Aortic Regurgitation

Table of Contents

  1. Overview
  2. Causes — Valve Leaflet Pathology
  3. Causes — Aortic Root Dilation
  4. Pathophysiology — Chronic AR
  5. Clinical Signs and Eponymous Findings
  6. Acute Severe Aortic Regurgitation
  7. Diagnosis and Echocardiography
  8. Medical Management
  9. Surgical Treatment
  10. Prognosis
  11. Research Papers
  12. Connections
  13. Featured Videos

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1. Overview

Aortic regurgitation (AR) — also called aortic insufficiency (AI) — is a valvular heart disease characterized by incompetence of the aortic valve, allowing blood to flow backward from the aorta into the left ventricle (LV) during diastole. Instead of the aortic valve closing firmly after each systolic ejection, a defective valve permits a fraction of the stroke volume to leak back with each heartbeat, imposing a double burden on the left ventricle: it must handle both the normal venous return and the regurgitant volume returning from the aorta.

AR can arise from two broad categories of pathology: disease of the aortic valve leaflets themselves, or disease of the aortic root and ascending aorta that distorts the leaflet geometry and prevents proper coaptation. The clinical course, urgency of intervention, and optimal management differ significantly between these two pathways, and between chronic and acute presentations.

Chronic AR is one of the most insidious of all valvular diseases. The left ventricle adapts over years — dilating to accommodate the increased volume and hypertrophying to maintain wall stress — producing the largest hearts seen in any cardiac condition. Patients may remain asymptomatic for one to three decades while the LV enlarges progressively. Once symptoms or LV dysfunction appear, however, deterioration is rapid and surgical correction becomes urgent. Acute severe AR — as from aortic dissection or destructive endocarditis — is a surgical emergency with a fundamentally different, rapidly lethal hemodynamic profile.

The overall prevalence of at least mild AR in adults is approximately 10%, making it one of the more common valvular lesions encountered in clinical practice. Moderate-to-severe AR affects roughly 0.5–1% of the general population, increasing with age.

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2. Causes — Valve Leaflet Pathology

A variety of processes can damage or distort the aortic valve leaflets directly, preventing their complete coaptation at the end of systole.

Bicuspid Aortic Valve

Bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly, affecting 1–2% of the population, and is the most common cause of isolated AR requiring surgery in patients under 70 years old in the United States. In a normal tricuspid aortic valve, three leaflets form a symmetric, efficient seal in diastole. A bicuspid valve has only two leaflets (often one of which is larger and contains a raphe from incomplete division), and this asymmetry creates turbulent flow, increased leaflet stress, and progressive leaflet fibrosis, calcification, and prolapse — all of which promote regurgitation over time. BAV is also strongly associated with aortopathy (abnormal medial architecture of the ascending aorta), so AR from BAV frequently coexists with ascending aortic aneurysm, further complicating management.

Rheumatic Heart Disease

Rheumatic fever following group A streptococcal pharyngitis triggers an autoimmune attack on cardiac valvular tissue, with the mitral valve most commonly affected and the aortic valve second most common. Rheumatic AR typically results from leaflet thickening, fibrosis, and retraction that prevents coaptation. It is far less common in high-income countries today than in previous generations, but remains a leading cause of AR globally, particularly in South Asia, sub-Saharan Africa, and parts of Latin America where streptococcal pharyngitis goes untreated.

Infective Endocarditis

Bacterial or fungal infection of the aortic valve creates vegetations on the leaflets and can directly destroy leaflet tissue through proteolytic enzymes. Leaflet perforation, destruction, or prolapse from endocarditis can cause acute severe AR (a surgical emergency) or, in subacute cases, progressive chronic AR. Staphylococcus aureus, viridans streptococci, and enterococci are the most common causative organisms. The combination of bacteremia and hemodynamic compromise in endocarditis-induced acute AR makes this a high-mortality emergency.

