Aortic Insufficiency

Outline Epidemiology Etiology Pathophysiology Clinical Presentation / Symptoms Natural History Diagnosis Physical Exam Echocardiography Treatment Medical Surgical What’s new?

Epidemiology Prevalence Framingham Offspring Study 13% in men; 8.5% in women Advanced age and male gender associated with AR Singh,et al. American Journal of Cardiology.1999:83:897-902 Strong Heart Study (Native American Population) 10% prevalence Advanced age and aortic root diameter associated with AR Lebowitz, et al. JACC. 2000;36:461-7. In both studies the majority of cases were mild

Etiology Valvular vs. Aortic Root Valvular Calcific AS in the elderly Infective endocarditis Congenital bicuspid More commonly stenosis Incomplete closure/prolapse can lead to isolated regurgitation Rheumatic fever Cusps become infiltrated with fibrous tissue and retract preventing cusp apposition during diastole Less Common Congenital: quadricuspid Inflammatory conditions: SLE, RA, AS, Whipple’s Disease, Takayasu Anorectic drugs

Etiology Aortic Root Disease Age related (degenerative) aortic dilation HTN longstanding HLD Cystic medial necrosis (+/- Marfans) Aortic dilation related to bicuspid valve Osteogenesis imperfecta Syphilitic aortitis AS, Bechets, Psoriatic arthritis, GCA

Pathophysiology Regurgitant flow produces increase in LVEDV Thereby raising wall tension (via Lapace’s law) Wall stress proportional to (Intraventricular pressure x radius)/wall thickness LV responds by compensatory eccentric hypertrophy of myocytes Replication in series and elongation of myocytes and myocardial fibers (Different from AS)  Dilation Chronic compensated AR: sufficient wall thickening occurs so that ratio of wall thickness to cavity radius remains normal. Maintains End diastolic wall stress normal LV responds to volume load with increase EDV, chamber compliance accommodating increased volume without increased pressure

Pathophysiology (con’t) During chronic compensated AR LV is able to adapt to increase in diastolic volume without increasing LV EDP. LV produces a larger total SV to compensate for regurgitant flow Over time progressive interstitial fibrosis reduces LV compliance leading to chronic decompensated phase. Chronic volume overload results in impaired LV emptying, increasing LVEDP and LVEDV causing further dilation and decreasing EF

Pathophysiology Patients with severe chronic AR have the largest LVEDV of those with any form of heart disease (cor bovinum) In contrast to AR, AS has pressure overload induced hypertrophy (concentric) with replication in parallel This leads to increased ratio of wall thickness to radius

Symptoms Exertional dyspnea Orthopnea Parosxysmal nocturnal dyspnea Angina pectoris Late in clinical course Uncomfortable awareness of heartbeat Laying down Thoracic pain PVCs great heave of volume loaded LV during post extrasystolic beat cause distress Complaints may be present for many years before symptoms of overt LV dysfunction manifest

Natural History of Chronic AR Asymptomatic patients with normal EF No large scale studies evaluating this population Current ACC recs derived from 9 published series involving 593 patients with mean F/U 6.6 years Progression to symptoms and/or LV dysfunction: <6%/yr Progression to asymptomatic dysfunction: <3.5%/yr Sudden Death: <0.2%/yr Two multivariate analysis identified two independent predictors of outcome (symptoms, death of LV dysfunction.) Age LVEDV EDV > 50 mm 19% annual EDV 40-49 mm 6%/yr EDV < 40 mm <1%/yr

Natural History of Chronic AR Patients with asymptomatic LV Dysfunction Most develop symptoms requiring AVR in 2-3 years Symptom onset 25% annually Patients with symptomatic AR No long term studies on this population as most proceed to AVR Mortality rate of 10% annually if pt has angina Mortality rate of 20% annually if pt has heart failure Bonow, Circulation 1991, 84:1296-302

Physical Exam Palpation Auscultation Apical impulse enlarged, displaced lateral to midclavicular line in 5th intercostal space Diastolic thrill and systolic thrill in second intercostal space (increased aortic flow) Auscultation Diminished S1 (prolonged PR, LV dysfunction, preclosure of MV) S2 soft, maybe paradoxically split S3 may be heard with LV dysfunction (indicating increased LV EDP) S4 often present (LA contraction into poorly compliant LV) Blowing diastolic decrescendo murmur starting immediately after A2. LUSB, diaphragm of stethoscope Sitting up and leaning forward Full expiration Severity correlates with length/duration not intensity of murmur May hear second diastolic murmur at apex in severe AR Austin Flint: middle to late diastolic rumble May hear short midsystolic ejection murmur at base radiating to neck reflecting increased ejection rate (don’t confuse with AS) Maneuvers Increase: isometric exercise, squatting, inotrope infusion Decrease: standing from squatting, valslava, inhalation of amyl nitrite LV enlargement: apical impulse Austin Flint: vibration of anterior mitral leaflet as it is struck by regurgitant jet, or by rapid antegrade flow across a mitral orifice that is narrowed by rapidly rising LVEDP AR murmur distinguished from PR murmur by its earlier onset (after A2 rather than P2) AR murmur due to valve dx heard best 3 or 4 LSB, ascending aorta AR heard better over RSB

