Aortic regurgitation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.; Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S; Usama Talib, BSc, MD [3] Mohammed Salih, MD. [4]

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, 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 > 50mm.^[1] 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).

Stage A = at risk;

Stage B = progressive (mild-moderate);

Stage C1 = asymptomatic severe with normal LVEF (>55%) and mild-moderate LV dilation; Stage C2 = asymptomatic severe with LVEF ≤55% or severe LV dilation (LVESD >50 mm);

Stage D = symptomatic severe^[1]

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 the pulse pressure ).There is decreased effective forward flow in aortic insufficiency.

In acute AR, the LV has not had time to dilate and compensate, leading to acute elevation of LV end-diastolic pressure, premature mitral valve closure, pulmonary edema, and cardiogenic shock. In chronic AR, eccentric hypertrophy and LV dilation serve as compensatory mechanisms to maintain forward stroke volume, but eventually lead to irreversible myocardial fibrosis and systolic dysfunction. ^[2]

---

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.While aortic root/ascending aorta dilation is an increasingly recognized cause, the relative frequency depends on the population studied. In Western countries, degenerative disease (including bicuspid aortic valve and calcific degeneration) and aortic root dilation are the leading causes, while rheumatic heart disease remains the most common cause globally^[2][3].It can also occur after surgical valve placement.

Drug-induced AR (e.g., from fenfluramine, pergolide, cabergoline) and AR associated with aortitis (e.g., giant cell arteritis, Takayasu arteritis, syphilitic aortitis) are other recognized causes^[2]

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. Clinically significant (moderate or greater) AR is much less common, affecting approximately 0.5% of the general population and increasing with age. ^[2]

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 aortic root dilation 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. Other important risk factors include ^[2][4]:

1. Connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome),
2. Bicuspid aortic valve-associated aortopathy,
3. hypertension-related aortic root dilation

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.

Current data indicate that untreated symptomatic severe AR carries a 1-year mortality exceeding 20%, and only 1 in 5 patients with severe AR and LVEF 30-50% are referred for SAVR. The prognosis is excellent after timely surgical intervention but poor without it.^[5][6]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.

Asymptomatic patients with severe AR and normal LV function have a rate of progression to symptoms or LV dysfunction of approximately 3-6% per year, and that once LVEF declines below 55% or LVESD exceeds 50 mm, outcomes worsen significantly even after surgery. ^[1][7]

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.

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)
• The murmur of AR is classically best heard at the left sternal border (Erb’s point, 3rd-4th intercostal space) with the patient sitting up and leaning forward. A murmur heard best at the right second intercostal space may suggest AR due to aortic root dilation. . The murmur may be soft in acute AR.
• S₃ and S₄ may be heard.

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.

Exercise testing should be routinely performed in “asymptomatic” patients with severe AR to unmask symptoms or abnormal hemodynamics (Class IIa, ACC/AHA 2020). Exercise testing is reasonable to confirm symptom status in Stage C patients^[1][2]

The echocardiogram is the single most useful diagnostic imaging study in the diagnosis and ongoing surveillance of the severity of aortic insufficiency. ECG findings in AR, which may include LV hypertrophy (voltage criteria), left axis deviation, and left atrial enlargement in chronic AR, or sinus tachycardia in acute AR

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.

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 > 50mm^[1]. Pulsed Doppler echocardiography is more sensitive than auscultation specially in patients in whom no murmur is observed. 3D echocardiography may provide more accurate volumetric assessment than 2D methods, though prognostic data remain limited.^[7]

The quantitative criteria for severe AR per current guidelines^[1]:

• jet width ≥65% of LVOT,
• vena contracta >0.6 cm,
• holodiastolic flow reversal in the proximal abdominal aorta
• , regurgitant volume ≥60 mL/beat,
• regurgitant fraction ≥50%,
• effective regurgitant orifice ≥0.3 cm²

GLS values worse than −18% to −19% predict higher mortality and disease progression in asymptomatic AR with preserved LVEF, and GLS <−15% confers a 2- to 3-fold increased mortality risk. The 2025 AHA scientific statement on speckle-tracking strain echocardiography and the 2025 ASE/EACI consensus statement both support GLS as a prognostic biomarker in AR^[2][8]

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 is recommended as an adjunct when echocardiography is inconclusive or discordant (Class I, ACC/AHA 2020). CMR is the reference standard for direct quantification of regurgitant volume and regurgitant fraction via phase-contrast velocity mapping. CMR-derived regurgitant fraction thresholds of 32-35% (lower than the echocardiographic threshold of 50%) predict adverse outcomes and need for surgery. Holodiastolic retrograde flow in the descending aorta on CMR is independently associated with a 2.8-fold increased risk of death or heart failure hospitalization^[2][1][7]

CMR provides volumetric indices (LVESVi ≥45 mL/m², LVEDVi ≥109 mL/m²) that are validated predictors of adverse outcomes and outperform linear dimensions, particularly in patients with preserved LVEF. The 2025 ESC/EACTS guidelines now emphasize these volumetric indices alongside conventional triggers.^[2]

CMR offers myocardial tissue characterization via late gadolinium enhancement and T1 mapping/extracellular volume quantification, which can detect focal and diffuse fibrosis — markers of subclinical injury from chronic volume overload that may be irreversible and are associated with impaired postoperative recovery.^[2]

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.

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).

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. Intra-aortic balloon pump is absolutely contraindicated in AR because it augments diastolic pressure and worsens regurgitation. Beta blockers are relatively contraindicated because they prolong diastole and increase regurgitant volume, except in aortic dissection where they are essential. The text should also note that emergency surgery should not be delayed for medical optimization in acute severe AR with hemodynamic instability^[2]

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.

There is no evidence that vasodilating drugs reduce severity of AR or alter the disease course in patients with significant AR in the absence of systemic hypertension. Vasodilator therapy is recommended only for:

(1) treatment of hypertension (systolic BP >140 mm Hg) in asymptomatic patients (Class I);

(2) GDMT for reduced LVEF (ACE inhibitors, ARBs, and/or sacubitril/valsartan) in patients with severe AR who have symptoms and/or LV dysfunction but prohibitive surgical risk (Class I).

Medical therapy should not delay timely referral for valve replacement. 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.

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.

