement may occur postoperatively.25
Evaluation of patients with aortic regurgitation For patients who do not require surgery, we pre-
combines clinical and Doppler assessment (Fig. 3) scribe prophylaxis against endocarditis. Despite
with quantitation of the regurgitant volume and limited evidence from clinical trials, for most pa-
orifice (Fig. 1 and 2). If the regurgitation is severe, tients with moderately severe or severe regurgita-
surgery is indicated in symptomatic patients (even tion, we prescribe vasodilators. We recommend fol-
those with mild symptoms), and it should be per- low-up echocardiography every two to five years in
formed promptly if aortic regurgitation is acute. In patients with mild regurgitation, every year in those
asymptomatic patients, particularly those who are with moderate-to-severe regurgitation and minimal
sedentary, cardiopulmonary exercise testing with ventricular dilatation, and every six months in pa-
measurement of oxygen consumption provides in- tients whose ventricular alteration is close to that
formation about functional capacity. constituting an indication for surgery.

references
1. Braunwald E, ed. Heart disease: a text- 3. Lebowitz NE, Bella JN, Roman MJ, et al. with severe aortic regurgitation: role of
book of cardiovascular medicine. 5th ed. Prevalence and correlates of aortic regurgi- symptoms. J Am Coll Cardiol 1997;30:746-
Philadelphia: Saunders, 1997. tation in American Indians: the Strong 52.
2. Singh J, Evans J, Levy D, et al. Prevalence Heart Study. J Am Coll Cardiol 2000;36:461- 5. Dujardin KS, Enriquez-Sarano M,
and clinical determinants of mitral, tricus- 7. Schaff HV, Bailey KR, Seward JB, Tajik AJ.
pid, and aortic regurgitation. Am J Cardiol 4. Klodas E, Enriquez-Sarano M, Tajik AJ, Mortality and morbidity of aortic regurgita-
1999;83:897-902. [Erratum, Am J Cardiol Mullany CJ, Bailey KR, Seward JB. Optimiz- tion in clinical practice: a long-term follow-
1999;84:1143.] ing timing of surgical correction in patients up study. Circulation 1999;99:1851-7.

