The presentation of the patient depends on the present valvular disease(s).

AS

The congenital form is typically asymptomatic until it insidiously presents in children and young adults between the ages of 10 to 20.

Generally, all types of AS feature a progressive disease and eventually the patient suffers from the SAD triad which consists of exertional syncope, angina, and dyspnea.

Note that AS leads to heart failure and ventricular fibrillation, an arrhythmia that may cause sudden death [6].

The physical exam findings include the hallmark feature, which is the crescendo-decrescendo ejection murmur typically auscultated at both the right and left upper sternal border in a sitting patient that is tilting forward.

Severe cases may exhibit a palpable apical S4 accompanied by a systolic thrill [7]. Furthermore, the pulse in these patients is characterized by the pulsus parvus pattern.

AR

In acute cases, the clinical picture is that of heart failure as well as cardiogenic shock. The exam reveals hypotension, tachycardia, S1 is not present but S3 is commonly heard. The Austin Flint murmur is frequently heard.

Patients with chronic AR are asymptomatic for years but eventually develop exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and palpitations. They feature a widened pulse pressure.

MS

The majority of patients do not exhibit symptoms until atrial fibrillation or pregnancy occurs. The clinical presentation resembles the features of heart failure and usually manifests at 15 to 40 years post-rheumatic fever. This may appear in children in the developing world due to under-treatment. Also, symptoms depict the severity of the disease.

The physical assessment reflects a crescendo-crescendo rumbling diastolic murmur and a loud S1. Also, the S1 and S2 are palpable. Note that jugular venous distention is present in cases with pulmonary hypertension.

MR

The symptoms of this valvular abnormality are those of congestive heart failure.

Auscultation is notable for a holosystolic murmur, which can radiate to the upper sternal borders, axilla, or the subscapular area. Valsalva, sitting, or standing makes the murmur more audible.

Furthermore, S1 is soft and S2 may exhibit a wide split. S3 is suggestive of severe MR although it is not always associated with cardiac failure [8].

MVP

Many patients with prolapse are asymptomatic. In others, there are nonspecific symptoms such as angina, dyspnea, dizziness, palpitations, presyncope, headaches and anxiety. Additionally, approximately a third of the cases experience palpitations following emotional stress.

Auscultation demonstrates a midsystolic click when the patient performs the Valsalva maneuver, sits, or stands.

PS

Typically, patients do not present with symptoms in childhood or adulthood. In fact, the majority of adults do not have manifestations. The presentation mimics the AS picture, ie the SAD triad.

The cardiac exam reveals a harsh crescendo-decrescendo ejection murmur at the 2nd or 4th left sternal border. Additionally, S1 is normal and the S2 split is widened.

PR

Most patients do not present with symptoms, lthough a few exhibit signs of RV impairment and heart failure.

The associated murmur is a high-pitched, early diastolic decrescendo murmur.

TR

This does not produce symptoms but severe cases feature fatigue, anorexia, and bloating. Some patients will have neck pulsations, atrial fibrillation and atrial flutter.

If present, the murmur is holosystolic, typically auscultated at the middle or lower left sternal borders in the upright or standing positions.

TS
This manifests with neck discomfort, fatigue, cold skin, as well as right upper quadrant discomfort.

The physical exam features a flickering wave, and possibly jugular venous distention that increases with inspiration, otherwise known as Kussmaul sign.

The uncommon murmur is a soft opening snap and mid-diastolic rumble. It becomes louder and longer with any physical activity that leads to an increase in venous return. In contrast, the opposite occurs with Valsalva and standing.

• Fever

  Mitral Stenosis (MS) Rheumatic fever accounts for most cases of MS. Mitral Regurgitation (MR) Chronic MR is caused by infective endocarditis, rheumatic fever, and MVP. [symptoma.com]

  The causes of heart valve disease typically include degenerative diseases such as congenital defects, and rheumatic fever or endocarditis, severe infections that can damage or scar the heart valves and prevent them from working properly. [montefiore.org]

  Rheumatic Fever Some people have heart valve disease due to untreated strep throat or other infections with strep bacteria that progress to rheumatic fever. [medicine.umich.edu]

  Prevention Get prompt treatment for a sore throat that lasts longer than 48 hours, especially if accompanied by a fever. Timely administration of antibiotics may prevent the development of rheumatic fever which can cause valvular heart disease. [hopkinsmedicine.org]