The 2025 ESC/EACTS guidelines now recommend intervention at lower thresholds than ACC/AHA, including Class IIb consideration for LVESDi >22 mm/m² or LVESVi ≥45 mL/m², and Class IIb (C) for LVESDi >20 mm/m² in low-risk patient^[2]

Aortic valve repair should be discussed as an increasingly viable alternative to replacement in selected patients. The 2025 ESC/EACTS guidelines give aortic valve repair a Class IIa recommendation in selected patients at experienced centers. Valve-sparing aortic root surgery (David procedure) is recommended particularly in patients <65 years with aortic root dilation and normal or near-normal cusps. Freedom from reoperation after repair is approximately 88% at 5 years and 73% at 10 years in experienced centers.^[1][2]

The Ross procedure (pulmonary autograft) should be mentioned as an expanding option for younger patients with AR, offering survival comparable to the general population in expert centers.^[2]

In chronic AR, aortic valve replacement (AVR) is indicated in patients with :

• Severe AR who are either symptomatic regardless of LV systolic function,
• Class I: Symptomatic severe AR (Stage D) regardless of LV function; asymptomatic severe AR with LVEF ≤55% (Stage C2); severe AR (Stage C or D) undergoing cardiac surgery for other indications.^[1]
• Class IIa: Asymptomatic severe AR with LVEF >55% but LVESD >50 mm or indexed LVESD >25 mm/m². ^[1]
• Class IIb: Asymptomatic severe AR with LVEF >55% and progressive decline in LVEF to 55-60% on ≥3 serial studies, or progressive increase in LVEDD >65 mm. ^[1]
• Class III (Harm): TAVR should not be performed in patients with isolated severe AR who are candidates for SAVR (ACC/AHA 2020). JACC^[1]

Per the 2020 ACC/AHA guidelines, TAVR is Class III (Harm) for isolated severe AR in surgical candidates.^[1]

However, the 2025 ESC/EACTS guidelines now give TAVR a Class IIb recommendation for inoperable/high-risk patients with suitable anatomy following heart team consensus.^[2]

The ALIGN-AR trial (2024-2025) demonstrated that transfemoral TAVR with a dedicated device (Trilogy valve) was effective in eliminating AR in high-risk patients, with substantial improvements in LV remodeling and functional status at 1 year.^[3][6]

Per the 2020 ACC/AHA guidelines and 2025 ESC/EACTS guidelines, recommended surveillance intervals are^[1][2]:

• Mild AR (Stage B): echocardiography every 3-5 years
• Moderate AR (Stage B): echocardiography every 1-2 years
• Severe asymptomatic AR (Stage C1): echocardiography every 6-12 months; more frequently if LV is dilating
• Annual history and physical examination for all patients with significant AR

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.

Per the 2020 ACC/AHA guidelines, antibiotic prophylaxis is not recommended for native valve AR (including bicuspid aortic valve). Prophylaxis is recommended only for the highest-risk groups: prosthetic cardiac valves (including TAVR), prosthetic material used for valve repair, previous IE, unrepaired cyanotic congenital heart disease, and cardiac transplant with valve regurgitation^[1].

Prophylaxis is recommended only before dental procedures involving manipulation of gingival tissue, the periapical region of teeth, or perforation of the oral mucosa. Prophylaxis is not recommended for nondental procedures (TEE, EGD, colonoscopy, cystoscopy) in the absence of active infection (Class III: No Benefit)^{[1] [9]}

Clindamycin is no longer recommended for IE prophylaxis due to increased risk of Clostridioides difficile infection. Preferred alternatives for penicillin-allergic patients include cephalexin, azithromycin, or doxycycline.^[9]

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.

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.

Isolated aortic insufficiency in pregnant patients can be managed with combination of diuretics and vasodilators. ACE inhibitors are contraindicated in pregnancy.ARBs are also contraindicated in pregnancy. For hypertension management in pregnant patients with AR, labetalol, nifedipine, or methyldopa are preferred agents per current guidelines^[1] 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.

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.

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.

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Vendhan Ramanujam M.B.B.S [3]; Usama Talib, BSc, MD [4]

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.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Aortic dissection^[1]
• Bacterial endocarditis^[2]

• Bicuspid aortic valve^[3]
• Senile or degenerative calcific aortic valve disease^[3]
• Rheumatic heart disease^[4]
• After Valvular Surgery^[5]

The cause of Aortic Regurgitation by location can be classified as following:^[1]

• Bicuspid aortic valve^[3]
• Collagen vascular disease
• Senile or degenerative calcific aortic valve disease
• Endocarditis
• Myxomatous aortic valve
• Rheumatic fever^[6]
• Rheumatoid arthritis ^[7]
• Sinus of Valsalva Aneurysm
• Systemic Lupus Erythematosus
• Trauma^[8][9]
• Turner’s Syndrome
• Ventricular Septal Defect
• Weight loss medications
• Post Aortic Valve Surgery^[10]
• Quadricuspid Aortic Valve ^[11]

• Ankylosing spondylitis ^[12]
• Aortic dissection ^[13]
• Arteriosclerosis ^[14]
• Bechterew’s Disease ^[12]
• Behcet’s syndrome
• Cystic medial necrosis of the aorta
• Ehlers-Danlos Syndrome
• Giant cell arteritis
• Hypertension^[15]
• Idiopathic dilation of the ascending aorta
• Marfan syndrome^[9]
• Osteogenesis imperfecta
• Polymyalgia Rheumatica
• Pseudoxanthoma Elasticum
• Psoriatic arthritis
• Reiter’s syndrome
• Relapsing polychondritis
• Senile aortic ectasia and dilation
• Spondyloarthropathy
• Syphilitic aortitis
• Takayasu arteritis^[16]
• Trauma
• Ulcerative colitis
• Whipple’s disease

