2IntroductionAortic 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 AVRsClinical presentation is highly variable and depends on multiple factors, including acuity of onset, aortic and LV compliance, hemodynamic conditions, and severity of the lesion.
3Epidemiology Incidence of clinically significant AR increases with age Typical peak in 4th to 6th decade of lifeMore common in men than womenOverall prevalence of AR was 4.9% in Framingham Heart Study and 10% in Strong Heart StudyPrevalence of moderate or greater severity was 0.5% and 2.7%, respectivelyMost common cause of AR in developing countries is RHDIn developed countries the leading cause of AR is either congenital (particularly due to bicuspid leaflets) or degenerative disease (including annuloaortic ectasia).
4Valve-Related Causes of AR Rheumatic diseaseCusps become fibrotic and retract (usually also stenotic); MV involved as wellAtherosclerotic degenerationInfective endocarditisLeaflet perforationVegetation interferes with coaptationTrauma (chest wall or deceleration injury)Bicuspid aortic valve (can be associated with aortic root dilation as well)
5Other Valve-Related Causes of AR Myxomatous degenerationStructural deterioration of bioprosthesisOther less common causes:Ankylosing spondylitis (can cause disease of both the leaflets and the aortic root)SLE, RATakayasu diseaseAnorectic drugsMembranous subaortic stenosis
6Aortic Root DiseaseDilation here is common; especially in AS; does not lead to ARBetween 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 ARDilation here is rare
7Aortic Root DiseaseDilation of the aortic ridge eliminates the normal overlap of the valves
8Aortic Root-Related Causes of AR Idiopathic aortic root dilationAortoannular ectasiaMarfan syndromeEhlers-Danlos syndromeOsteogenesis imperfectaAortic dissectionSyphilitic aortitisTraumaAnkylosing spondylitisBicuspid aortic valve with dilated aortic root
9Acute Aortic Regurgitation Most commonly caused by bacterial endocarditis, aortic dissection, or blunt chest traumaSudden 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 pressuresInability 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.
10Acute 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 demandIschemia and its consequences, including sudden death, occur commonly in acute AR.
11Chronic Aortic Regurgitation Chronic AR imposes both volume and pressure overload on the LV.Increased regurgitant volume increased LVEDV and increased wall stressIncreased chamber compliance accommodates increased volume w/o increasing filling pressuresCompensatory eccentric hypertrophy also occurs, helping to maintain normal stroke volume with the chamber enlargementLVEDV increases but LV wall compliance prevents increase in LVEDP
12Chronic AR - Pathophysiology Early CompensatedEnlarged chamber size ↑ afterload hypertrophy of LV which preserves compliance normal filling pressuresLVH ↑ LV mass normal LV vol/mass ratio & EFProgressive LV dilation and systolic HTN ↑ wall stress and vol/mass ratio↑ wall stress eventually leads to overt LV dysfunction.DecompensatedLV systolic dysfunction accompanied by decreased LV diastolic compliance due to hypertrophy and fibrosisLeads to high filling pressures and CHF symptomsExertional dyspnea common; angina can occur due to reduced coronary flow reserve with predominantly systolic coronary flow
13Different Stages of ARBekerdjian R, et al. Circulation 2005; 112:
14Physical Exam - Auscultation A2 often soft/absent, P2 normalS3 if LV function severely depressedHigh frequency decrescendo diastolic murmur over the 3rd or 4th intercostal space at left sternal borderBest heard sitting up, leaning forward at end expirationAustin 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.
15Physical Exam – Peripheral Findings Corrigan’s pulse – bounding “waterhammer” carotid pulsedeMusset’s sign – head bob with each heart beatMueller’s sign – systolic pulsation of uvulaTraube’s sign – pistol shot pulse over the femoral arteryDuroziez’s sign – systolic and diastolic bruits heard when femoral artery partially compressedBecker’s sign – visible pulsations of retinal arteries and pupilsHill’s sign – popliteal cuff systolic pressure exceeding brachial pressure by more than 60 mmHgMayne’s sign – more than 15 mmHg decrease in diastolic blood pressure with arm elevationRosenbach’s sign – systolic pulsations of the liverGerhard’s sign – systolic pulsations of the spleen
16Natural History of ARDepends on AR severity, aortic root pathology, and adaptive response of LV.Bonow et al:104 asymptomatic patients with severe AR and normal LVEFDeath, symptoms, or asymptomatic LV dysfunction was < 5%/year over 11-year follow-upRate of sudden death was only 0.4%/yearAt 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:
17Natural History of AR Dujardin et al: 246 patients with moderate-severe AR, mean follow-up 7 yearsNot all asymptomatic with normal LV systolic functionTen-year mortality rate 34%Independent predictors of survival were age, functional class, comorbidity index, atrial fibrillation, LVESD, and LVEFDujardin KS, et al. Circulation 1999; 99:
18Asymptomatic 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:
20Diagnostic 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.