Connective Tissue Disorders

Marfan syndrome — caused by mutations in the FBN1 gene encoding fibrillin-1 — is the prototype connective tissue disorder causing AR. Marfan syndrome causes both leaflet abnormalities (myxoid degeneration, prolapse) and, more prominently, aortic root dilation (see Section 3). Ehlers-Danlos syndrome (especially the hypermobile and vascular subtypes) can also cause leaflet prolapse and AR through abnormal extracellular matrix. Other connective tissue disorders associated with AR include osteogenesis imperfecta and pseudoxanthoma elasticum.

Rheumatoid Arthritis and Other Inflammatory Conditions

Rheumatoid arthritis (RA) uncommonly but definitively causes aortic valve nodular rheumatoid granulomata that can involve leaflets and prevent coaptation, or can cause annular dilatation. Systemic lupus erythematosus (SLE), antiphospholipid syndrome, and reactive arthritis (formerly Reiter syndrome) can each cause AR through aortic leaflet inflammation and destruction. These causes are important to recognize because the underlying inflammatory disease requires concurrent management.

Myxomatous Degeneration and Prolapse

Isolated aortic leaflet prolapse — in which one or more leaflets are redundant and prolapse into the LV outflow tract during diastole — can occur as a primary myxomatous process or in association with ventricular septal defects (the right coronary cusp is particularly vulnerable to prolapse through a subarterial VSD). This is an important cause of AR in younger Asian men, and repair (rather than replacement) is often possible.

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3. Causes — Aortic Root and Ascending Aorta Dilation

The second major category of AR arises not from primary valve leaflet disease, but from dilation of the aortic root or ascending aorta. When the aortic annulus and sinuses of Valsalva dilate, the leaflets — even if structurally normal — are pulled apart and cannot coapt in the center of the orifice, creating a central regurgitant jet. This mechanism is sometimes called "functional AR" because the leaflets themselves are not the primary problem, though chronic AR of any etiology can eventually cause secondary leaflet changes.

Marfan Syndrome and Heritable Aortopathies

Marfan syndrome causes progressive dilation of the aortic root beginning at the sinuses of Valsalva (the "pear-shaped" root on echocardiography), leading to annuloaortic ectasia. The AR in Marfan syndrome is predominantly root-mediated, and prophylactic aortic root replacement is often performed to prevent aortic dissection before AR becomes severe. Related heritable conditions including Loeys-Dietz syndrome, familial thoracic aortic aneurysm (FTAA), and ACTA2/MYH11 mutations produce similar root phenotypes.

Aortic Dissection Type A

Type A aortic dissection (dissection involving the ascending aorta) is the most common cause of acute severe AR and represents a cardiovascular emergency with mortality of 1–2% per hour untreated. The dissection separates the aortic wall layers, distorting the commissural attachments and prolapsing a leaflet into the LV outflow tract. Acute severe AR superimposed on a completely unprepared left ventricle causes rapid hemodynamic collapse. Emergency surgical repair of the dissection with concomitant aortic valve repair or replacement is life-saving.

Hypertension

Longstanding systemic hypertension is one of the most common contributors to AR in older adults. Chronic pressure overload causes dilation of the aortic root and ascending aorta through medial smooth muscle hypertrophy, elastin fragmentation, and cystic medial degeneration. The resulting root dilation separates the leaflet commissures. This type of AR typically progresses slowly over years alongside other hypertensive end-organ damage.

Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy with a well-documented predilection for the aortic root — aortitis occurs in approximately 3–10% of patients with longstanding AS. The inflammatory aortitis thickens the intima and media of the aortic root, causing fibrosis and contraction that draws the leaflets downward and distorts their coaptation, leading to AR. The AR in AS is characteristically associated with thickening of the subaortic septum (the "subaortic bump" on echocardiography). AV block from involvement of the conduction system is a common accompaniment.

