Diagnosis and Management of Chronic Aortic Regurgitation

I. Diagnosis and Management of Chronic Aortic Regurgitation: What every physician needs to know.

Aortic regurgitation (AR), also known as aortic insufficiency (AI), results from malcoaptation of the aortic cusps resulting in reflux of blood from the aorta into the left ventricle. AR results from diseases involving the aortic root, annulus, and/or aortic leaflets. The principle disorders encountered in clinical practice causing significant AR include:

Congenital anomalies (e.g., bicuspid valve)
Bacterial endocarditis
Degenerative calcific disease
Connective tissue diseases and other inflammatory conditions
Aortic aneurysms with annular enlargement or disruption of the aortic valve apparatus due to aortic dissection
Medications (e.g., fenfluramine/phentermine)

If the volume of regurgitation is significant, the left ventricle will remodel in order to maintain adequate forward output despite the valvular regurgitation. In general this adaptation to chronic aortic regurgitation, which takes place over years or even decades, features some combination of chamber dilation and hypertrophy—an increase in left ventricle mass/body size ratio.

The response to AR, however, is variable; some patients remain asymptomatic for decades, while others progress to heart failure in relatively short order. Physical exam features include a high-frequency, decrescendo diastolic murmur; in some, an Austin-Flint murmur is heard.

Chronic severe AR often results in a wide pulse pressure, which is the basis for a variety of eponymous physical examination signs. The cornerstone of diagnosis and monitoring of progression of AR is echocardiography. The most important factor in determining progression of disease is the presence of left ventricular dysfunction. Management includes both medical therapy with vasodilators and surgical intervention.

II. Diagnostic Confirmation: Are you sure your patient has Diagnosis and Management of Chronic Aortic Regurgitation?

In clinical practice, the diagnosis of AR is suggested by clinical signs and a compatible physical examination. In most cases the diagnosis is confirmed or even made by cardiac ultrasound. Doppler echocardiography allows qualitative and quantitative evaluation of the severity of AR.

A. History Part I: Pattern Recognition

One method of classifying patients with AR is to assign them to one of three categories: asymptomatic patients with normal LV function; asymptomatic patients with depressed systolic function; and symptomatic patients.

Asymptomatic individuals with normal LV function, arguably the largest category of AR patients, have an average rate of progression to symptoms and/or LV systolic dysfunction of <6% per year or progression to asymptomatic LV dysfunction of <3.5% per year. It is important to note that approximately 25% of patients with AR and normal LV function develop LV systolic dysfunction or die before the onset of symptoms. For this reason, the ACC/AHA Valvular Heart Disease Guidelines emphasize the need for “serial evaluation of asymptomatic patients”; the guideline document also characterizes quantitative evaluation of LV function as “indispensable.”

The majority of patients who are asymptomatic but have LV systolic dysfunction develop symptoms within 2 to 3 years, with a rate of symptom onset of >25% per year. Finally, those individuals with symptoms including dyspnea, angina, or heart failure have mortality rates that exceed 10% per year.

In our experience, the typical patient encountered in clinical practice with chronic severe AR usually has a congenital bicuspid aortic valve, often with an associated aortopathy.

Symptomatic individuals with chronic AR demonstrate signs and symptoms of exercise intolerance, including dyspnea with exertion, fatigue, or a vague uncomfortable sensation in the chest. A much less common presentation features signs/symptoms of left sided heart failure, such as pulmonary edema.

B. History Part 2: Prevalence

As noted above, the underlying reason for chronic AR is either primary aortic valve disease, disease of the aorta, or both (e.g., bicuspid aortic valve with aortopathy). Male gender and advanced age are predictors of AR. Although hypertension has been shown to increase aortic root size, this has not translated into an increased risk for the development of aortic regurgitation.

There are other causes of acute, severe AR, such as acute aortic dissection or endocarditis due to Staphylococcal aureus, which tend to present much more dramatically and require urgent intervention; however, these are not common etiologies for chronic AR.

C. History Part 3: Competing diagnoses that can mimic Diagnosis and Management of Chronic Aortic Regurgitation

Any cardiac condition that results in signs and symptoms of left sided heart failure should be included as differential diagnoses. This would include other cardiac valvular abnormalities (aortic stenosis, mitral valve stenosis, mitral valve regurgitation), cardiomyopathy (ischemic/nonischemic), hypertensive heart disease, and metabolic diseases (e.g., hypothyroidism).

D. Physical Examination Findings

The most common physical exam finding in patients with chronic AR is a high-frequency, decrescendo diastolic murmur heard over the third or fourth intercostal space at the left sternal border. A mid to late diastolic apical rumble (Austin-Flint murmur)—a result of turbulent regurgitation flow interacting with the anterior mitral valve leaflet—may occasionally be appreciated and almost always indicates severe AR.

