Aortic Regurgitation

Ali Mahajerin Echo Conference September 17, 2008

Introduction

   Aortic regurgitation (AR) is characterized by diastolic reflux of blood from the aorta to the LV.

AR may be caused by malfunction of the aortic valve leaflets themselves, by dilation of the aortic root and annulus, or a combination of these factors.

 Aortic root disease now accounts for >50% of all AVRs Clinical presentation is highly variable and depends on multiple factors, including acuity of onset, aortic and LV compliance, hemodynamic conditions, and severity of the lesion.

Epidemiology

    Incidence of clinically significant AR increases with age   Typical peak in 4 th to 6 th decade of life More common in men than women Overall prevalence of AR was 4.9% in Framingham Heart Study and 10% in Strong Heart Study  Prevalence of moderate or greater severity was 0.5% and 2.7%, respectively Most common cause of AR in developing countries is RHD In developed countries the leading cause of AR is either congenital (particularly due to bicuspid leaflets) or degenerative disease (including annuloaortic ectasia).

Valve-Related Causes of AR

     Rheumatic disease  Cusps become fibrotic and retract (usually also stenotic); MV involved as well Atherosclerotic degeneration Infective endocarditis   Leaflet perforation Vegetation interferes with coaptation Trauma (chest wall or deceleration injury) Bicuspid aortic valve (can be associated with aortic root dilation as well)

Other Valve-Related Causes of AR

   Myxomatous degeneration Structural deterioration of bioprosthesis Other less common causes:  Ankylosing spondylitis (can cause disease of both the leaflets and the aortic root)     SLE, RA Takayasu disease Anorectic drugs Membranous subaortic stenosis

Aortic Root Disease

Dilation here is common; especially in AS; does not lead to AR  Between the annulus and the ascending aorta is a collagenous segment that forms the sinuses of valsalva.

As little as 2mm of dilation here can cause AR Dilation here is rare

Aortic Root Disease

 Dilation of the aortic ridge eliminates the normal overlap of the valves

Aortic Root-Related Causes of AR

          Idiopathic aortic root dilation Aortoannular ectasia Marfan syndrome Ehlers-Danlos syndrome Osteogenesis imperfecta Aortic dissection Syphilitic aortitis Trauma Ankylosing spondylitis Bicuspid aortic valve with dilated aortic root

Acute Aortic Regurgitation

    Most commonly caused by bacterial endocarditis, aortic dissection, or blunt chest trauma Sudden large regurgitant volume is imposed on an LV of normal size that has not had time to accommodate the volume overload.

Abrupt increase in LVEDV leads to rapid and dramatic increase in LVEDP and LA pressures Inability of ventricle to develop compensatory chamber dilatation acutely results in a decrease in forward stroke volume.

 Tachycardia may develop as a compensatory mechanism to maintain cardiac output, but often insufficient.

Acute AR - Pathophysiology

  Patients often present with pulmonary edema or cardiogenic shock.

May present with myocardial ischemia: As LVEDP approaches diastolic aortic and coronary pressures, myocardial perfusion pressure in the subendocardium is diminished.

  LV dilation and thinning of LV wall result in increased afterload, and combined with tachycardia leads to increased myocardial O2 demand Ischemia and its consequences, including sudden death, occur commonly in acute AR.

Chronic Aortic Regurgitation

     Chronic AR imposes both volume and pressure overload on the LV.

Increased regurgitant volume  increased wall stress increased LVEDV and Increased chamber compliance accommodates increased volume w/o increasing filling pressures Compensatory eccentric hypertrophy also occurs, helping to maintain normal stroke volume with the chamber enlargement LVEDV increases but LV wall compliance prevents increase in LVEDP

Chronic AR - Pathophysiology

Early Compensated

  Enlarged chamber size  ↑ afterload LV which preserves compliance   hypertrophy of normal filling pressures LVH  ↑ LV mass  normal LV vol/mass ratio & EF   Progressive LV dilation and systolic HTN  ↑ wall stress and vol/mass ratio ↑ wall stress eventually leads to overt LV dysfunction.