Physical Exam: Peripheral Pulses Rapid upstroke followed by quick collapse Water-hammer/Corrigan’s pulse Head bob with each heartbeat De Musset’s sign Pistol shot sounds heard over femoral arteries in systole and diastole Traube’s sign Systolic pulsation of the uvula Muller’s sign Capillary pulsation visible in nailbed Quincke’s sign Popliteal cuff systolic pressure exceeding brachial cuff systolic pressure by > 60 mm hg Hill’s Sign Arterial pulsations visible in retinal arteries and pupils Becker’s sign

Laboratory Evaluation EKG and CXR Echocardiogram gold standard Two dimensional: cause of AR Rheumatic: thickening and retraction of leaflet tips failure of cusp apposition Endocarditis: leaflet fibrosis and retraction, leaflet perforation or flail of the valve cusp Aortic root seen on parasternal long axis Symmetric dilatation causes central jet Focal dilatation results in eccentric jet EKG: LVH, LAD, LAA, conduction abnormalities unusual (PACs and PVCs occur) CXR: marked cardiomegaly with heart displaced inferiorly and leftward

Echocardiogram M- Mode May reveal premature closure of the mitral valve (Fluttering in diastole) Diastolic opening of aortic valve (severe, acute) M-Mode’s rapid sampling best for picking up fluttering, early closure due to rapidly increasing LV diastolic pressure RV, IVS, LV (black space), Fluttering of mitral valve) the Posterior wall

Echocardiogram Color Flow Assessment of jet origin, size and direction Parasternal long axis and short axis (TTE) LVOT view (135 degree transducer position of TEE) Sensitivity 95%, specificity near 100% (Feigenbaum) FN rare: can occur in setting of increased HR (short diastole), should use CW for detection Max length of jet poorly correlated with angiographic severity of AR Short axis regurgitant jet area relative to short axis area of LVOT at aortic annulus correlates best with angiographic severity of AR

Echocardiography Continuous wave allows for measurement of: Density of jet (qualitative indication of the volume of regurgitation) Velocity Rate of deceleration Because AR jet invariably high velocity, continuous wave necessary for contour of envelope CW does well to differentiate between MS and AR

Echocardiogram Pulse wave Doppler relies on demonstration of turbulent flow during diastole in LVOT Highly sensitive but requires methodical and careful search for jet using multiple views and windows False positive: mitral stenosis or prosthetic mitral valve where turbulent diastolic flow can be mistaken for AR

ACC Guidelines on Echocardiogram Class I indications (LOA) Confirm presence and severity of acute or chronic AR (B) Diagnosis and assessment of cause of chronic AR and assessment of LV hypertrophy, EDV, and EF (B) Patient with enlarged aortic root to assess for regurgitation (B) Radionuclide angiography or MRI indicated for initial and serial assessments of LV volume and function at rest in pts with suboptimal TTE (B) Re-evaluate mild, moderate or severe AR in patient with new or changing symptoms (B)

Evaluating Severity of AR on ECHO Multiple methods for measuring AR, each with its own limitations Important to obtain multiple measurements in multiple views Size and extent of jet within LV Jet Width/LVOT diameter Jet area/LVOT diameter Pressure Half Time Quantify regurgitant volume and regurgitant fraction PISA Diastolic Flow Reversal

Severity: Color Flow Most common is to examine size of regurgitant jet and regurgitant volume Length of jet conveys unreliable information about overall severity. Important to examine at its origin (immediately downstream of AoV) Parasternal long axis Height (width) of jet just below valve measured Can also be expressed as percentage of LVOT dimension Limitations Eccentric jets Changes in gain, color scale, transducer frequent, wall filters Changes in View (apical vs. parasternal) Eccentric jets: become entrained along wall of LB altering their appearance and perception of severity Instrument dependant factors Views: apical views make width of jet appear larger

Severity Color Flow

Severity: Continuous Wave Compares density of envelope of the antegrade aortic flow and regurgitant jet Larger the volume the darker the jet Mild AR Compliant LV allows slow and modest increase in LVP and aortic diastolic pressure is maintained throughout Regurgitant velocity remains high = flat envelope (Long Pressure half time) Severe AR Increase LVP and rapid decrease in aortic pressure leads to rapid deceleration of regurgitant jet velocity Steep slope of Doppler wave (Pressure Half Time)

Severity: Continuous Wave

Severity Pulse Wave Pulse wave can be used to assess diastolic flow reversal in descending aorta Dependent of vessel compliance and stroke volume Holosystolic flow reversal in proximal descending aorta is diagnostic of severe AR

Severity: Other Can use PISA to calculate ERO Technical challenges of visualizing isovelocity shells Quantifying regurgitant volumes All four valves in series, SV across each is equal Total SV across AoV = Regurg Vol .+ Forward Vol. SV = CSA x TVI CSA = (pi)r2 = 0.785 x diameter2 Regurg Volume = SV AV – SV MR CSA: Cross sectional area TVI: Time velocity integral