In the setting of severe AR, a systolic ejection murmur may be noted due to increased ejection volumes. Owing to the volume load, most patients have systemic hypertension, a wide pulse pressure, and many of the eponymous findings due to this wide pulse pressure: head bobbing (de Musset sign), bounding carotid pulses (Corrigan pulse), bounding limb pulses (Watson water hammer pulse), bobbing uvula (Mueller sign), a pistol shot sound heard over the femoral artery during compression (Traube’s sign), systolic and diastolic murmurs over the femoral artery with compression (Duroziez sign), pulsations of the retinal vessels (Becker sign), and capillary pulsations with compression of the fingernails (Quincke sign).

E. What diagnostic tests should be performed?

Patients with AR should be monitored with echocardiography. Findings from echocardiography confirm the diagnosis and help guide appropriate treatment. In the symptomatic patient, we use echocardiography to document that regurgitation is volumetrically severe to diagnose associated valve conditions and to determine the integrity of LV systolic function.

None of these important characteristics is fully appreciated by history, physical examination, EKG, or chest x-ray. Knowledge of LV systolic function is important in determining the likelihood of a return of normal systolic function once the volume load is abolished by AVR.

In the asymptomatic patient, echocardiography is not only important in the initial evaluation but for further monitoring, as alluded to above. Evidence of left ventricular dysfunction, as demonstrated by reduced left ventricular ejection fraction or increased end-systolic diameter in the asymptomatic patient usually prompts referral for aortic valve replacement.

Echocardiography should be performed every 3 to 12 months depending on the end-systolic and end-diastolic diameters. Asymptomatic patients with normal LVEF undergoing their first echocardiogram or those with dynamic changes (increasing end-systolic/diastolic dimensions) should undergo a repeat echocardiogram in 3 months.

Patients with a stable end-systolic diameter (<50 mm) or end-diastolic diameter (<70 mm) should undergo annual echocardiograms, where as individuals with an end-systolic diameter >50 mm or end-diastolic diameter >70 mm should undergo biannual echocardiograms. Since symptoms in patients with AR might not be classic, especially in older patients with comorbidities, we often use treadmill exercise testing to provide objective data concerning functional capacity. Prior work has shown that a reduction in exercise capacity tends to occur at approximately the same time that LV systolic function deteriorates.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Until recently there were no specific laboratory tests that played a significant role in the management of AR. However, in 2011 B-type natriuretic peptide (BNP) was evaluated as a potential marker that could be used to help guide management.

In a prospective study of 294 patients with asymptomatic severe AR with preserved LF function, a BNP level >130 pg/mL categorized a subgroup of patients who may benefit from early surgical intervention. However, the value for BNP that would indicate the need for AVR awaits confirmation from large prospective studies

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Echocardiographic findings are discussed in the section “Clinical Criteria for Diagnosis.” A chest x-ray (CXR) is usually performed in the patient with chronic AR, and generally provides supportive, rather than diagnostic data.

The CXR may demonstrate left ventricular hypertrophy and a dilated aorta, as well as pulmonary edema. Cardiac MRI can be used to accurately measure regurgitant volumes, as noted above. However, at this time definitive guidelines for the interpretation of AR by cardiac MR have not been established. In our practice, however, we often use cardiac MR in the patient with chronic severe AR.

There are three reasons why we do this: first, to better quantitate LV volumes and ejection fraction, given that eccentric hypertrophy and a volume loaded ventricle may be incompletely imaged by 2-D echocardiography due to apical foreshortening; second, to determine the size of the ascending aorta; and third, to determine whether chronic pressure load has led to an LV scar, using the technique of delayed hyperenhancement. While there is no clinical trial data supporting the use of MR for any of these indications, we feel that the data provided by this test can help us make more informed decisions about the timing of AVR in an asymptomatic patient.

(See Figure 1, Figure 2, Figure 3, and Figure 4: normal CXR, CXR in chronic AR, normal cardiac MR, eccentric remodeling in chronic AR cardiac MR, respectively)

III. Management.

Before proceeding with reviewing our therapeutic approach, we must emphasize that the diagnosis of severe, chronic AR must clearly be established. This generally involves the demonstration of severe, volumetric AR by most cardiac ultrasound metrics (see above) and/or by contrast angiography or cardiac MR. Chronic severe AR should generally be supported by the finding of LV dilation. Once the diagnosis is established for symptomatic patients with preserved EF (e.g., >50%), the management is straightforward: AVR.