21Chest X-Ray Cardiomegaly Prominent Left Ventricle Ascending Aortic dilatationLAE only if severe LV dysfunction
23EchocardiographyMost important diagnostic test for evaluation of AR as well as for serial follow-upAllows for:Assessment of the anatomy of the aortic leaflets and the aortic rootDetection of the presence and severity of ARCharacterization of LV size and function
24M-Mode Echocardiography The aortic regurgitation jet can cascade across the anterior mitral leafletCreates a high-frequency fluttering of the anterior mitral leafletIncreased duration between E and A peaksIncreased 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-modeDue to rapidly increasing LV pressure
26AR by 2D Echo2D Echo will give you a detailed evaluation of the aortic valve and rootDetailed evaluation of LV size and functionMany important causes of AR easily seen on 2D imagingEven when AR is severe, sometimes 2D imaging is surprisingly normalIndirect signs of AR:Diastolic curving of anterior mitral leaflet with concavity towards ventricular septum due to the direct effect of the regurgitant jet
27Dilated aortic root due to aortoannular ectasia Large, mobile vegetationBicuspid aortic valve with characteristic elliptical openingAcute AR due to aortic dissectionBekerdjian R, et al. Circulation 2005; 112:
33Color Flow Doppler Color flow jet composed of 3 distinct segments: Proximal flow convergence zone = area of flow acceleration into the orificeVena contracta = narrowest and highest velocity region of the jet at or just downstream from the orificeThe jet itself occurs distal to the orifice in the LV cavityMeasurement 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 ARIf jet width/LVOT width > 65% specific for severe ARThis works best when regurgitant orifice is relatively round in shape.
34Color Flow DopplerColor flow Doppler is the most common technique to visualize ARSensitivity > 95%False negatives can occur in tachycardia with mild ARFrame rate allows only a few diastolic frames to be displayedCan be overcome by using CW -- has a higher sampling rateSpecificity ~100%Detects even trivial AR1% of subjects under age 4010-20% of patients greater than age 60
35Jet width/LVOT width > 65% Case of severe AR Eccentric AR jet Width measured at origin of jet adjacent to leafletsJet width/LVOT width is <25%Case of mild ARBekerdjian R, et al. Circulation 2005; 112:
41Vena Contracta The narrowest diameter of flow stream Independent of volume flow rate and driving pressure, relatively unaffected by instrument settingsNarrow range of values though, so care needed to obtain optimal images. Ideal sample is:Perpendicular to jet widthIn zoom modeNarrow sectorMinimum depthFor AR, vena contracta can be measured in parasternal long-axis view preferably in zoom mode.
42Vena ContractaVena 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:
43Proximal 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 2πr2Peak 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.
44PISA - LimitationsIsovelocity contour flattens as it approaches the orifice, underestimating flowProximal structures can distort the isovelocity contourSensitive to errors in radius measurement10% error in radius leads to 21% error in flow
45Continuous 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 velocitySignal intensity relative to antegrade flowTime course (shape) of velocity curveAR 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 AVMust also consider possibility of coexisting AS
46ARAntegradeSignal 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.
47CW Doppler: Pressure Half-Time Shape of AR velocity curve depends on time course of diastolic pressure difference across AVChronic 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 (P1/2 > 500 msec) is consistent with mild AR, and a steep slope (P1/2 < 200 msec) indicates severe AR.For a given severity of AR, P1/2 will be shortened by elevated LVEDP or vasodilator therapy that reduces AR.
48Pressure Half-TimeWith 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 ARAcute AR leads to much shorter values than chronic AR when LV is dilated with increased compliancePressure half-time varies with SVRVasodilators may shorten the pressure half-time even as the aortic regurgitant fraction improves.
50Regurgitant Volume or Fraction Can compare flow through AV versus MV or PVStroke volume at any valve annulus is derived as the product of CSA and VTI of flow at the annulusIn the absence of regurgitation, SV determinations at different sites (LVOT, mitral annulus, pulmonic annulus) should be equalIn the presence of regurgitation of one valve, without any intracardiac shunt the flow through the affected valve is larger than the other valvesRV is the difference between the two flowsRF is the RV divided by forward stroke volume through the regurgitant valve.
52Regurgitant Volume or Fraction Regurgitant Volume (fraction):Mild: < 30 cc (< 30%)Mild-moderate: cc (30-39%)Moderately severe: cc (40-49%)Severe: ≥60 cc (≥50%)Limitations:Assumes normal flow through comparison valveCannot be used in presence of shuntsSensitive to small measurement errors (measurement errors of the radius and tracing the VTI)
53RF by CW Doppler of Distal Arch RetrogradeAntegradeAortic regurgitant fraction can be estimated by ratio of reversed flow VTI / forward flow VTI in the distal aortic arch.
54Aortic Flow ReversalAn important supportive sign of severe AR is diastolic flow reversal in the descending aorta.Holodiastolic flow reversal usually indicates at least moderate ARBest 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.
58Cardiac 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 womenSupravalvular aortography = semiquantitative way to grade AR, based on amount of contrast in LV after aortographyMild 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 aortaSevere 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.
64Cardiac MRCMR 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.
65Cardiac MRGelfand 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:
66Cardiac MRThe mean CMR aortic regurgitant fractions for each echocardiographic grade was significantly different (p < 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:
74Serial 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 yearsAsx, severe AR, significant LV dilation (LVEDD > 60 mm), normal LV fx: echo q6-12 monthsAsx, 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.
75Chronic 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%/yrBonow RO, et al. Circulation 2006; 114: e84-e231.
76ACC/AHA 2006 GuidelinesClass I indications for AVR in chronic, severe AR:Symptomatic patientsAsymptomatic with LVEF ≤ 50% at restUndergoing CABG or other heart/aorta surgeryClass 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.
77Surgical 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:
78Post-Op OutcomesSurgery 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.
79Vasodilators?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).
80Vasodilators – 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:
82Vasodilators – 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 group16/32 (50%) of enalapril group13/32 (41%) of nifedipine group11% of patients dropped out of study, though on-treatment analysis yielded similar rates of progressionNo significant changes in SBP, DBP, or HR noted; furthermore saw no significant changes in LVEF, LVESD, LVEDVIEvangelista A, et al. NEJM 2005; 353:
83Evangelista A, et al. NEJM 2005; 353: 1342-1349.
84Current 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.