Decompensated

 LV systolic dysfunction accompanied by decreased LV diastolic compliance due to hypertrophy and fibrosis  Leads to high filling pressures and CHF symptoms  Exertional dyspnea common; angina can occur due to reduced coronary flow reserve with predominantly systolic coronary flow

Different Stages of AR

Bekerdjian R, et al. Circulation 2005; 112: 125-134.

Physical Exam - Auscultation

    A2 often soft/absent, P2 normal S3 if LV function severely depressed High frequency decrescendo diastolic murmur over the 3 rd or 4 th intercostal space at left sternal border  Best heard sitting up, leaning forward at end expiration Austin Flint murmur: mid-to-late diastolic apical rumble, possibly due to vibration of anterior mitral leaflet as it is struck by a posteriorly directed AR jet.

Physical Exam – Peripheral Findings

         

Corrigan’s pulse deMusset’s sign

– bounding “waterhammer” carotid pulse – head bob with each heart beat

Mueller’s sign Traube’s sign

– systolic pulsation of uvula – pistol shot pulse over the femoral artery

Duroziez’s sign

– systolic and diastolic bruits heard when femoral artery partially compressed

Becker’s sign

– visible pulsations of retinal arteries and pupils

Hill’s sign

– popliteal cuff systolic pressure exceeding brachial pressure by more than 60 mmHg

Mayne’s sign

– more than 15 mmHg decrease in diastolic blood pressure with arm elevation

Rosenbach’s sign Gerhard’s sign

– systolic pulsations of the liver – systolic pulsations of the spleen

Natural History of AR

  Depends on AR severity, aortic root pathology, and adaptive response of LV.

Bonow et al:      104 asymptomatic patients with severe AR and normal LVEF Death, symptoms, or asymptomatic LV dysfunction was < 5%/year over 11-year follow-up Rate of sudden death was only 0.4%/year At 11 years, 58% remained asymptomatic and had normal LV systolic function.

Further strengthened serial changes in LV systolic function and/or LV dilatation as important to clinical outcome in AR and potential reasons for AVR.

Bonow RO, et al. Circulation 1991; 84: 1625-1635.

Natural History of AR

 Dujardin et al:  246 patients with moderate-severe AR, mean follow up 7 years  Not all asymptomatic with normal LV systolic function  Ten-year mortality rate 34%  Independent predictors of survival were age, functional class, comorbidity index, atrial fibrillation, LVESD, and LVEF

Dujardin KS, et al. Circulation 1999; 99: 1851-1857.

   Asymptomatic patients with normal LV function generally have a favorable prognosis Decline in LVEF with exercise or serial follow up identifies patients who will likely require surgical intervention.

Even moderate symptoms or evidence of LV dilatation are at higher risk and should be considered for early intervention.

Dujardin KS, et al. Circulation 1999; 99: 1851-1857.

Natural History of Chronic AR

Diagnostic Tools: ECG

   LVH with or without strain pattern, LAD, LAE One study suggests that in asymptomatic or mildly symptomatic patients with pure AR, the absence of ECG changes predicts LV systolic dimension < 55mm, and LVEF >45% and >40% with exercise.

 Up to 83% of patients with rest or exercise ST segment abnormalities had an enlarged LV (>55mm) or reduced LVEF < 45%.

Conduction abnormalities rare except in late disease with severe LV dysfunction; sustained SVT or VT unusual in absence of significant LV dysfunction.