For those symptomatic patients with reduced LVEF, the decision is more difficult, as the presence of reduced systolic function may preclude a return to a normal EF following surgery. However, according to the ACC/AHA 2008 Valvular Heart Disease guidelines, AVR is indicated for symptomatic individuals with NYHA classes II-IV and an EF of 25% to 50%.

The reduction in diastolic heart size produced by abolishing the excessive volume load should improve diastolic function and filling pressures by moving the LV to a lower point on the diastolic pressure-volume relationship. This reduction in diastolic pressure should result in some improvement in symptoms of congestion. In addition, ventricular afterload will be reduced by AR, and some improvement in EF will occur due to afterload reduction alone, even if the EF does not return to the normal range.

For those individuals with an EF <25% and NYHA class IV symptoms, surgical mortality approaches 10%. However, in comparison to medical management, surgical intervention may still be a reasonable alternative. Fortunately, at least in our practice, due to the ubiquity of cardiac ultrasound, it is uncommon to encounter a patient with severe LV dysfunction due to untreated, chronic severe AR.

Management of asymptomatic chronic aortic regurgitation usually involves both medical therapy until the clinician and patient deem that the time for surgery has come. Medical therapy is directed at reducing afterload (e.g., systolic hypertension) with vasodilators, which reduce wall stress and thereby improve left ventricular ejection fraction.

In patients with chronic AR, vasodilators can be used: (1) for long-term therapy for patients with symptoms and/or LV dysfunction who are poor surgical candidates; (2) to improve symptoms and improve ventricular function and filling pressure before proceeding to AVR; and (3) to prolong the “compensated” state of asymptomatic patients with normal LVEF. However, it should be noted that the use of vasodilators in asymptomatic AR patients who have normal LV function is controversial.

Long-term management.

AVR should be elected after there is evidence of left ventricular dysfunction or the onset of symptoms. This includes a reduction in left ventricular function with an ejection fraction of less than 50% or left ventricular dilatation with an end-systolic diameter >55 mm, referred to as the “55 rule.” For men with end-systolic parameters that are approaching this value, echocardiography should be repeated every 6 months.

Also, as mentioned above, those patients with chronic severe AR and a demonstrable decrease in exercise tolerance should be referred for AVR. It should be noted that it is preferable to use the EF, rather than the end-systolic dimension, in patients with coronary artery disease, because this linear measure may not be reflective of LV function if distortions in LV geometry are present.

The “55 rule” has limited applicability in women, who tend to develop symptoms and LV dysfunction at smaller absolute chamber dimensions when compared with men, due to their relatively smaller body size. Women, as compared with men, have a decreased 10-year survival after undergoing aortic valve replacement (39% vs. 72%). As noted by Carabello, there have been few studies involving women.

In a small study involving 51 women, women had more preoperative symptoms, but did not have a higher incidence of postoperative systolic dysfunction. Since heart failure symptoms can result from both systolic and diastolic dysfunction, and there was no evidence to suggest that women had an increased incidence of systolic dysfunction, it may be that unrecognized diastolic dysfunction is the culprit for the increased postoperative risk in women.

What’s the Evidence for specific management and treatment recommendations?

Bekeredjian, R, Grayburn, PA. “Valvular heart disease: aortic regurgitation”. Circulation. vol. 112. 2005. pp. 125-34. (The review by Bekeredjian and Grayburn provides additional background information about aortic regurgitation, including both acute and chronic aortic regurgitation. Also included are echocardiographic images of the various measurements.)

Zoghbi, WA, Enriquez-Sarano, M, Foster, E. “Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography”. J Am Soc Echocardiogr. vol. 16. 2003. pp. 777-802. (The ASE guidelines provides recommendations for proper echocardiographic evaluation of all regurgitant valves, including aortic regurgitation.)

Bonow, RO, Carabello, BA, Chatterjee, K. “2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society for Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons”. Circulation. vol. 118. 2008. pp. e547-59. (The ACC/AHA VHD guidelines focuses on management and includes all of the prior studies that inform the currently published guidelines.)

Pizarro, R, Bazzino, OO, Oberti, PF. “Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation”. J Am Coll Cardiol. vol. 58. 2011. pp. 1705-14. (Pizarro, Bazzino, Oberti, et al demonstrate that BNP levels can be a useful marker in the management of patients with chronic severe aortic regurgitation.)

Carabello, BA. “Aortic regurgitation in women “Does the measuring stick need a change””. Circulation. vol. 94. 1996. pp. 2355-7. (This paper by Carabello underscores the fact that 10-year mortality for women undergoing aortic valve replacement is higher than that of men. He suggests that this may be because by the time the end systolic dimension in women with chronic severe aortic regurgitation reaches 55 mm, contractile dysfunction may be present.)

DRG Codes and Expected Length of Stay.

ICD-9: 424.1 (Aortic valve disorders)

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