Cardiovascular	Annuloaortic ectasia, aortic valvuloplasty, aortic dissection, arterial tortuosity syndrome, bacterial endocarditis, balloon valvotomy, bicuspid aortic valve, congenitally fenestrated cusp rupture, cystic medial necrosis, hypertension, marantic endocarditis, prosthetic valve dysfunction, senile aortic ectasia and dilation, senile or degenerative calcific aortic valve disease, sinus of valsalva aneurysm, subaortic stenosis, syphilitic aortitis, subpulmonic ventricular septal defect, tetralogy of Fallot, thoracic aortic aneurysm, unicuspid aortic valve, ventricular septal defect
Chemical / poisoning	No underlying causes
Dermatologic	Psoriatic arthritis
Drug Side Effect	Cabergoline, dexfenfluramine, dopamine agonists, fenfluramine, methysergide, pergolide, phentermine
Ear Nose Throat	No underlying causes
Endocrine	Acromegaly
Environmental	No underlying causes
Gastroenterologic	Inflammatory bowel disease, ulcerative colitis, Whipple disease
Genetic	Ankylosing spondylitis, autosomal dominant polycystic kidney disease, bicuspid aortic valve, Down syndrome, Ehlers-Danlos syndrome, Hurler syndrome, Marfan syndrome, Maroteaux-Lamy syndrome, mucolipidosis II alpha/beta, mucolipidosis III gamma, mucopolysaccharidosis, mucopolysaccharidosis type I Hurler/Scheie syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, rheumatoid arthritis, Scheie syndrome, Shprintzen-Goldberg syndrome, truncus arteriosus, Turner’s syndrome, unicuspid aortic valve
Hematologic	No underlying causes
Iatrogenic	Aortic valvuloplasty, balloon valvotomy, double switch operation, prosthetic valve dysfunction, radiation, Senning-Rastelli procedure
Infectious Disease	Bacterial endocarditis, perivalvular abscess, Q fever, rheumatic fever, syphilis, syphilitic aortitis
Musculoskeletal / Ortho	Ankylosing spondylitis, collagen vascular disease, Ehlers-Danlos syndrome, osteogenesis imperfecta, psoriatic arthritis, Reiter’s Syndrome, relapsing polychondritis, rheumatoid arthritis, spondyloarthropathy, systemic lupus erythematosus
Neurologic	No underlying causes
Nutritional / Metabolic	Mucolipidosis II alpha/beta, mucolipidosis III gamma
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	Autosomal dominant polycystic kidney disease
Rheum / Immune / Allergy	Ankylosing spondylitis, antiphospholipid syndrome, Bechterew’s disease, Behcet disease, collagen vascular disease, cystic medial necrosis, Ehlers-Danlos syndrome, giant cell arteritis, inflammatory bowel disease, Marfan syndrome, myxomatous aortic valve, osteogenesis imperfecta, polychondritis, polymyalgia rheumatica, pseudoxanthoma elasticum, psoriatic arthritis, reactive arthritis, Reiter’s syndrome, relapsing polychondritis, rheumatic fever, rheumatoid arthritis, sarcoidosis, spondyloarthropathy, systemic lupus erythematosus, Takayasu arteritis, ulcerative colitis, Whipple disease
Sexual	No underlying causes
Trauma	Chest trauma, traumatic aortic rupture
Urologic	No underlying causes
Miscellaneous	No underlying causes

The causes of Acute Aortic Insufficiency include the following:^{[33][34][35][10]}

• Aortic valvuloplasty^[10]
• A type A aortic dissection may disrupt the integrity of the valve leaflets causing malcoaptation of the aortic leaflets.^[36]
• In bacterial endocarditis the infection can erode the valve and cause a leaflet to become flail, or a vegetation can prevent coaptation of the leaflets.
• Blunt chest trauma can disrupt the supporting apparatus of the aortic valve.
• Myxomatous aortic valve can degenerate, leading to insufficiency.
• Prosthetic valve dysfunction^[37]
• Rheumatic fever^[6]
• Rupture of a congenitally fenestrated cusp^[38]

The cause of Chronic Aortic Insufficiency include the following:^[1][39]

• Ankylosing spondylitis can be associated with inflammation of the aorta (aortitis).^[40] The inflammatory process can also involve the septum and cause conduction disease.
• A type A aortic dissection may disrupt the integrity of the valve leaflets causing malcoaptation of the aortic leaflets.
• Bechterew’s disease
• Rarely, in 5% of cases with Behcet disease there is an aortitis that involves the ascending aorta and in some cases the coronary arteries are involved.
• Bicuspid aortic valve is the most common congenital abnormality of the heart. It is the most common cause of isolated aortic insufficiency requiring surgical repair. Bicuspid aortic valve is also associated with inflammation of the aorta (an aortopathy) which may lead to dilation of the aorta and/or aortic dissection that can worsen the aortic insufficiency.^[41]
• Cystic medial necrosis of the aorta
• Ehlers-Danlos syndrome
• Giant cell arteritis may also be associated with an aortitis as well as coronary artery disease.^[42]
• Hypertension
• Marfan Syndrome
• Myxomatous aortic valve
• Polymyalgia rheumatica
• Pseudoxanthoma elasticum
• Reiter’s syndrome
• Rheumatic fever remains a cause of AS in the Middle East, Northern Africa and Asia as well as some immigrant populations in the United States. It is less prevalent in the US than it was in the 20th century. AR occurs as a result of fibrosis of the valve that is associated with thickening and retraction of the leaflets of the aortic valve. This retraction results in regurgitation in the center of the valve. At the same time, there may also be fusion of the aortic leaflets which results in concurrent aortic stenosis. It should be noted that rheumatic disease of the mitral valve is usually present in the same patient.
• Rheumatoid arthritis rarely causes symptomatic AR, but it can cause granulomatous nodules on the aortic leaflets which leads to clinical aortic regurgitation.^[43]
• Sinus of valsalva aneurysm
• Syphilis
• Systemic lupus erythematosus can cause AR by tow mechanisms. SLE can cause inflammation and fibrosis of the aortic leaflets leading to their damage and retraction.^[44] SLE can also be associated with the development of sterile verrucous vegetations on the valves called Libman-Sacks endocarditis.^[45][46]
• Takayasu arteritis can involve the aorta in an aortitis, the aortic valve itself, and the coronary arteries.^[47]
• Turner’s syndrome
• Ventricular septal defect^[48]
• Weight loss medications including fenfluramine and dexfenfluramine (a.k.a. Phen-Fen). These drugs have been associated with degeneration of the aortic valve.
• Whipple disease can involve the aortic valve.^[49]

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Mohammed A. Sbeih, M.D. [2]; Usama Talib, BSc, MD [3]

Aortic insufficiency is the backward flow of blood from the aorta into the left ventricle through the aortic valve during systole due to abnormalities in the aortic valve or the aorta. 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.^[1]

Normally, the aortic valve is only open when the pressure in the left ventricle exceeds the pressure in the aorta. This allows the blood to be ejected from the left ventricle into the aorta during ventricular systole. The amount of blood that is ejected by the heart is known as the stroke volume. Under normal conditions, 50–70% of the blood in a filled left ventricle is ejected into the aorta to be used by the body (called the ejection fraction). In aortic insufficiency (AI), when the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve leaks, and the blood flows from the aorta into the left ventricle. As a result there is volume overload of the left ventricle.^{[2] [3]}

In acute aortic insufficiency, there is a sudden decrease in stroke volume and subsequent increase in left ventricular end diastolic volume thereby causing decrease cardiac output with resultant reflex tachycardia. The sharply rising high left ventricular end diastolic pressure and reflex tachycardia causes profound hypotension and cardiogenic shock. Initially, the rising left ventricle end diastolic pressure causes early closure of mitral valve during diastole thereby preventing backward blood flow. But in severe cases, the rapidly rising left ventricular end diastolic pressure equalizes with the aortic end-diastolic pressure leading to backward flow of blood progressing towards development of pulmonary edema.^{[4][5] [3]}

