What is the progression and natural history of Aortic (Aortic Valve) stenosis?

Progression and Natural History of Aortic Stenosis

Aortic stenosis (AS) typically progresses at an average rate of 0.3 m/s increase in jet velocity per year, 7-8 mmHg increase in mean gradient per year, and 0.1-0.15 cm² decrease in valve area per year, with marked individual variability in progression rates. 1

Pathophysiology and Development

Aortic stenosis is characterized by a prolonged latent period during which morbidity and mortality remain very low. The most common causes include:

• Calcification of normal trileaflet valves (typically presenting in patients >75 years)
• Congenital bicuspid valves (typically presenting a decade earlier)
• Rheumatic disease (less common in Western countries) 1

The left ventricle responds to AS with concentric hypertrophy to normalize wall stress, which initially compensates for increased afterload. This adaptation has important consequences:

• Reduced coronary blood flow per gram of muscle
• Limited coronary vasodilator reserve (even without epicardial coronary disease)
• Increased sensitivity to ischemic injury
• Development of diastolic dysfunction 1

Hemodynamic Progression

Rate of Progression

The average rate of progression in calcific AS of a trileaflet valve is:

• Increase in aortic velocity: ~0.3 m/s per year
• Increase in mean gradient: 7-8 mmHg per year
• Decrease in valve area: 0.1-0.15 cm² per year 1

However, there is marked individual variability in progression rates. Some patients may progress much faster ("fast progressors") or slower ("slow progressors") than average.

Factors Associated with Rapid Progression

Several factors have been identified as predictors of more rapid progression:

• Older age
• More severe valve calcification
• Presence of aortic regurgitation
• Male sex
• Elevated serum creatinine
• Higher left ventricular mass index
• Higher initial severity index (reflecting leaflet pathology)
• Atherosclerotic risk factors (hypertension, smoking, hyperlipidemia) 1, 2, 3

In bicuspid aortic valves, progression is typically faster in patients with greater closure line eccentricity and an anteroposterior-oriented line of closure 1.

Natural History and Clinical Outcomes

Asymptomatic Phase

During the asymptomatic phase:

• Prognosis is generally good with survival rates similar to age-matched controls
• Risk of sudden death is low (<1% per year) when patients are followed prospectively 1
• Event-free survival varies based on stenosis severity:
  • Jet velocity <3.0 m/s: 75-80% event-free survival at 2 years
  • Jet velocity ≥4.0 m/s: only 30-50% event-free survival at 2 years 1

In asymptomatic patients with severe AS and normal LV function:

• Development of asymptomatic LV dysfunction: <1.3% per year
• Sudden death: <0.2% per year
• Combined endpoint of symptoms, LV impairment, or death: 4.3% per year 1

Symptomatic Phase

Once symptoms develop (angina, syncope, or heart failure), prognosis deteriorates rapidly:

• Average survival after symptom onset:
  • Heart failure symptoms: ~2 years
  • Syncope: ~3 years
  • Angina: ~5 years 1
• Mortality rates after symptom onset:
  • ~25% at 1 year
  • ~50% at 2 years 1

In high-risk elderly patients with severe symptomatic AS treated medically, survival at 1 year may be as low as 50% 1.

Risk Stratification in Asymptomatic Severe AS

Several parameters help identify high-risk asymptomatic patients:

• Very severe stenosis (peak velocity ≥5.0 m/s or mean gradient ