Aortic Stenosis

Echo Clinical Conference

March 10, 2010

Anne B. Riley

Outline

• Epidemiology

• Etiology

• Disease Course

• Imaging evaluation

• Management

• New Technologies

Epidemiology

• Common disease: In a population-based echocardiographic study, 2% of persons 65 years of age or older had frank calcific AS, 29% exhibited age-related aortic valve sclerosis without stenosis

• Bicuspid valves present in 1-2% of population

• Calcific valve disease, even in the absence of valve obstruction, is associated with a 50% increased risk of CV death and MI

Braunwald’s Heart Disease.

Etiology

A. Normal Valve

B. Congenital Bicuspid valve

C. Rheumatic aortic stenosis

D. Calcific degenerative AS

Calcific Aortic Stenosis

Lipocalcific changes on aortic side of cusp

Sparing of commissures

Mechanical stress: highest at aortic side in the flexion area, near attachment to aortic root

Calcific Aortic Stenosis: PathologyCells, lipid and matrix in subendothelial location, elastic lamina displaced

Greater accumulation of cells, lipid and matrix in subendothelial location, elastic lamina fragmented

Freeman, et al. Spectrum of Calcific Aortic Valve Disease: Pathogenesis, Disease Progression, and Treatment Strategies. Circulation 2005.

Calcific AS: Pathogenesis

•Lipid accumulation

•Inflammation

•Calcification

Freeman, et al. Spectrum of Calcific Aortic Valve Disease: Pathogenesis, Disease Progression, and Treatment Strategies. Circulation 2005.

Bicuspid valvesExist in 1-2% of the populuation

More prevalent in men (70-80% of cases)

Subset of bicuspids have autosomal dominant inheritance with incomplete penetrance

Have associated dilatation of the ascending aorta (unrelated to degree of AS or AR), related to abnormalities of the media

Histopathology of calcific stenosis of a bicupsid valve is the same as that of a trileaflet valve

Increased turbulent flow and leaflet stress is felt to accelerate the changes-> earlier age of presentation (about 20 years earlier)

Roberts WC et al. Frequency by Decades of Unicuspid, Bicuspid, and Tricuspid Aortic Valves in Adults Having Isolated Aortic Valve Replacement for Aortic Stenosis, With or Without Associated Aortic Regurgitation. Circulation 2005.

Men No (%)

Unicuspid34 (6)

Bicuspid309 (53)

Tricuspid234 (40)

Uncertain7 (1)

Subtotal584 (100)

Women

Unicuspid12 (3)

Bicuspid149 (43)

Tricuspid183 (53)

Uncertain4 (1)

Subtotal348 (100)

Time period: January 1993 through June 2004, Baylor University

Procedure: AVR for isolated aortic stenosis

Exclusions: Mitral valve replacement or mitral stenosis, previous aortic valvoplasty

RESULTS:

Age <50 (7% of patients) 2/3 bicuspid, 1/3 unicuspid

Age 50-70 (40% of patients) 2/3 bicuspid, 1/3 tricuspid

Age >70 (53% of patients) 2/5 bicuspid, 3/5 tricuspid

Bicuspid Valves: Very Common reason for AVR

Rheumatic Heart Disease

• Fusion of commissures between the leaflets and leaflet vascularization-> leads to retraction and stiffening of free borders of the cusps

• Small round or triangular opening

• Calcific nodules develop on both surfaces

• Often have AI and AS• Usually involves the mitral

valve as well• Valve often regurgitant and

stenotic

Aortic Stenosis: Disease Course

Onset of symptoms to time of death

Heart failure: 2 years

Syncope: 3 years

Angina: 5 years

Hemodynamic progression

• Valve area 0.12 cm2/yr

• Aortic jet velocity 0.32 m/sec/yr

• Mean gradient increase 7 mm Hg/yr

Predicting Events

Rosenhek, R. et al. The Natural History of Very Severe Aortic Stenosis. Circulation 2010;121:151-156

Evaluation

• Echocardiography–M mode

– 2-D imaging

– Doppler

• Cardiac Catheterization

Echocardiography: M mode

Dense persistent echoes

Obscures normal leaflet motion

Two Dimensional Echocardiography

• Look for…– Extent of calcification of the leaflets and the aortic

root (including the aortic ring)

– Degree and pattern of leaflet motion• Doming pattern, asymmetric closure (? Bicuspid valve)

– Post-stenotic dilatation of the aortic root

– LVH

Doppler Echocardiography: Velocity

• Continuous wave doppler from multiple sites to sample flow across the valve

• To get highest velocity: need angle of interrogation to be as parallel with flow as possible

• Angles greater than 30 degrees result in major underestimation

From Velocity to Pressure:Bernoulli Equation

ΔP = ½ p (v22- v1

2) + p (dv/dt)dx + R(v)

ΔP Pressure gradient across valve (mm Hg)

p Mass density of blood (1.06 x 103 kg/m3)

v2 Velocity in stenotic jet

v1 Velocity proximal to stenosis

(dv/dt)dx Time-varying velocity at each distance along flowstream

R(v) Constant for viscous resistance

Modified Bernoulli

Simplified Bernoulli equation to obtain

peak instantaneous gradient

Peak pressure gradient= 4 x peak velocity²

Mean Pressure Gradient

ΔPmean = ΔPmax/1.45 + 2 mm Hg

Mean gradient is approximately 2/3 of the peak instantaneous gradient

Most often obtained by planimetry of the Doppler envelope

Doppler Echocardiography

Non-invasive assessment of aortic stenosis by Doppler Ultrasound. L Hatle et al. 1980; 43 284-292.

