AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

No specific laboratory blood tests are required in the workup of AR. However, serologic testing may be required when attempting to distinguish the various etiologies of AR.

Imaging Studies

• Two-dimensional echocardiography and Doppler
• • M-mode features of AR include the following:
  • • Diastolic flutter of the mitral valve (can be both anterior and posterior mitral valve leaflet)
    • Diastolic flutter of the aortic valve
    • Premature closure of the mitral valve (severe AR)
    • Premature opening of the aortic valve (severe elevated LV end-diastolic pressure)
    • Diastolic LV septal fluttering
    • LV volume overload (hyperkinesis of the LV walls with LV dilatation)
    • LVESD (>55 mm indicates poorer surgical outcome)
  • On 2-dimensional echocardiography, look for the following features:
  • • Flail aortic valve
    • Dilatation of the sinuses of Valsalva (particularly in patients with Marfan syndrome or bicuspid aortic valve problems)
    • Ascending aortic aneurysm
    • Incomplete closure of the aortic valve cusps on the parasternal short-axis view of the aortic valve
    • High-frequency diastolic fluttering of the anterior leaflet of the mitral valve during diastole
    • Reverse doming of the anterior mitral valve leaflet
    • LV volume overload pattern
    • Measurements of LV end-diastolic and end-systolic dimensions and volumes, shortening fractions, and EFs - Critical in determining the optimal time for valve replacement
  • Color-flow Doppler should be used as follows:
  • • Determine the regurgitant jet height and/or LV outflow tract (LVOT) height in the parasternal long-axis view (mild [1+] <25%, moderate [2+] 25-46%, moderately severe [3+] 47-64%, severe [4+] >65%).
    • Determine the regurgitant jet area and/or LVOT area in the parasternal short-axis view of the aortic valve (mild [1+] <20%, moderate [2+] 20-40%, moderately severe [3+] 40-60%, severe [4+] >60%).
    • Proximal acceleration (flow convergence) indicates aortic insufficiency is grade 3+ or 4+.
  • Continuous-wave Doppler should be used as follows:
  • • Determine the spectral strength of the regurgitant jet. Grade 1+ produces spectral tracing stain sufficient for detection but is not enough for clear delineation. In grade 2+, complete spectral tracing can barely be seen. In grade 3+, distinct darkening of spectral tracing is visible, but density is less than antegrade flow. Grade 4+ produces dark-stained spectral tracing.
    • Determine the slope of the aortic insufficiency spectral display. In general, steeper slopes indicate more severe aortic insufficiency.
    • Determine the pressure half-time of the aortic insufficiency spectral display. In general, a pressure half-time less than or equal to 300 m/s indicates significant aortic insufficiency.
  • Pulsed-wave Doppler should be used as follows:
  • • The pulse-wave mapping technique is used mostly prior to color Doppler.
    • Velocity of more than 1.5 m/s is consistent with marked AR.
    • Mitral inflow has a restrictive filling pattern.
    • Reversal of flow in the descending thoracic aorta and/or abdominal aorta indicates that aortic insufficiency is moderately severe (3+ or 4+). This phenomenon requires careful placement of the sample volume in the descending aorta, distal to the takeoff of the left subclavian artery. The flow in the descending aorta may also be seen with color-flow Doppler, although this method is more prone to error.
• Radionuclide imaging should be used as follows:
• • Radionuclide angiography findings can help determine the AR regurgitant fraction and the left-to-right ventricular stroke volume ratio. An accurate noninvasive assessment of the severity of AR can be determined if concomitant mitral regurgitation, tricuspid regurgitation, or pulmonary regurgitation is not present.
  • Left-to-right ventricular stroke volume ratio of 2 or more denotes severe AR.
• MRI or ultrafast CT scanning are as follows:
• • These techniques can provide accurate measurements of regurgitant volumes, ventricular end-systolic and diastolic volumes, ejection fraction, ventricular mass, and the regurgitant orifice.
• Chest radiograph findings are as follows:
• • In acute AR, little cardiac enlargement may be present, but, in chronic AR, enlargement is marked.
  • Dilatation of the ascending aorta may suggest that aortic root disease is responsible for AR.
  • Pulmonary congestion can be observed in patients who have developed LV dysfunction or in those with acute AR.