• Fatigue

  This leakage may prevent your heart from efficiently pumping blood to the rest of the body, and it can cause you to feel fatigued and/or short of breath. [medtronic.com]

  This results in fatigue or shortness of breath. [beaumont.org]

  This can cause fatigue, shortness of breath and the heart to work harder to circulate blood through the body. Aortic stenosis is one of the most common and most serious valve disease problems affecting the aortic valve. [novanthealth.org]

  Mitral regurgitation (leaking of the mitral valve) can produce symptoms of fatigue, breathlessness after exertion, and breathlessness while lying down. Pulmonic valve problems can produce symptoms of fatigue and fainting spells. [irishhealth.com]

  Exercise capacity (exercise time to limiting fatigue or dyspnea) increased from a mean of 8.3 minutes after placebo to 9.8 minutes after nitroglycerin (P less than 0.005). [ncbi.nlm.nih.gov]

• Congestive Heart Failure

  The most common cause is pulmonary hypertension or left side congestive heart failure. This results in fatigue, swelling of abdomen, liver and legs. [beaumont.org]

  Increased life expectancy and age-related valvular degeneration remain the predominant contributors to heart valve dysfunction, which if uncorrected lead to congestive heart failure and increased morbidity and mortality. [ncbi.nlm.nih.gov]

  In mild cases there may be no symptoms, while in advanced cases, valvular heart disease may lead to congestive heart failure and other complications. Treatment depends upon the extent of the disease. [hopkinsmedicine.org]

• Whipple Disease

  Other systemic disorders that may affect the aortic valve include lupus erythematosus, giant cell arteritis, Takayasu arteritis, ankylosing spondylitis, Jaccoud arthropathy, Whipple disease, and Crohn disease.1 Diseases that primarily affect the annulus [ncbi.nlm.nih.gov]

  […] vegetations, certain inherited metabolic disorders such as Fabry’s disease, mucopolysaccharidosis, Whipple’s disease, gout, rheumatic arthritis, lupus erythematosus, methysergide therapy, and cases related to previous implanted prosthesis or commisurotomy [textbookofcardiology.org]

• Heart Disease

  Valvular heart disease is when any valve in the heart has damage or is diseased. What is valvular heart disease? Valvular heart disease is when any valve in the heart has damage or is diseased. There are several causes of valve disease. [cdc.gov]

  Heart valve disease occurs when one or more of the heart valves do not open or close properly. When it affects more than one heart valve, it is called multiple valvular heart disease. [heartandstroke.ca]

  The Cardiology section is involved in treating patients with disorders of the heart and vascular tree including coronary artery disease, congestive heart failure, valve disease, congenital heart defects, cardiomyopathy and peripheral vascular disease. [hopkinsmedicine.org]

• Palpitations

  Most people with mitral valve prolapse never know it, but the condition can cause symptoms such as chest pain, palpitations, headaches and dizziness. [riversidehealthcare.org]

  Symptoms of aortic stenosis Many people with aortic stenosis may not experience any of the following symptoms until the blood flow becomes severely restricted: Breathlessness Chest pain (angina), pressure or tightness Fainting Palpitations or a feeling [novanthealth.org]

  Heart Health Heart Disease Causes & Risk Factors Diagnosis Treatment Living With Prevention Atrial Fibrillation Heart Attack Heart Valve Disease Palpitations & Arrhythmias Chest Pain & Angina View More What Is Aortic Stenosis? By Richard N. [verywellhealth.com]

  Individuals with heart valve disease may experience one of several symptoms including shortness of breath or palpitations. In some cases, patients experience no symptoms at all. [montefiore.org]

  In others, there are nonspecific symptoms such as angina, dyspnea, dizziness, palpitations, presyncope, headaches and anxiety. Additionally, approximately a third of the cases experience palpitations following emotional stress. [symptoma.com]

• Heart Murmur

  murmur and if you have underlying heart valve disease. [newheartvalve.com]

  If you’re seeking to better understand a heart valve problem, you may want to learn more about the possible link between a heart murmur and eventual valve disease. [heart.org]

  The main sign of heart valve disease is an unusual heartbeat sound called a heart murmur. Your doctor can hear a heart murmur with a stethoscope. But many people have heart murmurs without having a problem. [medlineplus.gov]

