Aortic Regurgitation

Overview

Definition

Aortic regurgitation (AR) or aortic insufficiency:

• The backflow of blood to the left ventricle (LV) through the aortic valve during diastole 
• Caused by the incomplete closure of the valve leaflets (which normally facilitate unidirectional flow of blood from the left ventricle)
• Abnormalities involve aortic root and/or aortic valves.
• Onset can be acute or chronic.

Epidemiology

• Rheumatic heart disease: most common cause of AR worldwide
• Men > women
• In developed countries, the most common causes are:
  • Aortic root dilation
  • Congenital bicuspid aortic valve 
  • Calcific aortic valve disease
• Prevalence increases in patients > 50 years of age.

Etiology

• Acute aortic regurgitation
  • 2 most common causes (native valve):
    • Infective endocarditis
    • Type A aortic dissection
  • Others:
    • Chest trauma
    • Myocardial infarction
    • Deterioration of prosthetic aortic valve
    • Iatrogenic (aortic balloon valvotomy or transcatheter aortic valve implantation)
• Chronic aortic regurgitation
  • Bicuspid valve (most common congenital cause of AR)
  • Rheumatic heart disease 
  • Hypertension
  • Connective tissue disorder: Marfan’s syndrome, Ehlers-Danlos syndrome
  • Tertiary syphilis (due to expanding aneurysm)
  • Vasculitis: giant cell arteritis, Takayasu’s arteritis
  • Ankylosing spondylitis (aortitis)
  • Rheumatoid arthritis
  • Medications: fenfluramine and dexfenfluramine (induce valvular degeneration)

Pathophysiology

Acute AR

• Abrupt dysfunction of aortic valve → failure of valve to coaptate
• Sudden increase in backflow of blood into the LV → increase in LV diastolic pressure
• LV unprepared for the increased volume → decreased cardiac output  → tachycardia to compensate
• Rapid rise in LV diastolic pressure closes the mitral valve prematurely → ↑ pulmonary venous pressure → pulmonary edema and cardiogenic shock

Chronic AR

• Aortic valve unable to close → portion of stroke volume leaks back to the LV
• Regurgitant flow → increases end-diastolic volume and wall stress 
• LV adapts to volume overload by eccentric hypertrophy and dilation → allows larger stroke volume 
• Over time, increased stroke volume → distends peripheral arteries and ↑ systolic pressure
• In advanced disease, LV reaches maximum diameter and cannot keep up with the hemodynamic load → LVEF gradually declines → left heart failure symptoms 
• Elevated LV mass → increases myocardial oxygen requirements → myocardial ischemia and exertional chest pain

Clinical Presentation

Acute AR

• Medical emergency!
• Signs and symptoms from pulmonary edema and cardiogenic shock → dyspnea, chest pain
• Exam shows:
  • Hypotension, tachypnea, tachycardia, diaphoresis
  • Soft S1 due to early mitral valve closure 
  • Soft systolic murmur (from increased blood volume) + early low-pitched diastolic AR murmur → “to-and-fro” murmur at the cardiac base

Chronic AR

Symptoms:

• Initially asymptomatic (when LV is able to compensate)
• Symptoms start with reduced LV function.
  • Palpitations (tachycardia)
  • Exertional dyspnea
  • Orthopnea, paroxysmal nocturnal dyspnea
  • Chest pain (nighttime angina due to ↓ sleep heart rate = ↓ diastolic pressure)

Signs:

