Aortic Regurgitation

Introduction
Background

Aortic regurgitation (AR) results from reverse flow through the aortic valve during diastole as a result of any of a number of potential causes, including intrinsic valvular abnormalities (infection, congenital, inflammation, rupture/tear, fistula, fibrosis, myxomatous degeneration, connective tissue disease) and extra-valvular abnormalities (aortic dissection, dilitation, inflammation, aneurysm, cardiac enlargement).

Primary disease of the aortic valve leaflets, the wall of the aortic root, or both may cause aortic regurgitation (AR). With the decline in the incidence of syphilitic aortitis and rheumatic valvulitis in the second half of the 20th century, various aortic root disorders such as Marfan disease and degeneration of bicuspid aortic valves have become the most common causes of AR.
Pathophysiology

Chronic AR produces left ventricular (LV) volume overload that leads to a series of compensatory changes, including LV enlargement and eccentric hypertrophy. The enlarged ventricle is more compliant and is well suited to deliver a large stroke volume. This occurs through rearrangement of myocardial fibers with the addition of new sarcomeres in series, causing the individual myocardial fibers to become longer. The dilated left ventricle can accommodate increased end-diastolic volume and deliver a larger stroke volume to compensate for the regurgitant aortic flow.

Wall thickness must increase to compensate for the increased ventricular dimensions. These compensatory changes are necessary to minimize or normalize wall stress according to the Laplace law (ie, wall tension/stress is related to the product of intraventricular pressure and radius divided by wall thickness). Increased wall thickness results from increased fiber diameter achieved by an increased number of sarcomeres in parallel. This type of hypertrophy observed in a volume-overload state usually is eccentric, as opposed to concentric hypertrophy observed in a pressure-overload state (ie, aortic stenosis). The increased myocardial mass in a hypertrophic heart enables individual sarcomeres to shorten to a normal degree.

As long as LV wall stress is maintained in the normal range, the LV preload reserve, contractility, and ejection fraction (EF) remain within the normal range. This is the chronic compensated stage. During this phase of the disease, most patients remain asymptomatic for decades because chronic AR generally is a slow and insidious disease with very low morbidity during a long asymptomatic phase.

With time, transition from a compensated to a decompensated state marks the progression of the disease. Progressive LV enlargement beyond that required by the valvular regurgitation occurs and is associated with a change of the left ventricle from an elliptical shape to a spherical shape.

The cause of this pathologic dilatation is not well understood, but loss of the collagen support system that acts as a skeleton for the heart may play a substantial role. These maladaptive changes in the interstitium of the heart are an intricate part of the LV hypertrophy process. In addition, diminished coronary flow reserve in this hypertrophied ventricle is thought to result in chronic subendocardial ischemia, even in the absence of epicardial coronary artery disease (CAD). Eventually, subendocardial necrosis and fibrosis occur, along with disruption of the collagen support system, with loss of LV systolic function. The neurohormonal response complicates the disease state further by its excessive growth stimuli, which are thought to be partially responsible for apoptosis (programmed cell death) of the remaining functional myocytes.

The vicious cycle continues until the decompensated stage develops over many years. Progressive LV enlargement, spherical LV shape, increased wall stress, decline in the contractility and EF, increased afterload, and decreased diastolic compliance with a rise in end-diastolic pressure characterize this stage. Frequently, development of congestive symptoms heralds this stage, but an insidious deterioration of ventricular function may occur without overt clinical signs.

In acute AR, the normal-sized left ventricle poorly tolerates the sudden large volume imposed on it. The left ventricle poorly accommodates the abrupt increase in end-diastolic volume, and diastolic filling pressure increases rapidly and dramatically. This leads to an acute decrease in forward stroke volume, and, although tachycardia develops as a compensatory mechanism to maintain cardiac output, this often is insufficient. The rise in LV filling pressure is transmitted to the left atrium, pulmonary veins, and pulmonary capillaries, leading to pulmonary edema and congestion. Acute AR usually is severe and rapidly leads to LV decompensation and/or failure and cardiogenic shock.

