Description

• Aortic stenosis (AS) is a narrowing of the aortic valve area (AVA) from leaflet fibrosis or calcification, leading to obstruction of the left ventricular (LV) outflow tract.
• AS has a long asymptomatic latency period.
• Development of severe obstruction, syncope, angina, and symptoms of congestive heart failure (CHF) have high mortality without surgical intervention.

Epidemiology

• AS is the most common acquired valve disease leading to operative intervention in Europe and North America (1).
• Cause by age at presentation: <30 years, congenital; 30 to 65 years, congenital or rheumatic fever (RF); >65 years, degenerative calcification of aortic valve

Prevalence

• Affects 1% of population 65 to 74 years old, 2% of 75 to 84 years old, 4% of >84 years old
• Bicuspid aortic valve present in 1–2% of population predisposes to AS at an earlier age.
• Progressive aortic leaflet thickening and calcification results in LV outflow obstruction. Obstruction causes increased afterload and decreased cardiac output.

Etiology and Pathophysiology

• An increase in LV systolic pressure is required to preserve cardiac output leading to concentric LV hypertrophy (LVH). This 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 AS interventions due to the presence of interstitial fibrosis.
• Degenerative calcific changes to aortic valve (2)
  • AS has an initiation phase caused by endothelial dysfunction and lipid deposition, followed by an inflammatory response, fibrosis, and calcification (3).
• Congenital: unicuspid valve, bicuspid valve, tricuspid valve with fusion of commissures, hypoplastic annulus
• RF: chronic scarring with fusion of commissures

Genetics
Bicuspid aortic valves display genetic variants involving mutations in NOTCH1 and GATA1 genes, which involve accelerated calcification in AS (3).

Risk Factors

• Congenital unicommissural valve or bicuspid valve
• RF
  • 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 include hypercholesteremia, hypertension, cigarette smoking, male gender, age, diabetes mellitus, and arterial hypertension

General Prevention

Optimal management of hypertension, cardiac comorbid conditions, and smoking cessation; angiotensin-converting enzyme (ACE) and ARB inhibitors decrease LV fibrosis.

Commonly Associated Conditions

• Coronary artery disease (CAD) (50% of patients); hypertension (40% of patients)
• Aortic insufficiency (common in calcified bicuspid valves and rheumatic disease)
• Mitral valve disease: 95% of patients with AS from RF also have mitral valve disease.
• LV dysfunction and CHF
• Acquired von Willebrand disease: Impaired platelet function and decreased von Willebrand factor 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