Clinical manifestations and diagnosis of chronic aortic regurgitation in adults

INTRODUCTION — Aortic regurgitation (AR, also called aortic insufficiency) is caused by inadequate closure of the aortic valve leaflets. It can be induced either by disease of the aortic valve leaflets or by distortion or dilation of the aortic root and ascending aorta.

This topic will review the causes, epidemiology, pathophysiology, and major clinical features of chronic AR. Issues related to course and therapy and to acute AR are discussed separately. (See "Natural history and management of chronic aortic regurgitation in adults" and "Acute aortic regurgitation in adults".)

EPIDEMIOLOGY — At least trace AR by color Doppler echocardiography is common, even in healthy subjects. A study from the Framingham Heart Study found that, in a population-based cohort, AR of at least trace severity on color Doppler echocardiography was present in 13 percent of men and 8.5 percent of women [1].

The prevalence of AR varied with age and disease severity [1]. More than trace AR was unusual before age 50 and then increased progressively.

●For mild AR, the prevalence was 3.7, 12.1, and 12.2 percent in men at ages 50 to 59, 60 to 69, and 70 to 83, respectively. The comparable values in women were 1.9, 6.0, and 14.6 percent.

●For moderate to severe AR, the prevalence was 0.5, 0.6, and 2.2 percent in men at ages 50 to 59, 60 to 69, and 70 to 83, respectively. The comparable values in women were 0.2, 0.8, and 2.3 percent.

CAUSES — Chronic AR is caused by disease of the valve leaflets or enlargement of the aortic root. In the developing world, the most common cause of AR is rheumatic heart disease. However, in developed countries, AR is most often due to aortic root dilation, congenital bicuspid aortic valve, and calcific valve disease (table 1) [2].

PATHOPHYSIOLOGY — All forms of AR produce a similar hemodynamic abnormality. The inability of the aortic valve leaflets to remain closed or coapted during diastole results in a portion of the left ventricular (LV) stroke volume leaking back from the aorta into the LV. The added volume of regurgitant blood produces an increase in LV end-diastolic volume and an elevation in wall stress. The ventricle responds and adapts with compensatory eccentric hypertrophy (figure 1A-B).

The combination of LV eccentric hypertrophy with chamber enlargement raises the total stroke volume. The net effect is that forward stroke volume and systemic blood flow are initially maintained despite the regurgitant lesion. Although LV volume is increased, end-diastolic pressure remains normal due to an increase in ventricular compliance. Thus, the heart initially adapts well to chronic AR, functioning as a compliant high-output pump.

The increased stroke volume results in an increase in systolic pressure. Regurgitation into the LV leads to a rapid fall in arterial pressure with quick collapse of the arteries and a low diastolic pressure that may approach LV diastolic pressure in severe disease. The resulting wide pulse pressure leads to a number of characteristic physical findings. (See 'Arterial pulse and related findings' below.)

CLINICAL MANIFESTATIONS

Symptoms — Patients with AR may remain asymptomatic for decades, even if there is progressive ventricular dilation.

Symptoms that develop in some patients with severe AR (stage D) include exertional dyspnea, angina, and other symptoms of heart failure (table 2).

Exertional dyspnea develops in some patients with severe AR, particularly (but not exclusively) in patients who have developed LV systolic dysfunction. More severe heart failure symptoms such as orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema may develop without appropriate treatment.

Exertional angina develops in some patients with severe AR. Angina can occur even in the absence of underlying coronary artery disease, though the coronary arteries are typically large. With severe AR, angina is caused by reduced coronary flow reserve as epicardial coronary flow shifts from predominantly diastolic to predominantly systolic. Angina can also occur at night when the heart rate slows, arterial diastolic pressure falls, and regurgitant volume increases, thus reducing coronary diastolic perfusion pressure. Some patients with severe AR also develop nocturnal abdominal discomfort due to splanchnic ischemia. (See "Approach to the patient with suspected angina pectoris".)

Some patients with severe AR may complain of symptoms related to the increased LV size and stroke volume. Such symptoms differ from those that generally lead to consideration of aortic valve replacement (eg, dyspnea, angina). These include a sense of pounding, an uncomfortable awareness of the heartbeat, and atypical chest pains. These symptoms are especially pronounced when lying down or lying on the left side which brings the LV apex closer to the chest wall, augmenting the sensation of cardiac activity.

Physical examination — Examination of the peripheral pulses, precordial inspection and palpation, and auscultation of the heart are all helpful in patients with AR. The physical examination in patients with chronic severe AR is often dramatic and frequently establishes the diagnosis, though findings are frequently more subtle in patients with milder disease.