n engl j med 351;15 www.nejm.org october 7, 2004 1545

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
 clinical practice

6. Bonow RO, Lakatos E, Maron BJ, Ep- mance of heart valve prostheses. Curr Probl in the United States. N Engl J Med 2002;346:
stein SE. Serial long-term assessment of the Cardiol 2000;25:73-154. 1128-37.
natural history of asymptomatic patients 19. Tarasoutchi F, Grinberg M, Spina GS, et 30. Gott VL, Cameron DE, Alejo DE, et al.
with chronic aortic regurgitation and nor- al. Ten-year clinical laboratory follow-up af- Aortic root replacement in 271 Marfan pa-
mal left ventricular systolic function. Circu- ter application of a symptom-based thera- tients: a 24-year experience. Ann Thorac
lation 1991;84:1625-35. peutic strategy to patients with severe Surg 2002;73:438-43.
7. Klodas E, Enriquez-Sarano M, Tajik AJ, chronic aortic regurgitation of predominant 31. Tornos MP, Permanyer-Miralda G,
Mullany CJ, Bailey KR, Seward JB. Surgery rheumatic etiology. J Am Coll Cardiol 2003; Evangelista A, et al. Clinical evaluation of a
for aortic regurgitation in women: contrast- 41:1316-24. prospective protocol for the timing of sur-
ing indications and outcomes compared 20. Bonow R, Carabello B, DeLeon AC Jr, et gery in chronic aortic regurgitation. Am
with men. Circulation 1996;94:2472-8. al. Guidelines for the management of pa- Heart J 1990;120:649-57.
8. Davies RR, Goldstein LJ, Coady MA, et tients with valvular heart disease: executive 32. Levine H, Gaasch WH. Vasoactive drugs
al. Yearly rupture or dissection rates for tho- summary: a report of the American College in chronic regurgitant lesions of the mitral
racic aortic aneurysms: simple prediction of Cardiology/American Heart Association and aortic valves. J Am Coll Cardiol 1996;28:
based on size. Ann Thorac Surg 2002;73:17- Task Force on Practice Guidelines (Commit- 1083-91.
28. tee on Management of Patients with Valvular 33. Lin M, Chiang HT, Lin SL, et al. Vasodi-
9. Coady MA, Rizzo JA, Hammond GL, et Heart Disease). Circulation 1998;98:1949- lator therapy in chronic asymptomatic aor-
al. What is the appropriate size criterion for 84. tic regurgitation: enalapril versus hydrala-
resection of thoracic aortic aneurysms? 21. Acar J, Luxereau P, Ducimetiere P, Cadil- zine therapy. J Am Coll Cardiol 1994;24:
J Thorac Cardiovasc Surg 1997;113:476-91. hac M, Jallut H, Vahanian A. Prognosis of 1046-53.
10. Borer JS, Hochreiter C, Herrold EM, et surgically treated chronic aortic valve dis- 34. Scognamiglio R, Rahimtoola SH, Fasoli
al. Prediction of indication for valve replace- ease: predictive indicators of early postoper- G, Nistri S, Dalla Volta S. Nifedipine in
ment among asymptomatic or minimally ative risk and long-term survival based on asymptomatic patients with severe aortic re-
symptomatic patients with chronic aortic re- 439 cases. J Thorac Cardiovasc Surg 1981; gurgitation and normal left ventricular func-
gurgitation and normal left ventricular per- 82:114-26. tion. N Engl J Med 1994;331:689-94.
formance. Circulation 1998;97:525-34. 22. Bonow RO, Picone AL, McIntosh CL, et 35. Scognamiglio R, Fasoli G, Ponchia A,
11. Zoghbi WA, Enriquez-Sarano M, Foster al. Survival and functional results after valve Dalla-Volta S. Long-term nifedipine unload-
E, et al. Recommendations for evaluation of replacement for aortic regurgitation from ing therapy in asymptomatic patients with
the severity of native valvular regurgitation 1976 to 1983: impact of preoperative left chronic severe aortic regurgitation. J Am
with two-dimensional and Doppler echo- ventricular function. Circulation 1985;72: Coll Cardiol 1990;16:424-9.
cardiography. J Am Soc Echocardiogr 2003; 1244-56. 36. Shores J, Berger KR, Murphy EA, Pyeritz
16:777-802. 23. Klodas E, Enriquez-Sarano M, Tajik AJ, RE. Progression of aortic dilatation and the
12. Desjardins VA, Enriquez-Sarano M, Mullany CJ, Bailey KR, Seward JB. Aortic re- benefit of long-term beta-adrenergic block-
Tajik AJ, Bailey KR, Seward JB. Intensity of gurgitation complicated by extreme left ven- ade in Marfan’s syndrome. N Engl J Med
murmurs correlates with severity of valvular tricular dilatation: long-term outcome after 1994;330:1335-41.
regurgitation. Am J Med 1996;100:149-56. surgical correction. J Am Coll Cardiol 1996; 37. American Heart Association. Wallet card
13. Tribouilloy CM, Enriquez-Sarano M, 27:670-7. page. (Accessed September 13, 2004, at http:
Mohty D, et al. Pathophysiologic determi- 24. Iung B, Gohlke-Barwolf C, Tornos P, et //www.americanheart.org/downloadable/
nants of third heart sounds: a prospective al. Recommendations on the management heart/1023826501754walletcard.pdf.)
clinical and Doppler echocardiographic of the asymptomatic patient with valvular 38. Reimold SC, Orav EJ, Come PC, Caguioa
study. Am J Med 2001;111:96-102. heart disease. Eur Heart J 2002;23:1253-66. ES, Lee RT. Progressive enlargement of the
14. Tribouilloy CM, Enriquez-Sarano M, 25. Chaliki HP, Mohty D, Avierinos JF, et al. regurgitant orifice in patients with chronic
Fett SL, Bailey KR, Seward JB, Tajik AJ. Ap- Outcomes after aortic valve replacement in aortic regurgitation. J Am Soc Echocardiogr
plication of the proximal flow convergence patients with severe aortic regurgitation and 1998;11:259-65.
method to calculate the effective regurgitant markedly reduced left ventricular function. 39. Boucher CA, Wilson RA, Kanarek DJ, et
orifice area in aortic regurgitation. J Am Coll Circulation 2002;106:2687-93. al. Exercise testing in asymptomatic or min-
Cardiol 1998;32:1032-9. 26. Wisenbaugh T, Spann JF, Carabello BA. imally symptomatic aortic regurgitation: re-
15. Enriquez-Sarano M, Seward JB, Bailey Differences in myocardial performance and lationship of left ventricular ejection frac-
KR, Tajik AJ. Effective regurgitant orifice ar- load between patients with similar amounts tion to left ventricular filling pressure
ea: a noninvasive Doppler development of of chronic aortic versus chronic mitral re- during exercise. Circulation 1983;67:1091-
an old hemodynamic concept. J Am Coll gurgitation. J Am Coll Cardiol 1984;3:916- 100.
Cardiol 1994;23:443-51. 23. 40. Gillinov AM, Blackstone EH, White J, et
16. Reimold SC, Ganz P, Bittl JA, et al. Effec- 27. Bonow RO, Dodd JT, Maron BJ, et al. al. Durability of combined aortic and mitral
tive aortic regurgitant orifice area: descrip- Long-term serial changes in left ventricular valve repair. Ann Thorac Surg 2001;72:20-7.
tion of a method based on the conservation function and reversal of ventricular dilata- 41. Kouchoukos NT. Aortic allografts and
of mass. J Am Coll Cardiol 1991;18:761-8. tion after valve replacement for chronic aor- pulmonary autografts for replacement of
17. Tribouilloy CM, Enriquez-Sarano M, tic regurgitation. Circulation 1988;78:1108- the aortic valve and aortic root. Ann Thorac
Bailey KR, Seward JB, Tajik AJ. Assessment 20. Surg 1999;67:1846-8.
of severity of aortic regurgitation using the 28. Edwards FH, Peterson ED, Coombs LP, 42. Acar J, Iung B, Boissel JP, et al. AREVA:
width of the vena contracta: a clinical color et al. Prediction of operative mortality after multicenter randomized comparison of
Doppler imaging study. Circulation 2000; valve replacement surgery. J Am Coll Cardiol low-dose versus standard-dose anticoagula-
102:558-64. 2001;37:885-92. tion in patients with mechanical prosthetic
18. Grunkemeier GL, Li HH, Naftel DC, 29. Birkmeyer JD, Siewers AE, Finlayson EV, heart valves. Circulation 1996;94:2107-12.
Starr A, Rahimtoola SH. Long-term perfor- et al. Hospital volume and surgical mortality Copyright © 2004 Massachusetts Medical Society.

1546 n engl j med 351;15 www.nejm.org october 7 , 2004

The New England Journal of Medicine

Downloaded from nejm.org on August 13, 2014. For personal use only. No other uses without permission.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.