  However, many people have benign heart murmurs that don't indicate heart valve disease or other heart problems. In advanced cases, symptoms of heart valve disease are similar to those of heart failure. [pulseheartinstitute.org]

  Major Signs and Symptoms The main sign of heart valve disease is an unusual heart sound called a heart murmur. Your doctor can hear a heart murmur with a stethoscope. [medicine.umich.edu]

• Diastolic Murmur

  Murmurs which occur when the heart contracts (squeezes) are called systolic murmurs and those that occur when the heart relaxes are called diastolic murmurs. The murmur may also occur if blood moves rapidly through normal valves. [irishheart.ie]

  The associated murmur is a high-pitched, early diastolic decrescendo murmur. TR This does not produce symptoms but severe cases feature fatigue, anorexia, and bloating. Some patients will have neck pulsations, atrial fibrillation and atrial flutter. [symptoma.com]

  An aortic diastolic murmur occurs in 50% due to aortic regurgitation. Wide pulse pressure may be absent. After a period of pain, cardiac failure may result from gross aortic regurgitation. Cardiac tamponade can cause hypotension and syncope. [patient.info]

  However, when the left ventricle decompensates, the gradient between the left ventricle and the aorta at end diastole is diminished, shortening the murmur.25,26 The Austin-Flint murmur, a mid to late diastolic rumble heard best at the apex, is similar [ncbi.nlm.nih.gov]

  […] relaxing (a diastolic murmur). [drugs.com]

• Hypotension

  Hypotension indicates a poor prognosis, as it may be due to cardiac tamponade or myocardial infarction. An aortic diastolic murmur occurs in 50% due to aortic regurgitation. Wide pulse pressure may be absent. [patient.info]

  The exam reveals hypotension, tachycardia, S1 is not present but S3 is commonly heard. The Austin Flint murmur is frequently heard. [symptoma.com]

  An abnormal hemodynamic response (eg, hypotension) in a patient with severe AS is sufficient reason to consider AVR. [ahajournals.org]

  […] decrease and a disproportionately lowering of diastolic blood pressure causes a wide pulse pressure.[21] Inferior vena caval obstruction from a gravid uterus in the supine position can result in an abrupt decrease in cardiac preload, which leads to hypotension [en.wikipedia.org]

  […] patients with none of the findings listed under asymptomatic patients with severe AS; Class III AVR is also recommended in asymptomatic patients with severe AS and the following: LV systolic dysfunction; Class IIa Abnormal response to exercise (eg, hypotension [emedicine.medscape.com]

Evaluation of the patient includes the assessment of symptoms, personal and family history, the physical exam with cardiovascular focus, and echocardiography. 

Echocardiology will reveal details about the valvular anatomy, function, blood flow, and transvalvular pressure gradient. It also provides measurements of the cardiac chambers and overall cardiac performance.

Chest radiography depicts the heart size, changes in the chambers, edema, and underlying lung diseases.

The electrocardiogram (EKG) demonstrates the rate and rhythm and will identify arrhythmias, ischemia, and hypertrophy.

• Pericardial Effusion

  There were 11 (11%) cases of cardiac rehospitalization: 4 patients for pericardial effusion, 4 for pulmonary oedema, 2 for permanent pacemaker implantation and 1 for sternal dehiscence. [icvts.oxfordjournals.org]

• Ejection Fraction Decreased

  Advanced myocardial dysfunction may occur while LV ejection fraction is still well within the normal range.35 Thus, outcome after MV surgery is poorer in patients with a preoperative ejection fraction of less than 60% than in those with higher ejection [ncbi.nlm.nih.gov]

• T Wave Inversion

  A variety of ST-T-wave changes, including T-wave inversion and sometimes ST-segment depression, particularly in the inferior leads, can be found in patients with symptomatic mitral valve prolapse. [textbookofcardiology.org]

  Onset of ischemic or repolarization abnormalities (ST depression, T-wave inversion) over left precordium at rest. IIb Table 39. [ahajournals.org]

• Left Ventricular Hypertrophy

  […] ventricle.[12] ECG typically shows left ventricular hypertrophy in patients with severe stenosis, but it may also show signs of left heart strain.[13] Echocardiography is the diagnostic gold standard, which shows left ventricular hypertrophy, leaflet [en.wikipedia.org]