Arterial pulse and related findings — A variety of physical findings are caused by the wide pulse pressure in patients with chronic AR:

●Corrigan pulse – A "water hammer" or "collapsing" pulse is characterized by a rapidly rising and falling arterial pulse with a wide pulse pressure. This finding is best appreciated by palpation of the radial or brachial arteries (exaggerated by raising the arm) or the carotid pulses.

●de Musset sign – A head bob occurring with each heartbeat.

●Traube sign – A pistol shot pulse (systolic and diastolic sounds) heard over the femoral arteries.

●Duroziez sign – A systolic and diastolic bruit heard when the femoral artery is partially compressed.

●Quincke pulses – Capillary pulsations in the fingertips or lips.

●Mueller sign – Systolic pulsations of the uvula.

●Becker sign – Visible pulsation of the retinal arteries.

●Landolfi sign – Constriction and dilation of the pupils with each heartbeat.

●Hill sign – Popliteal cuff systolic pressure exceeding brachial cuff pressure by more than 20 mmHg with patient in the recumbent position.

●Mayne sign – More than a 15 mmHg decrease in diastolic blood pressure with arm elevation from the value obtained with the arm in the standard position.

●Rosenbach sign – Systolic pulsations of the liver.

●Gerhard sign – Systolic pulsations of the spleen.

Although all of these clinical signs have been described as ancillary findings useful in the diagnosis of AR, there are few published studies that have assessed the predictive value of any of these findings [3]. Among the four signs with sufficient literature for review (Corrigan pulse, Duroziez sign, Hill sign, and Austin Flint murmur [discussed below]), information on specificity was strongest for the Hill sign (specificity 71 to 100 percent overall) and the Hill sign is more frequent with more severe AR (sensitivity 75 to 100 percent among patients with moderate to severe or severe AR).

Precordial examination — On precordial inspection and palpation, the combination of LV enlargement and forceful systolic function results in the apical impulse being displaced laterally and inferiorly and being diffuse and hyperdynamic. A prominent pulsation (and occasionally a thrill) may be felt at the sternal notch due to concurrent dilation of the ascending aorta. (See "Examination of the precordial pulsation".)

Cardiac auscultation — Chronic AR is associated with a distinctive early diastolic murmur as well as less specific sounds (such as a mid-systolic ejection murmur) that may be heard in addition to or instead of the characteristic murmur. The heart sounds typically have the following characteristics (see "Auscultation of cardiac murmurs in adults", section on 'Aortic regurgitation' and "Auscultation of heart sounds"):

●S1 may be soft, often reflecting a long PR interval

●S2 is variable; it may be soft, absent, or single

●A2 is often soft or absent while P2 may be normal, but obscured by the diastolic murmur

●A systolic ejection sound may be due to abrupt aortic distension caused by the large stroke volume

●A third heart sound (S3 gallop) is heard when LV function is severely depressed

A diastolic murmur is a key sign favoring the diagnosis of AR, though absence of a diastolic murmur does not exclude the diagnosis. In a review of the literature, the presence of an early diastolic murmur, as heard by a cardiologist, was the most useful finding for establishing the presence of AR (positive likelihood ratio 8.8 [ie, the odds of AR are increased 8.8-fold]) and its absence the most useful finding for reducing the likelihood of AR (negative likelihood ratio 0.2 to 0.3) [4]. However, the reported frequency of a diastolic murmur among patients with chronic AR has varied widely (14 to 73 percent) [5,6].

The diastolic murmur of AR begins immediately after A2 (movie 1A-C). It is high pitched, often blowing in quality, and may be sustained in intensity or decrescendo. It may be soft and barely audible, often appreciated only when the patient is sitting up, leaning forward, and holding his or her breath in end-expiration.

The intensity of the diastolic murmur does not correlate well with the severity of AR. The timing and duration of the murmur may be helpful in assessing the severity of AR. However, the physical findings are not sufficiently reliable and echocardiography is typically used to assess severity.

●In mild AR, the murmur occurs only in early diastole and is blowing.

●As the regurgitation becomes more severe, the murmur extends through more of diastole, may become holodiastolic, and is often rougher in quality. Patients with a longer diastolic murmur, a displaced LV impulse, a wide pulse pressure, and the peripheral findings of a wide pulse pressure cited in the previous section are considered to have severe AR.

●In very severe regurgitation with ventricular decompensation, the murmur may become soft or even absent. This change in character reflects the near equalization of aortic diastolic and LV diastolic pressures, which diminish regurgitant flow. A similar situation can occur when AR is acute and the LV diastolic pressure is very high.

