Aortic regurgitation overview

# Overview
Aortic insufficiency refers to the retrograde or backward flow of blood from the aorta into the left ventricle during diastole. When the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve is not able to completely close. This causes a leaking of blood from the aorta into the left ventricle. The percentage of blood that regurgitates back through the aortic valve due to AI is known as the regurgitant fraction. The prevalence of aortic regurgitation varies with age, geographic location, and gender.  Aortic insufficiency is unusual before the age of 50 and then increases progressively later in life.  Aortic regurgitation is more commonly seen in men as compared to women. Worldwide the most common cause of aortic insufficiency is the rheumatic heart disease, particularly in the Asia, the Middle East, and the North Africa. In the United States, senile degenerative calcific aortic valve disease and bicuspid aortic valve disease are the most common causes. The Framingham Heart Study, a prospective epidemiological study, evaluated the prevalence and severity of aortic regurgitation and other valvular diseases by color Doppler examinations in 1,696 men and 1,893 women. In acute aortic insufficiency symptoms of heart failure often develop acutely. Chronic aortic insufficiency is usually insidious and progressive and the patient may remain asymptomatic for years. Once left ventricular dilation and left ventricular failure occur, dyspnea on exertion and exercise intolerance begin to occur. Later symptoms such as angina, syncope, and other symptoms of heart failure are present. There are two main parameters that reflect the overall outcome in patients with aortic insufficiency: ejection fraction (the lower the ejection fraction, the poorer the outcome) and end systolic diameter. Left ventricular dysfunction develops in patients with aortic insufficiency after decades of the onset of the symptoms. This lag period is longer than that of mitral regurgitation. A detailed history and physical exam and diagnostic techniques like electrocardiogram, chest X-ray, echocardiography and a cardiac MRI can be used to diagnose aortic regurgitation. The symptoms of acute aortic regurgitation (AR) include dyspnea, chest pain (when aortic dissection is the cause of AR), weakness, and symptoms of congestive heart failure. Chronic AR may be without symptoms for several years until there is a decrease in the stroke volume and cardiac output due to heart failure progression. Symptoms of chronic aortic insufficiency include exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and palpitations. The echocardiogram is the single most useful diagnostic imaging study in the diagnosis and ongoing surveillance of the severity of aortic insufficiency. Echocardiography allows for serial assessment of left ventricular volumes which can be critical in determining the timing of aortic valve replacement.  Echocardiography is used to assess the following parameters: end-diastolic diameter, end systolic diameter, and ejection fraction. Aortic valve replacement should be performed if the LVEF is  55% or if left ventricular end-systolic dimension is > 55mm. Pulsed Doppler echocardiography is more sensitive than auscultation specially in patients in whom no murmur is observed. Cardiac MRI may be used for assessing individuals with valvular heart disease in which evaluation of valvular stenosis, regurgitation, para- or perivalvular masses, perivalvular complications of infectious processes, or prosthetic valve disease are needed. CMR may be useful in identifying serial changes in LV volumes or mass in patients with valvular dysfunction. Aortic insufficiency can be treated either medically with vasodilators or surgically with aortic valve replacement, depending upon the acuteness of presentation, the symptoms and signs associated with the disease process, and the degree of left ventricular dysfunction. Nitroprusside and ionotropes can be used to maintain blood pressure.  Treatment options that are contraindicated include intra aortic balloon pump, pressors, and beta blockers (except in aortic dissection, where beta blockers can be used cautiously).

# Pathophysiology
In aortic insufficiency (AI), when the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve is not able to completely close. This causes a leaking of blood from the aorta into the left ventricle. This means that some of the blood that was already ejected from the heart is regurgitating back into the heart. The percentage of blood that regurgitates back through the aortic valve due to AI is known as the regurgitant fraction. For instance, if an individual with AI has a stroke volume of 100ml and during ventricular diastole 25ml regurgitates back through the aortic valve, the regurgitant fraction is 25%. This regurgitant flow causes a decrease in the diastolic blood pressure in the aorta, and therefore an increase in the pulse pressure (systolic pressure - diastolic pressure). Thus, physical examination will reveal a bounding pulse, especially in the radial artery. The percentage of blood that regurgitates back through the aortic valve due to AI is known as the regurgitant fraction. This regurgitant flow causes a decrease in the diastolic blood pressure in the aorta, and therefore a widening or increase in the pulse pressure (systolic pressure - diastolic pressure). As a result, the physical examination will often reveal a bounding pulse, especially in the radial artery. There is decreased effective forward flow in aortic insufficiency.

