Aortic Regurgitation Topic Review

Pathophysiology | Etiology | Symptoms | Physical Examination | Peripheral Signs | Diagnosis | Treatment

Introduction

aortic_regurgitation

Aortic regurgitation occurs when blood flows backwards, or retrograde, across the aortic valve from the aorta into the left ventricle during diastole. This abnormal backflow of blood leads to pathologic changes in the heart in order to compensate for the decreased effective cardiac output that results.

Aortic regurgitation occurs from either damage to the aortic valve leaflets or dilation of the aortic annulus. As the disease progresses, symptoms of congestive heart failure eventually occur. The ultimate treatment is surgical aortic valve replacement; however, medical therapy can improve symptoms.

Pathophysiology – Aortic Regurgitation

The abnormal backflow of blood that occurs leads to pathologic changes that are highly dependent on aortic regurgitation severity and pace of disease development.

Left ventricular chamber enlargement and hypertrophy take place to help maintain a normal cardiac output in chronic aortic regurgitation. The LV dilates and hypertrophies (eccentrically) slowly over time. These changes help to maintain normal LV pressures in the setting of a significantly increased LV volume. In fact, patients with severe chronic AR may have the largest LV end-diastolic volumes produced by any cardiac disease state, yet their LV end-diastolic pressures are not significantly elevated.

When acute aortic regurgitation occurs, however, these changes are not able to take place. The cardiac pressures increase quickly in this setting, and heart failure — as well as cardiogenic shock —  may occur. The small increase in left ventricular end diastolic volume, or LVEDV, due to the acute AR would lead to a greatly increased left ventricular end diastolic pressure, or LVEDP. This increased pressure is automatically transmitted to the pulmonary vasculature, leading to severe symptoms of left heart failure, including flash pulmonary edema.

As aortic regurgitation worsens, allowing larger volumes of blood to be regurgitated during diastole, aortic diastolic pressures drop significantly. These low diastolic pressures, coupled with increased systolic pressures produced by the hypertrophied left ventricle to maintain cardiac output, produce a widened pulse pressure and a very large stroke volume. This large stroke volume leads to a number of unusual peripheral physical exam findings discussed below in Peripheral Signs. The low diastolic pressures can significantly affect coronary perfusion pressures, as the coronary arteries fill during diastole.

The afterload is an important factor in degree of aortic regurgitation. When systemic pressures are high, a larger volume of blood will flow backwards into the left ventricle. Therefore, the mainstay of pharmacotherapy in aortic regurgitation is aimed at reducing afterload.

Etiology – Aortic Regurgitation

Aortic regurgitation can result from abnormalities of the aortic valve leaflets, dilation of the aortic root or a severe increase in afterload. When the aortic leaflets are involved, there is frequently a destructive process such as infective endocarditis or rheumatic valvular disease ocurring. Any disease process that leads to aortic root dilation — i.e. Marfan’s syndrome or aortic dissection — will cause the aortic valve annulus to stretch, resulting in failure of the leaflets to coapt properly in diastole and, ultimately, aortic regurgitation. Frequently, repairs to the aortic root and valve are required in this scenario.

Below is a list of etiologies for aortic regurgitation:

Aortic leaflet/cusp abnormalities

  • Infectious: Bacterial endocarditis, rheumatic fever
  • Congenital: Bicuspid aortic valve calcification
  • Inflammatory: Systemic lupus erythematosus, or SLE, rheumatoid arthritis, or RA, Behcet’s syndrome
  • Degenerative: Myxomatous (floppy valve), senile calcification
  • Others: Trauma, post-aortic valve valvuloplasty, diet drug valvopathy, carcinoid valve disease (requires lung metastases or patent foramen ovale, or PFO)

Aortic root abnormalities

  • Aortic root dilation: Marfan’s syndrome, syphilitic aortitis, idiopathic aortitis, Ehlers-Danlos syndrome, relapsing polychondritis
  • Loss of commissural support: Aortic dissection, trauma, supracristal ventricular septal defect, or VSD

Increased afterload

  • Uncontrolled systemic hypertension
  • Supravalvular aortic stenosis (can occur in William’s syndrome)
  • Coarctation of the aorta

Symptoms – Aortic Regurgitation

As chronic aortic regurgitation develops slowly over time, the left ventricle slowly and easily compensates, as described previously. Therefore, no symptoms occur early in disease — for a long period of time. Once they occur, the aortic regurgitation symptoms are mostly from congestive heart failure.

