> Table of Contents > Aortic Valvular Stenosis
Aortic Valvular Stenosis
Michael T. Tanoue, MD
Parag Goyal, MD
James M. Horowitz, MD, FACC
image BASICS
DESCRIPTION
Aortic stenosis (AS) is a narrowing of the aortic valve area causing obstruction to left ventricular (LV) outflow. The disease has a long asymptomatic latency period, but development of severe obstruction or onset of symptoms such as syncope, angina, and congestive heart failure (CHF) are associated with a high mortality rate without surgical intervention.
EPIDEMIOLOGY
  • Most common cause of LV outflow obstruction in both children and adults
  • Predominant age
    • <30 years: congenital
    • 30 to 65 years: congenital or rheumatic fever
    • >65 years: degenerative calcification of aortic valve
Prevalence
  • Affects 1.3% of population 65 to 74 years old, 2.4% 75 to 84 years old, 4% >84 years old (1)
  • Bicuspid aortic valve: 1-2% of population. Bicuspid aortic valve predisposes to development of AS at an earlier age (1).
ETIOLOGY AND PATHOPHYSIOLOGY
  • Progressive aortic leaflet thickening and calcification results in LV outflow obstruction. Obstruction causes increased afterload and over time, decreased cardiac output.
  • Increase in LV systolic pressure is required to preserve cardiac output; this leads to development of concentric left ventricular hypertrophy (LVH). The compensatory LVH preserves ejection fraction but adversely affects heart functioning.
    • LVH impairs coronary blood flow during diastole by compression of coronary arteries and reduced capillary ingrowth into hypertrophied muscle.
    • LVH results in diastolic dysfunction by reducing ventricular compliance.
  • Diastolic dysfunction necessitates stronger left atrial (LA) contraction to augment preload and maintain stroke volume. Loss of LA contraction by atrial fibrillation can induce acute deterioration.
  • Diastolic dysfunction may persist after relief of aortic stenosis due to the presence of interstitial fibrosis.
  • Angina: increased myocardial demand due to higher LV pressure. Myocardial supply is compromised due to LVH.
  • Syncope (exertional): can be multifactorial from inability to augment cardiac output due to the fixed obstruction to LV outflow; arrhythmias; or most commonly, abnormal baroreceptor response resulting in failure to appropriately augment blood pressure
  • Heart failure: Eventually, LVH cannot compensate for increasing afterload resulting in high LV pressure and volume, which are accompanied by an increase in LA and pulmonary pressures.
  • Degenerative calcific changes to aortic valve (2)
    • Mechanism involves mechanical stress to valve leaflets as well as atherosclerotic changes to the valve tissue. Bicuspid valves are at higher risk for mechanical stress.
    • Early lesions: subendothelial accumulation of oxidized LDL and macrophages and T lymphocytes (inflammatory response)
    • Disease progression: fibroblasts undergo transformation into osteoblasts. Protein production of osteopontin, osteocalcin, and bone morphogenic protein-2 (BMP-2), which modulates calcification of leaflets.
  • Congenital: unicuspid valve, bicuspid valve, tricuspid valve with fusion of commissures, hypoplastic annulus
  • Rheumatic fever: chronic scarring with fusion of commissures
RISK FACTORS
  • Congenital unicommissural valve or bicuspid valve (1)
    • Unicommissural valve: Most cases were detected during childhood.
    • Bicuspid valve: predisposes to the development of AS earlier in adulthood (4th to 5th decade) compared to tricuspid valve (6th to 8th decade)
  • Rheumatic fever (1)
    • Prevalence of chronic rheumatic valvular disease has declined significantly in the United States.
    • Most cases are associated with mitral valve disease.
  • Degenerative calcific changes
    • Most common cause of acquired AS in the United States
    • Risk factors are similar to that of coronary artery disease (CAD) and include the following: hypercholesterolemia, hypertension, smoking, male gender, age, and diabetes mellitus.
COMMONLY ASSOCIATED CONDITIONS
  • CAD (50% of patients)
  • Hypertension (40% of patients): results in “double-loaded” left ventricle (dual source of increased afterload as a result of obstruction from AS, and hypertension)
  • Aortic insufficiency (common in calcified bicuspid valves and rheumatic disease)
  • Mitral valve disease: 95% of patients with AS from rheumatic fever (RF) also have mitral valve disease
  • LV dysfunction and CHF
  • Acquired von Willebrand disease: Impaired platelet function and decreased vWF results in bleeding (ecchymosis and epistaxis) in 20% of AS patients. Severity of coagulopathy is directly related to severity of AS.
  • Gastrointestinal arteriovenous malformations (AVMs)
  • Cerebral or systemic embolic events due to calcium emboli
image DIAGNOSIS
PHYSICAL EXAM
  • Auscultation (3)
    • Harsh, systolic crescendo-decrescendo murmur is best heard at 2nd right sternal border and radiates into the carotid arteries. Peak of murmur correlates with severity of stenosis; later peaking murmur suggests greater severity.