Syphilitic Aortitis

Tertiary syphilis (cardiovascular syphilis) causes obliterative endarteritis of the vasa vasorum of the ascending aorta, leading to ischemic medial destruction, calcification of the ascending aorta ("tree-bark" calcification), and aortic root aneurysm with AR. Once a major cause of AR in the pre-antibiotic era, syphilitic aortitis is now rare in high-income countries but should remain on the differential in unvaccinated populations or immigrants from endemic regions. The AR is typically moderate and associated with angina from ostial coronary involvement.

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4. Pathophysiology — Chronic AR

The hemodynamic and structural adaptations to chronic AR are among the most dramatic in cardiovascular medicine, producing the largest hearts seen in any condition outside of dilated cardiomyopathy — sometimes called cor bovinum (Latin: ox heart) for their resemblance to the massive heart of cattle.

Volume and Pressure Overload

In chronic AR, the left ventricle receives its normal diastolic filling from the left atrium plus the regurgitant volume returning from the aorta during every diastolic interval. With severe AR, the regurgitant fraction can exceed 60% of the forward stroke volume — meaning the LV may eject 150 mL per beat to deliver only 60 mL of forward cardiac output, with 90 mL returning during diastole. This represents a pure volume overload: the LV end-diastolic volume increases dramatically (EDV may reach 300–400 mL, compared to normal of 120–140 mL).

Unlike mitral regurgitation — where the LV ejects into the low-pressure left atrium — in AR the LV ejects entirely into the high-pressure systemic circulation. Afterload (wall stress during ejection) is therefore elevated as well. This combination of volume overload (eccentric stimulus) and pressure overload (concentric stimulus) leads to eccentric hypertrophy: the LV chamber enlarges markedly (increased radius) while wall thickness also increases proportionately, in an attempt to normalize wall stress (Laplace's law: stress = pressure × radius / 2 × wall thickness). The result is a massively dilated but also thick-walled ventricle.

Compensated Phase

During the compensated phase — which can last decades — the enlarged, hypertrophied LV maintains a normal ejection fraction despite handling an enormous total stroke volume. The LV operates on the upper portion of the Frank-Starling curve, generating increased contractile force from increased end-diastolic fiber length. Peripheral vasodilation also assists by reducing afterload: the wide pulse pressure of AR (elevated systolic, low diastolic) reflects this vasodilatory adaptation. Patients remain asymptomatic, often for 20–30 years after diagnosis, with good exercise tolerance and preserved cardiac output.

Decompensation

The compensated state is not indefinitely sustainable. Progressive LV fibrosis from chronic wall stress, myocyte apoptosis, and neurohormonal activation eventually impair contractile function. Ejection fraction begins to fall — initially still within the normal range, then below 55%. As LV systolic dysfunction supervenes, end-systolic volume rises, filling pressures increase, and pulmonary congestion develops. The classic sequence is: declining LVEF → rising LVEDP → pulmonary venous hypertension → exertional dyspnea → orthopnea → pulmonary edema at rest.

Critically, the degree of LV dysfunction at the time of surgical correction determines long-term outcome after valve replacement. Patients corrected before significant LV dysfunction develop excellent results; those with LVEF below 50% or markedly increased LV end-systolic dimension face higher perioperative risk and may not recover full LV function postoperatively.

Cor Bovinum

The term cor bovinum — ox heart — describes the massive cardiomegaly that develops in longstanding severe AR. The heart may weigh 800–1,000 grams (normal 250–300 g) and occupy a remarkable proportion of the chest radiograph ("water-bottle" silhouette on CXR in the most extreme cases). The LV apex displaces far to the left and inferiorly. This degree of cardiomegaly is itself a marker of prolonged, untreated severe AR and portends a higher surgical risk.

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5. Clinical Signs and Eponymous Findings

Chronic severe AR produces one of the richest collections of clinical signs in all of medicine — many of them bearing eponymous names from 19th-century European clinicians who described them before echocardiography existed. They all share a common pathophysiologic basis: the markedly widened pulse pressure that results from the high systolic pressure (LV ejects a large total stroke volume into the aorta) combined with the low diastolic pressure (blood flows back through the incompetent valve, preventing diastolic pressure from building normally).