# Causes
Aortic insufficiency can be an acute illness or a chronic illness and the causes differ depending upon the acuity of the disease. In general, aortic insufficiency is due to abnormalities of the aortic valve itself or the aortic root. Aortic regurgitation secondary to dilation of the ascending aorta has overtaken the valvular aortic disease as the most common cause of aortic regurgitation.It can also occur after surgical valve placement.

# Epidemiology and Demographics
The prevalence of aortic regurgitation varies with age, geographic location, and gender.  Aortic insufficiency is unusual before the age of 50 and then increases progressively later in life.  Aortic regurgitation is more commonly seen in men as compared to women. Worldwide the most common cause of aortic insufficiency is the rheumatic heart disease, particularly in the Asia, the Middle East, and the North Africa. In the United States, senile degenerative calcific aortic valve disease and bicuspid aortic valve disease are the most common causes. .The Framingham Heart Study, a prospective epidemiological study, evaluated the prevalence and severity of aortic regurgitation and other valvular diseases by color Doppler examinations in 1,696 men and 1,893 women.The study revealed that the prevalence of aortic regurgitation (ranging in severity from trace to  moderate regurgitation) is 13.0% in men and 8.5% in women. The prevalence of aortic regurgitation increases with age. It is infrequent in young patients, and occurs in < 1% of subjects under the age of 70. However people with congenital aortic valve/root defects such as bicuspid aortic valve disease and Marfan syndrome may develop aortic regurgitation much earlier in life.

# Risk Factors
In the past, the most common risk factor for aortic valvular disease had been the rheumatic fever, with subsequent fibrosis of the scarred valve then leading to retraction of the aortic valve cusps and prevention of their apposition during diastole. In the modern era, a more common risk factor for acquired aortic regurgitation is degenerative disease of the aorta and aortic valve in which case there is calcification and fibrosis of the cusps. Infective endocarditis remains an important risk factor and cause of aortic insufficiency. Congenital conditions such as congenital bicuspid aortic valve or a ventricular septal defect can also result in aortic insufficiency. Patients with bicuspid aortic valve are at increased risk of developing aortic dissection.

# Natural History, Complications and Prognosis
In acute aortic insufficiency symptoms of heart failure often develop acutely. Chronic aortic insufficiency is usually insidious and progressive and the patient may remain asymptomatic for years. Once left ventricular dilation and left ventricular failure occur, dyspnea on exertion and exercise intolerance begin to occur. Later symptoms such as angina, syncope, and other symptoms of heart failure are present.  There are two main parameters that reflect the overall outcome in patients with aortic insufficiency: ejection fraction (the lower the ejection fraction, the poorer the outcome) and end systolic diameter.  Left ventricular dysfunction develops in patients with aortic insufficiency after decades of the onset of the symptoms. This lag period is longer than that of mitral regurgitation. A detailed history and physical exam and diagnostic techniques like electrocardiogram, chest X-ray, echocardiography and a cardiac MRI can be used to diagnose aortic regurgitation.The prognosis and survival of patients with symptomatic aortic regurgitation has improved significantly over the last decade. The five year survival rate for symptomatic patients is now more than 80 percent. The prognosis among patients with aortic insufficiency is poor with a high mortality and morbidity due to the acute onset of left ventricular failure, pulmonary edema, or myocardial ischemia due to the abrupt rise in LV wall stress and sudden cardiac death. Early surgical intervention improves the prognosis in these patients.

# Diagnosis

## History and Symptoms
The symptoms of acute aortic regurgitation (AR) include dyspnea, chest pain (when aortic dissection is the cause of AR), weakness, and symptoms of congestive heart failure. Chronic AR may be without symptoms for several years until there is a decrease in the stroke volume and cardiac output due to heart failure progression.  Symptoms of chronic aortic insufficiency include exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and palpitations.