Other Tests

• Electrocardiography findings can reveal the following, although they are not an accurate predictor of the severity of AR:
• • LV hypertrophy
  • Left axis deviation
  • Left atrial enlargement
  • LV volume overload pattern (prominent Q waves in leads I, aVL, and V₃ to V₆ and relatively small r waves in V₁)
  • LV conduction defect (late in disease process)
• Exercise treadmill testing
• • Assessment of functional capacity and symptomatic responses in patients with a history of equivocal symptoms
  • Evaluation of symptoms and functional capacity before participation in athletic activities

Procedures

• Cardiac catheterization
• • Indications
  • • This should be performed for coronary angiography studies before aortic valve surgery in patients at risk for CAD, including men older than 35 years, premenopausal women older than 35 years with coronary risk factors, and postmenopausal women.
    • It can be used to assess the severity of regurgitation when noninvasive test results are inconclusive or discordant with clinical findings regarding the severity of regurgitation or the need for surgery.
    • Use cardiac catheterization to assess LV function when noninvasive test results are inconclusive or discordant with clinical findings regarding LV dysfunction and the need for surgery in patients suspected of having severe AR.
  • Qualitative assessment (aortic angiogram)
  • • In mild AR (1+), a small amount of contrast enters the left ventricle during diastole and clears with each systole.
    • In moderate AR (2+), contrast enters the LV with each diastole, but the LV chamber is less dense than the aorta.
    • In moderately severe AR (3+), the LV chamber is equal in density with the ascending aorta.
    • In severe AR (4+), complete dense opacification of the LV chamber occurs on the first beat and the left ventricle is more densely opacified than the ascending aorta.
  • Simultaneous aortic and LV pressure tracing (signs of severe AR)
  • • Wide pulse pressure may be present.
    • Brisk aortic pressure upstroke can be observed.
    • LV diastolic pressure increases rapidly.
    • Near equilibration of aortic and LV pressure occurs at diastole.

Histologic Findings

Histological changes in the left ventricle include fiber hypertrophy and increased interstitial fibrous tissue. In decompensated LV, disruption of the collagen support system and subsequent fiber layer slippage occur. In the subendocardium, evidence of necrosis, replacement fibrosis, and apoptosis is abundant.

Recent data suggest that patients with a wide variety of congenital heart lesions (including bicuspid aortic valves) have underlying distortion of the aortic root. These patients have abnormalities of smooth muscle, elastin, collagen, and ground substance in the ascending aorta. Programmed cell death (apoptosis) of neural crest derivative cells within the proximal aorta has also been demonstrated in patients with bicuspid aortic valve problems.

These aortic abnormalities predispose to progressive proximal aortic dilatation, aneurysm formation, or aortic rupture. These proximal aortic changes occur regardless of the underlying severity of aortic valvular disease and can be observed in patients with nonregurgitant bicuspid valves.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical versus surgical treatment

Medical therapy is appropriate for many patients with mild to moderate chronic AR. The appropriate use of vasodilators, as described below, is associated with improvement in symptoms and is thought to slow the development of LV enlargement and dysfunction and the need for surgery. That said, physicians treating patients with chronic AR must be attentive to any changes that suggest worsening LV function and the need for surgery. Annual echocardiography to assess LV size and function is useful.

Patients with acute, significant AR represent an entirely different group. Surgical treatment is almost always indicated and medical therapy (typically using intravenous medications titrated to blood pressure, as described below) is recommended only as an interim measure.

Medical Care

Vasodilator therapy is designed to optimize LV loading conditions and achieve a favorable remodeling process through systolic unloading and reduction in regurgitant volume. Treat asymptomatic patients with chronic severe AR and dilated but normal LV systolic function medically, and monitor their cases for development of indications for aortic valve surgery. Patients with mild AR and normal LV size require no therapy other than endocarditis prophylaxis.