“In 57 of 63 patients with aortic stenosis, the aortic jet could be reached by the ultrasound beam and, in 37 of these, peak pressure drop by ultrasound was compared with that obtained at catheterization. In patients less than 50 years of age the aortic jet was easy to find, the measurement was reproducible, and underestimation of the pressure drop obtained at catheterization was within 25 per cent in 17 of 18 patients. In patients over 50 years Doppler signals from the aortic jet were more difficult to obtain, and pressure drop was significantly underestimated in one-third, but time of maximum velocity in systole could indicate whether moderate or severe aortic stenosis was present. “

Velocity and AVA

Vmax (m/s) Severity

>4 Severe

3-4 Moderate

1.6-3 Mild

<1.5 Normal

2006 AHA/ACC Guidelines

AVA: Continuity Equation

SV=Cross Sectional Area * TVIAVA= CSAot * TVI ot/TVI av

CSA = r²Simplified continuity equation: AVA= CSA ot * Vot/Vav

Stroke volume proximal to aortic valve must equal the stroke volume through the stenotic orifice

Bernoulli alone vs. Continuity Equation

• Increasing stroke volume increases the gradient– Coexisting AR

– Hyperdynamic LV function

• Decreasing stroke volume decreases the gradient even in presence of severe stenosis– Severe LV dysfunction

– Coexisting MR

• Continuity equation should not be affected

Case Example

Cardiac Catheterization

Otto. Textbook of Clinical Echocardiography.

Measures peak to peak gradients vs. Dopplers instantaneous gradients

Peak to peak gradients never actually exist

Mean gradients correlate better between cath and echo

Gorlin Equation

AVA (cm²) = CO ÷ [44.3 x SEP x HR x ΔP]

SV = stroke volume (mL per beat)

SEP = systolic ejection period (sec per beat)

ΔP = mean systolic pressure gradient between the left ventricle and aorta (mmHg)

Echo challenges

The Aortic Jet• Search for the highest frequency signal- assumed

to present the nearest-parallel angle between the ultrasound in the direction of the jet

• Intercept angles within 15 degrees of parallel result in error of velocity of <5%

• Pitfalls: Inability to align the interrogation angle parallel to flow, mistakenly identify the jet (MR, TR, VSD, PA stenosis, Subaortic stenosis)

• Variability in velocity in irregular heart rhythms (afib, PVCs)

Echo Challenges (cont)

Outflow tract diameter• Measured in mid-systole, just proximal to and

parallel to the plane of the stenotic AV from the inner edge of the septal endocardial echo to the leading edge of the base of the anterior mitral leaflet

• Parasternal long axis view• This measurement shows the greatest intraoberver

and interobserver variability• Small errors in measurement lead to larger errors

in CSA

Echo Challenges (cont)

Outflow tract velocity• Measured using pulsed doppler echo

• Outflow tract diameter and velocity signals need to be recorded at the same anatomic site

• Measure both immediately adjacent to the valve

Therapy: Medical

The Statin Story

• SALTIRE Trial: Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (NEJM 2005)– 155 calcific AS patients (aortic jet velocity>2.5 m/s, calcification seen on TTE, mean AVA

1.03 cm2)– Randomized to atorvastatin 80 mg vs. placebo– Endpoints: change in aortic jet velocity and aortic valve calcium score– 25 month follow up: no difference in progression of aortic valve calcification or rate of

increase in aortic jet velocity

• RAAVE Study: Rosuvastatin Affecting Aortic Valve Endothelium (JACC 2007)– 121 patients with moderate to severe AS

– Non-random assignment to rosuvastatin 20 mg if LDL > 130 mg/dL or to no statin if LDL < 130 mg/dL

– Endpoints: aortic valve area, aortic jet velocity

– 73 weeks follow up, patients treated with rosuvastatin had significantly slower rates of deterioration in mean aortic valve area and aortic jet velocity

Statins, continued

SEAS Trial: Simvastatin and Ezetimibe in Aortic Stenosis (NEJM 2008

• 1873 adults with mild to moderate aortic stenosis• Randomly assigned to treatment with simvastatin 40 mg plus ezetimibe 10 mg or

placebo• At 52 months follow up: no difference in the primary endpoint: CV death, AVR,

non-fatal MI, hospitalized unstable angina, CHF as a result of progression of AS, CABG, PCI, and non-hemorrhagic stroke.

• No difference in the rate of aortic valve replacement (28 versus 30 percent) or in the rate of hemodynamic progression of aortic stenosis

• Fewer ischemic events in the treatment group, due to a lower rate of CABG at the time of aortic valve surgery

• Higher rate of cancers in simvastatin-ezetimibe group

Therapy: Surgical

ACC/AHA 2006 guidelines

Up and Comers: Medtronic CoreValve®

• Aortic porcine trileaflet valve on self-expanding frame

• Perform valvuloplasty first, then deploy valve

• Delivered through an 18 French catheter

• US clinical trial scheduled to start Summer 2010

Medtronic CoreValve

Edwards SAPIENTM Percutaneous Valve

Equine pericardial trileaflet valve is sewn within a stainless steel frameDeployed via transfemoral or transapical approachBalloon inflation used to deploy the valvePARTNER trial underway