## Physical Examination
A patient with suspected aortic insufficiency may have an early diastolic heart murmur which is usually a high-pitched sound best heard at the left sternal border. An ejection systolic 'flow' murmur may also be present. The apex beat is typically displaced down and to the left. A patient with chronic aortic insufficiency may present with signs of congestive heart failure.  Other significant findings on physical exam include:
- Bounding pulses may be present.
- Head nodding (de Musset's sign) - rhythmic nodding or bobbing of the head in synchrony with the beating of the heart.
- Capillary pulsations (Quincke's sign) - pulsation of arteriolar and venous plexuses of the nail bed causing alternate blanching and flushing.
- Corrigan's pulse - A rapid upstroke and collapse of the carotid artery pulse.
- Duroziez's sign - 'pistol' shot sounds (audible diastolic murmur heard over the femoral artery)
- Early diastolic murmur best heard in the right second intercostal space. The murmur may be soft in acute AR.
- S3 and S4 may be heard.

## Cardiac Stress Test
A cardiac stress test (CST) is an evaluation modality used in cardiology in which the ability of the heart to respond to stress, either actually induced by exercise or stimulated by pharmacologic agents, is measured in a controlled clinical setting. CST for chronic aortic insufficiency is reasonable for assessment of functional capacity and symptomatic response in patients with a history of equivocal symptoms.

## Electrocardiogram
The echocardiogram is the single most useful diagnostic imaging study in the diagnosis and ongoing surveillance of the severity of aortic insufficiency. Echocardiography allows for serial assessment of left ventricular volumes which can be critical in determining the timing of aortic valve replacement. Aortic valve replacement should be performed if the LVEF is  55% or if left ventricular end-systolic dimension is > 55mm.

## Chest X Ray
Chest x ray findings associated with aortic insufficiency may include left ventricular enlargement, cardiomegaly, prominent aortic root with valvular calcification, prosthetic valve dis-lodgement, or aortic dilation. If aortic insufficiency is severe, signs of pulmonary edema may also be present.

## Echocardiography
The echocardiogram is the single most useful diagnostic imaging study in the diagnosis and ongoing surveillance of the severity of aortic insufficiency. Echocardiography allows for serial assessment of left ventricular volumes which can be critical in determining the timing of aortic valve replacement.  Echocardiography is used to assess the following parameters: end-diastolic diameter, end systolic diameter, and ejection fraction. Aortic valve replacement should be performed if the LVEF is  55% or if left ventricular end-systolic dimension is > 55mm. Pulsed Doppler echocardiography is more sensitive than auscultation specially in patients in whom no murmur is observed.

## Cardiac MRI
Cardiac MRI may be used for assessing individuals with valvular heart disease in which evaluation of valvular stenosis, regurgitation, para- or perivalvular masses, perivalvular complications of infectious processes, or prosthetic valve disease are needed. CMR may be useful in identifying serial changes in LV volumes or mass in patients with valvular dysfunction. For patients with suboptimal echocardiograms showing aortic regurgitation, radionuclide angiography or magnetic resonance imaging is indicated to assess left ventricular volume and function at rest. CMR can also be used to determine the severity of AR in patients with suboptimal echocardiograms.

## Cardiac Catheterization
Although echocardiography is now the primary imaging modality used to evaluate aortic insufficiency, cardiac catheterization is often performed in patients with aortic insufficiency primarily to assess for the presence of epicardial coronary artery disease prior to surgical aortic valve replacement. Aortography can also be performed to assess the severity of aortic insufficiency. The presence or absence of an aortic dissection can be evaluated. Left ventricular function (hemodynamics), size, and systolic function (ejection fraction) can also be evaluated.

# Treatment
Aortic insufficiency can be treated either medically with vasodilators or surgically with aortic valve replacement, depending upon the acuteness of presentation, the symptoms and signs associated with the disease process, and the degree of left ventricular dysfunction. Nitroprusside and ionotropes can be used to maintain blood pressure.  Treatment options that are contraindicated include intra aortic balloon pump, pressors, and beta blockers (except in aortic dissection, where beta blockers can be used cautiously).

## Acute Aortic Insufficiency
Patients with acute severe aortic regurgitation (AR) are managed with emergency aortic valve replacement or repair. Medical therapy is used for the stabilization of patients prior to surgery.