• Earlier studies revealed that long-term vasodilator therapy with nifedipine reduces or delays the need for AVR in asymptomatic patients with severe AR and normal LV function. Nifedipine was also shown to reduce LV size and mass significantly. However, use of nifedipine in patients with LV dysfunction should be cautioned because calcium channel blockers are generally contraindicated in patients with CHF.
• Enalapril therapy achieves significant LV mass regression, LV end-diastolic and end-systolic volume index reduction, and renin-angiotensin system suppression. Enalapril may have favorable influence on the natural history of chronic AR by delaying the need for aortic valve surgery. 
• Recent publications have yielded conflicting results on the use of vasodilators. One recent follow-up study confirmed the positive effects of using nifedipine in severe asymptomatic AR; nifedipine delayed the onset of LV dysfunction, prolonged survival and protected the myocardium after AVR, even if stopped at surgery. Patients in this study had moderate to severe hypertension at entry into the study. A separate study comparing the use of nifedipine, enalapril, and placebo was unable to show a benefit to vasodilator therapy in a cohort of normotensive patients. In this study, vasodilator therapy with nifedipine or enalapril did not delay the need for AVR or improve parameters such as regurgitant volume, LV size, or LV systolic function.
• The main goal of medical therapy is to significantly reduce the systolic hypertension associated with chronic severe AR.
• Digoxin and diuretics can be used to relieve symptoms of congestion. 
• Antibiotic prophylaxis for endocarditis is discussed as follows:
• • AR leads to damaged endothelial lining of the valve and predisposes the valve to platelet and fibrin deposition.
  • In the presence of bacteremia, colonization of platelets and/or fibrin deposition can lead to bacterial endocarditis; thus, antibiotic prophylaxis is important for preventing this serious complication.
• Acute AR usually is severe and rapidly leads to LV decompensation, failure, and cardiogenic shock. The treatment of choice for acute AR is AVR. Medical therapy can be used as a bridge to surgery but should not replace it.
• • Dobutamine reduces afterload and assists with forward outflow. It also has a positive inotropic effect.
  • Vasodilators achieve significant LV mass regression, LV end-diastolic and end-systolic volume index reduction, and renin-angiotensin system suppression.
  • Intra-aortic balloon pump is contraindicated in AR.
• Percutaneous transcatheter implantation of a heart valve prosthesis may be available in the future, but these techniques are investigational at this time.

Surgical Care

Surgical treatment of AR usually requires replacement of the diseased valve with a prosthetic valve. However, valve repair is now an option for many individuals because of recent improvements in valve sparing surgical techniques. The surgical mortality rate for AVR is probably 3%, although the mortality rate may be higher if patients also need coronary artery bypass grafts. In addition, the long-term complications of prosthetic valves need to be considered.

• Aortic valve surgery is indicated in patients with normal systolic function (defined as EF >0.50 at rest) who have New York Heart Association (NYHA) functional class III or IV symptoms. Also consider patients with Canadian Heart Association functional class II-IV angina pectoris for surgery. In many patients with NYHA functional class II dyspnea, the etiology of symptoms is often unclear and clinical judgment is required. 
• Patients with NYHA functional class II, III, or IV symptoms and with mild-to-moderate LV systolic dysfunction (EF 0.25-0.49) should undergo aortic valve surgery. Patients with functional class IV symptoms have worse postoperative survival rates and a lower likelihood of recovery of systolic function when compared with patients with less severe symptoms, but aortic valve surgery improves ventricular loading conditions and expedites subsequent management of LV dysfunction. 
• Symptomatic patients with severe LV dysfunction (EF <0.25) pose difficult management issues. Most patients develop irreversible myocardial damage and may not show improved LV function or NYHA functional class after aortic valve surgery; however, some patients may gain meaningful recovery of LV function. Surgery carries an operative mortality rate of approximately 10%, but medical therapy alone carries a mortality rate of higher than 20% per year; thus, high-risk aortic valve surgery may be a viable option when compared with the even worse prognosis associated with medical therapy alone.  
• Asymptomatic patients with evidence of LV systolic dysfunction (EF <0.50) should undergo aortic valve surgery. The postoperative recovery of LV function and survival is strongly associated with preoperative LV function; thus, do not delay aortic valve surgery for patients with evidence of LV dysfunction. 
• Asymptomatic patients with severe AR and normal LV function but with severe LV dilatation (end-diastolic dimension >75 mm or end-systolic dimension >55 mm) should undergo aortic valve surgery. These patients tend to progress to symptomatic or LV dysfunction rapidly. Postoperative survival and reduction of LV dimension in this subgroup of patients are excellent.  
• Preoperative predictors of poor postoperative survival and LV function include the following: 
• • LVESD greater than 55 mm 
  • LVEF less than 0.50 
  • NYHA CHF class III, IV 
  • Duration of CHF symptoms longer than 12 months

