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Aortic Stenosis: Epidemiology

and Natural History

Jonathan J. Passeri, M.D.

Co-Director, Heart Valve Program

Director, Interventional Echocardiography

Echo Florida 2013

Disclosures

• Edwards LifeSciences

Alexander Fleming (1881-1955)

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The Changing Face of Valve Disease

• Shift from rheumatic to “degenerative” etiologies

• Moderate to severe valve disease occurs in*:

1.9% people 55 to 64 years-old

8.5% people 65 to 74 years-old

13.2% people 75 years and older

• Prevalence of valve disease increase as the elderly

population continues to grow

• Elderly have an inherent increase in risks associated with

surgery and complexity of medical management

*Nkomo et al. Lancet. 2006; 368: 1005-11.

Prevalence of Valve Disease by Age

Nkomo et al. Lancet. 2006; 368: 1005-11.

Distribution of Native Heart Valve Disease

Iung et al. Nat. Rev. Cardiol. 2011;8: 162-172

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Eveborn G W et al. Heart 2012 [epub ahead of print]

Prevalence of Aortic Stenosis in Norway

Aortic Valve Stenosis: Etiology

• Calcific aortic stenosis

– With any underlying aortic valve morphology

• Congenital aortic stenosis

– Typically bicuspid or unicuspid aortic valve

• Rheumatic heart disease

• Rare causes (e.g., radiation-induced)

Valve Morphology in Patients Undergoing

Surgery for Aortic Stenosis by Age

Roberts et al. Circulation 2005;111:920-925.

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Calcific Aortic Stenosis: Risk Factors

• Male gender

• Hypertension

• Elevated LDL cholesterol

• Cigarette smoking

• Underlying bicuspid or unicuspid aortic valve

• End-stage renal disease

• Paget’s disease

Calcific Aortic Stenosis: Genetics

• NOTCH1 (signaling and transcription regulator)

– Associated with aggressive calcific aortic stenosis,

bicuspid aortic valve, and thoracic aortic aneurysm

– Promote calcification by decreasing RunX2 activity,

which regulates osteoblasts

• vitamin D receptor gene

• apolipoprotein E2 allele

Calcific Aortic Stenosis: Mechanisms

• Calcific aortic stenosis is a biologically

active process

• Lipid accumulation

– LDL accumulation and oxidation

• Inflammation

– T-cells, monocytes, inflammatory

mediators, cytokines

• Calcification

– Osteoblast expression, bone formation

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Mohty, D. et al. Arterioscler Thromb Vasc Biol 2008;28:187-193

Oxidized LDL in Aortic Vale Remodeling

Calcific Aortic Stenosis: Mechanisms

Rajamannan et al. Nature Clinic Prac CV Med 2007;4:254

PET-CT Imaging of Aortic Valve Inflammation

and Calcification

Marincheva-Savcheva G, et al. JACC 2011;57:2507-15.

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PET-CT Imaging of Aortic Valve Inflammation

and Calcification

Marincheva-Savcheva G, et al. JACC 2011;57:2507-15.

Otto C M et al. Circulation 1997;95:2262-2270

Hemodynamic Progression of Aortic Stenosis

Aortic jet velocity

0.32 ±0.34 m/sec per year

Mean gradient

7 ± 7 mmHg per year

Aortic valve area

0.12 ± 0.19 sqcm per year

Eveborn G W et al. Heart 2012 [epub ahead of print]

Hemodynamic Progression of Aortic Stenosis

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Pathophysiology Aortic Stenosis

Aortic Stenosis

LV outflow obstruction

LVSP LVET LVDP Aortic P

LV Mass

LV dysfunction Myocardial O2

consumption Diastolic time

Myocardial O2

supply Myocardial

ischemia LV failure

Natural History of Aortic Stenosis

Ross J Jr, Braunwald E. Circulation 1968; 38: 61–67

Survival with Symptomatic Aortic Stenosis

Schwarz F et al. Circulation 1982;66: 1105-10.