Frequency
United States

With the advent of Doppler echocardiogram studies, many cases of mild AR have been identified in the general population. In some studies, up to 8.5% of women and 13% of men were found to have some degree of AR. In surgical literature, up to 20% of all aortic valve surgeries are performed because of pure AR; however, aortic stenosis remains the most frequent indication for aortic valve replacement (AVR). Multiple logistic regression analysis revealed age and male gender to be predictors of AR.
Mortality/Morbidity

A long asymptomatic period with a relatively rapid downhill course after the onset of cardiac symptoms characterizes the natural history of chronic AR. Data from several studies concerning the natural history of chronic severe AR with normal LV function found the rate of progression to symptoms and/or LV dysfunction (LV ejection fraction [LVEF] <0.50) to be approximately 4.5% per year. The incidence rate of sudden cardiac death was very low, at less than 0.2% per year. Sudden cardiac death has generally not been considered an important risk for patients with AR who are asymptomatic and have normal LV function at rest. AVR can be postponed safely until the appearance of cardiac symptoms and/or LV dysfunction (LVEF <0.50) at rest.

The prognosis of severe AR in asymptomatic patients with normal LV function remains excellent, but extra vigilance is required in monitoring these patients to ensure that the optimal time for surgical intervention is not overlooked.

The risks associated with chronic severe AR are as follows:
In asymptomatic patients with normal LV systolic function, the rate of progression to symptoms and/or LV dysfunction is less than 5% per year, the rate of progression to asymptomatic LV dysfunction is less than 2% per year, and the rate of sudden death is less than 0.2% per year.
For asymptomatic patients with LV systolic dysfunction, the rate of progression to cardiac symptoms is higher than 25% per year. In symptomatic patients, the mortality rate associated with angina is higher than 10% per year and, with congestive heart failure (CHF), is higher than 20% per year.
The rates of death, symptoms, or LV dysfunction in patients with LV end-systolic dimension (LVESD) greater than 55 mm is 19% per year, in patients with an LVESD of 40-49 mm is 6% per year, and in patients with LVESD less than 40 mm is 0% per year.
Because angina and dyspnea have long been considered an indication for surgery in this patient population, no large-scale recent studies exist of the natural history of symptomatic AR. These patients remain at high risk and mortality rates are estimated between 10% and 20%. For these reasons, the Guidelines for the Management of Patients with Valvular Heart Disease presented by the American College of Cardiology (ACC) and American Heart Association (AHA) recommend AVR for patients with class II-IV symptoms of angina or dyspnea and chronic severe AR.
Race

Incidence of AR is similar across various racial populations.
Sex

AR affects males and females equally.
Age

Significant AR can be found in patients of any age; however, the age at which AR becomes clinically significant varies based on etiology. Patients with Marfan disease and those with bicuspid aortic valve problems tend to present earlier in life and generally are free of disability from LV dysfunction at the time of presentation. If left untreated, significant cardiac symptoms commonly appear in the fifth decade of life and beyond, usually after considerable cardiomegaly and myocardial dysfunction have occurred.
Clinical
History

The natural history of AR is a slow and insidious disease process, with many patients remaining asymptomatic for decades. In asymptomatic patients, a cardiac murmur found during a routine medical examination often leads to diagnosis; however, once cardiac symptoms develop, clinical deterioration may progress rapidly.

The principal symptoms associated with severe AR are exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. These symptoms appear when pulmonary venous pressure is elevated in association with significant cardiomegaly and myocardial dysfunction. These changes occur late in the natural history of the disease.
Angina pectoris may occur without CAD because coronary perfusion is inadequate to meet the demands of the enlarged and hypertrophic left ventricle. Less commonly, aortitis can involve the origin of the coronary arteries, leading to angina.
Palpitations are a common complaint associated with a hyperdynamic and tachycardic left ventricle in significant AR. Palpitations also may be due to frequent premature ventricular contractions.
Syncope is an uncommon symptom associated with AR.
Sudden cardiac deaths have been relatively rare in asymptomatic patients with normal LV function (<0.2% per year).
In contrast to chronic AR, symptoms of acute AR (commonly from infective endocarditis, aortic dissection, or trauma) develop rapidly and are very poorly tolerated. In acute AR, the normal-sized ventricle is unable to adapt to the sudden increase in regurgitant volume, in addition to the normal left atrial inflow. Thus, patients develop pulmonary congestion associated with LV failure and, possibly, cardiogenic shock.

