Aortic Regurgitation

Aortic Regurgitation 

Aortic regurgitation (AR) is abnormal retrograde blood flow into the left ventricle from the aorta due to an inadequately closing aortic valve (AV).

The inadequate closure of the valve can result from either disease of the ascending aorta (ex. Dilation) and aortic root or disease of aortic valve leaflets.

In addition, it can be acute or chronic in nature.

Stages of chronic aortic regurgitation:

  • •Stage A = at risk of aortic insufficiency (AI) without even trace AR (e.g., bicuspid AV, AV sclerosis, diseases of the ascending aorta, history of rheumatic heart disease, or infective endocarditis)
  • •Stage B = progressive AI with mild to moderate AR and preserved left ventricular ejection fraction (LVEF)
  • •Stage C = asymptomatic severe AR with preserved (stage C1) or reduced (stage C2) LVEF
  • •Stage D = symptomatic severe AR

Synonyms

  • Aortic insufficiency
  • AI
  • AR

Epidemiology & Demographics

Prevalence varies with severity of AR, age, and gender, as summarized in the below table

  • •Most common cause in the developing world is rheumatic heart disease.
  • •Most common causes in developed countries are aortic root dilation, congenital bicuspid aortic valve, and calcific valve disease.
  • •Infectious endocarditis (IE) is the most frequent cause of acute AR.

Prevalence of Aortic Regurgitation (AR)

From Singh JP et al: Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study), Am J Cardiol 83:897, 1999.

Mild AR PrevalenceMaleFemales
Age 50-593.7 %1.9%
Age 60-6912.1%6%
Age 70-8312.2%14.6%
Moderate-Severe AR PrevalenceMaleFemales
Age 50-590.5%0.2%
Age 60-690.6%0.8%
Age 70-832.2%2.3%

Physical Findings & Clinical Presentation

Clinical presentation varies depending on whether AR is acute or chronic. Chronic AR is well tolerated (except when secondary to IE), and patients remain asymptomatic for years. Common manifestations after significant deterioration of LVEF are dyspnea on exertion, syncope, chest pain, and congestive heart failure (CHF). The stages of chronic AR are summarized in the below table. Acute severe AR manifests primarily with hypotension caused by a sudden fall in cardiac output and resultant cardiogenic shock. A rapid rise in left ventricular diastolic pressure results in a further decrease in coronary blood flow.

Stages of Chronic Aortic Regurgitation

From Nishimura RA et al: 2014 AHA/ACCF guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 63:e57, 2014. In Mann DL et al: Braunwald’s heart disease, ed 10, Philadelphia, 2015, Elsevier.

StageDefinitionValve AnatomyValve HemodynamicsHemodynamic ConsequencesSymptoms
AAt risk of ARBicuspid aortic valve (or other congenital valve anomaly)Aortic valve sclerosis
Diseases of the aortic sinuses or ascending aorta
History of rheumatic fever or known rheumatic heart disease
IE
AR severity none or traceNoneNone
BProgressive ARMild to moderate calcification of a trileaflet valve bicuspid aortic valve (or other congenital valve anomaly)Dilated aortic sinuses
Rheumatic valve changes
Previous IE
Mild AR: Jet width <25% of LVOT vena contracta
<0.3 cm
RVol
<30 ml/beat
RF <30%
ERO
<0.10 cm2
Angiography grade 1+
Moderate AR:
Jet width 25-64% of LVOT
Vena contracta 0.3-0.6 cm
RVol 30-59 ml/beat
RF 30-49% ERO 0.10-0.29 cm2
Angiography grade 2+
Normal LV systolic functionNormal LV volume or mild LV dilationNone
CAsymptomatic severe ARCalcific aortic valve diseaseBicuspid valve (or other congenital abnormality)
Dilated aortic sinuses or ascending aorta
Rheumatic valve changes
IE with abnormal leaflet closure or perforation
Severe AR: Jet width ≥65% of LVOT
Vena contracta >0.6 cm
Holodiastolic flow reversal in the proximal abdominal aorta
RVol ≥60 ml/beat
RF ≥50%
ERO ≥0.3 cm2
Angiography grade 3+ to 4+
In addition, diagnosis of chronic severe AR requires evidence of LV dilation
C1: Normal LVEF (≥50%) and mild-to-moderate LV dilation (LVESD ≤50 mm) C2: Abnormal LV systolic function with depressed LVEF (<50%) or severe LV dilation (LVESD >50 mm or indexed LVESD >25 mm/m2)None; exercise testing is reasonable to confirm symptom status
DSymptomatic severe ARCalcific valve diseaseBicuspid valve (or other congenital abnormality)
Dilated aortic sinuses or ascending aorta
Rheumatic valve changes
Previous IE with abnormal leaflet closure or perforation
Severe AR: Doppler jet width ≥65% of LVOT
Vena contracta >0.6 cm
Holodiastolic flow reversal in the proximal abdominal aorta
RVol ≥60 ml/beat
RF ≥50%
ERO ≥0.3 cm2
Angiography grade 3+ to 4+
In addition, diagnosis of chronic severe AR requires evidence of LV dilation
Symptomatic severe AR may occur with normal systolic function (LVEF ≥50%), mild-to-moderate LV dysfunction (LVEF 40%-50%), or severe LV dysfunction (LVEF <40%)Moderate-to-severe LV dilation is presentExertional dyspnea or angina, or more severe HF symptoms