Consultations

• Cardiologist
• Cardiothoracic surgeon

Diet

Place patients on a low-sodium diet with fluid restriction when CHF symptoms appear.

Activity

Asymptomatic patients with normal LV systolic function may participate in all forms of normal daily physical activity, including mild forms of exercise and, in some cases, competitive athletics; however, isometric exercise (eg, weight lifting) should be avoided. Patients with evidence of LV dysfunction or low cardiac reserve should not engage in vigorous sports or heavy exertion.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Vasodilator therapy has reduced severity of AR and LV volume and mass successfully, postponing the need for surgical intervention.

Drug Category: Angiotensin-converting enzyme inhibitors

Competitive inhibitors of angiotensin-converting enzyme (ACE). Reduce angiotensin II levels, decreasing aldosterone secretion.

Drug Category: Calcium channel blockers

Inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity.

Drug Category: Cardiac glycosides

Inhibit sodium-potassium ATPase. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and calcium. Vagomimetic action leads to reduced activity of sympathetic nervous system.

Drug Category: Diuretics

Increase urine flow. These agents are ion transport inhibitors that decrease the reabsorption of sodium at different sites in the nephron. Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension, in which their diuretic action causes decreased blood volume.

Drug Category: Direct-acting adrenergic agonists

Act directly on alpha- and beta-receptors, producing effects similar to those that occur following stimulation of sympathetic nerves or release of the hormone epinephrine from the adrenal medulla.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

Admit patient for testing and surgical intervention.

Further Outpatient Care

• Close monitoring for symptom development is warranted.
• Serial echocardiograms should be performed to evaluate LV function, LV dimensions (end-systolic and end-diastolic), and the severity of AR.
• In patients in whom an adequate echocardiogram cannot be obtained, serial multigated radionuclide angiogram scans should be performed to monitor the LVEF and the volume of the left ventricle. Alternatively, serial cardiac MRIs can be obtained in centers experienced with this procedure.   
• Serial multigated angiogram scans should be performed to monitor the LVEF and the volume of the left ventricle.
• Exercise stress testing should be performed to determine functional capacity and symptomatic response in patients with a history of equivocal symptoms.
• Carefully monitor medication doses and adverse effects.

In/Out Patient Meds

• Medications include calcium channel blockers and ACE inhibitors.
• Avoid calcium channel blockers in patients with CHF.
• Use digoxin and diuretics for patients with CHF.

Transfer

Transfer may be required for further diagnostic evaluation and surgical intervention.

Deterrence/Prevention

• Endocarditis prophylaxis is discussed as follows:
• • AR leads to damaged endothelial lining of the valve and predisposes the valve to platelet and fibrin deposition.
  • In the presence of bacteremia, colonization of platelets and/or fibrin deposition can lead to bacterial endocarditis; thus, antibiotic prophylaxis is important for preventing this serious complication.
• Patients with LV dysfunction or CHF symptoms should not engage in vigorous sports or heavy exertion.

Complications

• Congestive heart failure (See also, Medscape's Heart Failure Resource Center.)
• Infective endocarditis
• Arrhythmia
• Sudden death

Prognosis

• Asymptomatic patients with normal LV function have a mortality rate of less than 0.2% per year. The rate of progression to symptoms and/or LV dysfunction is less than 5% per year.
• Patients with angina have a mortality rate of higher than 10% per year.
• Patients with CHF have a mortality rate of higher than 20% per year.