The intensity of the murmur can also be affected by certain maneuvers. As examples, the murmur increases with squatting and decreases with the Valsalva maneuver (table 3). (See "Physiologic and pharmacologic maneuvers in the differential diagnosis of heart murmurs and sounds".)

The site at which the murmur is best heard varies with the cause. The murmur is heard best along the left sternal border, at the third and fourth intercostal space, when AR is due to valvular disease. In contrast, abnormalities of the aortic root produce murmurs that are best heard at the right sternal border and apex.

A mid-systolic murmur is heard in many patients with AR [5,7]. A study found that a systolic murmur was more frequently heard than a diastolic murmur by noncardiologists in patients with trace to moderate AR [5]. The systolic murmur typically resembles the ejection type of murmur heard in aortic stenosis, ie, a crescendo-decrescendo harsh murmur beginning after S1. This murmur is caused by a large ejection volume and thus does not necessarily reflect concurrent aortic stenosis.

A second type of diastolic murmur (the Austin Flint murmur) may also be appreciated. This murmur is a low-pitched, mid to late diastolic rumble, heard at the apex. The murmur has been attributed to the effects of competing antegrade turbulent diastolic blood flow from the left atrium and the retrograde regurgitant flow from the aorta. The sensitivity and specificity of the Austin Flint murmur is uncertain. A review found a higher sensitivity (57 to 100 percent) among patients with severe AR compared with patients with mild to moderate disease (0 to 50 percent) [3]. (See "Auscultation of cardiac murmurs in adults" and "Auscultation of heart sounds".)

Chest radiograph — A chest radiograph is not indicated for the diagnosis of AR but may be obtained in selected patients with AR such as those in whom the cause of dyspnea is uncertain. In patients with severe AR, the chest radiograph shows cardiomegaly due to the dilation of the LV, which enlarges in an inferior and leftward direction. The heart size on a chest radiograph may vary by about one centimeter from end diastole to end systole. Therefore, an apparent increase in heart size on serial examinations does not necessarily indicate progressive LV chamber enlargement. The ascending aorta (and often the aortic arch or knob) are typically markedly dilated.

Left atrial enlargement does not occur unless there is significant LV dysfunction. Thus, its presence in patients with mild to moderate AR suggests associated mitral valve disease.

Electrocardiogram — An electrocardiogram (ECG) is not indicated for diagnosis of AR but is commonly included in the evaluation of patients with AR to exclude concurrent conditions (eg, arrhythmia), and to establish a baseline for future comparison.

The ECG reflects the adaptive changes that occur in the LV as a result of the volume overload, typically with findings for LV eccentric hypertrophy.

Conduction abnormalities are usually not seen, but can occur late in the course of AR when significant LV dysfunction occurs. Isolated atrial and ventricular premature beats are common, but sustained supraventricular or ventricular tachyarrhythmias are unusual in the absence of significant LV dysfunction.

DIAGNOSIS AND EVALUATION

When to suspect chronic aortic regurgitation — Chronic AR should be suspected in patients with physical examination findings consistent with AR. This includes patients with typical exam findings (eg, early diastolic murmur) as well as those with less specific findings (eg, a systolic ejection murmur or wide pulse pressure). Symptoms such as dyspnea are present only late in the disease. In addition, AR should be suspected in patients with dilated aortic sinuses or ascending aorta and in patients with bicuspid aortic valve [8], even if no murmur is apparent.

Approach to diagnosis and evaluation — AR is generally diagnosed and evaluated by echocardiography. Cardiovascular magnetic resonance (CMR) imaging is indicated for evaluation of patients with moderate or severe AR with suboptimal or inconclusive echocardiographic assessment. Invasive angiography is indicated for diagnosis and evaluation when noninvasive tests are inconclusive or provide discrepant results from clinical findings [8].

An ECG is not indicated for diagnosis of AR but is commonly included in the evaluation of patients with chronic AR.

Echocardiogram — Echocardiography is indicated in patients with known or suspected valve disease. A transthoracic echocardiogram (TTE) is generally the key test in diagnosis and evaluation of AR. A transesophageal echocardiogram (TEE) is indicated in selected patients with AR such as those with technically suboptimal TEE or endocarditis with nondiagnostic TTE (algorithm 1).

Echocardiography confirms the diagnosis of AR, establishes its severity, provides an assessment of aortic root and ascending aorta dilation, and evaluates LV size and function. (See "Echocardiographic evaluation of the aortic valve" and "Transesophageal echocardiography in the evaluation of aortic valve disease".)