In chronic aortic insufficiency, initially the left ventricle remains complaint, thereby compensates for increased left ventricular end diastolic volume by progressive left ventricular dilatation and left ventricular hypertrophy, which maintains normal ratio of wall thickness to the cavity radius, thereby maintaining normal wall stress. Overtime, when the left ventricular hypertrophy fails to keep up with chronic volume overload, end systolic wall stress rises and at this point the left ventricle fails and results in left ventricle decompensation causing reduction in the left ventricular wall compliance with resultant congestive heart failure.^{[6][7] [8]}

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.^{[9] [8] [8]}

Note that while diastolic blood pressure is diminished and the pulse pressure widens, systolic blood pressure generally remains normal or can even be slightly elevated.^[9]This is because sympathetic nervous system and the renin-angiotensin-aldosterone axis of the kidneys compensate for the decreased cardiac output. Catecholamines will increase the heart rate and increase the strength of ventricular contraction, directly increasing cardiac output. Catecholamines will also cause peripheral vasoconstriction, which causes increased systemic vascular resistance and ensures that core organs are adequately perfused. Renin, a proteolytic enzyme, cleaves angiotensinogen to angiotensin I, which is converted to angiotensin II, which is also a potent vasoconstrictor. In chronic aortic insufficiency with resultant cardiac remodeling, heart failure may develop, and as a result, the systolic blood pressure will decline.

Aortic insufficiency causes both volume overload (elevated preload) and pressure overload (elevated afterload due to the increased stroke volume) of the heart. Regurgitation of blood into the left ventricle causes volume overload and a rise in preload. The pressure overload causes left ventricular hypertrophy (LVH). There is both concentric hypertrophy and eccentric hypertrophy in AI. The concentric hypertrophy is due to the increased left ventricular systolic pressures associated with AI, while the eccentric hypertrophy is due to volume overload caused by the regurgitant fraction. This pathophysiology is in contrast to that of mitral regurgitation where there is also an increase in preload, but there is a decrease in afterload due to ejection of blood into the low pressure system of the pulmonary circuit.^[10]

A complete list of aortic valve diseases that causes aortic insufficiency can be found on the page dedicated to the causes of aortic insufficiency.

One of the most common causes of aortic valvular disease in the past has been rheumatic fever in which case the aortic cusps are infiltrated with fibrous tissue. This then leads to retraction of the cusps and prevents their apposition during diastole. The cusps may also fuse and this may cause a component of aortic stenosis. It is therefore not uncommon for these patients to have mixed aortic regurgitation and aortic stenosis. Often these patients will have involvement of the mitral valve as well.^[11]

In the modern era, a more common cause of acquired aortic valve regurgitation is degenerative disease of the aorta and aortic valve in which case there is calcification and fibrosis of the cusps. As is the case with rheumatic fever, there is similar retraction of the cusps that results in aortic insufficiency.^[8]

A third not uncommon cause of acquired aortic regurgitation is infective endocarditis. In this disease state, regurgitation develops as a result of a hole or perforation that develops in the leaflet, or alternatively the cusps may not oppose each other due to a vegetation lying between the cusps which prevents their apposition.^[3]

Drugs such as dopamine agonists cause activation of serotonin-2B receptors (located in aortic valve and mitral valve) resulting in stimulation of fibroblast growth and fibrogenesis, thereby causing aortic insufficiency.^[12][13][14]

A final not uncommon cause of acquired aortic insufficiency is following a blunt chest trauma or a deceleration injury which causes traumatic aortic valve rupture resulting in distortion of the valve architecture leading to failure of the cusps to oppose.^[15][16]

Congenital conditions such as congenital bicuspid aortic stenosis or a ventricular septal defect can also result in aortic insufficiency. Patients with bicuspid aortic valve are at increased risk of developing aortic dissection.^[17]

Aortic root disease as a cause of aortic insufficiency has overtaken acquired forms of valvular disease and congenital forms of valvular disease as the leading cause of aortic regurgitation. A complete list of conditions that lead to dilation of the aortic root and thereby cause aortic insufficiency can be found on the page dedicated to the causes of aortic insufficiency.^{[6] [18]}

Acute aortic insufficiency is often secondary to infective endocarditis, aortic dissection,^[19] or traumatic aortic rupture.^[15][20]

In acute aortic insufficiency, the left ventricle becomes acutely volume overloaded by the retrograde flow of blood from the aorta. The left ventricle cannot dilate acutely to accommodate this large volume of regurgitant blood. As a result, the left ventricular end diastolic pressure rises abruptly and this rise in pressure is transmitted backward to the pulmonary circulation resulting in pulmonary edema. There is also a sudden decrease in forward cardiac output due to a reduction in stroke volume secondary to regurgitation of blood into left ventricle. The very high left ventricular end diastolic pressure causes reflex tachycardia as does the reduction in stroke volume. As a result of all of the above, hypotension and cardiogenic shock may ensue.

Initially there may be a wide pulse pressure, but as the left ventricle fails, the pulse pressure may narrow as the left ventricular end diastolic pressure rises to equal the diastolic blood pressure, and the stroke volume of the left ventricle declines reducing the systolic blood pressure.^[9]In some cases, the sharply rising left ventricular end diastolic pressure causes the mitral valve to close earlier during diastole. This early closure fortunately prevents backward flow of blood into the pulmonary vascular bed and often keeps the aortic diastolic pressure from falling too low and sometimes there may not be a wide pulse pressure. ^{[21] [1]}

Chronic aortic insufficiency differs from the acute aortic insufficiency in so far as the left ventricle has time to adapt to the chronic volume overload through a series of compensatory changes, namely dilation and eccentric hypertrophy.^[7][3][22]

The increasing regurgitant volume causes the stroke volume to fall. In order to compensate for a fraction of the blood going backwards, the heart compensates by ejecting a larger total volume of blood forward. The ejection fraction is preserved and perhaps even increased to compensate for the regurgitant fraction. In order to eject a larger volume of blood, the left ventricle must dilate. According to the Frank-Starling mechanism, left ventricular dilation up to a point is associated with greater contractility. The way the ventricle dilates is to lengthen the muscle fibers and the way it does this is to add sarcomeres in series. While the heart is normally shaped like a football, as it dilates, it begins to assume a more round, globular, and spherical shape. During this initial period, the left ventricle is fairly compliant. The patient is generally asymptomatic during this period.

As the heart dilates, there is a greater stress on the wall due to Laplace’s Law. In order to compensate for the increased wall stress, eccentric hypertrophy develops.