Chest X-Ray

 Cardiomegaly  Prominent Left Ventricle  Ascending Aortic dilatation  LAE only if severe LV dysfunction

Chest X-Ray

Echocardiography

 Most important diagnostic test for evaluation of AR as well as for serial follow-up  Allows for:  Assessment of the anatomy of the aortic leaflets and the aortic root  Detection of the presence and severity of AR  Characterization of LV size and function

M-Mode Echocardiography

  The aortic regurgitation jet can cascade across the anterior mitral leaflet    Creates a high-frequency fluttering of the anterior mitral leaflet Increased duration between E and A peaks Increased distance between the maximal anterior motion of the mitral valve in early diastole (E point) and the most posterior motion of the interventricular septum (e.g., increased E-point septal separation [EPSS]) In acute AR, premature closure of the MV can also be seen by M-mode  Due to rapidly increasing LV pressure

AR by 2D Echo

     2D Echo will give you a detailed evaluation of the aortic valve and root Detailed evaluation of LV size and function Many important causes of AR easily seen on 2D imaging Even when AR is severe, sometimes 2D imaging is surprisingly normal Indirect signs of AR:  Diastolic curving of anterior mitral leaflet with concavity towards ventricular septum due to the direct effect of the regurgitant jet

Dilated aortic root due to aortoannular ectasia Bicuspid aortic valve with characteristic elliptical opening Bekerdjian R, et al. Circulation 2005; 112: 125-134.

Large, mobile vegetation Acute AR due to aortic dissection

Color Flow Doppler

  Color flow jet composed of 3 distinct segments:    Proximal flow convergence zone = area of flow acceleration into the orifice Vena contracta = narrowest and highest velocity region of the jet at or just downstream from the orifice The jet itself occurs distal to the orifice in the LV cavity Measurement of the jet area or penetration into the LV cavity is not accurate in assessing AR severity, though:    If jet width/LVOT width < 25%  specific for mild AR If jet width/LVOT width > 65%  specific for severe AR This works best when regurgitant orifice is relatively round in shape.

Color Flow Doppler

    Color flow Doppler is the most common technique to visualize AR Sensitivity > 95%    False negatives can occur in tachycardia with mild AR Frame rate allows only a few diastolic frames to be displayed Can be overcome by using CW -- has a higher sampling rate Specificity ~100% Detects even trivial AR   1% of subjects under age 40 10-20% of patients greater than age 60

    Eccentric AR jet Width measured at origin of jet adjacent to leaflets Jet width/LVOT width is <25% Case of mild AR   Jet width/LVOT width > 65% Case of severe AR

Bekerdjian R, et al. Circulation 2005; 112: 125-134.

(Same patient – aortic valve endocarditis as cause of AR)

AR jet directed toward anterior mitral leaflet

Vena Contracta

    The narrowest diameter of flow stream Independent of volume flow rate and driving pressure, relatively unaffected by instrument settings Narrow range of values though, so care needed to obtain optimal images. Ideal sample is:  Perpendicular to jet width    In zoom mode Narrow sector Minimum depth For AR, vena contracta can be measured in parasternal long-axis view preferably in zoom mode.

Vena Contracta

  Vena contracta width of ≥ 6 mm correlates well with severe AR (sensitivity 95%, specificity 90%) Vena contracta width of < 3 mm specific for mild AR.

Enriquez-Sarano M, et al. NEJM 2004; 351: 1539-1546.

Proximal Isovelocity Surface Area

   Acceleration of flow occurs proximal to the valve plane with a series of isovelocity “surfaces” leading to the high-velocity jet in the regurgitant orifice.

 Velocity for a PISA can be determined as the aliasing velocity where a distinct red-blue interface seen (at this interface, velocity is equivalent to Nyquist limit). Assuming a hemispherical shape, the surface area of the PISA region is 2πr 2 Peak regurgitant flow obtained by multiplying surface area by aliasing velocity, and effective regurgitant orifice area (EROA) is peak regurgitant flow divided by peak velocity obtained by CW Doppler.

PISA - Limitations

   Isovelocity contour flattens as it approaches the orifice, underestimating flow Proximal structures can distort the isovelocity contour Sensitive to errors in radius measurement  10% error in radius leads to 21% error in flow

Continuous Wave Doppler

   Because AR jet is high velocity, CW Doppler necessary to record envelope of jet.