    • High-pitched blowing diastolic murmur suggests associated aortic insufficiency.
    • Paradoxically split S2 or absent A2. Note: Normally split S2 reliably excludes severe AS.
    • S4 due to stiffening of the left ventricle
  • Other associated signs (3) include Pulsus parvus et tardus: decreased and delayed carotid upstroke. LV heave. Findings of CHF: pulmonary and/or lower extremity edema
DIFFERENTIAL DIAGNOSIS
  • Mitral regurgitation: high-frequency, pansystolic murmur, best heard at the apex, often radiates to the axilla
  • Hypertrophic obstructive cardiomyopathy: also systolic crescendo-decrescendo murmur but best heard at left sternal border and may radiate into axilla. Murmur intensity increases by changing from squatting to standing and/or by Valsalva maneuver.
  • Discrete fixed subaortic stenosis: 50-65% has associated cardiac deformity (patent ductus arteriosus [PDA], ventricular septal defect [VSD], aortic coarctation)
  • Aortic supravalvular stenosis: Williams syndrome, homozygous familial hypercholesterolemia
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Chest x-ray (CXR) (1)
    • May be normal in compensated, isolated valvular AS
    • Boot-shaped heart reflective of concentric hypertrophy
    • Poststenotic dilatation of ascending aorta and calcification of aortic valve (seen on lateral PA CXR)
  • ECG: often normal ECG (ECG is nondiagnostic), or may show LVH, LA enlargement, and nonspecific ST-and T-wave abnormalities
  • Echo indications
    • Initial workup
  • Doppler echocardiogram: primary test in the diagnosis and evaluation of AS
  • Assesses valve anatomy and severity of disease
  • Assesses LV wall thickness, size, and function, and pulmonary artery pressure
    • In known AS and changing signs/symptoms
    • In known AS and pregnancy due to hemodynamic changes of pregnancy
  • Echo findings
    • Aortic valve thickening, calcification
    • Decreased aortic valve excursion
    • Reduced aortic valve area
    • Transvalvular gradient across aortic valve
    • LVH and diastolic dysfunction
    • LV ejection fraction
    • Wall-motion abnormalities suggesting CAD
    • Evaluate for concomitant aortic insufficiency or mitral valve disease.
  • AS severity based on echo values (4)
    • Stage A (at risk): bicuspid aortic valve, sclerosis, or other congenital abnormality; mean pressure gradient: 0 mm Hg; jet vel. <2 m/s
    • P.71

    • Stage B (progressive): bicuspid or trileaflet valve
      • Mild: mean pressure gradient: <20 mmHg; jet vel. 2.0 to 2.9 m/s
      • Moderate: mean pressure gradient: 20 to 40 mm Hg; jet vel. 3.0 to 3.9 m/s
    • Stage C (asymptomatic severe AS):
      • C1 (without LV dysfunction): AVA ≤1.0 or AVAi ≤0.6 cm2/m2; mean pressure gradient: 40 to 60 mm Hg; jet vel. ≥4 to 5 m/s
      • C2 (with LV dysfunction): AVA ≤1.0 or AVAi ≤0.6 cm2/m2; mean pressure gradient: ≥40 mm Hg; jet vel. ≥4 m/s
    • Stage D (symptomatic severe AS):
      • D1 (high-gradient): AVA ≤1.0 cm2; mean pressure gradient: >40 mm Hg; jet vel. >4 m/s
      • D2 (low-flow/low-gradient with reduced EF <50%): AVA ≤1.0 cm2; mean pressure gradient: <40 mm Hg; jet vel. <4 m/s
      • D3 (low-gradient, normal EF ≥50% or paradoxical low-flow severe AS): AVA ≤1.0 cm2; AVAi ≤0.6 cm2/m2 and stroke volume index <35 mL/m2; mean pressure gradient: <40 mm Hg; jet vel. <4 m/s
Diagnostic Procedures/Other
  • Exercise stress testing
    • Asymptomatic patients with severe AS (5)[B]: helpful to uncover subtle symptoms or changes, abnormal BP (increase <20 mm Hg), and ECG changes (ST depressions). 1/3 of patients develop symptoms with exercise testing; STOP testing at this point.
    • Symptomatic patients (5)[B]: DO NOT perform exercise stress testing, as it may induce hypotension or ventricular tachycardia.
    • CHF patients (5)[B]: Dobutamine stress echocardiography is reasonable to evaluate patients with low-flow/low-gradient AS and LV dysfunction.
  • Cardiac catheterization
    • Perform prior to aortic valve replacement in patients with suspected CAD (5)[B]. Determines need for coronary artery bypass graft (CABG). If unambiguous diagnosis of AS, perform only coronary angiography.
    • Can also use if noninvasive testing is inconclusive or if there is discrepancy between severity of symptoms and findings on echo
    • Measures transvalvular flow and transvalvular pressure gradient, which facilitates calculation of effective valve area
    • Hemodynamic measurements with infusion of dobutamine can be useful for evaluation of patients with low-flow/low-gradient AS and LV dysfunction.