While the left ventricular dilation is associated with the increased cardiac output according to the Frank-Starling mechanism, at a certain point of left ventricular dilation, the left ventricle begins to fail as left ventricular contractility falls. Once wall thickening fails to keep up with the hemodynamic load, end systolic wall stress rises and at this point the left ventricle fails. The dramatic enlargement of the heart that is seen with aortic insufficiency is called cor bovinum. The left ventricle also stiffens over time due to increased interstitial fibrosis. ^{[21] [1]}

At this point, the left ventricular ejection fraction falls. The left ventricular end systolic volume begins to rise. Next the left ventricular end diastolic volume begins to rise and this causes dyspnea or frank pulmonary edema. The first symptoms of the rise in left ventricular end diastolic pressure may be an increase in dyspnea on exertion.

Patients with chronic aortic insufficiency may also develop myocardial ischemia. This is due to the fact that they have an increase in demand due to an increased thickness of the left ventricle and also a reduction in the supply due to a lower perfusion pressure during diastole.^{[21] [1]}

It has been said that ‘aortic regurgitation begets aortic regurgitation‘. The high oscillatory shear associated with aortic regurgitation may lead to further dilation of the aorta, which in turn may lead to further worsening of aortic regurgitation.

The mitral valve ring may also dilate leading to mitral regurgitation which further can progress to the development of left atrium dilatation. Left atrial dilation may in turn cause atrial fibrillation which further reduces left ventricular filling.^{[21] [1]}

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Vendhan Ramanujam M.B.B.S [3]; Usama Talib, BSc, MD [4]

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.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Aortic dissection^[1]
• Bacterial endocarditis^[2]

• Bicuspid aortic valve^[3]
• Senile or degenerative calcific aortic valve disease^[3]
• Rheumatic heart disease^[4]
• After Valvular Surgery^[5]

The cause of Aortic Regurgitation by location can be classified as following:^[1]

• Bicuspid aortic valve^[3]
• Collagen vascular disease
• Senile or degenerative calcific aortic valve disease
• Endocarditis
• Myxomatous aortic valve
• Rheumatic fever^[6]
• Rheumatoid arthritis ^[7]
• Sinus of Valsalva Aneurysm
• Systemic Lupus Erythematosus
• Trauma^[8][9]
• Turner’s Syndrome
• Ventricular Septal Defect
• Weight loss medications
• Post Aortic Valve Surgery^[10]
• Quadricuspid Aortic Valve ^[11]

• Ankylosing spondylitis ^[12]
• Aortic dissection ^[13]
• Arteriosclerosis ^[14]
• Bechterew’s Disease ^[12]
• Behcet’s syndrome
• Cystic medial necrosis of the aorta
• Ehlers-Danlos Syndrome
• Giant cell arteritis
• Hypertension^[15]
• Idiopathic dilation of the ascending aorta
• Marfan syndrome^[9]
• Osteogenesis imperfecta
• Polymyalgia Rheumatica
• Pseudoxanthoma Elasticum
• Psoriatic arthritis
• Reiter’s syndrome
• Relapsing polychondritis
• Senile aortic ectasia and dilation
• Spondyloarthropathy
• Syphilitic aortitis
• Takayasu arteritis^[16]
• Trauma
• Ulcerative colitis
• Whipple’s disease

Cardiovascular	Annuloaortic ectasia, aortic valvuloplasty, aortic dissection, arterial tortuosity syndrome, bacterial endocarditis, balloon valvotomy, bicuspid aortic valve, congenitally fenestrated cusp rupture, cystic medial necrosis, hypertension, marantic endocarditis, prosthetic valve dysfunction, senile aortic ectasia and dilation, senile or degenerative calcific aortic valve disease, sinus of valsalva aneurysm, subaortic stenosis, syphilitic aortitis, subpulmonic ventricular septal defect, tetralogy of Fallot, thoracic aortic aneurysm, unicuspid aortic valve, ventricular septal defect
Chemical / poisoning	No underlying causes
Dermatologic	Psoriatic arthritis
Drug Side Effect	Cabergoline, dexfenfluramine, dopamine agonists, fenfluramine, methysergide, pergolide, phentermine
Ear Nose Throat	No underlying causes
Endocrine	Acromegaly
Environmental	No underlying causes
Gastroenterologic	Inflammatory bowel disease, ulcerative colitis, Whipple disease
Genetic	Ankylosing spondylitis, autosomal dominant polycystic kidney disease, bicuspid aortic valve, Down syndrome, Ehlers-Danlos syndrome, Hurler syndrome, Marfan syndrome, Maroteaux-Lamy syndrome, mucolipidosis II alpha/beta, mucolipidosis III gamma, mucopolysaccharidosis, mucopolysaccharidosis type I Hurler/Scheie syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, rheumatoid arthritis, Scheie syndrome, Shprintzen-Goldberg syndrome, truncus arteriosus, Turner’s syndrome, unicuspid aortic valve
Hematologic	No underlying causes
Iatrogenic	Aortic valvuloplasty, balloon valvotomy, double switch operation, prosthetic valve dysfunction, radiation, Senning-Rastelli procedure
Infectious Disease	Bacterial endocarditis, perivalvular abscess, Q fever, rheumatic fever, syphilis, syphilitic aortitis
Musculoskeletal / Ortho	Ankylosing spondylitis, collagen vascular disease, Ehlers-Danlos syndrome, osteogenesis imperfecta, psoriatic arthritis, Reiter’s Syndrome, relapsing polychondritis, rheumatoid arthritis, spondyloarthropathy, systemic lupus erythematosus
Neurologic	No underlying causes
Nutritional / Metabolic	Mucolipidosis II alpha/beta, mucolipidosis III gamma
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	Autosomal dominant polycystic kidney disease
Rheum / Immune / Allergy	Ankylosing spondylitis, antiphospholipid syndrome, Bechterew’s disease, Behcet disease, collagen vascular disease, cystic medial necrosis, Ehlers-Danlos syndrome, giant cell arteritis, inflammatory bowel disease, Marfan syndrome, myxomatous aortic valve, osteogenesis imperfecta, polychondritis, polymyalgia rheumatica, pseudoxanthoma elasticum, psoriatic arthritis, reactive arthritis, Reiter’s syndrome, relapsing polychondritis, rheumatic fever, rheumatoid arthritis, sarcoidosis, spondyloarthropathy, systemic lupus erythematosus, Takayasu arteritis, ulcerative colitis, Whipple disease
Sexual	No underlying causes
Trauma	Chest trauma, traumatic aortic rupture
Urologic	No underlying causes
Miscellaneous	No underlying causes

The causes of Acute Aortic Insufficiency include the following:^{[33][34][35][10]}