Classification of Severity

Cardiac Catherization For patients with poor echo images aortography provides semi quantitative assessment of AR severity 1+ - mild – contrast incompletely opacifies LV but clears with each beat 2+ - moderate – faint complete opacification of LV, rapidly clears 3+ - mod-severe – opacification of LV matching aorta 4+ - severe – opacification of entire LV on first beat, more intense than aorta, slow clearing Coronary angiography indicated prior to surgery in patient’s > 50 years old

ACC Guidelines on Catherization in AR Class I Assessment of severity of AR, EF, or aortic root size when noninvasive tests are inconclusive or discordant with clinical findings in patients with AR (B) Coronary angiography indicated before AR in patients at risk for CAD (C) Class III Not indicated for assessment of EF, aortic root size, or severity of AR before AVR when non-invasive tests are adequate and concordant (C) Not indicated for assessment of LV function and severity of AR in asymptomatic patients (C)

Medical Therapy Surgical Indications Serial Follow Up Management Medical Therapy Surgical Indications Serial Follow Up

Medical Therapy Vasodilating agent therapy designed to improved forward SV and reduce regurgitant volume Decrease LV EDV Decrease wall stress Decrease afterload Hydralazine, nitroprusside produce acute hemodynamic changes Decrease EDV Increase EF Nifedipine or felodipine Inconsistent results

Randomly assigned 95 patients with asymptomatic severe AR and normal LV EF to open label nifedipine, open label enalapril or placebo Mean 7 year follow up Primary end points: LV dimension on TTE, symptoms, need for surgery

Vasodilators? Exclusion: EF< 50%, other valvular disease, DBP > 90, Afib, Hx CAD Defined severe AR as: Regurg fraction > 60% or Jet width > 10 mm AND jet area > 7 cm2 No reduction in development of symptoms or LV dysfunction warranting surgery No difference in LV dimension, EF, or mass

Medical Therapy ACC Guidelines Class I Vasodilator therapy indicated for chronic therapy in severe AR with symptoms or LV dysfunction when surgery not recommended Class IIa Vasodilator therapy is reasonable for short term therapy to improve hemodynamic profile prior to surgery Class IIb Vasodilator therapy considered for long term therapy in asymptomatic patients with severe AR, LV dilatation and normal systolic function

Medical Therapy: ACC Guidelines Class III Vasodilator therapy not indicated in asymptomatic patients with mild to moderate AR and normal EF Not indicated in asymptomatic patients with LF systolic dysfunction who can undergo surgery Not indicated in patients with normal EF or mild to moderate LV systolic dysfunction who are candidates for AVR

Indications for Surgery Indications for repair and replacement are the same Symptomatic Patients with normal EF (>50%) AVR for NYHA Class III or IV AVR indicated for Canadian Class angina II – IV Symptomatic Patients with LV dysfunction AVR indicated for NYHA class II-IV and EF 25-50% Class IV have worse post op survival NYHA IV and EF < 25% difficult management scenario Some get meaningful LV recovery post op Many have developed irreversible damage

Indications for Surgery Asymptomatic patients Controversial topic Generally agreed Indicated in patients with LV dysfunction on 2 consecutive measurements 1 month apart or Two modalities Indicated for severe LV dilatation EDD > 75 mm or ESD > 55 mm Aortic Root Root > 5 cm in diameter and ANY degree of AR

Serial Follow Up Goal is to detect changes in hemodynamic parameters prior to symptoms Asymptomatic patients with mild AR, little or no LV dilatation, normal EF Q1 year exams No need for annual TTE Asymptomatic patients with normal EF but severe AR and LV dilation ( > 60 mm) Q 6 month exam and echo Immediate TTE in any patient with onset of symptoms Serial exercise testing, radionuclelide v-grams or MIR not indicated

What’s New in AI

Average age 35 (+/- 16 years) Main Outcomes: 642 consecutive bicuspid AoV patient presenting to Canadian Congenital Heart Clinic Followed for 9 years Average age 35 (+/- 16 years) Main Outcomes: All cause mortality Cardiac death Intervention on aortic valve or ascending aorta CHF requiring hospitalization JAMA 9/17/08 200(11): 1317-1325

Results 161 had primary cardiac events (1 or more) 17 deaths 142 interventions on aorta or AoV 11 Aortic dissections or aneurysms 16 CHF exacerbations requiring hospitalization Independent predictors of primary cardiac events Age > 30 (Hazard ratio with CI: 3.01, 2.15-4.19) Moderate to severe AS (5.67, 4.16-7.8) Moderate to severe AR (2.68, 1.93-3.76) 10 year survival not significantly different from population estimates

References 2008 Focus Update Incorporated into 2006 ACC/AHA guidelines for Management of Patients with Valvular disease. JACC. 2008:52 e1-e142. Braunwald et all. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine 8th edition. Feigenbaum et al. Echocardiography. p288-302 Oh et al. Basics in Echocardiography Topol et al Manual of Cardiovascular Medicine. p 192-202.