Aortic Regurgitation

Denisa Hagau, M.D.

Basic Information

Definition

Aortic regurgitation (AR) is retrograde blood flow into the left ventricle from the aorta as a result of an incompetent aortic valve.

Stages of chronic aortic regurgitation:

Stage A = at risk of AR (e.g., bicuspid AV, AV sclerosis) but no aortic regurgitation.
Stage B = progressive AR with mild and moderate aortic regurgitation.
Stage C = asymptomatic severe AR.
Stage D = symptomatic severe AR.

Synonyms

Aortic insufficiency
AI
AR

ICD-10CM CODES
I35.1	Nonrheumatic aortic (valve) insufficiency
I35.2	Nonrheumatic aortic (valve) stenosis with insufficiency
Q23.1	Congenital insufficiency of aortic valve

Epidemiology & Demographics

•

Prevalence ranges from 4.9% to 10% and increases with age.
•

The most common cause of isolated severe AR is aortic root dilation.
•

Infectious endocarditis is the most frequent cause of acute AR.

Physical Findings & Clinical Presentation

The clinical presentation varies depending on whether aortic insufficiency is acute or chronic. Chronic aortic insufficiency is well tolerated (except when secondary to infective endocarditis), and the patients remain asymptomatic for years. Common manifestations after significant deterioration of left ventricular function are dyspnea on exertion, syncope, chest pain, and congestive heart failure (CHF). The stages of chronic AR are summarized in Table 1. Acute aortic insufficiency manifests primarily with hypotension caused by a sudden fall in cardiac output and resultant cardiogenic shock. In addition, a rapid rise in left ventricular diastolic pressure results in a further decrease in coronary blood flow.

TABLE1 Stages of Chronic Aortic RegurgitationFrom Nishimura RA, Otto CM, Bonow RO, 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, Zipes DP, Libby P, Bonow RO: Braunwald’s Heart Disease, ed 10, Philadelphia, 2015, Elsevier.

Stage	Definition	Valve Anatomy	Valve Hemodynamics	Hemodynamic Consequences	Symptoms
A	At risk of AR	Bicuspid 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 trace	None	None
B	Progressive AR	Mild 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 function Normal LV volume or mild LV dilation	None
C	Asymptomatic severe AR	Calcific aortic valve disease Bicuspid 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
D	Symptomatic severe AR	Calcific valve disease Bicuspid 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 present	Exertional dyspnea or angina, or more severe HF symptoms
ERO, effective regurgitant orifice; HF, heart failure; IE, infective endocarditis; 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 aortic insufficiency include the following:

•

Widened pulse pressure (markedly increased systolic blood pressure, decreased diastolic blood pressure). Fig. 1 illustrates characteristics of AR murmur.

FIG.1

Aortic regurgitation as an example of an early diastolic murmur.

From Epstein O: Pocket Guide to Clinical Examination, ed 4, 2009.
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Findings associated with the widened pulse pressure:
1. 1.
  
  Bounding pulses, “water hammer” or collapsing pulse (Corrigan’s pulse), can be palpated at the wrist or on the femoral artery and is caused by rapid rise and sudden collapse of the arterial pressure during late systole.
2. 2.
  
  Head “bobbing” with each systole (de Musset’s sign).
3. 3.
  
  “Pistol shot femorals” (Traube’s sign) is a term used to describe a loud sound over the femoral artery.
4. 4.
  
  Capillary pulsations (Quincke’s sign) may occur at the base of the nail beds.
•

A to-and-fro Duroziez double intermittent femoral murmur may be heard over femoral arteries with slight compression with the edge of the stethoscope.
•

Popliteal systolic pressure is increased more than 20 mm Hg over brachial systolic pressure (Hill’s sign), with a 40 to 60 mm difference representing moderate AR and >60 mm difference severe AR.
•
Other findings associated with AR, which are more of historical than practical interest, include:
1. 1.
  
  Mueller’s sign—Systolic pulsations of the uvula.
2. 2.
  
  Becker’s sign—Visible pulsations of the retinal arteries and pupils.
3. 3.
  
  Mayne’s 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. 4.
  
  Rosenbach’s sign—Systolic pulsations of the liver.
5. 5.
  
  Gerhard’s sign—Systolic pulsations of the spleen.
•
Cardiac auscultation reveals:
1. 1.
  
  Displacement of cardiac impulse downward and to the patient’s left
2. 2.
  
  S₃ heard over the apex
3. 3.
  
  Decrescendo, blowing diastolic murmur heard along left sternal border
4. 4.
  
  Low-pitched apical diastolic rumble (Austin-Flint murmur)—the precise etiology of the murmur is uncertain, but it is generally believed to be related to increased velocity of mitral inflow consequent to the AR
5. 5.
  
  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. 1.
  
  Infective endocarditis
2. 2.
  
  Rheumatic fibrosis (most common cause in developing countries)
3. 3.
  
  Trauma with valvular rupture
4. 4.
  
  Congenital bicuspid aortic valve (most common cause in the United States)
5. 5.
  
  Myxomatous degeneration
6. 6.
  
  Fenfluramine, dexfenfluramine, pergolide, cabergoline
7. 7.
  
  Ankylosing spondylitis
•
Aortic root or ascending aorta abnormalities:
1. 1.
  
