Aortic Valvular Stenosis: Causes, Risk Factors, Diagnosis, Treatment by NJE

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Aortic Valvular 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 the development of severe obstruction or onset of symptoms such as syncope, angina, and congestive heart failure (CHF) is 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.

Prevalence

  • Affects 1.3% of the population 65 to 74 years old, 2.4% 75 to 84 years old, 4% >84 years old.
  • Bicuspid aortic valve: 1-2% of the population. Bicuspid aortic valve predisposes to the development of AS at an earlier age.
Aortic Valvular Stenosis

ETIOLOGY AND PATHOPHYSIOLOGY OF AORTIC VALVULAR STENOSIS

  • Progressive aortic leaflet thickening and calcification result 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.
    •  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 the 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 OF AORTIC VALVULAR STENOSIS

  • Congenital unicommissural valve or bicuspid valve.
    • Unicommissural valve: Most cases were detected during childhood.
    • Bicuspid valve: predisposes to the development of AS earlier in adulthood (4th to 5thdecade) compared to tricuspid valve (6th to 8th decade).
  • Rheumatic fever 
    • The prevalence of chronic rheumatic valvular disease has declined significantly in the UnitedStates.
    • 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 OF AORTIC VALVULAR STENOSIS

  • CAD (50% of patients)
  • Hypertension (40% of patients): results in Òdouble-loadedÓ left ventricle (dual source ofincreased 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 valvedisease
  • LV dysfunction and CHF
  • Acquired von Willebrand disease: Impaired platelet function and decreased vWF results inbleeding (ecchymosis and epistaxis) in 20% of AS patients. Severity of coagulopathy is directlyrelated to severity of AS.
  • Gastrointestinal arteriovenous malformations (AVMs)
  • Cerebral or systemic embolic events due to calcium emboli.

DIAGNOSIS OF AORTIC VALVULAR STENOSIS

HISTORY

  • Primary symptoms: angina, syncope, and heart failure (3). Angina is the most frequent symptom. Syncope is often exertional. Heart failure symptoms include fatigue, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and shortness of breath.
  • Palpitations
  • Neurologic events (transient ischemic attack or cerebrovascular accident) secondary to embolization
  • Geriatric patients may have subtle symptoms such as fatigue and exertional dyspnea.
  • Note: Symptoms do not always correlate with valve area (severity of AS) but most commonly occur when aortic valve area is <1 cm2, jet velocity is > 4.0 m/s, or the mean transvalvular gradient is ≥ 40 mm Hg.

PHYSICAL EXAM

  • Auscultation 
    •  Harsh, systolic crescendo-decrescendo murmur is best heard at 2nd right sternal border andradiates 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 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 butbest heard at left sternal border and may radiate into axilla. Murmur intensity increases bychanging from squatting to standing and/or by Valsalva maneuver.
  • Discrete fixed subaortic stenosis: 50-65% has associated cardiac deformity (patent ductusarteriosus [PDA], ventricular septal defect [VSD], aortic coarctation).
  • Aortic supravalvular stenosis: Williams syndrome, homozygous familial hypercholesterolemia.

DIAGNOSTIC TESTS & INTERPRETATION OF AORTIC VALVULAR STENOSIS

Initial Tests (lab, imaging)

  • Chest x-ray (CXR) 
    • May be normal in compensated, isolated valvular AS. 
    • Boot-shaped heart reflective of concentric hypertrophy.     
    • Post stenotic 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, andnonspecific 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
    • Stage A (at risk): bicuspid aortic valve, sclerosis, or other congenital abnormality; mean pressure gradient: 0 mm Hg; jet vel. <2 m/s.
    • 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: ≥40mm 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 pressuregradient: <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

  • Exercise stress testing
    • Asymptomatic patients with severe AS (5)[B]: helpful to uncover subtle symptoms orchanges, abnormal BP (increase <20 mm Hg), and ECG changes (ST depressions). 1/3 ofpatients develop symptoms with exercise testing; STOP testing at this point.
    • Symptomatic patients (5)[B]: DO NOT perform exercise stress testing, as it may inducehypotension 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 an 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 an 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.

TREATMENT OF AORTIC VALVULAR STENOSIS

MEDICATION 

  • No effective medical therapy for severe or symptomatic AS.
  • Prevention: currently no recommended medical therapy. Statins have been thought to slowprogression 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.
  • 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.
    • Asymptomatic, severe AS and LVEF < 50%.
    • Severe AS (stage C or D) when undergoing other cardiac surgery.
  • AVR surgery is reasonable in patients who are:
    • Asymptomatic with severe AS with jet vel. ≥5 m/s and low surgical risk, decreased exercise tolerance, or have an exercise fall in blood pressure.
    • Symptomatic stage D2, with a low-dose dobutamine stress with jet vel. ≥4.0 m/s or meanpressure gradient ≥40 mm Hg with ≤1.0 cm2 at any dobutamine dose.
    • Symptomatic stage D3 with LVEF >50% if clinical and hemodynamic data support valveobstruction as likely cause of symptoms. 
    • Stage B who are undergoing other cardiac surgery, or asymptomatic stage C1 with rapiddisease progression and low surgical risk.
  • Transcatheter aortic valve replacement (TAVR) offers a less invasive option for some patients.
    • For those who are high at surgical risk and considered inoperable, TAVR has demonstratedsuperiority to medical therapy.
    • For those who are high at surgical risk, TAVR has demonstrated noninferiority to surgicalAVR.
    • For those who are intermediate at surgical risk, TAVR may emerge as a reasonablealternative to surgical risk, though this indication has not yet been approved in the UnitedStates.
    • Valve-in-valve TAVR can be considered in high-risk patients with failed surgically implantedbioprosthetic valves.
  • Percutaneous balloon valvuloplasty may have role in palliation or as a bridge to valvereplacement in hemodynamically unstable or high-risk patients but is not recommendedas an alternative to valve replacement.

FOLLOW-UP RECOMMENDATIONS

  • Advise patients to immediately report symptoms referable to AS.
  • Asymptomatic patients: yearly history and physical.
  • Serial ECHO: yearly for severe AS, every 1 to 2 years for moderate AS, every 3 to 5 years for mild AS.

PATIENT EDUCATION

Physical activity limitations

  • Asymptomatic mild AS: no restrictions.
  • Asymptomatic moderate to severe AS: Avoid strenuous exercise. Consider exercise stress test.

PROGNOSIS

  • 25% mortality/year in symptomatic patients who do not undergo valve replacement; averagesurvival is 2 to 3 years without AVR surgery.
  • Median survival in symptomatic AS (3): heart failure: 2 years; syncope: 3 years; angina: 5years
  • Perisurgical mortality: AVR surgery has 4% mortality rate; AVR + CABG has 6.8% mortalityrate
  • Adverse postoperative prognostic factors: age, heart failure (HF) New York Heart Association(NYHA) class III/IV, cerebrovascular disease, renal dysfunction, CAD

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