AR, Aortic regurgitation; ERO, effective regurgitant orifice; HF, heart failure; IE, infective endocarditis; LV, left ventricle; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; LVOT, left ventricular outflow tract; RF, regurgitant fraction; RVol, regurgitant volume.

Physical findings in chronic AR:

  • •Widened pulse pressure (markedly increased systolic blood pressure with decreased diastolic blood pressure). 
  • Findings associated with widened pulse pressure:
    • 1.Bounding, “water hammer,” or collapsing pulse (Corrigan pulse) can be palpated at the wrist or femoral artery and is caused by the rapid rise and sudden collapse of arterial pressure during late systole
    • 2.Head “bobbing” with each heart beat (de Musset sign)
    • 3.“Pistol shot femorals” (Traube sign) describes a loud sound over the femoral artery with systole and diastole
    • 4.Capillary pulsations (Quincke sign) may occur on the lips or at the base of the nail beds
  • •A to-and-fro intermittent femoral murmur (Duroziez sign) may be heard with slight compression of the femoral arteries. Popliteal systolic pressure increased >20 mm Hg over the brachial systolic pressure (Hill sign); a 40 to 60 mm difference represents moderate AR and >60 mm difference, severe AR
  • •Findings more of historical than practical interest, which are neither sensitive nor specific, include:
    • 1.Mueller sign—Systolic pulsations of the uvula
    • 2.Becker sign—Visible pulsations of the retinal arteries and pupils
    • 3.Mayne sign—More than a 15 mm Hg decrease in diastolic blood pressure with arm elevation from the value obtained with the arm in the standard position
    • 4.Rosenbach sign—Systolic pulsations of the liver
    • 5.Gerhard sign—Systolic pulsations of the spleen
    • 6.Landofi sign —Pupil dilation and constriction with each heart beat on the ocular exam

Cardiac auscultation reveals:

  • •Displacement of cardiac impulse downward and to the patient’s left
  • •S3 heard over the apex
  • •Decrescendo, blowing diastolic murmur heard along left sternal border
  • •Low-pitched apical diastolic rumble (Austin Flint murmur)—the precise etiology is uncertain, but it is generally believed to be related to increased velocity of mitral inflow consequent to the AR
  • •Early systolic ejection sound and systolic ejection murmur

In patients with acute aortic insufficiency both the wide pulse pressure and the large stroke volume are absent. A short, blowing diastolic murmur may be the only finding on physical examination.