Several types of info can be derived:   

Antegrade flow velocity Signal intensity

relative to antegrade flow

Time course

(shape) of velocity curve AR results in increased antegrade volume flow rate across AV, which is reflected in an increase in the antegrade velocity across the valve.

  The greater the severity of AR, the higher the antegrade velocity across the AV Must also consider possibility of coexisting AS

AR Antegrade    Signal intensity is proportional to # RBCs contributing to regurgitant signal.

Can compare intensity of regurgitant signal to antegrade flow as a qualitative estimate of regurgitant severity.

Weak signal reflects mild severity; signal nearly equal to antegrade flow reflects severe regurgitation.

CW Doppler: Pressure Half-Time

    Shape of AR velocity curve depends on time course of diastolic pressure difference across AV Chronic severe AR results in increased aortic pulse pressure with low aortic EDP. Rapid rate of decline in aortic pressure is reflected in steeper diastolic deceleration slope (even if LVEDP remains low).

 Thus, diastolic deceleration slope provides a semiquantitative measure of AR severity.

A flat slope (P 1/2 > 500 msec) is consistent with mild AR, and a steep slope (P 1/2 < 200 msec) indicates severe AR.

For a given severity of AR, P elevated LVEDP or vasodilator therapy that reduces AR.

1/2 will be shortened by

Pressure Half-Time

  With acute AR, LV compliance has not yet adapted leading to significant increase in LVEDP. In extreme cases, aortic and LV EDP may equalize at end-distole, resulting in a triangular-shaped CW-Doppler with linear deceleration slope from maximum velocity to baseline.

Limitations of pressure half-time assessment:   Pressure half-time sensitive to chronicity of AR  Acute AR leads to much shorter values than chronic AR when LV is dilated with increased compliance Pressure half-time varies with SVR  Vasodilators may shorten the pressure half-time even as the aortic regurgitant fraction improves.

Pressure Half-Time

Regurgitant Volume or Fraction

    Can compare flow through AV versus MV or PV Stroke volume at any valve annulus is derived as the product of CSA and VTI of flow at the annulus In the absence of regurgitation, SV determinations at different sites (LVOT, mitral annulus, pulmonic annulus) should be equal In the presence of regurgitation of one valve, without any intracardiac shunt the flow through the affected valve is larger than the other valves   RV is the difference between the two flows RF is the RV divided by forward stroke volume through the regurgitant valve.

Regurgitant Volume or Fraction

Regurgitant Volume or Fraction

 Regurgitant Volume (fraction):  Mild: < 30 cc (< 30%)  Mild-moderate: 30-44 cc (30-39%)  Moderately severe: 45-59 cc (40-49%)  Severe: ≥60 cc (≥50%)  Limitations:  Assumes normal flow through comparison valve  Cannot be used in presence of shunts  Sensitive to small measurement errors (measurement errors of the radius and tracing the VTI)

RF by CW Doppler of Distal Arch

Retrograde Antegrade  Aortic regurgitant fraction can be estimated by ratio of reversed flow VTI / forward flow VTI in the distal aortic arch.

Aortic Flow Reversal

     An important supportive sign of severe AR is diastolic flow reversal in the descending aorta.

Holodiastolic flow reversal usually indicates at least moderate AR Best measured with PW Doppler from a suprasternal probe position.

If observed in the proximal abdominal aorta (from the subcostal position), is even more sensitive (100%) and specific (97%) for severe AR.

False positives may occur if a PDA is present.

Zoghbi WA, et al. JASE 2003; 16: 777-802.

Zoghbi WA, et al. JASE 2003; 16: 777-802.

Cardiac Catheterization

   May be needed to evaluate coronary anatomy in patients requiring surgical intervention.