• Inspection: hyperdynamic apical impulse displaced laterally and inferiorly
• Auscultation:
  • AR murmur:
    • Early diastolic murmur, high-pitched; sustained or decrescendo
    • Becomes holodiastolic in severe AR
    • Heard best at left sternal border, 3rd and 4th intercostal space
    • ↑ With squatting, ↓ with Valsalva maneuver
  • Austin Flint murmur:
    • Low-pitched, diastolic rumble at the apex
    • Premature closure of mitral valve (effect of AR jet)
  • S3 gallop in LV dysfunction
• Widened pulse pressure (systolic hypertension, ↓ diastolic pressure)
  • Hill’s sign:
    • Strong specificity
    • Popliteal cuff systolic pressure exceeds brachial cuff pressure by > 20 mm Hg on recumbent position
  • Corrigan pulse:
    • “Water hammer” or “collapsing pulse” in radial/brachial/carotid arteries
    • Abrupt distention of peripheral arteries (rapid rise of arterial pulse) with quick collapse
  • Bisferiens pulse: biphasic pulse from the backflow of blood (early diastole)
  • Becker’s sign: visible systolic pulsation in retinal arterioles
  • Landolfi’s sign: constriction and dilation of pupils with heartbeat
  • Traube’s sign:
    • “Pistol shot” pulse
    • Booming systolic and diastolic sounds in femoral arteries
  • Muller’s sign: systolic pulsations of the uvula
  • Duroziez’s sign:
    • Systolic murmur on proximal compression of femoral artery
    • Diastolic murmur on distal compression of femoral artery
  • Mayne’s sign: drop of at least 15 mm Hg in diastolic blood pressure when arm is raised
  • Quincke’s pulse: visible pulsations in fingernail bed on compression of fingernail
  • de Musset’s sign: head bobbing with heartbeat
  • Rosenbach’s sign: systolic pulsations of the liver
  • Gerhard’s sign: systolic pulsations of the spleen

Audio:

This audio clip is an example of aortic regurgitation. It is characterized by a blowing, decrescendo murmur occurring right after S2.

Diagnosis

Transthoracic echocardiography (TTE)

• Confirms diagnosis and severity of AR; also used for serial monitoring
• Evaluates aortic root and aortic valve anatomy 
• Evaluates LV:
  • Size
  • Ejection fraction (LVEF)
• Doppler: evaluates central jet width and regurgitant volume/flow/orifice area
• Findings in both acute and chronic AR: 
  • Abnormal or normal but stretched valve
  • Severe AR: ↑ central jet width/↑ regurgitant volume/↑ regurgitant orifice area/holodiastolic flow reversal in descending aorta
  • Mitral valve: anterior mitral leaflet shows diastolic fluttering 
• Findings in acute AR:
  • Done bedside
  • LV size usually normal
• Findings in chronic AR: 
  • LV size and volume increased initially, unchanged LVEF
  • In advanced stage or decompensated state, ↓ LVEF
  • TTE serial monitoring (guides therapeutic management)

Transesophageal echocardiography (TEE)

• Performed if TTE is suboptimal
• Other indications:
  • Infective endocarditis
  • Aortic dissection (helps determine surgical options)

Electrocardiogram (ECG)

• Acute AR: nonspecific ST-T wave changes
• Chronic AR:
  • Left ventricular hypertrophy
  • Left axis deviation 
  • Ischemic changes in advanced disease

Chest X-ray

• Acute AR:
  • Prominent aortic root
  • Enlarged cardiac silhouette (in aortic dissection + pericardial effusion)
  • Pulmonary edema
• Chronic AR: 
  • Aortic dilation/calcification
  • Cardiomegaly

Cardiac Magnetic Resonance (CMR)

• Used if TEE is suboptimal in chronic AR
• Evaluates AR severity
• Most accurate non-invasive technique for LV end-systolic and diastolic volumes
• Not for widespread use due to expense and limited availability 
• Incompatible with metallic hardware

Cardiac Catheterization

• Utilized to assess coronary anatomy prior to surgery (for chronic AR)
• Provides additional information if with conflicting clinical findings:
  • LV size and EF 
  • Number of leaflets 
  • Severity of AR
  • Aortic root size

Treatment and Prognosis

Acute AR

• Emergency aortic valve replacement or repair
• While awaiting surgery, interim use of:
  • IV vasodilators such as nitroprusside (afterload reduction) 
  • Inotropic agents such as dobutamine (↑ cardiac output)
• Temporary delay in surgery so antibiotics can be given in infective endocarditis 
  • If patient is stable
  • Immediate surgery in hemodynamic instability or abscess formation
• Avoid intra-aortic balloon pump (worsens AR)
• Avoid beta-blockers (↓ compensatory tachycardia, ↓ cardiac output)