Etiology

  • •Leaflet abnormalities:
    • 1.Infective endocarditis
    • 2.Rheumatic fibrosis (most common cause in developing countries)
    • 3.Trauma with valvular rupture
    • 4.Congenital heart disease (bicuspid aortic valve—most common cause in the U.S., sinus of Valsalva aneurysm)
    • 5.Myxomatous degeneration
    • 6.Calcific AV disease
    • 7.Drug-induced (fenfluramine, dexfenfluramine, pergolide, cabergoline)
    • 8.Systemic rheumatic disorders (ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus)
    • 9.Iatrogenic (ex. Aortic balloon valvotomy)
  • •Aortic root or ascending aorta abnormalities:
    • 1.Annuloaortic ectasia
    • 2.Genetic syndromes (Ehlers-Danlos, Marfan)
    • 3.Trauma
    • 4.Ankylosing spondylitis
    • 5.Syphilitic aortitis
    • 6.Systemic hypertension
    • 7.Aortic dissection
  • •Postprocedural AR, usually due to a paravalvular leak, occurs in 10% to 20% of patients undergoing transcatheter aortic valve replacement (TAVR). Patients with more than mild AR after TAVR have worse outcomes than those without AR

Differential Diagnosis

  • •Patent ductus arteriosus, pulmonary regurgitation, and other valvular abnormalities.
  • •The differential diagnosis of cardiac murmurs is described in Sections II and III.

Workup

  • •Echocardiogram, chest radiograph, electrocardiogram (ECG), cardiac magnetic resonance (CMR) imaging, and cardiac catheterization (selected patients)
  • •Medical history and physical examination focused on dyspnea on exertion, syncope, chest pain, and CHF

Imaging Studies

  • •Chest radiography:
    • 1.Left ventricular hypertrophy (LVH) (chronic AR).
    • 2.Aortic dilation.
    • 3.Normal cardiac silhouette with pulmonary edema: Possible in patients with acute AR.
  • •ECG is not useful for diagnostic purposes but is commonly used in evaluation of patients with chronic AR to exclude associated arrythmia. Typical findings on an ECG are LVH as a result of volume overload.
  • •Echocardiography is the main imaging modality to diagnose AR and assess left ventricular size and function. Quantification of the severity of regurgitation can be made either qualitatively by Doppler vena contracta width (severe if >0.6 cm) or quantitatively by effective regurgitant orifice area (severe if >0.30 cm2) and/or regurgitant volume (severe if >60 ml per/beat).
  • •Echocardiography can also be used for periodic monitoring of asymptomatic patients with normal LV systolic function and chronic AR. Based on 2014 AHA/ACC valve guideline, Mild AR is followed every 3 to 5 yr, Moderate AR is followed every 1 to 2 yr, and Severe AR should be followed every 6 to 12 mo or more frequently if there is worsening of LV dilatation.
  • •CMR is indicated (class 1) in patients with moderate or severe AR and suboptimal echocardiographic images for the assessment of AR severity as well as LV systolic function and volumes.
  • •Cardiac catheterization is indicated in selected patients to assess the degree of left ventricular dysfunction and AR when echocardiographic parameters are inconclusive, and to determine if there is coexistent coronary artery disease.
  • •Serial evaluation of the size and morphology of the aortic sinuses and ascending aorta by echocardiography, CMR, or CT angiography is recommended in patients with a bicuspid AV and an aortic diameter >4.0 cm, with the examination interval determined by the degree and rate of progression of aortic dilation and by family history. Patients with an aortic diameter >4.5 cm should be evaluated annually (Class 1).

Treatment

Nonpharmacologic Therapy

  • •Avoidance of competitive sports and heavy weight lifting if: Severe AR, patient is symptomatic, ejection fraction <50%, AR is associated with aortic root dilation
  • •Salt restriction
  • •Endocarditis prophylaxis is not recommended for chronic AR patients with native valves undergoing invasive procedures. However, antibiotic prophylaxis is recommended for patients with a prior history of infective endocarditis or a presence of prosthetic heart valve

Acute General Treatment

  • •Emergent AV replacement (preferred) or repair for acute, severe AR
  • •Intraaortic balloon pump is contraindicated
  • •Afterload reduction: Angiotensin-converting enzyme (ACE) inhibitors and vasodilators (i.e., nitroprusside) in acute AR; diuretics for pulmonary edema
  • •Avoid beta-blockers that can prolong diastole
  • •Emergent surgical referral for cardiogenic shock

Chronic Treatment

Management depends on whether patients are symptomatic and candidates for valve surgery. ACC/AHA guidelines for aortic valve replacement for chronic aortic regurgitation are summarized in the below table.