  The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension. JACC 1988; 7: 639-50 5 Helak JW, Reichek N. [ecocardio.com]

  Left ventricular hypertrophy is the main feature of aortic regurgitation, with or without associated repolarization abnormalities. Left axis deviation may be present. [textbookofcardiology.org]

  Left ventricular hypertrophy is often present, as is left atrial enlargement. Left ventricular systolic function is usually normal. If heart failure has developed, the left ventricle may be enlarged and systolic function depressed. [ncbi.nlm.nih.gov]

The therapeutic approach is decided upon by a multidisciplinary team composed of cardiologists, cardiovascular surgeons, and other specialists who will collectively select the best intervention for the particular patient.

AS

Asymptomatic patients should undergo periodic evaluation and echocardiography to assess timing for valvular replacement. The surgery is beneficial in symptomatic patients and those who demonstrate particular findings on an echocardiographic assessment.

In asymptomatic patients, valvular replacement is advised for those with one of the following: 1) left ventricular ejection fraction below 50%, 2) patients with moderate or severe stenosis undergoing heart surgery for different reasons, and 3) severe cases in good surgical candidates.

AR

If the aortic root dilatation contributes to the pathogenesis of AR in a hypertensive patient, angiotensin-receptor blockers may be beneficial [9].

Surgical intervention is warranted for severe regurgitation with an ejection fraction below 50%.

Poor surgical candidates warrant therapy used in heart failure. Note that beta blockers may mask the compensatory tachycardia and exacerbate the regurgitation.

MS

Asymptomatic individuals require prophylaxis against the recurrence of rheumatic fever [10].

Patients with mild symptoms may benefit from diuretics. When the patient exhibits tachycardia or atrial fibrillation, then beta blockers or calcium channel blockers are useful. Additionally, thromboembolism prophylaxis with anticoagulants should be used in those with atrial fibrillation or embolism.

Percutaneous balloon commissurotomy is the preferred intervention for younger individuals and in those where stenosis is not associated with severe MR, significantly calcified commissures, subvalvular deformities, or thrombi in the left atria. In fact, the latter three phenomena may benefit from surgical commissurotomy.

MR

Repair is indicated for patients with 1) moderate to severe symptoms, 2) ejection fraction below 60% or 3) an end systolic dimension that nears 45mm.

Repair of the mitral valve is correlated to a lower surgical fatality rate and has better outcomes than valvular replacement.

MVP

No therapy is indicated for prolapse.

PS

Balloon valvuloplasty is warranted for a peak gradient greater than 40 to 50 mm Hg.

PR

The etiology should be treated.

TR

The underlying conditions such as infective endocarditis and heart failure require appropriate management.

Severe regurgitation necessitates surgery at the onset of symptoms or in patients with worsening right ventricular impairment. The procedures are valvular repair, replacement or annuloplasty.

TS

Severe stenosis should be treated surgically in patients that are symptomatic or undergoing heart surgery for different reasons. One procedure is percutaneous balloon tricuspid commissurotomy.

The prognosis of valvular disease correlates with the particular abnormality and the degree of severity.

AS

Severe AS is associated with mortality and almost half of all deaths are sudden. In fact, in asymptomatic individuals with severe disease, it is expected that 3% to 6% will manifest with symptoms or LV dysfunction annually. Therefore, these patients should undergo surveillance.

AR

In mild to moderate disease, the 10 years survival rate is 80% to 95%. Moreover, severe cases are correlated with very poor outcomes.

MS

This is a progressive disease and is life-threatening in patients with atrial fibrillation and pulmonary hypertension. Mortality does occur and is secondary to heart failure and emboli in the lungs or cerebrovasculature.

MVP

This benign disease progresses to regurgitation in the presence of myxomatous degeneration.

PS

The outcomes are good without treatment but become better with intervention.

TR

Severe regurgitation of the tricuspid valve ultimately leads to RV decompensation, which is associated with poor prognosis.

The causes of each disease are explained below.

Aortic Stenosis (AS)

The etiology of AS depends on the age group. In the elderly, this is a degenerative valvular disease that is preceded by aortic sclerosis. This valve undergoes fibrosis and calcification as it progresses over the years. The risk factors for the development of AS are hypertension, diabetes, tobacco smoking, and hyperlipidemia [1].

However, in individuals younger than 70 years of age, the most frequent etiology of AS is a congenital bicuspid aortic valve.