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All Cause Mortality (ITT)

All

Ca

use

Mo

rta

lity (%

)

Months

Standard Rx

TAVR

∆ at 2 yr = 24.7% NNT = 4.0 pts

68.0%

43.3%

∆ at 1 yr = 20.0% NNT = 5.0 pts

50.7%

30.7%

Numbers at Risk

TAVR 179 138 124 110 83 47 14

Standard Rx 179 121 85 62 42 19 5

HR [95% CI] = 0.57 [0.44, 0.75]

p (log rank) < 0.0001

Event-free survival without valve replacement for 123 subjects with initially asymptomatic aortic stenosis

Otto C M et al. Circulation 1997;95:2262-2270

Baseline Echo Variables

Maximum aortic jet velocity, m/s

3.6±0.6

Mean aortic gradient, mm Hg 29±11

Aortic valve area, cm

1.3±0.5

Cox regression analysis showing event-free survival in groups defined by aortic jet velocity at entry

Otto C M et al. Circulation 1997;95:2262-2270

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Aortic Jet Velocity and Aortic Valve Area in subjects who developed symptoms requiring aortic valve replacement or died (AVR/Died) compared with those who remained asymptomatic for the baseline and final studies.

Otto C M et al. Circulation 1997;95:2262-2270

Survival Free of Symptoms Censored at Aortic Valve Surgery

Pellikka P A et al. Circulation 2005;111:3290-3295

Baseline Echo Variables

Maximum aortic jet velocity, m/s

4.4±0.4

Mean aortic gradient, mm Hg 46±8

Aortic valve area, cm

0.9±0.2

Survival of patients with AS compared with that of Minnesota white population (referent group) matched for age and sex.

Pellikka P A et al. Circulation 2005;111:3290-3295

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Outcomes of Patients with Initially

Asymptomatic Aortic Stenosis: Causes of Death

Pellikka P A et al. Circulation 2005;111:3290-3295

Sudden Death in Non-Surgical Patients

• 11 patients with sudden death not preceded by aortic

valve replacement or known symptoms (4.1% overall or ~1%/year)

• No medical follow-up for >1 year in 5 of these patients

• Ages ranged from 55 to 92 years

• Aortic valve velocities ranging from 4.0 to 5.8 m/sec

• Aortic valve areas ranging from 0.53 to 1.28 sqcm

Pellikka P A et al. Circulation 2005;111:3290-3295

Kaplan–Meier Analysis of Overall Survival Among 126 Patients with Asymptomatic Severe Aortic Stenosis, as

Compared with Age- and Sex-Matched Persons Controls

Rosenhek R et al. N Engl J Med 2000;343:611-617.

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Mean Rate of Progression of Aortic-Jet Velocity among 41 Patients Who Had Cardiac Events and 29 Who Did Not.

Rosenhek R et al. N Engl J Med 2000;343:611-617.

Event-free Survival among Patients with Mild Aortic-Valve Calcification Compared with Moderate or Severe Calcification

Rosenhek R et al. N Engl J Med 2000;343:611-617.

Kaplan–Meier event-free survival rate for patients with asymptomatic very severe aortic stenosis stratified according

to peak aortic jet velocity and aortic valve area

Rosenhek R et al. Circulation 2010;121:151-156

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Summary

• Aortic stenosis is the most common aquired valve disease

in developed nations

• Aortic stenosis is a hemodynamically progressive disease

• Uncorrected symptomatic severe aortic stenosis is

associated with a dismal prognosis

• Aortic valve replacement stabilizes long term prognosis

and improves symptoms

Summary: Asymptomatic Aortic Stenosis

• Patients with asymptomatic aortic stenosis have a

generally favorable prognosis with “watchful waiting”

• Low incidence of sudden cardiac death

• Variable rates of progression

• Early valve replacement for asymptomatic pateints

remains controversial

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