TEST INTERPRETATION
  • Aortic valve: nodular calcification on valve cusps (initially at bases), cusp rigidity, cusp thickening, and fibrosis
  • LVH, myocardial interstitial fibrosis
  • 50% incidence of concomitant CAD
image TREATMENT
MEDICATION
  • No effective medical therapy for severe or symptomatic AS
  • Prevention: currently no recommended medical therapy. Statins have been thought to slow progression if initiated during mild disease. However, this has not been supported by large, randomized controlled trials.
  • Antibiotic prophylaxis against recurrent RF is indicated for patients with rheumatic AS (penicillin G 1,200,000 U IM q4wk; duration varies with age and history of carditis).
  • Antibiotic prophylaxis is no longer indicated for prevention of infective endocarditis (5).
  • Comorbidities: hypertension: angiotensin-converting enzyme (ACE) inhibitors, start with low dose and increase cautiously. Be cautious of vasodilators, which may cause hypotension.
SURGERY/OTHER PROCEDURES
  • The only proven treatment for AS is valve replacement.
  • Indications for aortic valve replacement (AVR) surgery:
    • Symptomatic and severe high-gradient AS by history or exercise testing (4)[B]
    • Asymptomatic, severe AS and LVEF < 50% (4)[B]
    • Severe AS (stage C or D) when undergoing other cardiac surgery (4)[B]
  • AVR surgery is reasonable in patients who are:
    • Asymptomatic with severe AS (C1) with jet vel. ≥5 m/s and low surgical risk, decreased exercise tolerance, or have an exercise fall in blood pressure (4)[B]
    • Symptomatic stage D2, with a low-dose dobutamine stress with jet vel. ≥4.0 m/s or mean pressure gradient ≥40 mm Hg with ≤1.0 cm2 at any dobutamine dose (4)[B]
    • Symptomatic stage D3 with LVEF >50% if clinical and hemodynamic data support valve obstruction as likely cause of symptoms (4)[C]
    • Stage B who are undergoing other cardiac surgery, or asymptomatic stage C1 with rapid disease progression and low surgical risk (4)[C]
  • Transcatheter aortic valve replacement (TAVR) offers a less invasive option for some patients (6).
    • For those who are high at surgical risk and considered inoperable, TAVR has demonstrated superiority to medical therapy.
    • For those who are high at surgical risk, TAVR has demonstrated noninferiority to surgical AVR (6).
    • For those who are intermediate at surgical risk, TAVR may emerge as a reasonable alternative to surgical risk, though this indication has not yet been approved in the United States.
    • Valve-in-valve TAVR can be considered in high-risk patients with failed surgically implanted bioprosthetic valves.
  • Percutaneous balloon valvuloplasty may have role in palliation or as a bridge to valve replacement in hemodynamically unstable or high-risk patients (5)[C] but is not recommended as an alternative to valve replacement.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Advise patients to immediately report symptoms referable to AS.
  • Asymptomatic patients: yearly history and physical (5)[C]
  • Serial ECHO: yearly for severe AS, every 1 to 2 years for moderate AS, every 3 to 5 years for mild AS (5)[B]
PATIENT EDUCATION
Physical activity limitations
  • Asymptomatic mild AS: no restrictions
  • Asymptomatic moderate to severe AS: Avoid strenuous exercise. Consider exercise stress test prior to starting exercise program.
PROGNOSIS
  • 25% mortality/year in symptomatic patients who do not undergo valve replacement; average survival is 2 to 3 years without AVR surgery.
  • Median survival in symptomatic AS (3): heart failure: 2 years; syncope: 3 years; angina: 5 years
  • Perisurgical mortality: AVR surgery has 4% mortality rate; AVR + CABG has 6.8% mortality rate
  • Adverse postoperative prognostic factors: age, heart failure (HF) New York Heart Association (NYHA) class III/IV, cerebrovascular disease, renal dysfunction, CAD
REFERENCES
1. Carabello BA, Paulus WJ. Aortic stenosis. Lancet. 2009;373(9667):956-966.
2. Otto CM. Calcific aortic stenosis—time to look more closely at the valve. N Engl J Med. 2008;359(13):1395-1398.
3. Grimard BH, Larson JM. Aortic stenosis: diagnosis and treatment. Am Fam Physician. 2008;78(6):717-724.
4. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg. 2014;148(1):e1-e132.
5. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006;114(5):e84-e231.
6. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.
Codes
ICD10
  • I35.0 Nonrheumatic aortic (valve) stenosis
  • I06.0 Rheumatic aortic stenosis
  • Q23.0 Congenital stenosis of aortic valve
Clinical Pearls
  • AS is diagnosed on physical exam by a systolic crescendo-decrescendo murmur and delayed and diminished pulses.
  • Symptomatic AS most commonly presents as angina, syncope, and heart failure.
  • Symptomatic AS has a very poor prognosis, unless treated with surgical intervention.