• Aortic valvuloplasty^[10]
• A type A aortic dissection may disrupt the integrity of the valve leaflets causing malcoaptation of the aortic leaflets.^[36]
• In bacterial endocarditis the infection can erode the valve and cause a leaflet to become flail, or a vegetation can prevent coaptation of the leaflets.
• Blunt chest trauma can disrupt the supporting apparatus of the aortic valve.
• Myxomatous aortic valve can degenerate, leading to insufficiency.
• Prosthetic valve dysfunction^[37]
• Rheumatic fever^[6]
• Rupture of a congenitally fenestrated cusp^[38]

The cause of Chronic Aortic Insufficiency include the following:^[1][39]

• Ankylosing spondylitis can be associated with inflammation of the aorta (aortitis).^[40] The inflammatory process can also involve the septum and cause conduction disease.
• A type A aortic dissection may disrupt the integrity of the valve leaflets causing malcoaptation of the aortic leaflets.
• Bechterew’s disease
• Rarely, in 5% of cases with Behcet disease there is an aortitis that involves the ascending aorta and in some cases the coronary arteries are involved.
• Bicuspid aortic valve is the most common congenital abnormality of the heart. It is the most common cause of isolated aortic insufficiency requiring surgical repair. Bicuspid aortic valve is also associated with inflammation of the aorta (an aortopathy) which may lead to dilation of the aorta and/or aortic dissection that can worsen the aortic insufficiency.^[41]
• Cystic medial necrosis of the aorta
• Ehlers-Danlos syndrome
• Giant cell arteritis may also be associated with an aortitis as well as coronary artery disease.^[42]
• Hypertension
• Marfan Syndrome
• Myxomatous aortic valve
• Polymyalgia rheumatica
• Pseudoxanthoma elasticum
• Reiter’s syndrome
• Rheumatic fever remains a cause of AS in the Middle East, Northern Africa and Asia as well as some immigrant populations in the United States. It is less prevalent in the US than it was in the 20th century. AR occurs as a result of fibrosis of the valve that is associated with thickening and retraction of the leaflets of the aortic valve. This retraction results in regurgitation in the center of the valve. At the same time, there may also be fusion of the aortic leaflets which results in concurrent aortic stenosis. It should be noted that rheumatic disease of the mitral valve is usually present in the same patient.
• Rheumatoid arthritis rarely causes symptomatic AR, but it can cause granulomatous nodules on the aortic leaflets which leads to clinical aortic regurgitation.^[43]
• Sinus of valsalva aneurysm
• Syphilis
• Systemic lupus erythematosus can cause AR by tow mechanisms. SLE can cause inflammation and fibrosis of the aortic leaflets leading to their damage and retraction.^[44] SLE can also be associated with the development of sterile verrucous vegetations on the valves called Libman-Sacks endocarditis.^[45][46]
• Takayasu arteritis can involve the aorta in an aortitis, the aortic valve itself, and the coronary arteries.^[47]
• Turner’s syndrome
• Ventricular septal defect^[48]
• Weight loss medications including fenfluramine and dexfenfluramine (a.k.a. Phen-Fen). These drugs have been associated with degeneration of the aortic valve.
• Whipple disease can involve the aortic valve.^[49]

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

The differential diagnosis of aortic regurgitation includes other valvular abnormalities and diseases that can cause a similar clinical presentation.

The heart murmur of aortic regurgitation must be differentiated from that of other valvular diseases. Acute aortic regurgitation (AR) is characterized by the presence of a low pitched early diastolic murmur that is best heard at the right 2nd intercostal space, decreased or absent S1, and increased P2. Chronic AR is characterized by the presence of a high pitched holodiastolic decrescendo murmur that is best heard at the upper left sternal border and that increases with sitting forward, expiration, and handgrip.

The differential diagnosis of aortic regurgitation includes other valvular abnormalities:^{[1][2][3][4][5][6] [1]}

• Aortic stenosis: The murmur of aortic stenosis is harsh and best heard at the right second intercostal space.
• Mitral regurgitation: The murmur of mitral regurgitation is blowing, soft and best heard at the apex.
• Mitral stenosis: The murmur of mitral stenosis is mid-diastolic, rumbling, and best heard after the opening snap.
• Tricuspid regurgitation: The murmur of tricuspid regurgitation is blowing, holosystolic, and best heard over the fourth intercostal area at the left sternal border.
• Tricuspid stenosis: The murmur of tricuspid stenosis is characterized by a mid diastolic murmur best heard over the left sternal border with rumbling character and tricuspid opening snap with wide splitting of S1.

Aortic regurgitation should also be differentiated from other diseases that might cause similar clinical presentation, such as:^{[7][8][9][10]}

• Acute coronary syndrome
• Anemia
• Heart failure
• Infective endocarditis
• Patent ductus arteriosus
• Pregnancy
• Thyrotoxicosis
• Volume depletion
• Wet beriberi

Following are the cardiac conditions having similar presentation as Aortic regurgitation:^{[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]}