  Annuloaortic ectasia
2. 2.
  
  Ehlers-Danlos syndrome
3. 3.
  
  Marfan’s syndrome
4. 4.
  
  Trauma: ankylosing spondylitis
5. 5.
  
  Syphilitic aortitis
6. 6.
  
  Systemic hypertension
7. 7.
  
  Aortic dissection
•

Postprocedural aortic regurgitation, usually due to a paravalvular leak, occurs in 10% to 20% of patients undergoing transcatheter aortic valve replacement. Patients with more than mild aortic regurgitation after transcatheter aortic valve replacement have worse outcomes than those without aortic regurgitation.

Diagnosis

Differential Diagnosis

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Patent ductus arteriosus, pulmonary regurgitation, and other valvular abnormalities.
•

The differential diagnosis of cardiac murmurs is described in Sections II and III.

Workup

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Echocardiogram, chest radiograph, electrocardiogram (ECG), cardiac magnetic resonance imaging, and cardiac catheterization (selected patients).
•
Medical history and physical examination focused on the following clinical manifestations:
1. 1.
  
  Dyspnea on exertion.
2. 2.
  
  Syncope.
3. 3.
  
  Chest pain.
4. 4.
  
  CHF.

Imaging Studies

•
Chest radiography:
1. 1.
  
  Left ventricular hypertrophy (LVH) (chronic AR).
2. 2.
  
  Aortic dilation.
3. 3.
  
  Normal cardiac silhouette with pulmonary edema: possible in patients with acute AR.
•

ECG: LVH.
•

Echocardiography (Fig. E2) 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).

FIG.E2

Composite of echocardiograms recorded in patients with aortic regurgitation. The two top panels were recorded in the same patient and show, on the left, an apical long-axis view and, on the right, a parasternal short-axis view. In the apical long-axis view, note the fairly extensive confetti-like aortic regurgitation jet arising from the proximal aorta and traversing to the left ventricular apex. Note also that the aortic regurgitation jet velocities merge with the mitral inflow velocities, rendering quantitation problematic. The top right panel is recorded in the same patient and shows a central aortic regurgitation jet. The bottom left panel is a transesophageal echocardiogram recorded in a longitudinal view. Note the highly eccentric aortic regurgitation jet that appears to fill the entire width of the left ventricular outflow tract. This apparent filling of the left ventricular outflow tract is due to the posterior to anterior jet direction (white arrow) rather than to a substantial true width of the jet. The bottom right panel is a color M-mode echocardiogram recorded in a patient with aortic insufficiency in which the normal systolic flow can be appreciated as well as a continuous diastolic flow in the lumen of the aorta that represents aortic insufficiency. The two downward-pointing arrows denote the duration of systole, and the two upward-pointing arrows indicate the duration of diastole. Ao, Aorta; LA, left atrium; LV, left ventricle; RA, right atrium; RVOT, right ventricular outflow tract.

From Zipes DP et al [eds]: Braunwald’s heart disease, ed 7, Philadelphia, 2005, Saunders.
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Cardiac magnetic resonance 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, to assess the degree of 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 aortic valve and an aortic diameter greater than 4.0 cm, with the examination interval determined by the degree and rate of progression of aortic dilation and by family history. In patients with an aortic diameter greater than 4.5 cm, this evaluation should be performed annually (Class 1).

Treatment

Nonpharmacologic Therapy

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Avoidance of competitive sports and heavy weight lifting if the AR is severe and associated with aortic root dilation.
•

Salt restriction.
•

In 2007, the American Heart Association (AHA) guidelines for prevention of infectious endocarditis were revised; and routine antibiotic prophylaxis to undergo dental or other invasive procedures is no longer recommended, unless the patient has a prior history of endocarditis.

Medical

Acute General Rx

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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 Rx

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Long-term vasodilator therapy with ACE inhibitors or nifedipine in patients who have concomitant hypertension. In one 1994 study (Scognamiglio et al) nifedipine delayed the need for aortic valve surgery compared to digoxin, but in a second randomized trial (Evangelista et al) comparing placebo to nifedipine and enalapril, there was no reduction in need for aortic valve surgery when followed up to 7 years. Therefore 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-25 yr) with Marfan’s syndrome, with similar outcomes of aortic regurgitation severity, surgery, aortic dissection, and death at 3 years.
•

Fig. 3 describes a management strategy for patients with chronic severe AR.

FIG.3

Management strategy for patients with chronic severe AR. AVR, Aortic valve replacement (valve repair may be appropriate in selected patients); ERO, effective regurgitant orifice; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; RF, regurgitant fraction; RVol, regurgitant volume.

From Nishimura RA, Otto CM, Bonow RO, 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, Zipes DP, Libby P, Bonow RO: Braunwald’s heart disease, ed 10, Philadelphia, 2015, Elsevier.

Surgical Reserved for: Referral

Reserved for:

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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%.
•
Asymptomatic patients with severe AR and left ventricular ejection fraction >50%, but with left ventricular dilation:
1. 1.
  
  Echocardiographic end-systolic dimension >50 mm (Class IIa level of evidence) or
2. 2.
  
  Echocardiographic end-diastolic dimension >65 mm with low surgical risk (Class IIb).

Ferri – Aortic Regurgitation