In the developing world, the most common cause of AS is rheumatic fever, regardless of age.

Aortic Regurgitation (AR)

The predominant etiologies of acute cases are infective endocarditis and aortic dissection. In contrast, adult chronic AR is a consequence of diseases such as degenerative aortic valve and root [2], rheumatic fever, infective endocarditis, myxomatous degeneration and trauma. Chronic AR in children is attributed to a ventricular septal defect that is accompanied by aortic valve prolapse.

Mitral Stenosis (MS)

Rheumatic fever accounts for most cases of MS.

Mitral Regurgitation (MR)

Chronic MR is caused by infective endocarditis, rheumatic fever, and MVP [3].

Mitral Valve Prolapse (MVP)

The most prevalent condition that leads to MVP is myxomatous degeneration, which is usually idiopathic but may be inherited in an autosomal dominant pattern.

Pulmonic Stenosis (PS)

This is typically congenital and found in children as part of the Tetralogy of Fallot constellation.

Pulmonic Regurgitation (PR)

Pulmonary hypertension is responsible for the majority of PR cases.

Tricuspid Regurgitation (TR)

This ensues after RV dilation in conditions such as pulmonary hypertension, heart failure and impaired pulmonary outflow.

Tricuspid Stenosis (TS)

Rheumatic fever is the preceding event in approximately all patients with TS.

Congenital AS is observed in 3 to 5 of 1000 live births. As for patient demographics, there is a male gender preference. 

Another abnormality, MVP, is prevalent in 1% to 3% of normal populations. There is no gender preference. 

Hemodynamic changes and heart structural changes often develop in valvular diseases.

AS

AS leads to an elevated pressure load, resulting in compensatory LV hypertrophy (LVH). Note that LV dysfunction will not improve if the impaired contractility cannot be reversed [4].

AR

Chronic regurgitation is associated with a gradual elevation in stroke volume. This is followed by LVH and dilatation of the LV. Ultimately, the left ventricle decompensates.

MS

In this disease, the mitral valve undergoes structural changes characterized by thickening and firming of the leaflets. Also, the commissures fuse and obstruct the orifice.

Stenosis may be accompanied by regurgitation. Additionally, compensatory mechanisms feature the enlargement of the LA and an increase in pressure. If the pressure in the pulmonary vasculature is elevated, one of the main consequences is pulmonary hypertension. The latter leads to further complications.

Note that dilatation of the LA can cause atrial fibrillation which in turn may lead to the formation of emboli.

MR

Chronic cases result in volume overload and the compensatory LV hypertrophy (LVH) and LA hypertrophy (LAH). The compensatory stage can last for many years [5]. Eventually, the disease progresses to a state of decompensation and LV dysfunction, reduced ejection fraction, and pulmonary involvement.

MVP

Prolapse is described as the ballooning of valvular leaflets into the LA during contraction. The pathology responsible for the changes in the leaflets is due to myxomatous degeneration, in which the valve becomes thinner and mucoid substances gather on the leaflets. Furthermore, rupture of the defected chorda may result in regurgitation.

PR

This is associated with RV dilatation and the resultant heart failure.

Prophylactic treatment is indicated with certain valvular replacements. The clinician should consult the guidelines when managing patients with valve pathologies.

Aortic stenosis secondary to arteriosclerosis may be prevented with lifestyle modifications, such as the treatment of hypertension, achieving glycemic control, smoking cessation, and maintaining a healthy weight.

Infective endocarditis due to intravenous drug use can be prevented with safe life choices.

Heart valve disease comprises multiple cardiovascular conditions in which one or more of the valves are damaged or deformed. The valvular diseases have complex underlying pathologies and profound manifestations. Additionally, valve abnormalities may coexist with others as well, hence complicating the clinical sequelae.

Aortic stenosis (AS) is the obstruction of blood flow from the left ventricle (LV) to the aorta in the systolic phase while aortic regurgitation (AR) is characterized by backflow of blood into the LV during diastole. Both are associated with poor outcomes.

Mitral stenosis (MS) is the obstruction of the mitral valve opening that hinders the flow of blood from the left atrium (LA) to the LV. Another disease of this valve is the mitral regurgitation (MR), in which blood fluxes back to the LA.