 Men age > 35 years, pre-menopausal women age > 35 years with risk factors for CAD, or postmenopausal women Supravalvular aortography = semiquantitative way to grade AR, based on amount of contrast in LV after aortography  Mild AR (1+): contrast appears in LV but clears after each beat.

   Moderate AR (2+): faint opacification of entire LV over several cardiac cycles.

Mod-severe AR (3+): opacification of entire LV with same intensity as aorta Severe AR (4+): opacification of entire LV on first heart beat with intensity higher than aorta.

Subjective, depends on amount of contrast injected and the size of the LV, and correlates poorly with regurgitant volume particularly in patients with dilated LVs.

Cardiac MR

    CMR is widely recognized as the non-invasive gold standard for quantification of LV volumes and ejection fraction.

 Can overcome the limitations of echo, such as studies limited by body habitus or cases with eccentric regurgitant jets.

Phase velocity encoding is used to calculate forward stroke volume through the AV; total LV stroke volume is determined from LVEDV and LVESV, and the difference between aortic and LV stroke volumes is the regurgitant volume.

Volumetric CMR assessment of AR has been shown to be accurate and reproducible.

CMR has the potential to be a very useful tool for serial evaluations, though referring physicians are often more comfortable with qualitative interpretations of regurgitation severity such as those provided by echo assessment.

Cardiac MR

   Gelfand et al. addressed the issue of concordance between quantitative CMR and qualitative echocardiographic determinations of regurgitant severity.

Compared echo and CMR findings in 141 consecutive patients with varying degrees of MR and/or AR, to identify CMR regurgitant fractions that correlated with qualitative mild, moderate, and severe regurgitaion by echo.

Average age 53 ± 15 yr, 43% female. 24 with AR, 83 with MR, 35 with no MR/AR. Median interval 31 days between CMR and Echo.

Gelfand EV, et al. Journal of CMR 2006; 8: 503-507.

Cardiac MR

  The mean CMR aortic regurgitant fractions for each echocardiographic grade was significantly different (p < 0.001 for trend, p<0.05 for each pairwise comparison) The CMR-RF thresholds with maximal agreement for aortic regurgitation: 

Mild ≤ 15%

 

Moderate 16-27% Mod-sev or severe > 27%

  These thresholds yielded 100% concordance within 1 regurgitation grade.

For patients without AR on echo, the CMR aortic regurgitant fraction was 2 ± 2%.

Gelfand EV, et al. Journal of CMR 2006; 8: 503-507.

Serial Testing with Echo

     If chronic nature of lesion uncertain and no initial surgical indication, should repeat exam and echo within 2-3 months after initial evaluation.

Asx, mild AR, little/no LV dilation, normal LV systolic function: see yearly, echo q2-3 years Asx, severe AR, significant LV dilation (LVEDD > 60 mm), normal LV fx: echo q6-12 months Asx, severe AR, severe LV dilation (LVEDD > 70 mm), normal LV fx: echo q4-6 months.

Repeat echo for onset of symptoms, equivocal history of changing symptoms or exercise tolerance, or clinical findings to suggest worsening regurgitation or progressive LV dilatation.

Bonow RO, et al. Circulation 2006; 114: e84-e231.

Chronic AR Management - Surgery

 AR is a surgical disease. The timing of surgery is clinically dependent.

 In patients with pure, chronic AR, AVR should be considered only if AR is severe.

 Operative mortality for AVR ~4%, higher with concomitant aortic root replacement or CABG or if comorbidities such as advanced age.  Death rate for Asx with normal LV <0.2%/year.

 Symptomatic pts with chronic severe AR: >10%/yr

Bonow RO, et al. Circulation 2006; 114: e84-e231.