Patient Education

Educate patients about symptoms associated with severe AR.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Antibiotic prophylaxis for prevention of aortic valve endocarditis is an important part of continuing medical care of patients with significant AR.
• Intra-aortic balloon pump use for hemodynamic support is contraindicated in patients with hemodynamically significant (ie, moderate or severe) AR.
• Symptomatic patients (NYHA class III, IV) with severe AR should undergo valve replacement, regardless of LV systolic function.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  The light blue jet represents the aortic regurgitant flow on this 2-dimensional color Doppler echocardiogram showing severe aortic regurgitation.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). J Am Coll Cardiol. Nov 1998;32(5):1486-588. [Medline].
• Bekeredjian R, Grayburn PA. Valvular heart disease: aortic regurgitation. Circulation. Jul 5 2005;112(1):125-34. [Medline].
• Bonow RO, Dodd JT, Maron BJ, et al. Long-term serial changes in left ventricular function and reversal of ventricular dilatation after valve replacement for chronic aortic regurgitation. Circulation. Nov 1988;78(5 Pt 1):1108-20. [Medline].
• Bonow RO, Nikas D, Elefteriades JA. Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction. Cardiol Clin. Feb 1995;13(1):73-83, 85. [Medline].
• Bonow RO, Picone AL, McIntosh CL, et al. Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function. Circulation. Dec 1985;72(6):1244-56. [Medline].
• Bonow RO, Rosing DR, McIntosh CL, et al. The natural history of asymptomatic patients with aortic regurgitation and normal left ventricular function. Circulation. Sep 1983;68(3):509-17. [Medline].
• Borer JS, Bonow RO. Contemporary approach to aortic and mitral regurgitation. Circulation. Nov 18 2003;108(20):2432-8. [Medline].
• Borer JS, Hochreiter C, Herrold EM, et al. Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance. Circulation. Feb 17 1998;97(6):525-34. [Medline].
• Clark DG, McAnulty JH, Rahimtoola SH. Valve replacement in aortic insufficiency with left ventricular dysfunction. Circulation. Feb 1980;61(2):411-21. [Medline].
• Daniel WG, Hood WP, Siart A, et al. Chronic aortic regurgitation: reassessment of the prognostic value of preoperative left ventricular end-systolic dimension and fractional shortening. Circulation. Apr 1985;71(4):669-80. [Medline].
• Evangelista A, Tornos P, Sambola A, Permanyer-Miralda G, Soler-Soler J. Long-term vasodilator therapy in patients with severe aortic regurgitation. N Engl J Med. Sep 29 2005;353(13):1342-9. [Medline].
• Fioretti P, Roelandt J, Sclavo M, et al. Postoperative regression of left ventricular dimensions in aortic insufficiency: a long-term echocardiographic study. J Am Coll Cardiol. Apr 1985;5(4):856-61. [Medline].
• Forman R, Firth BG, Barnard MS. Prognostic significance of preoperative left ventricular ejection fraction and valve lesion in patients with aortic valve replacement. Am J Cardiol. Jun 1980;45(6):1120-5. [Medline].
• Gaasch WH, Andrias CW, Levine HJ. Chronic aortic regurgitation: the effect of aortic valve replacement on left ventricular volume, mass and function. Circulation. Nov 1978;58(5):825-36. [Medline].
• Gaasch WH, Carroll JD, Levine HJ, Criscitiello MG. Chronic aortic regurgitation: prognostic value of left ventricular end- systolic dimension and end-diastolic radius/thickness ratio. J Am Coll Cardiol. Mar 1983;1(3):775-82. [Medline].
• Goldschlager N, Pfeifer J, Cohn K, et al. The natural history of aortic regurgitation. A clinical and hemodynamic study. Am J Med. May 1973;54(5):577-88. [Medline].
• Greenberg B, Massie B, Bristow JD, et al. Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial. Circulation. Jul 1988;78(1):92-103. [Medline].