Left heart failure results in symptoms related to low cardiac output. The condition causes dyspnea from high pressure in the left ventricle transmitting into the pulmonary vasculature. During physical activity, with the heart demanding output unable to be met in states of heart failure, increasing left heart pressures cause transient pulmonary edema.

As those increased pressures from the left heart affect the right ventricle, right heart failure can ensue. The most common cause of right HF is left HF.

Right heart failure symptoms include lower extremity-dependent edema. When the legs are elevated at night, the fluid redistributes centrally, causing pulmonary edema that results in orthopnea (dyspnea while lying flat) or paroxysmal nocturnal dyspnea. Hepatic congestion can also occur, producing right upper quadrant abdominal pain.

Palpitations may result from the large stroke volumes and forceful LV contractions. Angina may occur in the absence of atherosclerotic coronary disease, as the low diastolic pressures in severe aortic regurgitation compromise coronary filling, and the left ventricular hypertrophy increases oxygen demand. Other symptoms related to low cardiac output include fatigue, weakness and, in extreme cases, cardiac cachexia.

Unlike in chronic aortic regurgitation, almost all patients with significant acute aortic regurgitation are symptomatic. Signs of acute left heart failure — including severe dyspnea, even at rest, orthopnea and PND — arise. Hypotension, flash pulmonary edema and shock can also occur.

Physical Examination – Aortic Regurgitation

In chronic aortic regurgitation, visible cardiac and arterial pulsations are common due to the large stroke volume. The carotid pulse can commonly be seen. The point of maximal impulse, or PMI, is displaced laterally and caudally due to the LV dilation and hypertrophy that occurs. On auscultation, the typical murmur of aortic regurgitation is a soft, high-pitched, early diastolic decrescendo murmur heard best at the third intercostal space on the left, known as Erb’s Point, on end expiration with the patient sitting up and leaning forward.

AR

This murmur is often difficult to distinguish from the Graham-Steele murmur of pulmonic insufficiency. If aortic root disease is the cause of the aortic regurgitation, the murmur will be heard best at the right upper sternal border — not at Erb’s point. As aortic regurgitation worsens, the murmur becomes shorter in duration, as less time is needed for left ventricular and aortic pressure equalization.

In addition to the above murmur, a systolic ejection murmur may be present at the right upper sternal border, simply due to the large stroke volume passing through the aortic valve with each LV systolic contraction. An early diastolic rumble may also be heard at the apex, due to the regurgitant jet striking the anterior leaflet of the mitral valve and causing it to vibrate; this murmur is termed the Austin-Flint murmur.

A widened pulse pressure is often present due to the high-flow state as previously described. When severe heart failure develops, the pulse pressure decreases and the peripheral signs of aortic regurgitation, listed below, are lessened. A fourth heart sound (S4) develops when LVH becomes severe and limits diastolic filling. A third heart sound (S3) is often present, due to increased early diastolic filling into a compliant, dilated left ventricle.

Acute aortic regurgitation will cause a very short, early diastolic decrescendo murmur with the aortic and left ventricular pressures equalized quickly, as the left ventricle has not had time to dilate or hypertrophy.

Peripheral Signs – Aortic Regurgitation

The peripheral signs of aortic regurgitation are mostly due to the high-flow state, large stroke volume and wide pulse pressure seen in aortic regurgitation.

In 19th century Europe, the infection syphilis was widespread. Syphilitic aortitis, resulting in aortic root dilation and severe aortic valve regurgitation, was quite common. With no good therapy — medical or surgical — available during that period, the disease was allowed to progress; many individuals developed severe congestive heart failure from the aortic valve regurgitation. This resulted in physical examination findings described by multiple physicians, attempting to diagnose aortic regurgitation as the cause of an individual’s congestive heart failure.

Many peripheral signs of aortic regurgitation have been identified and named after the physician that first described it; they are listed below. The sensitivity of these findings are low. While intellectually and historically interesting, they are not always clinically useful.

  • Corrigan’s pulse: A rapid and forceful distension of the arterial pulse with a quick collapse
  • De Musset’s sign: Bobbing of the head with each heartbeat (like a bird walking)
  • Muller’s sign: Visible pulsations of the uvula
  • Quincke’s sign: Capillary pulsations seen on light compression of the nail bed
  • Traube’s sign: Systolic and diastolic sounds heard over the femoral artery (“pistol shots”)
  • Duroziez’s sign: Gradual pressure over the femoral artery leads to a systolic and diastolic bruit
  • Hill’s sign: Popliteal systolic blood pressure exceeding brachial systolic blood pressure 60 mm Hg or more (most sensitive sign for aortic regurgitation)
  • Shelly’s sign: Pulsation of the cervix
  • Rosenbach’s sign: Hepatic pulsations
  • Becker’s sign: Visible pulsation of the retinal arterioles
  • Gerhardt’s sign (aka Sailer’s sign): Pulsation of the spleen in the presence of splenomegaly
  • Mayne’s sign: A decrease in diastolic blood pressure of 15 mm Hg when the arm is held above the head (very nonspecific)
  • Landolfi’s sign: Systolic contraction and diastolic dilation of the pupil