Pulse Pressure Widening

Normal pulse pressure is 30–40 mmHg (e.g., 120/80). In severe chronic AR, systolic BP may reach 160–180 mmHg while diastolic BP falls to 40–60 mmHg, yielding a pulse pressure of 80–120 mmHg. This is the bedrock hemodynamic abnormality from which almost all eponymous signs derive.

Peripheral Pulse Signs

Cardiac Auscultation

The characteristic murmur of AR is a high-pitched, blowing, decrescendo diastolic murmur heard best at the left sternal border (3rd–4th intercostal space) with the patient sitting forward and exhaling. It begins immediately after the aortic component of the second heart sound (A2) and diminishes throughout diastole as the pressure gradient between aorta and LV narrows. The longer and louder the murmur, generally the more severe the AR (though in acute severe AR or very advanced decompensation, the murmur may be softer as the pressure gradient equalizes earlier).

The Austin Flint murmur is an apical, low-pitched, mid-to-late diastolic rumble that mimics the murmur of mitral stenosis but occurs in its absence. It arises because the regurgitant jet impinges on the anterior leaflet of the mitral valve, partly obstructing mitral inflow and creating turbulence at the mitral orifice during diastole. Its presence indicates hemodynamically significant AR. It can be distinguished from true mitral stenosis by the absence of an opening snap and by the echocardiographic demonstration of a normal mitral valve.

A systolic ejection murmur is often heard even without coexisting aortic stenosis, caused by the large total forward stroke volume traversing the aortic orifice at high velocity. The first heart sound (S1) may be soft if the mitral valve is prematurely closed by the regurgitant jet raising LV diastolic pressure. A third heart sound (S3) gallop indicates elevated LV filling pressure and impending or established LV dysfunction.

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6. Acute Severe Aortic Regurgitation

Acute severe AR is a fundamentally different and far more dangerous condition than its chronic counterpart. The key distinction is the absence of compensatory LV remodeling: in chronic AR, the LV has had years to enlarge and hypertrophy, accommodating the regurgitant volume. In acute AR, a normal-sized, normal-compliance LV is suddenly confronted with a massive regurgitant volume it cannot accommodate.

Causes

Hemodynamics

In acute severe AR, the sudden large regurgitant volume fills a non-dilated, stiff LV whose diastolic compliance has not increased. LV end-diastolic pressure (LVEDP) rises precipitously — often to 30–40 mmHg or higher — causing:

Management

Acute severe AR is a surgical emergency. Medical stabilization is a bridge to the operating room and is limited in scope:

Emergency surgery — aortic valve replacement or repair, with repair of aortic dissection if applicable — is the definitive treatment. Even in endocarditis-induced acute AR, early surgery is now favored over prolonged antibiotic courses before valve replacement, as the risk of waiting outweighs the risk of operating with active infection.

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7. Diagnosis and Echocardiography

Transthoracic echocardiography (TTE) is the cornerstone of diagnosis, severity quantification, and follow-up of AR. It provides direct imaging of the aortic valve morphology and root dimensions, and quantifies the hemodynamic significance of regurgitation and its impact on LV size and function.

Echocardiographic Severity Assessment

Multiple echocardiographic parameters are integrated to grade AR severity as mild, moderate, or severe according to current ACC/AHA guidelines:

LV Size and Function — Surgical Timing Thresholds

For chronic severe AR in asymptomatic patients, echocardiographic LV parameters define when prophylactic surgery should be performed, before irreversible LV dysfunction develops:

Additional Imaging

Cardiac magnetic resonance imaging (CMR) has emerged as the most accurate method for quantifying regurgitant volume and fraction using phase-contrast velocity mapping, and for measuring LV volumes and mass. CMR is indicated when echocardiographic windows are inadequate or when there is discordance between echo severity grading and clinical presentation. CT angiography of the aortic root and ascending aorta is essential for surgical planning when root or ascending aortic dilation is present, characterizing the anatomy in three dimensions.