Pulmonary outflow is affected in pulmonic stenosis (PS) in which case blood returns from the pulmonary artery back to the right ventricle (RV) in pulmonary regurgitation (PR).

In tricuspid stenosis (TS), the valve is narrowed and therefore, impeding blood flux to the RV whereas regurgitation (TR) is the insufficiency of blood flow to the right atrium (RA).

The clinical pictures of these conditions vary according to their severity. Moreover, clinical assessment includes the history of the patient and family, evaluation of current symptoms, a thorough physical exam, and imaging techniques such as echocardiography.

There are novel diagnostic modalities and advances in surgical approaches which include repair, replacement, or valvuloplasty. Additionally, better understanding of these diseases and their outcomes have helped guide the decision-making process.

What are valve diseases?

Abnormal and defective valves constitute a significant group of heart diseases. When the heart valves are affected, this results in many heart problems such as enlarged heart chambers and heart failure.

Valves are the channels that allow blood to flow from one chamber to another, from a blood vessel to a heart chamber, or from a heart chamber to a vessel.The heart is made up of 4 chambers. The top chambers are known as the right and left atria. The bottom chambers are known as the right and left ventricles.

How does blood flow through the heart?

Blood coming from the body enters the right atrium, which then pumps the blood through the tricuspid valve to the right ventricle. The blood then travels from the right ventricle through the pulmonic valve to the pulmonary artery. After the blood flows through the lungs to receives oxygenation, it travels back to the heart, specifically into the left atrium.The blood then flows through the mitral valve to the left ventricle. Finally, the blood travels through the aortic valve into the large blood vessel known as the aorta. The aorta distributes the oxygenated blood to the brain and the rest of the body.

What are the valvular diseases?

The valves are classified according to their defect. When a valve is associated with stenosis, it means there is a narrowing of the opening. Therefore, blood flow is obstructed.When a valve involves regurgitation, the blood returns back to the chamber or vessel it came from. The following are valvular diseases:

• Aortic stenosis:
• Aortic regurgitation:
• Mitral stenosis
• Mitral regurgitation
• Tricuspid stenosis
• Tricuspid regurgitation
• Pulmonic stenosis
• Pulmonic regurgitation

Each one of these is associated with causes, complications, its own set of outcomes/prognosis, and treatment. Also, a vast majority of valve diseases may not present with any symptoms until later in life.

How are these diseases diagnosed?

The diagnosis is achieved by evaluation of the patient’s symptoms (if present), personal and family history, an echocardiogram and other imaging techniques if needed. The echocardiogram is an ultrasound of the heart. This very important and useful test will provide information about the anatomy and function of the valves as well as the function and size of the heart.

How are they treated?
Treatment depends on the valve disease, the degree of severity, the presence of symptoms, the age of the patient, and other heart and medical problems present in the patient. Also, it is very important, if the patient is suitable for surgery or not. The surgical treatment will involve repair or replacement of the valve.

Patients before and after surgery need to be monitored so that prompt treatment may be provided.

1. Otto CM, Bonow RO. Valvular heart disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, editors. , eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine 8th ed.Philadelphia, PA: WB Saunders; 2007:1625-1712
2. Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation. 2009; 119(6):880-90.
3. Carabello BA, Crawford FA. Valvular heart disease. New England Journal of Medicine. 1997; 337(1):32–41
4. Bonow RO, Carabello BA, Chatterjee K, et al. 2006 Writing Committee Members, American College of Cardiology/American Heart Association Task Force. Circulation. 2008;118(15):523-661.
5. Bonow RO, Carabello B, de Leon AC, et al. Guidelines for the management of patients with valvular heart disease: executive summary. 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). Circulation. 1998; 98:1949–84.
6. Ross J Jr, Braunwald E. Aortic Stenosis. 1968; 38(1):61-7.
7. Rahimtoola SH. Aortic valve disease. In: Fuster V, O'Rourke RA, Walsh RA, Poole-Wilson P, editors. , eds. Hurst's The Heart12th ed.New York, NY: McGraw-Hill; 2008:1697-1730
8. Otto CM. Valvular heart disease. Philadelphia: Saunders,. 1999:118,271.
9. Lin M, Chiang HT, Lin SL, et al. Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy. Journal of the American College of Cardiology. 1994; 24(4):1046-53.
10. Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice. A long-term follow-up study. Circulation. 1999; 99(14):1851-7.