In acute aortic regurgitation, the above listed peripheral signs are absent, as the heart does not have time to compensate for the increased LV volume. Additionally, the murmur of aortic regurgitation is short in duration and may be difficult to hear with the aortic pressure and the LV pressure (elevated in acute AR) equalizing quickly in diastole. A soft first heart sound may be present, due to early closure of the mitral valve.

Diagnosis – Aortic Regurgitation

Aortic regurgitation is best diagnosed by echocardiography, as the murmur can be missed on physical examination in many cases. Almost 100% sensitive and specific for the detection of aortic regurgitation, echocardiography is also crucial in determining etiology and estimating severity.

The actual regurgitant jet can be directly visualized using color flow Doppler; this is extremely important in patients with acute AR, because the physical examination may not reveal any valvular abnormality.

Regarding etiology, structural abnormalities, such as a bicuspid aortic valve or prolapse of the AV may be seen. Vegetations on the aortic valve, indicating endocarditis as the cause, may also be identified — though transesophageal echocardiography is more sensitive. Further, the size of the aortic root can be measured and aortic dissections identified.

The severity of aortic regurgitation can be estimated using three parameters on echocardiography:

  1. Regurgitant jet size
  2. Pressure half-time
  3. Regurgitant fraction

Regurgitant jet size represents the ratio of the aortic regurgitation jet diameter just below the leaflets of the aortic valve to the size of the LV outflow diameter. Ideally, the ratio should be zero because no regurgitant jet should be present. A ratio of below 24 is mild, between 25 and 45 moderate, between 46 and 64 moderately severe, and higher than 65 severe.

The pressure half-time index is the time it takes for the initial maximal pressure gradient in diastole to fall by 50%. In patients with mild aortic regurgitation, this fall in pressure is gradual. In the setting of severe aortic regurgitation, a rapid drop in pressure gradient occurs. A pressure half-time of greater than 500 milliseconds is considered mild aortic regurgitation, from 500 ms to 349 ms is moderate, from 349 ms to 200 ms is moderately severe, and less than 200 ms is severe. The severity of aortic regurgitation assessed by using the pressure half-time is overestimated in patients with a significantly increased LVEDP.

The regurgitant fraction is perhaps a more straightforward means of assessing aortic regurgitation severity. The regurgitant fraction is the percentage of stroke volume that returns to the left ventricle from the aorta during diastole. For example, a regurgitant fraction of 33% would indicate that one-third of the total stroke volume returns to the LV retrograde across the aortic valve during diastole. A regurgitant fraction of less than 20% indicates mild aortic regurgitation, from 20% to 35% moderate aortic regurgitation, from 36% to 50% moderately severe aortic regurgitation, and greater than 50% severe aortic regurgitation.

  Jet Size Ratio Pressure Half-Time Regurgitant Fraction (%)
Mild <24 >500 <20
Moderate 25-45 500-349 20-35
Moderate-severe 46-64 349-200 56-50
Severe > 65 < 200 > 50

It is important to note that the severity of aortic regurgitation assessed using echocardiography is dependent on the hemodynamic status of the patient at the time of the evaluation — most importantly, the afterload.

Cardiac catheterization with aortography and hemodynamic measurements is not necessary in the majority of patients with aortic regurgitation because of the accuracy of echocardiography. During cardiac catheterization, aortic regurgitation can be detected by injecting contrast into the aortic root and visualizing the appearance of contrast in the left ventricle.

Catheterization can also assess for aortic root disease. Several factors affect the grading of severity of aortic regurgitation during the procedure. If the catheter is positioned too closely to the aortic valve, the amount of aortic regurgitation will be overestimated. The volume and rapidity of injection of contrast into the aortic root affects the amount of aortic regurgitation visualized. As previously mentioned, the hemodynamic parameters at the time of assessment also affect the severity of aortic regurgitation — again, mostly afterload.