Diseases	History	Symptoms	Physical Examination	Murmur	Diagnosis				Other Findings
					ECG	CXR	Echocardiogram	Cardiac Catheterization
Mitral Stenosis	Age ( Mitral annular calcification in older patients) Rheumatic fever Endocarditis	Dyspnea on exertion Paroxysmal nocturnal dyspnea Orthopnea New onset atrial fibrillation	Mitral facies Heart murmur Jugular vein distension Apical impulse displaced laterally or not palpable Diastolic thrill at the apex Signs of heart failure in severe cases	Diastolic murmur Low pitched Opening snap followed by decrescendo-crescendo rumbling murmur Best heard with the bell of the stethoscope at apex at end-expiration in left lateral decubitus position Intensity increases after a valsalva maneuver, after exercise and after increased after load (eg., squatting, isometric hand grip)	P mitrale Atrial fibrillation: No P waves and irregularly irregular rhythm Right axis deviation Right ventricular hypertropy: Dominant R wave in V1 and V2	Straightening of the left border of the heart suggestive of enlargement of the left atrium Double right heart border (Enlarged left atrium and normal right atrium) Prominent left atrial appendage Splaying of subcarinal angle (>120 degrees) Calcification of mitral valve Kerley B lines	Reduced valve leaflet mobility Valve calcification Doming of mitral valve Valve thickening Enlargement of left atrium	Right heart catheterization: Pulmonary capillary wedge pressure (left atrial pressure) Left heart catheterization: Pressures in left ventricle Determines the gradient between the left and right atrium during ventricular diastole (marker of the severity of mitral stenosis)	Hemoptysis (heart failure) Ortner’s syndrome
Mitral Regurgitation	CAD MI Rheumatic fever Endocarditis Mitral valve prolapse Cardiomyopathy Radiation therapy Trauma	Palpitations Symptoms of heart failure in severe cases	Palpation Brisk carotid upstroke and hyperdymanic carotid impulse on palpation Apical impulse is displaced to left S3 and a palpable thrill Auscultation Murmur	Holosystolic murmur High pitched, blowing Radiates to axilla Best heard with the diaphragm of the stethoscope at apex in left lateral decubitus position Intensity increases with hand grip or squatting Decrease in intensity on standing or valsalva maneuver	P mitrale in lead II Increased QRS voltage Right axis deviation Atrial fibrillation	Acute MR Kerley B lines No enlargement of cardiac silhouette Chronic MR Enlarged cardiac silhouette Straightening of left heart border Splaying of subcarinal angle Calcification of mitral annulus Double right heart border	Enlargement of left atrium and ventricle Identify valve abnormality Valve calcification Severity of regurgitation	Grading of MR is done with left ventriculography	Decompensated and acute MR may lead to heart failure
Atrial septal defect	Frequent respiratory or lung infections Dyspnea Tiring when feeding (Infants) Shortness of breath on exertion Palpitations Swelling of feet	Shortness of breath Fatigue Failure to thrive Swelling of feet and abdomen (Right heart failure) Palpitations Respiratory infections	Inspection Precordial bulge Precordial lift Palpation Right ventricular impulse Pulmonary artery pulsations Thrill Auscultation Murmur	Midsystolic (ejection systolic) murmur Widely split, fixed S2 Upper left sternal border	Normal Prolonged PR interval Right bundle branch block ECG findings varies according to the underlying type of ASD	Increased pulmonary markings Cardiomegaly Triangular appearance of heart Schimitar sign	Gold standard test for diagnosis of atrial septal defect (for more information click Atrial septal defect echocardiography)	Defect size Pulmonary venous return Pulmonary vascular resistance Pulmonary artery hypertension	Asymptomatic until later part of their life May be associated with migraine with aura
Left Atrial Myxoma	Dyspnea Orthopnea Pulmonary edema Hyperpigmentation of skin and endocrine activity Cerebral embolism	Symptoms may mimic mitral stenosis	Skin Signs of an embolic phenomenon Raynaud’s phenomenon Swelling Clubbing Auscultation: Lung: Fine crepitations Heart: Characteristic “tumor plop”	Early diastolic sound as “tumor plop” Low frequency diastolic murmur may be heard if the tumor obstructing mitral valve	Often normal	Often normal Rare findings: cardiomegaly Left atrial enlargement tumor calcification etc.,	Initial and most useful diagnostic study For more information click Myxoma echocardiography or ultrasound	Useful to detect vascular supply of the tumor by the coronary arteries	Associated with Carney complex (genetic predisposition)
Prosthetic Valve Obstruction	History of valve replacement Systemic embolism	Shortness of breath Fatigue	Ausculation Muffling of murmur	Muffling or disappearance of prosthetic sounds Appearance of new regurgitant or obstructive murmur			Degree of stenosis Assess thrombus size and location Differentiate between thrombus, pannus and vegetations		Causes: Thrombus Pannus formation
Cor Triatriatum	Dyspnea on exertion Recent onset of congestive heart failure	Dsypnea on exertion Orthopnea Tachypnea Palpitations Growth failure	Auscultation Murmur Other findings Signs of heart failure	Diastolic murmur with loud P2 No opening snap or a loud S1	Non specific but may have Right axis deviation Right atrial enlargement Right ventricular hypertrophy	Normal cardiac silhouette Hemodynamic changes similar to mitral stenosis (non specific findings)	Direct visualization of membrane through the atrium +/- visualization of accessory chamber	Normal left ventricular hemodynamic profile with a trans atrial gradient	Types Cor triatriatum sinistrum Cor triatriatum dextrum
Congenital Mitral Stenosis	Respiratory distress shortly after birth Recurrent severe pulmonary infections Other associated congenital cardiovascular anamolies Atrial fibrillation	Infants: Exhaustion and sweating on feeding Rapid breathing Failure to thrive Pulmonary infections Chronic cough Older patients: Dyspnea Orthopnea Paroxysmal nocturnal dyspnea Peripheral edema Fatigue	Auscultation Murmur Other findings Signs of heart failure	Mild-Moderate Loud S1 Loud P2 Low frequency diastolic murmur best heard at the apex Severe Soft S1 Loud pulmonic component of S2 with minimal respiratory splitting of S2 Holodiastolic murmur with presystolic accentuation best heard at the apex Early diastolic murmur of pulmonic valve regurgitation	Sharp P waves in leads I and II Inversion of P wave in lead III Marked Q waves in leads II and III	Left atrial dilation Moderate enlargement of right heart Pulmonary venous congestion Esophageal compression	Reduced valve leaflet mobility Left atrial size Severity of mitral stenosis		Very rare condition
Supravalvular Ring Mitral Stenosis	Other associated congenital heart defects Fatigue Frequent respiratory infections Failure to thrive Poor feeding Precocious congestive heart failure	Shortness of breath Tachypnea Dyspnea Nocturnal cough Heamoptysis Syncope	Auscultation: Lungs: Fine, crepitant rales and rhonchi or wheezes may be present Heart: Murmur	An apical mid diastolic murmur with presystolic accentuation No opening snap The murmur is more prominent if associated with VSD or PDA		Left atrial and ventricular enlargement Alveolar edema	Supramitral ring: Associated with normal mitral valve apparatus Intramitral ring: Hypomobility of the posterior leaflet Reduced interpapillary muscle distance Reduced chordal length Dominant papillary muscle Hypoplastic mitral annulus (Difficult to visualize membrane <1mm in size)	Persistently elevated pulmonary venous pressures Increased pulmonary artery pressure	Types Supramitral Intramitral It is attached between the opening of the atrial appendage and the mitral annulus which helps in differentiating with Cor triatriatum sinister. Intramitral type is associated with shone complex

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Mohammed A. Sbeih, M.D. [2]; Usama Talib, BSc, MD [3]

The prevalence of aortic regurgitation varies with age, geographic location, and gender.^[1] aortic regurgitation is unusual before the age of 50 and then increases progressively later in life. Worldwide the most common cause of aortic regurgitation 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.^[2]

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.^{[1] [3]}

The prevalence of aortic regurgitation increases with age.^[1][4][5] 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.^[6][7]

Shown below are tables depicting the prevalence of AR by age and severity in men and women according the results of the Framingham Heart Study.^[1]