Characteristic echocardiographic findings include the following:

●The valve leaflets may be abnormal or may be normal but stretched due to aortic dilation, depending upon the etiology of the AR. Abnormalities that may be seen include thickening, vegetations, calcification, a bicuspid valve, and prolapsed or flail leaflets (movie 2).

●The aortic sinuses are often dilated with or without dilation of the ascending aorta. A thoracic aortic aneurysm is defined as an aortic diameter is at least 50 percent greater than the expected normal diameter but many patients have valve dysfunction due to aortic enlargement with a smaller degree of dilation. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Definition of TAA'.)

●There is often restriction of opening of the anterior mitral leaflet and M-mode showing high frequency diastolic fluttering, which are due to the diastolic regurgitant jet of blood from the aorta.

●Doppler echocardiography (transthoracic or transesophageal) is the most sensitive noninvasive technique for detecting the regurgitant AR jet (figure 2 and movie 3A-D).

●The LV end-systolic and end-diastolic dimensions and volumes are increased in chronic AR (movie 2). Wall motion is increased in parallel with the large stroke volume, but the ejection fraction does not increase. When LV decompensation occurs, the ejection fraction declines and end-systolic dimension and volume increases.

In conjunction with clinical evaluation of patient symptoms, echocardiography helps define the stage of the disease according to valve anatomy, severity of AR, and LV size and function (table 2), which in turn determines the need for corrective surgery. (See "Natural history and management of chronic aortic regurgitation in adults".)

Severity of AR — Echocardiography is generally the key modality for determining the severity of AR. Severe chronic AR is considered to be present if one or more of the following findings are present on echocardiography (or CMR imaging) (table 2) [8-11]:

●Central jet width ≥65 percent of LV outflow tract

●A vena contracta width >6 mm

●Holodiastolic flow reversal in the abdominal aorta

●A regurgitant fraction ≥50 percent

●A regurgitant volume ≥60 mL/beat (which should be considered relative to body size)

●An effective regurgitant orifice area ≥0.30 cm² (which is difficult to measure)

Bicuspid aortic valve and aortic disease — Complications of bicuspid aortic valve include aortic stenosis and AR, which may occur in combination, particularly among older patients. Evaluation of patients with bicuspid aortic valve includes assessment of the aortic root and ascending aorta given the risks of aortic aneurysm and dissection, as discussed separately. (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults".)

Cardiovascular magnetic resonance — In patients with moderate or severe AR with suboptimal or inconclusive echocardiographic assessment, CMR imaging is indicated to quantify AR severity, measure LV diastolic and systolic volumes, and assess LV systolic function [8]. Aortic regurgitant volume and regurgitant orifice area can be quantified by CMR [12-14]. No ionizing radiation or exogenous contrast is required for this assessment.

Invasive angiography — The role of contrast invasive angiography in the assessment of chronic AR is increasingly limited because of the use of echocardiography. Aortic root angiography and cardiac catheterization with measurement of LV pressures are indicated when noninvasive tests are inconclusive or provide discrepant results from clinical findings [8]. Angiography enables assessment of the following parameters (see "Hemodynamics of valvular disorders as measured by cardiac catheterization"):

●A semiquantitative assessment of the severity of AR

●Aortic valve movement and the number of leaflets

●Determination of LV size, systolic function (ejection fraction), and pressures

●Aortic root dimension and associated disorders (eg, dissection, sinus of Valsalva aneurysm)

By invasive angiography, severe AR is diagnosed by the presence of 4+ regurgitation and identification of a high regurgitant fraction. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization", section on 'Chronic aortic regurgitation'.)

The indications for coronary angiography before valve surgery are discussed separately [8]. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Cardiac catheterization'.)

DIFFERENTIAL DIAGNOSIS — Some of the physical examination findings of AR are seen in other conditions. A transthoracic echocardiogram is used to confirm the diagnosis of AR and can also identify other conditions that produce similar physical findings.

As an example, the exaggerated or bounding pulses are not specific for AR and can be seen in any condition associated with a marked increase in stroke volume and a hyperdynamic circulation. Included in this group are sympathetic hyperactivity, anemia, fever, pregnancy, thyrotoxicosis, large arteriovenous fistula, patent ductus arteriosus, and severe bradycardia. Severe mitral regurgitation also can cause rapid rising arterial pulses, but the pulse pressure is not increased. (See "Examination of the arterial pulse", section on 'Water hammer pulse'.)

The characteristic early diastolic murmur of AR may not be distinguishable from the murmur of pulmonic regurgitation. Rarely, left anterior descending coronary artery stenosis can produce a murmur similar to the murmur of AR. Among patients with end-stage kidney disease, a transient murmur of AR may be induced by the effects of volume overload; the murmur disappears after dialysis, when the excess fluid has been removed [4].