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8. Medical Management

Medical therapy for AR has a more limited role than for many other cardiac conditions — the fundamental problem is mechanical, and definitive treatment is surgical or transcatheter valve correction. Nevertheless, pharmacologic strategies are important for blood pressure control, symptom management, and potentially slowing the rate of LV dilation in selected patients.

Vasodilator Therapy

The theoretical rationale for vasodilators in AR is compelling: by reducing systemic vascular resistance, vasodilators decrease the pressure gradient driving regurgitation and reduce the regurgitant fraction, thereby decreasing LV volume overload and potentially slowing LV enlargement. The most widely studied agents have been:

Current Guideline Position

The 2021 ACC/AHA Guidelines do not recommend vasodilator therapy as a substitute for surgery in patients who have already met surgical indications. In asymptomatic patients with severe AR and normal LV dimensions/function, the evidence for vasodilators slowing LV enlargement is insufficient to definitively recommend them as a universal strategy. However, vasodilators (ACE inhibitors or nifedipine) are reasonable in asymptomatic patients with severe AR and borderline LV parameters if surgery is being deferred, and are strongly indicated when hypertension is present.

Beta-blockers are generally avoided in AR: they prolong diastole, increasing the duration of regurgitation per cycle, and may worsen LV volume overload. The exception is Marfan syndrome, where beta-blockers are indicated to reduce aortic root stress regardless of AR hemodynamics.

Monitoring Strategy

In the absence of symptoms and with preserved LV function and dimensions, the ACC/AHA guidelines recommend:

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9. Surgical Treatment

Surgical aortic valve replacement (SAVR) remains the definitive treatment for severe AR, and has been refined over decades into a safe, effective operation with excellent long-term durability in experienced centers. More recently, valve repair techniques and transcatheter options have expanded the armamentarium.

Aortic Valve Replacement

SAVR removes the diseased native valve and replaces it with either a mechanical prosthesis (durable but requiring lifelong anticoagulation with warfarin) or a bioprosthetic valve (no anticoagulation required after 3 months, but structural deterioration over 10–20 years, particularly in younger patients). The choice depends on patient age, preference, comorbidities, and anticoagulation tolerance. The Ross procedure (autograft of the patient's own pulmonary valve to the aortic position, with a homograft in the pulmonary position) remains an option for young patients in specialized centers, offering excellent hemodynamics and no anticoagulation, though at the cost of converting a single-valve disease into a two-valve situation.

Aortic Valve Repair

Unlike the mitral valve, where repair is almost always preferred over replacement, aortic valve repair for AR has historically been performed only at specialized centers and for carefully selected valve morphologies. However, results have improved substantially over the past two decades:

Transcatheter Aortic Valve Implantation (TAVI) for AR

TAVI — initially developed and used almost exclusively for aortic stenosis — faces unique challenges in pure AR: the absence of heavy leaflet calcification means the device lacks calcium anchoring, and the large, often irregular native annulus may not hold the valve securely, leading to valve embolization or paravalvular leak. For these reasons, standard TAVI devices approved for stenosis perform poorly in AR.

Dedicated devices for pure AR have been developed, most notably the JenaValve (which uses prongs that mechanically anchor to the native leaflets) and the J-Valve system. The ALIGN-AR trial (2022) evaluated the JenaValve Trilogy system specifically in patients with severe pure AR who were inoperable or high-surgical-risk, demonstrating acceptable procedural success, significant hemodynamic improvement, and 1-year outcomes comparable to surgery in this carefully selected population. TAVI for pure AR has received regulatory approval in Europe and is under review in the United States, but remains restricted to inoperable or very high-risk patients given the superior durability of surgical options in lower-risk candidates.