Chronic AR

• Monitor disease course (TTE):
  • Frequency of examination depends on symptoms, AR severity, LV size and function
  • In case of bicuspid aortic valve: Also monitor aneurysm if present.
• Physical activity:
  • The following are recommended for athletes with AR:
    • Yearly history and physical exam with Doppler echocardiogram 
    • Exercise testing (to level of competition): to confirm asymptomatic status and blood pressure response to activity
• Endocarditis prophylaxis (for procedure):
  • Not recommended in native valve disease
  • Indicated in prosthetic heart valve or prior infective endocarditis
• Medical management: 
  • For symptomatic patients with severe AR (surgical and non-surgical candidates), medications include:
    • Diuretics
    • Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) 
    • Beta-blockers
    • Mineralocorticoid receptor antagonists 
    • Digoxin
  • For asymptomatic patients with severe AR + LV dysfunction (non-surgical candidates): ACE inhibitors or ARBs
  • Hypertension control: ACE inhibitors, ARBs, or calcium channel blockers
• Surgical management (aortic valve replacement or AVR): 
  • Symptomatic severe AR
  • Asymptomatic:
    • Severe AR LVEF < 50%
    • Severe AR with normal LVEF ( ≥ 50%) but with an end-systolic dimension of > 50 mm
    • Severe AR with normal LVEF ( ≥ 50%) but with progressive severe LV dilation (LV end-diastolic dimension > 65 mm); with low surgical risk
    • Severe AR who are undergoing cardiac surgery for other indications
    • Moderate AR who are undergoing other cardiac surgery

Prognosis

• Patients with acute AR: high operative risk
• Patients with asymptomatic chronic AR:
  • Favorable prognosis 
  • When monitored, LV dysfunction is detected early, even before symptoms
• Symptomatic chronic AR: 
  • New York Heart Association (NYHA) class II symptoms: 6% mortality per year
  • NYHA class III or IV symptoms: 25% mortality per year

Differential Diagnosis

Differential diagnoses of AR include the following conditions:

• Aortic stenosis (AS): one of the most common valvular heart diseases; characterized by narrowing of the aortic outlet. This narrowing leads to restriction of blood flow from the LV to the aorta. Aortic stenosis is heard as a systolic crescendo-decrescendo murmur in the 2nd intercostal space. Diagnosis is by echocardiography. Patients with chronic AS develop exertional dyspnea, angina, and syncope.
• Mitral regurgitation: a mitral valve pathology that leads to leakage of blood from the LV to the left atrium during systole. Examination shows a holosystolic murmur at the apex (left 5th intercostal space at the midclavicular line). Diagnosis is confirmed by echocardiography. Presenting symptoms are frequently exertional dyspnea and fatigue.
• Aortic dissection: a tear in the intima of the aorta that can expand back into the heart, causing dilation and insufficiency of the aortic valve. Aortic dissection in the ascending aorta or aortic root is manifested as severe tearing chest pain. Computed tomography angiogram establishes the diagnosis.
• Aortic aneurysm: an abnormal dilation of the aorta, usually caused by degenerative aortic disease; can lead to progressive dilation of the aortic root. Aortic aneurysm is often asymptomatic, found incidentally on CT or echocardiogram. Symptoms are noted when the aneurysm compresses surrounding structures. Ruptured aneurysm is a life-threatening emergency.
• Myocardial infarction: an acute blockage of the coronary arteries supplying the heart, which can predispose structural valvular incompetence. The condition commonly presents with chest pain and is diagnosed with ECG and cardiac enzymes.
• Infective endocarditis: an infection of the lining of the heart,  most frequently affecting the cardiac valves. The condition is frequently caused by Staphylococci, Streptococci, and Enterococci. Examination shows fever with a new heart murmur. Diagnosis is by history, blood cultures, and echocardiography.
• Atrial fibrillation: a form of supraventricular arrhythmia. Diagnosis is by ECG, which shows “irregularly irregular” heartbeat with no distinct P waves and narrow QRS complexes. Chronic mitral regurgitation may lead to dilation of the left atrium, which can lead to the development of atrial fibrillation.
• Congestive heart failure with systolic dysfunction: a chronic, progressive condition characterized by left ventricular dysfunction from impaired myocyte contractility, which leads to subsequent volume overload. Risk factors include hypertension, coronary artery disease, and diabetes mellitus. Congestive heart failure can develop with or without valvular abnormalities.