The systolic murmur heard in patients with AR sounds similar to the murmurs of aortic valve sclerosis or aortic stenosis. The mid-diastolic Austin Flint murmur of AR may be confused with that of mitral stenosis. Distinguishing features from mitral stenosis include the absence of both a loud S1 and an opening snap of the mitral valve. (See "Auscultation of cardiac murmurs in adults" and "Auscultation of heart sounds".)

STAGING — Chronic AR is staged according to valve anatomy, valve hemodynamics, hemodynamic consequences, and symptoms, as indicated in the 2020 American Heart Association/American College of Cardiology valve guidelines (table 2) [8]:

●Stage A includes patients at risk of AR who have no or trace current AR, including those with bicuspid aortic valve (or other congenital valve anomaly), aortic valve sclerosis, diseases of the aortic sinuses or ascending aorta, history of rheumatic fever or known rheumatic heart disease, or infective endocarditis.

●Stage B includes patients with progressive AR who have mild or moderate AR with normal LV systolic function and normal or mildly dilated LV volumes.

●Stage C includes patients with asymptomatic severe AR. Severe AR is identified using Doppler echocardiographic measures, cardiovascular magnetic resonance, or cardiac catheterization.

•In Stage C1, the LV ejection fraction (LVEF) is normal (≥50 percent), and there is mild to moderate increase in LV end systolic dimension (LVESD ≤50 mm). This is the compensated phase of chronic AR. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Natural history'.)

•In Stage C2, the LVEF is <50 percent and/or there is a marked increase in LVESD (LVESD >50 mm or indexed LVESD >25 mm/m² body surface area [BSA]). This is the transitional phase of chronic AR, which precedes the development of overt heart failure.

●Stage D includes patients with symptomatic severe AR. The LVEF may be normal, mildly to moderately depressed (40 to 50 percent), or severely depressed (LVEF <40 percent). There is a moderate to severe increase in the LVESD (>40 to >50 mm).

SERIAL MONITORING — New-onset dyspnea or angina are indications for follow-up echocardiography. The frequency of serial clinical and echocardiographic monitoring in patients with asymptomatic aortic regurgitation varies with the severity of the disease, the LV ejection fraction, LV dimensions, and whether previous studies have revealed progressive disease. The recommended schedule is presented separately. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Monitoring'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Aortic regurgitation in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Causes – Aortic regurgitation (AR) is caused by disease of the valve leaflets or enlargement of the aortic root. In developed countries, AR is most often due to aortic root dilation or a congenital bicuspid aortic valve (table 1). In the developing world, the most common cause of AR is rheumatic heart disease. (See 'Causes' above.)

●Symptoms – Patients with AR may remain asymptomatic for decades, even if there is progressive ventricular dilation. Exertional dyspnea develops in some patients with severe AR, particularly (but not exclusively) in patients who have developed left ventricular (LV) systolic dysfunction. (See 'Symptoms' above.)

●Signs – Examination of the peripheral pulses, precordial inspection and palpation, and auscultation of the heart are all helpful in patients with AR. Patients with chronic severe AR have a wide pulse pressure and the apical impulse is displaced laterally and inferiorly and is diffuse and hyperdynamic. An early diastolic murmur is characteristic of AR but its absence does not exclude AR (movie 1B and movie 1C and movie 1A). (See 'Physical examination' above.)

●Diagnosis and evaluation (See 'Diagnosis and evaluation' above.)

•Echocardiography – Echocardiography is helpful in confirming the diagnosis of AR, determining its severity, as well as assessing LV size and systolic function (movie 2 and movie 3A and movie 3C and movie 3D). (See 'Echocardiogram' above.)

•CMR – In patients with moderate or severe AR with suboptimal or inconclusive echocardiographic assessment, cardiovascular magnetic resonance imaging (CMR) is indicated to quantify AR severity, measure LV diastolic and systolic volumes, and assess LV systolic function. (See 'Cardiovascular magnetic resonance' above.)

•Cardiac catheterization – In patients with AR, cardiac catheterization is indicated only when noninvasive tests are inconclusive or provide discrepant results or for coronary angiography prior to valve surgery in patients at risk for coronary disease. (See 'Invasive angiography' above.)

●Staging – Chronic AR is staged according to valve anatomy, valve hemodynamics, hemodynamic consequences, and symptoms (table 2) [8]. (See 'Staging' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William H Gaasch, MD (deceased), who contributed to earlier versions of this topic review.