## Chronic Aortic Insufficiency
In the management of chronic aortic regurgitation, the left ventricular size and function should be monitored closely along with the exercise tolerance of the patient. If the patient develops heart failure symptoms and the disease starts to be symptomatic, then aortic valve replacement or valve repair is indicated. Annual echocardiographic studies are indicated in all patients with significant AR. Vasodilators such as ACE inhibitors, nifedipine, sodium nitroprusside, and hydralazine may slow the rate of progression of AR. The greatest benefit of medical therapy is among symptomatic patients and those with heart failure symptoms due to advanced disease, but in general, medical therapy has a limited role in AR because symptomatic cases should be treated with valve replacement if the patient is a good candidate for surgery. Warfarin and long-term anticoagulation is not recommended in AR if there are no other indications for anticoagulation.

## Surgery
Severe acute AR requires emergency surgery if there are no absolute contraindications to surgery. The surgery should be performed as early as possible without a delay, particularly if hypotension, decreased perfusion, or pulmonary edema are present. In chronic AR, aortic valve replacement (AVR) is indicated in patients with severe AR who are either symptomatic regardless of LV systolic function, or those who are asymptomatic and have left ventricular ejection fraction <55%, or in patients with stage C or D AR who are undergoing cardiac surgery for other indications.

# Prevention

## Primary prevention
Limiting the factors that lead to the development of Aortic regurgitation will decrease its incidence. Optimal blood pressure control, especially in elderly population is of utmost importance. cessation of smoking and opting for a healthy life style that includes balanced diet and regular exercise. Prevention of the initial development of acute rheumatic fever by prompt diagnosis and antibiotic treatment of group A streptococcal (GAS) infection predominantly due to tonsillopharyngitis. In tropical countries, a link between GAS pyoderma and subsequent ARF/RHD is highly likely.

## Secondary prevention
Aortic reguritation is associated with a higher rate of infection of the valve, that is infective endocarditis.To reduce the risk of developing infective endocarditis among high-risk patients, antibiotic prophylaxis should be considered prior to certain dental/medical/surgical procedures. Such procedures may include dental extraction, deep scaling of the teeth, gum surgery, dental implants, treatment of esophageal varices, dilation of esophageal strictures, gastrointestinal surgery where the intestinal mucosa will be disrupted, prostate surgery, urethral stricture dilation, and cystoscopy. Secondary prevention of recurrent ARF with continuous antibiotic prophylaxis is recommended for patients with definite history of ARF or diagnosis of definite RHD. Continuous antimicrobial prophylaxis is recommended because recurrent ARF can be triggered by GAS infection even if asymptomatic. Patients should be registered in regional ARF prevention programs, where available.

# Special Scenarios

## Elderly patients
The incidence of aortic regurgitation in the elderly is low in comparison to the incidence of aortic stenosis and mitral regurgitation. The majority of elderly patients have combined aortic stenosis and aortic insufficiency and the incidence of pure aortic insufficiency is rare.

## Pregnancy
Isolated aortic insufficiency in pregnant patients can be managed with combination of diuretics and vasodilators. ACE inhibitors are contraindicated in pregnancy. Patients with signs and symptoms of left ventricular failure should be monitored throughout labor and delivery with strict attention to volume status and blood pressure.

## Young Adults
Congenital aortic insufficiency rarely occurs alone and is often associated with aortic stenosis or ventricular septal defect. It may occasionally be observed in adolescents and young adults with a bicuspid aortic valve, discrete subaortic obstruction, or prolapse of one of the aortic cusp into a ventricular septal defect. Turner syndrome, osteogenesis imperfecta, tetralogy of Fallot, and truncus arteriosus are other congenital disorders that are associated with aortic insufficiency in young patients. Rheumatic heart disease is one of the important causes for acquired aortic insufficiency in young patients in developing countries. It can also occur following an episode of infective endocarditis or as a consequence of attempts to relieve aortic stenosis by either balloon valvuloplasty or surgical valvulotomy, or when the pulmonary artery is relocated in the aortic position during repair of transposition of great vessels.

## End-stage Renal Disease
Aortic insufficiency in patients with end stage renal disease can be due to either valvular calcification or infective endocarditis. Valvular/annular thickening, and calcification of heart valves occur commonly in patients undergoing dialysis, thereby leading to valvular regurgitation and/or stenosis. Hyperparathyroidism occurring secondary to renal disease is one of the most significant predisposing factor for valular calcification. Aortic insufficiency is seen less commonly than mitral or tricuspid insufficiency. In a study on 75 patients with end stage renal disease (ESRD) undergoing hemodialysis, 38% of patients were found to have developed aortic insufficiency.