Physical
Hemodynamically severe AR causes a widened pulse pressure, often greater than 100 mm Hg, associated with a low diastolic pressure, often less than 60 mm Hg.
The de Musset sign is when patients' heads frequently bob with each heartbeat.
The Corrigan pulse is when patients' pulses are of the water-hammer or collapsing type, with abrupt distention and quick collapse.
The Quincke sign is when light transmitted through the patient's fingertip shows capillary pulsations.
The Hill sign is when popliteal cuff systolic pressure exceeds brachial cuff pressure by more than 40 mm Hg.
The Duroziez sign is when a systolic murmur is heard over the femoral artery when compressed proximally and when a diastolic murmur is heard when the femoral artery is compressed distally.
The Müller sign is systolic pulsations of the uvula.
The Traube sign (also called pistol-shot sounds) refers to booming systolic and diastolic sounds heard over the femoral artery.
The apical impulse in chronic AR is diffuse, hyperdynamic, and displaced inferiorly and leftward.
S3 gallop correlates with development of LV dysfunction.
The typical diastolic murmur of AR has a decrescendo shape. A high-frequency early diastolic murmur often occurs in mild AR, whereas a rough holodiastolic or decrescendo diastolic murmur occurs more commonly in severe AR. The volume and velocity of blood across the incompetent aortic valve tapers off in mid-to-last diastole as the aortic and LV pressures equilibrate. The diastolic murmur of AR is usually best heard adjacent to the sternum in the second to fourth left intercostal space. A concomitant systolic ejection murmur is common in moderate-to-severe AR due to the increased volume of blood flowing across the aortic valve.
The murmur associated with acute AR may not be impressive. If cardiac decompensation is present, the diastolic murmur of acute AR may be very soft and surprisingly short.
Antegrade flow across a partially closed mitral valve is thought to cause an Austin Flint murmur, which is a mid- and late-diastolic apical low-frequency murmur or rumble. The rumble occurs during premature closure of the mitral valve, which occurs when LV diastolic pressure is rising rapidly because of severe aortic reflux. Its presence indicates severe AR.
Causes
Acute aortic regurgitation
Infective endocarditis may lead to destruction or perforation of the aortic valve leaflet. The vegetation can also interfere with proper coaptation of the valve leaflets and can sometimes lead to frank prolapse or flail of a leaflet.
In acute ascending aortic dissection (type A), the retrograde proximal dissection undermines the suspensions of the aortic valve leaflets. Varying levels of aortic valve malcoaptation and prolapse occur.
Prosthetic valve malfunction can lead to AR.
Chest trauma may lead to a tear in the ascending aorta and disruption of the aortic valve support apparatus.
Chronic aortic regurgitation
While a congenital bicuspid aortic valve often leads to progressive aortic stenosis, incomplete closure or prolapse can also lead to significant regurgitant flow across the valve. This common congenial lesion remains the most common cause of isolated AR requiring aortic valve surgery. Histologic abnormalities of the bicuspid root frequently lead to proximal aortic dilatation and further exacerbation of AR.
Connective tissue disorders syndrome, including Marfan syndrome, Ehlers-Danlos syndrome, floppy aortic valve, aortic valve prolapse, sinus of Valsalva aneurysm, and aortic annular fistula can all lead to significant chronic AR.
The use of diet drugs such as fenfluramine and dexfenfluramine (commonly referred to as Phen-Fen) may lead to chronic AR.
Rheumatic fever was a common cause of AR in the first half of the 20th century. The cusps become thickened with fibrous tissues and retract, which causes central valvular regurgitation. Most commonly, some fusion of the cusps occurs, resulting in some degree of aortic stenosis and regurgitation. Associated rheumatic mitral valve disease is always present.
Syphilitic aortitis leads to dilatation of the ascending aorta. The aortic annulus becomes dilated, and coaptation of the cusps is lost.
Takayasu arteritis involves the aorta and its major branches. AR may complicate type I and type III of this disease.
Ankylosing spondylitis leads to shortening and thickening of the aortic valve cusps and dilatation of the aortic root.
Reiter syndrome presents similarly to ankylosing spondylitis. Dilatation of the aortic root and associated AR occurs. Reiter syndrome may involve the coronary ostium rarely, producing angina.
Rheumatoid arthritis can produce granulomata involving the valve leaflets and rings. The central portion of the leaflets is usually involved, with sparing of the peripheral portions.
Systemic lupus erythematosus (SLE) is associated with Libman-Sacks endocarditis (noninfectious), and these verrucous vegetations can produce mitral and aortic regurgitation. Distinct from endocarditis, SLE can produce valvulitis, leading to thickened, calcific, and dysfunctional valves.
Behcet disease is a diffuse aortitis, often leading to proximal aortic dilatation and severe AR.
Whipple disease is a gastrointestinal condition in which aortic root dilatation and aortic valve insufficiency may be present.

http://emedicine.medscape.com/article/150490-overview