  • •Symptomatic patients with severe AR who are candidates for valve surgery should proceed with valve replacement after medical optimization of heart failure. When surgery is contraindicated, TAVR is currently under assessment for treatment of native AR.
  • •Asymptomatic patients with severe AR and systolic dysfunction who are not surgical candidates should receive ACE/ARBs.
  • •Other medical treatments for AR are based on limited studies. Beta-blocker use is controversial but has been associated with a higher survival rate in severe AR. Vasodilatory therapies (nifedipine and enalapril) have failed to show benefit in reducing the need for or delaying AV replacement in asymptomatic, severe AR with normal systolic function, but ACE/ARB therapy may indeed benefit moderate to severe AR. Long-term vasodilator therapy with ACE inhibitors or nifedipine may be used in patients who have concomitant hypertension. There is no current definitive indication of medical therapy with afterload reduction for aortic regurgitation other than hypertension control.
  • •Beta-blockers in combination with ACE inhibitors are reasonable in patients with symptomatic severe AR or LV dysfunction when surgery cannot be performed because of concomitant comorbidities. In a retrospective cohort study of 756 patients with chronic AR, beta-blocker therapy was associated with decreased mortality. Patients treated with beta-blockers were more likely to be taking ACE inhibitors and dihydropyridine calcium channel blockers as well (53% vs. 40%). In the same study, patients treated with beta-blockers and undergoing AVR were also noted to have a mortality benefit.
  • •Diuretics and sodium restriction for CHF.
  • •Comparable efficacy of losartan and atenolol was shown in curbing aortic root dilatation growth in children and young adults (6 mo to 25 yr) with Marfan syndrome with similar outcomes of aortic regurgitation severity, surgery, aortic dissection, and death at 3 yr. 

American College of Cardiology/American Heart Association Guidelines for Aortic Valve Replacement (AVR) for Chronic Aortic Regurgitation (AR)

From Zipes DP et al: Braunwald’s heart disease, a textbook of cardiovascular disease, ed 11, Philadelphia, 2019, Elsevier.

ClassIndicationLOE
IAVR for symptomatic patients with severe AR regardless of LV systolic function (stage D).B
AVR for asymptomatic patients with chronic severe AR and LV systolic dysfunction (LVEF <50%) (stage C2).B
AVR for patients with severe AR (stage C or D) while undergoing cardiac surgery for other indications.C
IIaAVR is reasonable for asymptomatic patients with severe AR with normal LV systolic function (LVEF ≥50%), but severe LV dilation (stage C2, LVESD >50 mm).B
AVR is reasonable in patients with moderate AR (stage B) who are undergoing other cardiac surgery.C
IIbAVR may be considered for asymptomatic patients with severe AR and normal LV systolic function (stage C1, LVEF ≥50%) but severe LV dilation (LVEDD >65 mm) if surgical risk is low. C

LOE, Level of evidence; LV, left ventricular; LVEDD, LV end-diastolic dimension; LVEF, LV ejection fraction; LVESD, LV end-systolic dimension.

∗ Particularly in the setting of progressive LV enlargement.

Referral

Surgical referral is reserved for the following patients:

  • •Patients with acute severe AR (i.e., infective endocarditis) and cardiogenic shock
  • •Symptomatic patients with severe AR regardless of LV systolic function (class I)
  • •Patients with hemodynamically stable severe AR undergoing CABG or surgery on the aorta or other heart valves
  • •Evidence of systolic dysfunction with left ventricular ejection fraction of less than 50% and asymptomatic patients with chronic severe AR
  • •Asymptomatic patients with severe AR and left ventricular ejection fraction >50%, but with left ventricular dilation:
    • 1.Echocardiographic end-systolic dimension >50 mm (Class IIa level of evidence) or;
    • 2.Echocardiographic end-diastolic dimension >65 mm with low surgical risk (Class IIb)

Suggested Readings

  • Gilard M., et al.: Registry of transcatheter aortic valve implantation in high risk patients. N Engl J Med 2012; 366: pp. 1705-1715.
  • Nishimura RA et al: AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol Circulation 135:e1159-e1195, 2017. 63(22):2438-2488, 2014.
  • Yoon S.H., et al.: Transcatheter aortic valve replacement in pure native aortic valve regurgitation. J Am Coll Cardiol 2017; 70: pp. 2752-2763.
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