Aortic Stenosis

Overview

Definition

Aortic stenosis (AS) is the narrowing of the aortic valve aperture.

• Causes varying degrees of blood flow obstruction between the left ventricle (LV) and the aorta
• Consequently, produces left ventricular pressure overload
• If left untreated, results in left ventricular dysfunction and heart failure

Epidemiology

• Most common valvular heart disease
• Rheumatic heart disease: most common cause of AS worldwide
• In developed countries, most common causes are:
  • Calcific aortic valve disease
  • Congenital bicuspid aortic valve (affects 1%–2% of the population)
• Prevalence increases with age.
• Men > women

Etiology

• Senile calcific AS:
  • Also known as degenerative AS
  • Dystrophic calcification of the aortic valve
  • Most common cause in adults > 70 years in developed countries
  • Risk factors:
    • Hypertension
    • Diabetes
    • Smoking
    • End-stage kidney disease
    • Disturbances in mineral metabolism
• Rheumatic heart disease:
  • Most common cause in the developing world
  • Often associated with mitral stenosis
  • Presents in the 3rd to 5th decade of life
• Congenital bicuspid aortic valve:
  • Most common congenital heart valve defect
  • More predominant in men
  • Most common cause in adults < 70 years in developed countries
  • Predisposes to early calcification and subsequent stenosis
  • Can present with other cardiac abnormalities (e.g., coarctation of the aorta)
• Radiation 
• Unicuspid valve

Pathophysiology

Mechanisms of valvular damage

• Senile calcific AS:
  • Hemodynamic stress results in progressive valve thickening and damage, which predispose to calcification.
  • Risk factors and calcification of the leaflet bodies → aortic valve stenosis and obstruction
  • Gross morphologic hallmark: calcified masses on the outflow cusp surfaces (which limit full opening)
• Rheumatic heart disease:
  • Inflammation of the valve causes necrosis and injury.
  • Postinflammatory fibrosis of the valve leaflets leads to commissural fusion → calcification and stenosis
• Bicuspid valve:
  • 2 cusps, which are often of unequal size
  • Malformed valves contribute to turbulence of blood flow, which eventually leads to calcific degeneration.

Mechanism of heart failure

• Normal aortic valve opening: cross-sectional area approximately 3–4 cm²
• Change in gradient noted when the orifice area is < ½ of normal
• Gradual progression of stenosis allows adaptive changes.
• Obstruction of transvalvular blood flow → increased left ventricular pressure to maintain cardiac output (CO) → Left ventricular hypertrophy (LVH) occurs, in order to overcome the increased afterload.
• Hypertrophic left ventricle leads to decreased compliance → ↑ left ventricular end diastolic pressure (LVEDP)
• LVH, ↑ LVEDP, and continuous valvular obstruction increase LV oxygen demand → ↑ ischemia and myocardial fibrosis
• Changes result in decreased contractility and CO → heart failure. 
• Other complications:
  • Arrhythmias (e.g., atrial fibrillation)
  • Pulmonary hypertension

Clinical Presentation

Symptoms

• Asymptomatic for years
• Exertional dyspnea and fatigue (initial symptoms)
• Classic triad (late in the course of the disease):
  1. Exertional angina or chest pain (from ischemia)
  2. Syncope:
     • On exertion (exercise-induced vasodilation, under the setting of obstruction with fixed CO, leads to hypotension)
     • At rest (from associated arrhythmias)
  3. Left heart failure: 
     • Orthopnea
     • Paroxysmal nocturnal dyspnea
     • Pulmonary edema

Signs

• Unremarkable early in the course
• Pulse and blood pressure:
  • Narrow pulse pressure with severe AS
  • Pulsus parvus et tardus (low-amplitude (parvus), delayed (tardus) peak in the carotid arterial pulse)
• Cardiac inspection and auscultation:
  • Hyperdynamic left ventricle leading to heave with a double or laterally displaced apical impulse
  • Heart sounds may have:
    • Single soft S2 (aortic valve closure diminished or absent; synchronous A2P2)
    • Paradoxical splitting of S2 (pulmonic valve closure, P2, is followed by aortic valve closure, A2)
    • S4: reflects a strong atrial contraction against LVH
    • Ejection click in children and young adults (congenital AS)
  • Murmur:
    • Systolic low-pitched crescendo-decrescendo murmur heard best in the right upper sternal border and radiating to the carotids
    • Gallavardin effect: occasional downward radiation of AS murmur to the cardiac apex (may be confused with mitral regurgitation murmur)
  • Provocative maneuvers: 
    • Decreased murmur: Valsalva maneuver, standing (decreased intracardiac volume) or sustained handgrip (increased afterload)
    • Increased murmur: leg raising, squatting, and after a premature ventricular beat (increased preload)

Audio:

This audio clip is an example of severe aortic stenosis. This is a harsh, crescendo-decrescendo murmur occurring between S1 and S2. Due to the severity of the aortic stenosis, the S2 heart sound is inaudible.