• Greves J, Rahimtoola SH, McAnulty JH, et al. Preoperative criteria predictive of late survival following valve replacement for severe aortic regurgitation. Am Heart J. Mar 1981;101(3):300-8. [Medline].
• Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. Jul 1975;56(1):56-64. [Medline].
• Hwang MH, Hammermeister KE, Oprian C, et al. Preoperative identification of patients likely to have left ventricular dysfunction after aortic valve replacement. Participants in the Veterans Administration Cooperative Study on Valvular Heart Disease. Circulation. Sep 1989;80(3 Pt 1):I65-76. [Medline].
• Kawanishi DT, McKay CR, Chandraratna PA, et al. Cardiovascular response to dynamic exercise in patients with chronic symptomatic mild-to-moderate and severe aortic regurgitation. Circulation. Jan 1986;73(1):62-72. [Medline].
• Klodas E, Enriquez-Sarano M, Tajik AJ, et al. Aortic regurgitation complicated by extreme left ventricular dilation: long-term outcome after surgical correction. J Am Coll Cardiol. Mar 1 1996;27(3):670-7. [Medline].
• Klodas E, Enriquez-Sarano M, Tajik AJ, et al. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symptoms. J Am Coll Cardiol. Sep 1997;30(3):746-52. [Medline].
• Krayenbuehl HP, Hess OM, Monrad ES, et al. Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement. Circulation. Apr 1989;79(4):744-55. [Medline].
• Kumpuris AG, Quinones MA, Waggoner AD, et al. Importance of preoperative hypertrophy, wall stress and end-systolic dimension as echocardiographic predictors of normalization of left ventricular dilatation after valve replacement in chronic aortic insufficiency. Am J Cardiol. Apr 1 1982;49(5):1091-100. [Medline].
• Lin M, Chiang HT, Lin SL, et al. Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy. J Am Coll Cardiol. Oct 1994;24(4):1046-53. [Medline].
• Niwa K, Perloff JK, Bhuta SM, et al. Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses. Circulation. Jan 23 2001;103(3):393-400. [Medline]. [Full Text].
• Scognamiglio R, Negut C, Palisi M, Fasoli G, Dalla-Volta S. Long-term survival and functional results after aortic valve replacement in asymptomatic patients with chronic severe aortic regurgitation and left ventricular dysfunction. J Am Coll Cardiol. Apr 5 2005;45(7):1025-30. [Medline].
• Scognamiglio R, Rahimtoola SH, Fasoli G, et al. Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function. N Engl J Med. Sep 15 1994;331(11):689-94. [Medline].
• Siemienczuk D, Greenberg B, Morris C, et al. Chronic aortic insufficiency: factors associated with progression to aortic valve replacement. Ann Intern Med. Apr 15 1989;110(8):587-92. [Medline].
• Singh JP, Evans JC, Levy D, et al. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). Am J Cardiol. Mar 15 1999;83(6):897-902. [Medline].
• Stone PH, Clark RD, Goldschlager N, et al. Determinants of prognosis of patients with aortic regurgitation who undergo aortic valve replacement. J Am Coll Cardiol. May 1984;3(5):1118-26. [Medline].
• Tornos MP, Olona M, Permanyer-Miralda G, et al. Clinical outcome of severe asymptomatic chronic aortic regurgitation: a long-term prospective follow-up study. Am Heart J. Aug 1995;130(2):333-9. [Medline].
• Turina J, Turina M, Rothlin M, Krayenbuehl HP. Improved late survival in patients with chronic aortic regurgitation by earlier operation. Circulation. Sep 1984;70(3 Pt 2):I147-52. [Medline].
• Verheul HA, van den Brink RB, Bouma BJ, et al. Analysis of risk factors for excess mortality after aortic valve replacement. J Am Coll Cardiol. Nov 1 1995;26(5):1280-6. [Medline].
• Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin- angiotensin-aldosterone system. Circulation. Jun 1991;83(6):1849-65. [Medline].

Article Last Updated: Jun 26, 2007