The grading scale for aortic regurgitation used during catheterization is below. Cardiac catheterization can also measure LVEDV and LVEDP, which can be helpful in determining aortic regurgitation. Cardiac catheterization with coronary angiography is indicated if aortic valve replacement is planned, so the coronary arteries can be imaged. If significant coronary atherosclerosis is present, coronary artery bypass grafting, or CABG, can be done at the same time as the valve replacement.

  Amount LV contrast Intensity Contrast clearance
I (mild) Some contrast seen Aorta > LV Completely cleared each beat
II (moderate) Completely filled LV after many beats Aorta > LV Incomplete clearance each beat
III (mod-sev) Completely filled after several beats Aorta = LV Slow clearance
IV (severe) Completely filled after only one beat Aorta < LV Very slow clearance
 

The ECG in patients with aortic regurgitation is non-specific and may show left ventricular hypertrophy and left atrial enlargement. In acute aortic regurgitation, sinus tachycardia due to the increased sympathetic nervous tone may be the only abnormality on ECG. The chest radiograph is also nonspecific in aortic regurgitation. Cardiomegaly is present in patients with chronic AR. In acute AR, pulmonary edema is almost universally present. If the AR is due to an aortic dissection, the mediastinum may appear widened.

Treatment – Aortic Regurgitation

In patients with mild to moderate aortic regurgitation, no specific treatment is required. These patients should be monitored yearly to assess disease progression. Antibiotic prophylaxis is recommended to prevent bacterial endocarditis.

Patients with moderate to severe aortic regurgitation who are symptomatic should undergo AVR if they fall into New York Heart Association functional class III-IV heart failure. Those in NYHA class II should receive an exercise stress test to assess endurance and exercise capacity and treated with diuretics and afterload reducers — commonly angiotensin converting enzyme inhibitors — until AVR is indicated.

If moderate to severe aortic regurgitation is present but the patient is asymptomatic, AVR is not clearly indicated. Afterload reducers are given and frequent echocardiographic assessment is recommended to monitor LV dysfunction. The ideal time for AVR is late enough in the course of the disease to justify the risk-benefit ratio of surgery, yet early enough to prevent potential irreversible myocardial damage from occurring. The LV ejection fraction has been shown to correlate best with surgical outcome.

Although reducing afterload with medications can lessen AR and improve symptoms, there is no evidence that this approach delays the need for surgical AVR. The most commonly used medications for this purpose include ACE inhibitors, such as lisinopril or ramipril, and dihydrophridine calcium channel blockers, such as amlodipine and nifedipine.

Surgical replacement — not repair — of the aortic valve is the definitive therapy.

The indications, according to American College of Cardiology/American Heart Association guidelines, include the following:

  • Symptomatic heart failure (class I)
  • Equivocal symptoms and poor performance on a treadmill exercise test (class I)
  • No symptoms, but left ventricular ejection fraction < 50% (class I)
  • No symptoms, normal left ventricular ejection fraction, but left ventricular enlargement with end-systolic dimension of 55 mm and end-diastolic of 75 mm (class IIa)
  • Severe aortic regurgitation with no symptoms, a normal left ventricular ejection fraction, but left ventricular end systolic dimension between 50-55 mm or end diastolic dimension between 70-75 mm (class IIb)

The indications for aortic valve replacement, when endocarditis is the etiology, include the following:

  • Congestive heart failure from valvular regurgitation
  • Failure of antibiotic therapy to successfully suppress infection, or infection with difficult-to-treat organisms (fungal, Pseudomonas, Brucella, drug-resistant organisms)
  • Valvular annular abscess
  • Peripheral embolism of vegetation
  • Size of vegetation > 1.0 cm

Acute aortic regurgitation carries a very high mortality if prompt surgical intervention in the form of aortic valve replacement (AVR) is not undertaken. Treatment of pulmonary edema and afterload reduction can help relieve symptoms, buying the patient some time before surgery is performed. Nitroprusside is the treatment of choice, as it reduces both preload and afterload with great efficacy. Dobutamine may be needed if the patient remains hypotensive with a low cardiac output. The use of intra-aortic balloon counterpulsation is contraindicated in severe aortic regurgitation; further, the approach is not commonly used in acute aortic regurgitation as it is in acute mitral regurgitation. If the acute aortic regurgitation is due to infective endocarditis, at least 7 days of IV antibiotics are often given before valve replacement.

References:
1. ACC/AHA Guidelines: Valvular Heart Disease
2. Bekeredjian R and Grayburn PA. Aortic Regurgitation. Circulation2005;doi:10.1161/CIRCULATIONAHA.104.488825.
3. Braunwalds Heart Disease: A Textbook of Cardiovascular Medicine
4. Hursts the Heart, 13th Edition