... College of Cardiology/American Heart Association Tas

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Aortic Stenosis When the Window of Opportunity
is Closing

• CPT Bradley K. Harrison, MD
• 2009 USAFP Annual Meeting
• 1545-1630, 04 April 2009

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Objectives

• Review the pathophysiology and classic
  presentations of aortic stenosis
• Understand when to refer for diagnostic testing
  and/or consultation
• Comprehend the definitive management of aortic
  stenosis
• Review literature in reference to medical
  management

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Case Presentation

• 66 y/o male presents for a physical.
• Wife mentions decreased amount of physical
  activity over 2 yearsattributed to getting
  older.
• Smoker (40 pack/year), sedentary
• BP 139/85, HR 88, RR 13, T 99.0
• 2/6 late-peaking systolic ejection murmur, heard
  at the right upper sternal border radiating to
  the neck

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Aortic Stenosis (AS)

• Active, inflammatory process associated with
  cardiovascular risk factors
• Age, sex, cholesterol, blood pressure, diabetes,
  metabolic syndrome, smoking
• Increased risk of death from cardiovascular
  causes1 (even in absence of CAD)
• Histopathologic changes in valve leaflets similar
  to other atherosclerotic diseases2

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Aortic Stenosis (cont.)

• Key initiating factor likely mechanical stress
• The most important cardiac valve disease in
  developed countries
• Affecting 3-5 of persons gt65 years old
• 1-2 with bicuspid aortic valve
• AS develops with age (Senile aortic stenosis)

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Compensatory Mechanisms

• Adaptive and maladaptive
• Progressive worsening of left ventricular outflow
  obstruction leads to hypertrophy
• Compensatory hypertrophy required to maintain
  wall stress (afterload)
• Augmented preload with increased atrial kick
  preserve LV systolic function

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Heart Failure

• Changes in LV function may no longer be adequate
  to overcome the outflow obstruction
• Hypertrophic remodeling leads to diastolic
  dysfunction
• Afterload excess results in decreased ejection
  fraction systolic dysfunction
• 50 presentation
• 50 die in 2 years

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Angina

• Progressive LV hypertrophy from aortic stenosis
  leads to increased myocardial oxygen needs3
• Hypertrophy may compress the coronary arteries
• Reduced diastolic filling may result in classic
  angina, even in the absence of coronary artery
  disease4
• 35 presentation
• 50 die in 5 years

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Syncope

• Cardiac output no longer increases with exercise5
• A drop in systemic vascular resistance that
  normally occurs with exertion may lead to
  hypotension and syncope6
• 15 presentation
• 50 die in 3 years

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Signs

• Harsh, crescendo-decrescendo systolic murmur that
  is loudest over the 2nd right intercostal space
  and radiates to the carotid arteries
• Increased incidence of atherosclerosis and
  hypertension may mask the classic carotid
  findings
• It is difficult to rule out AS with physical
  examination findings alone
• Physical examination does not correlate with
  severity

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Murmur

• 2/6 systolic murmur
• Older patients with vague complaints and
  asymptomatic patients undergoing preoperative
  medical assessment
• 3/6 systolic murmur
• ACC/AHA guidelines recommend echocardiography in
  asymptomatic patients with a grade 3/6 or louder
  systolic murmur7

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Symptoms

• Classic symptoms of AS
• Dyspnea and other symptoms of heart failure
• Angina
• Syncope
• Indicate hemodynamically significant AS and is a
  critical point for management decisions
• Non-classic symptoms of AS
• May present as a decrease in exertional tolerance
  without recognizing the classic symptoms

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Case 66 y/o male

• Decreased activity, getting older
• Remains asymptomatic
• Refer for echocardography
• Ejection fraction 50
• Peak transaortic flow velocity 4.0 m/s
• Aortic valve area 1.0 cm2

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Diagnostic Testing

• Doppler echocardiography is the recommended
  initial test for patients with classic symptoms
  of AS7
• Estimates aortic jet velocity, mean gradiant, and
  aortic valve area
• Echocardiography is well validated and compares
  with cardiac catheterization
• Provides information regarding LV function and
  coexisting abnormalities of other valves

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Classifications of Severity7
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Severity

• Normal
• Jet velocity lt2.5 m/s
• Valve area 3-4 cm2

• Mild-to-Moderate
• Jet velocity 3-4 m/s
• Valve area 1-1.5 cm2

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Treatment

• Aortic valve replacement is the only effective
  treatment for hemodynamically significant AS
• No prospective randomized trials comparing
  medical versus surgical treatment
• The effect of aortic valve replacement on
  survival, Circulation 1982

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Survival among Patients with Severe Symptomatic
Aortic Stenosis Who Underwent Valve Replacement
and Similar Patients Who Declined to Undergo
Surgery10
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Treatment-Symptomatic

• Mortality increases dramatically
• Overall survival of 2-3 years without surgical
  treatment
• 10-year survival rate after aortic valve
  replacement almost identical to that in age- and
  sex-matched persons11
• Well-accepted recommendation that aortic valve
  replacement should be performed promptly in
  symptomatic patients7

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Treatment-Symptomatic (cont.)