Diagnosis

Transthoracic and Doppler echocardiography

• Diagnostic imaging of choice
• Details provided:
  • Structure and function of the valve
  • Valvular findings: decreased aortic valve opening, valvular calcification, bicuspid valve
  • Other findings: LV hypertrophy, aortic wall abnormalities, systolic and diastolic function 
  • Systolic dysfunction or LV ejection fraction (EF) < 50%: important in determining AS management
• Parameters of stenosis (from Doppler echocardiography):
  • Transvalvular gradient (in mm Hg)
  • Flow velocity with decreased valvular area 
  • Aortic valve area (in cm²):
    • Severe AS: valve area < 1 cm²
    • Moderate AS: valve area 1–1.5 cm²
    • Mild AS: valve area 1.5–2 cm²
• Additional information provided:
  • Other coexisting valvular disease
  • Hypertrophic cardiomyopathy
  • Ascending aortic aneurysm associated with bicuspid valves
  • Coarctation of aorta

Other tests

• ECG:
  • Results vary and depend on associated structural abnormalities and arrhythmias.
  • May demonstrate left ventricular hypertrophy, left atrial enlargement, and left axis deviation
• Chest X-ray:
  • On lateral views, aortic valve calcification can be seen.
  • Pulmonary congestion from LV failure can be visualized.
• Exercise stress testing or exercise tolerance test (ETT):
  • Contraindicated in symptomatic severe AS 
  • Performed in select cases (e.g., unclear level of physical activity, low-gradient AS)
• Cardiac catheterization and coronary arteriography:
  • Provides information on the pressure gradient between the left ventricle and aorta, and overall hemodynamic assessment when other tests are inconclusive
  • Evaluation of coronary artery disease: an important consideration prior to valvular surgery
• Multidetector computed tomography (MDCT):
  • Helps in evaluation of low-gradient AS
  • Quantification of aortic valve calcification correlates with severity of stenosis.

Management

General principles

• Aortic valve replacement (AVR): mainstay of treatment of symptomatic AS
• To determine candidates for AVR, the following details are obtained:
  • Symptom status
  • Severity of AS: 
    • Severe AS: aortic jet velocity ≥ 4 m/sec, mean transvalvular gradient of ≥ 40 mm Hg
    • Severe AS: typically with < 1 cm² area (but is not required)
  • LV systolic function: LVEF < 50% = systolic dysfunction
• Indications for AVR:
  • Asymptomatic severe AS:
    • Abnormal ETT (decreased exercise tolerance)
    • With LVEF < 50%
    • Undergoing other cardiac surgery
    • With low surgical risk
    • Rapid disease progression and low surgical risk
  • Symptomatic severe AS
• For less severe or moderate AS, performing AVR depends on multiple factors:
  • Symptoms
  • Aortic valve area < 1 cm²
  • LVEF 
  • ETT, dobutamine stress echocardiography
  • If undergoing other cardiac surgery

Surgical management

• For patients with life expectancy > 1 year and if surgery is likely to improve quality of life
• Transcatheter aortic valve implantation (TAVI):
  • In patients with intermediate-high surgical risk
  • In patients with low surgical risk meeting feasibility for TAVI
• Surgical aortic valve replacement (SAVR):
  • In patients with low or intermediate risk and TAVI is not feasible
  • Presence of another indication for cardiac surgery
• Percutaneous aortic balloon valvuloplasty (PABV):
  • Not a substitute for valve replacement
  • Has high rate of re-stenosis
  • Consider as a bridge to TAVI or SAVR in severe symptomatic AS
  • Palliation for patients who are not good candidates for AVR
  • Has a role for young and adolescent patients

General recommendations for non-surgical management

• Periodic monitoring: 
  • TTE every 6–12 months in asymptomatic severe AS
  • TTE every 1–2 years for moderate AS and every 3–5 years for mild AS 
• Activity:
  • Avoid strenuous physical activity and competitive sports in severe AS.
  • Avoid dehydration (to protect against CO reduction).
• Medications:
  • Endocarditis prophylaxis: with history of infective endocarditis
  • General guidelines: Start with low dose and slowly titrate.
  • Angiotensin-converting enzyme (ACE) inhibitors: may improve LV fibrosis in addition to blood pressure control
  • Beta blockers:
    • Reduce contractility 
    • Continue with coexisting coronary artery disease or atrial fibrillation
    • For hypertension, consider a low dose but generally avoid with symptomatic AS and heart failure.
  • Diuretics: 
    • Excessive decrease in preload should be avoided.
    • Use with caution if the patient has symptomatic AS (because it reduces ventricular volume).

Prognosis

• If untreated with surgery, 50% of patients die within 3 years of symptom onset (angina, syncope, or heart failure). 
• Surgical mortality rate for valve replacement including the elderly is 2%–5%.

Differential Diagnosis

• Hypertrophic cardiomyopathy: a cardiac condition characterized by a thickened left ventricular wall leading to left ventricular outflow obstruction and diastolic dysfunction. Patients present with exertional dyspnea, syncope, and, in extreme cases, sudden cardiac death. The systolic murmur increases with the Valsalva maneuver and standing. Diagnosis is by echocardiography. Management includes negative inotropic agents with surgical options to reduce the LV outflow obstruction. An implantable defibrillator is placed for those at risk for sudden death.
• Myocardial infarction: an acute blockage of the coronary arteries supplying the heart, which can predispose to structural valvular incompetence. This condition commonly presents with chest pain and is diagnosed with ECG and cardiac enzyme tests.
• Aortic regurgitation: characterized by the backflow of blood from the aorta to the left ventricle, commonly caused by rheumatic heart disease, and congenital and degenerative valvular disorders. Examination shows an early diastolic high-pitched decrescendo murmur, heard best in the left sternal border. Diagnosis is by echocardiography. The acute form is a medical emergency requiring immediate surgery.
• Congestive heart failure (CHF) with systolic dysfunction: a chronic, progressive condition characterized by left ventricular dysfunction from impaired myocyte contractility. This leads to subsequent volume overload. Risk factors include hypertension, coronary artery disease, and diabetes mellitus. Congestive heart failure can develop with or without valvular abnormalities.