ACC/AHA 2006 Guidelines

 Class I indications for AVR in chronic, severe AR:  Symptomatic patients  Asymptomatic with LVEF ≤ 50% at rest  Undergoing CABG or other heart/aorta surgery  Class IIa for AVR in chronic, severe AR:  Asymptomatic, normal LV systolic function (LVEF ≥ 50%) but with severe LV dilatation (LVEDD > 75 mm or LVESD > 55 mm)

Bonow RO, et al. Circulation 2006; 114: e84-e231.

 

Surgical Outcomes

450 patients with severe AR:  Operative mortality 14%, 6.7%, and 3.7% for those with LVEF <35%, 36-49%, and ≥ 50%, respectively.

Post-op outcome for pts with reduced LVEF pre-op depends on magnitude of reduction.

  Pre-op LVEF < 35%, 10 year post-op survival rate is 41% Pre-op LVEF 35-49%, survival 56%.

 Pre-op LVEF ≥ 50%, survival 70% at 10 years post-op.

Chaliki HP, et al. Circulation 2002; 106: 2687-2693.

Post-Op Outcomes

    Surgery for symptomatic patients with severe AR reduces LV volumes, LV mass, wall stress and increases LVEF. If asymptomatic, some say surgery is ideally performed when LVEF 50-55%. Dilated LV or low LVEF pre-op can still benefit from surgery.

Patients with markedly decreased LVEF should not be denied surgery – these patients generally have an improvement in LVEF post-op as a result of relief of high afterload, especially if LV dysfunction has lasted less than one year.  It is almost never “too late” to operate in chronic, severe AR.

Vasodilators?

   Short-term studies on the effects of vasodilators in acute severe AR have suggested improvement in hemodynamic and structural parameters.

The long-term benefit of vasodilator therapy in chronic severe AR is unclear.

A total of 10 studies of vasodilator therapy in asymptomatic patients with chronic, severe AR have yielded conflicting and quite inconsistent results.  Only two studies have assessed clinical outcomes such as time to AVR (the remainder have only reported hemodynamic and/or structural parameters).

Vasodilators – Clinical Outcomes

     Scognamiglio et al. randomized 143 asymptomatic patients with chronic, severe AR to nifedipine or digoxin.

Patients treated with nifedipine had a significantly lower rate of progression to AVR than digoxin patients.

By 6 years, a mean of 34% ± 6% of digoxin patients underwent AVR, while 15% ± 3% of nifedipine patients underwent AVR.

Twenty digoxin pts. required AVR for reduced LV fx and/or onset of symptoms, while all 6 nifedipine pts who needed surgery were d/t reduced LVEF.

Post-op LVEF after AVR significantly higher in nifedipine versus digoxin (65% ± 4% vs. 58% ± 8%).

Scognamiglio R, et al. NEJM 1994; 331: 689-694.

Scognamiglio R, et al. NEJM 1994; 331: 689-694.

Vasodilators – Clinical Outcomes

    Evangelista et al. randomly assigned 95 patients with chronic, severe AR to nifedipine, enalapril, or placebo.

Followed patients for ~7 years.

Rates of AVR were not significant across the 3 groups:    12/31 (39%) of control group 16/32 (50%) of enalapril group 13/32 (41%) of nifedipine group  11% of patients dropped out of study, though on-treatment analysis yielded similar rates of progression No significant changes in SBP, DBP, or HR noted; furthermore saw no significant changes in LVEF, LVESD, LVEDVI

Evangelista A, et al. NEJM 2005; 353: 1342-1349.

Evangelista A, et al. NEJM 2005; 353: 1342-1349.

Current Guidelines for Vasodilators

   Class I:  Chronic therapy in severe AR with symptoms or LV dysfunction when not a surgical candidate.

Class IIa:  Short-term therapy to improve hemodynamics in patients with severe CHF Sx and severe LV dysfunction before proceeding with AVR.

Class IIb:  Long-term therapy in asymptomatic patients with severe AR who have LV dilatation but normal systolic function (previously a class I indication before the Evangelista article).

Bonow RO, et al. Circulation 2006; 114: e84-e231.

Thank You!