• Surgery has an average perioperative mortality
  rate of 48
• Risk of prosthetic valve failure of 1 per year9
• Mechanical valve
• Durability versus Anticoagulation (INR 2-3)
• Biological valve
• Xenograft
• Allograft/homograft
• Ross procedure

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Treatment-Asymptomatic

• Aortic valve replacement recommended for
  asymptomatic patients with severe AS accompanied
  by LV dysfunction (EFlt50)12
• Watchful waiting recommended in most asymptomatic
  patients, even severe AS
• Survival in patients with watchful waiting is
  comparable
• Surgical risk (4) outweighs the approximately
  1-2 annual risk of sudden death in asymptomatic
  patients

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Asymptomatic?

• Important to distinguish patients who may have a
  decreased routine activity level
• ACC/AHA guidelines recommend exercise stress
  testing be performed under the direct observation
  of an experienced cardiologist7
• Safe in mild to moderate AS
• Aortic valve replacement should be considered13
• Symptoms occur at lt80 of predicted maximum heart
  rate

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Asymptomatic-Other Considerations14

• High risk of developing symptoms
• Very severe AS (lt0.6 cm or 5 m/s)
• More rapid increase in aortic jet velocity over
  time (0.3 m/s or more per year)
• Severe valve calcification
• Patients who do not live near a medical care
  facility
• Predicted operative mortality rate 1 (70 years
  or younger without comorbidities)

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Monitoring

• Watchful waiting is appropriate in most
  asymptomatic patients
• Serial echocardiography (ACC/AHA guidelines7)
• Annually Severe AS
• 1-2 years Moderate AS
• 3-5 years Mild AS
• Symptoms are best indicator of hemodynamic
  significance
• Patients should be educated about their
  importance and promptly reported to their
  physician

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Referral

• Cardiology referral is recommended
• All patients with symptomatic AS
• AS accompanied by LV dysfunction
• Asymptomatic patients with very severe or rapidly
  progressive calcification
• Cardiology referral should be considered in
  patients with subtle or atypical presentations
• Decreased exercise tolerance

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Medical Management

• No medical treatments have been proven to delay
  the progression of aortic valve disease or to
  improve survival
• Many patients have concurrent cardiac conditions
• Hypertension (40)
• Atrial fibrillation (5)
• Coronary artery disease

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Coronary Risk Reduction16

• Smoking cessation
• Aspirin prophylaxis in adults with 10-year risk
  of cardiovascular disease 6
• Participation in regular exercise
• Mild AS should not be restricted from physical
  activity
• Asymptomatic with moderate to severe AS should
  avoid competitive or vigorous activities, other
  exercise is safe7,17

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Statins?

• Can statins slow the progression of AS?
• Initial observational studies (retrospective or
  case-control) suggested a significantly lower
  rate of progression18
• Randomized prospective study (SALTIRE) showed no
  statistical difference19
• Intensive Lipid Lowering with Simvastatin and
  Ezetimibe in Aortic Stenosis (SEAS)20

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SEAS20

• Randomized, double-blind, placebo controlled,
  N1873
• 1 composite of major cardiovascular events
• 2 aortic-valve stenosis, ischemic cardiovascular
  events
• 45-85y, asymptomatic, mild-to-moderate (2.5-4
  m/s)
• Excluded for CAD or equivalent

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SEAS20

• Progression of AS
• Placebo 3.71, increase of 0.62
• S E 3.69, increase of 0.61
• Aggressive lipid lowering does not effect
  hemodynamic progression

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SEAS20
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Not Atherosclerosis?

• Calcific aortic stenosis is not atherosclerosis
• Tissue calcification more severe
• Mechanism is increased leaflet stiffness
• Not plaque rupture
• Severity of CAD and valve disease not related

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Case 66 y/o male

• While in primary care office
• BP 139/85
• Start ACE inhibitor
• Start Aspirin
• Smoker
• Encourage smoking cessation
• Statin?
• Framingham Risk (Chol 200, HDL 40) 19
• Stress test?

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Antibiotic Prophylaxis

• Recommended for patients who have undergone
  aortic valve replacement
• No longer recommended for patients with acquired
  valve diseases21

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Case 66 y/o male

• Experienced cardiologist performed exercise
  stress testing
• Earlier-than-predicted fatigue/dyspnea (gt80
  predicted maximum heart rate)
• Referred for aortic valve replacement

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Challenges

• Valve diseases progress over decades
• Clinical trials only a few years
• End points difficult to assess
• Subjective
• Therapies affect other cardiovascular outcomes
• Ideal endpoint is valve tissue changes

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Future Implications

• Mutations in NOTCH1 gene
• Phenotypic transformation to end stage severe
  valve calcification?
• Cellular and molecular pathways must mediate
  disease progression

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Conclusion

• 3 classic symptoms heart failure, syncope,
  angina
• Indications for referral and/or consultation
• Definitive management of aortic stenosis

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References

• Cosmi JE, Kort S, Tunick PA, et al. The risk of
  the development of Aortic Stenosis in patient
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• Otto CM, Kuusisto J, Reichenback DD, et al.
  Characterization of the early lesion of
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  histological and immunohistochemical studies.
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References (cont.)

• Vaquette B, Corbineau H, Laurent M, et al. Valve
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• Das P, Rimingtom H, Chambers J. Exercise testing
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• Antonini-Canterin F, Huang G, Cervesato E, et al.
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• Rosenhek R, Rader F, Loho N, et al. Statins but
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