Severity of AR	Prevalence of AR by age in men
	26-29	40-49	50-59	60-69	70-83
No AR (%)	96.7	95.4	91.1	74.3	75.6
Trace (%)	3.3	2.9	4.7	13	10
Mild (%)	0	1.4	3.7	12.1	12.2
Moderate or severe (%)	0	0.3	0.5	0.6	2.2

Severity of AR	Prevalence of AR by age in women
	26-29	40-49	50-59	60-69	70-83
No AR (%)	98.9	96.6	92.4	86.9	73
Trace (%)	1.1	2.7	5.5	6.3	10.1
Mild (%)	0	0.7	1.9	6	14.6
Moderate or severe (%)	0	0	0.2	0.8	2.3

aortic regurgitation is more common in men than in women.^[1][4][5] In the Framingham heart population cohort study, aortic regurgitation (more than or equal to trace severity on echocardiography) was observed in 13 percent of men and 8.5 percent of women.^[1] The higher prevalence of marfan syndrome and bicuspid aortic valve in males could explain in part the greater prevalence of aortic regurgitation in men.^[6][7]

The prevalence of aortic regurgitation does not show any variation by race in United States. However, internationally there is significant variation in the prevalence of predisposing conditions such as rheumatic heart disease which is more common in the Asia, the Middle East, and the North Africa.^[8]

In developed countries where rheumatic heart disease is rare, aortic regurgitation may be due to bicuspid aortic valve disease or senile degenerative calcific aortic valve disease which may present in the fourth to sixth decade. Endocarditis and aortic dissection are other causes. The prevalence of any aortic regurgitation in the Framingham study was reported to be 4.9%, with regurgitation of moderate or greater severity occurring in 0.5%.^[1]

In developing countries, rheumatic heart disease is the most common cause of aortic regurgitation and may present in second or third decade of life.^[9]

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2]; Lakshmi Gopalakrishnan, M.B.B.S. [3]; Mohammed A. Sbeih, M.D. [4] ; Usama Talib, BSc, MD [5]

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 regurgitation. Congenital conditions such as congenital bicuspid aortic valve or a ventricular septal defect can also result in aortic regurgitation. Patients with bicuspid aortic valve are at increased risk of developing aortic dissection.

Risk factors for the development of aortic regurgitation due to aortic root disease include:^{[1][2][3][4][5][6]}

Risk factors for the development of aortic regurgitation due to aortic valve disease include:^{[2][3][7][8][9] [10]}

The risk factors for Acute Aortic Regurgitation include the following:^{[2][3][11][12][13]}

The risk factors for Chronic Aortic Regurgitation include:^{[5][12][14][15][16] [17]}

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S; Usama Talib, BSc, MD [2]

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.^[1]

In acute aortic insufficiency symptoms of heart failure such as pulmonary edema often develop acutely. Acute aortic insufficiency is often secondary to either trauma or infective endocarditis. While the heart can accommodate the changes of chronic aortic insufficiency over time, the acute changes of acute aortic insufficiency are not well accommodated by the left ventricle.

The rapid rise in left ventricular pressure causes the mitral valve to close earlier during diastole. This early closure fortunately prevents backwards flow of blood into the pulmonary vascular bed. The very high left ventricular end diastolic pressure often keeps the aortic diastolic pressure from falling too low and thus there is often not a wide pulse pressure. Indeed absence of a wide pulse pressure in the patient with acute aortic insufficiency should alert the clinician to potential failure of the left ventricle.^[2]

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. The hemodynamic impact of aortic regurgitation causes progressive dilation and hypertrophy of the left ventricle. The mitral valve ring may also dilate which may lead in turn to mitral regurgitation. The left atrium may dilate as a result of the mitral regurgitation. It has been said that ‘aortic regurgitation begets aortic regurgitation‘. The high oscillatory shear associated with aortic regurgitation may lead to further dilation of the aorta, which in turn may lead to further aortic regurgitation.^[1]

Volume overload associated with aortic regurgitation leads to left ventricular hypertrophy. The sarcomeres replicate in series and there is elongation of the myocytes and myocardial fibrils. As a result of this hypertrophy the ratio of the ventricular wall thickness to cavity radius remains normal and therefore wall stress is normal. In aortic regurgitation there is eccentric hypertrophy where as in aortic stenosis there is concentric hypertrophy where there is replication of the sarcomeres in parallel. Once wall thickening fails to keep up with the hemodynamic load, end systolic wall stress rises and at this point the left ventricle fails. The dramatic enlargement of the heart that is seen with aortic regurgitation is called cor bovinum. Over time the left ventricle will decompensate and there will be increasing interstitial fibrosis and a stiffening or a reduction in the compliance of the left ventricular wall. At this point the patient will experience a rise in the end diastolic pressure and volume. The first decline is seen with exercise and then the patient begins to have a reduction in forward output at rest. ^[3]

Patients with chronic aortic insufficiency may also develop myocardial ischemia. This is due to the fact that they have an increase in demand due to an increased thickness of the LV and also a reduction in the supply due to a lower perfusion pressure during diastole.^[3]

The complications of Acute Aortic Insufficiency include^[1][4]

1. Left ventricular volume overload in a non-compliant left ventricle with acute left ventricular failure
2. Pulmonary edema
3. Sudden cardiac death

The complications of Chronic Aortic Insufficiency include:^[5][6][7]

1. Heart failure
2. Arrhythmia
3. Myocardial ischemia
4. Aortic dissection in patients with bicuspid aortic valve
5. Infective endocarditis

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.^[4] Early surgical intervention improves the prognosis in these patients.^[2]

The prognosis of a patient with Chronic Aortic Insufficiency can be summarised as follows:^[8]

The prognosis of asymptotic patients with Aortic Stenosis can be summarised as follow:^[1][9]

• Mortality rate ≈ 2.8% per year

• Asymptomatic patients with normal ejection fraction:

• Rate of progression to symptoms or left ventricular dysfunction ≤ 6% per year
• Rate of progression to asymptomatic left ventricular dysfunction ≤ 3.5% per year
• Rate of sudden death ≤ 0.2% per year

• Asymptomatic patients with reduced ejection fraction:

• Rate of progression to symptoms ≥ 25% per year

The prognosis of symptomatic Aortic Regurgitation patients includes:

• Mortality rate ≥ 10% per year
• NYHA class I – 3.0% per year
• NYHA class II – 6.3% per year
• NYHA class III-IV – 24.6% per year

The prognosis of the conservative management of Chronic Severe Aortic Insufficiency includes:^[10]

• Death from any cause – 4.7% per year
• Congestive heart failure – 6.2% per year
• Aortic valve surgery – 14.6% per year

Template:WH Template:WS CME Category::Cardiology