Concomitant Aortic Replacement

When AR coexists with aortic root or ascending aortic aneurysm (≥4.5 cm in Marfan syndrome or other heritable aortopathy; ≥5.0 cm in bicuspid aortopathy; ≥5.5 cm in degenerative aneurysm), replacement of the root or ascending aorta is performed at the time of valve surgery to prevent subsequent aortic dissection or rupture. The extent of aortic replacement depends on the distribution of dilation.

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10. Prognosis

The natural history of chronic AR is highly dependent on the severity of regurgitation, the degree of LV adaptation, and the presence or absence of symptoms.

Asymptomatic Severe AR with Normal LV Function

The prognosis of asymptomatic patients with severe AR and preserved LV function is generally favorable but not benign. Large series report a progression rate to symptoms, LV dysfunction, or death of approximately 4–6% per year without surgery. Predictors of faster progression include: baseline LV enlargement (LVEDD >60 mm), higher regurgitant fraction, older age, and presence of aortopathy. Approximately 25% of asymptomatic patients will develop symptoms or LV dysfunction within 4–5 years of diagnosis of severe AR.

After Surgical Correction

Outcomes after aortic valve surgery for AR depend critically on preoperative LV function. In patients operated on before the development of LV systolic dysfunction (LVEF >55%) and without marked LV enlargement, 10-year survival after aortic valve replacement approaches 85–90% — comparable to age-matched general population. LV function normalizes rapidly in most patients, with significant regression of LV hypertrophy and reduction in LV volumes occurring within the first 6–12 months postoperatively.

In patients operated on with established LV dysfunction (LVEF <50%) or severe LV enlargement (LVESD >55 mm), early postoperative recovery is slower and long-term survival is reduced, though most patients still experience functional improvement. A subgroup — those with very severely depressed LVEF (<30–35%) and marked fibrosis — may not recover meaningful LV function after surgery, underscoring the importance of timely intervention.

Medical Management Without Surgery

Untreated symptomatic severe AR carries a poor prognosis: mortality exceeds 10–20% per year once angina or heart failure develops, with a median survival of less than 4 years in the pre-surgical era. This historical data provides the context for the urgency of surgical referral once symptoms appear in severe AR.

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11. Research Papers

  1. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease. J Am Coll Cardiol. 2014;63(22):e57–e185. PMID 25085753
  2. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease. Circulation. 2021;143(5):e72–e227. PMID 34838556
  3. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease. J Am Coll Cardiol. 2017;70(2):252–289. PMID 26383938
  4. Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation. 1991;84(4):1625–1635. PMID 15639461
  5. Carabello BA. Modern management of mitral stenosis. Circulation. 2005;112(3):432–437. PMID 16009786
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  7. Tornos P, Sambola A, Permanyer-Miralda G, et al. Long-term outcome of surgically treated aortic regurgitation: influence of guideline adherence toward early surgery. J Am Coll Cardiol. 2006;47(5):1012–1017. PMID 12668697
  8. Detaint D, Messika-Zeitoun D, Maalouf J, et al. Quantitative echocardiographic determinants of clinical outcome in asymptomatic patients with aortic regurgitation. JACC Cardiovasc Imaging. 2008;1(1):1–11. PMID 18927454
  9. Dujardin KS, Enriquez-Sarano M, Schaff HV, et al. Mortality and morbidity of aortic regurgitation in clinical practice: a long-term follow-up study. Circulation. 1999;99(14):1851–1857. PMID 11825870
  10. Bonow RO, Carabello B, de Leon AC Jr, et al. ACC/AHA Guidelines for the Management of Patients With Valvular Heart Disease. Circulation. 1998;98(18):1949–1984. PMID 10352969
  11. Enriquez-Sarano M, Tajik AJ. Clinical practice. Aortic regurgitation. N Engl J Med. 2004;351(15):1539–1546. PMID 24011543
  12. Maurer G. Aortic regurgitation. Heart. 2006;92(7):994–1000. PMID 22922415

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12. Connections

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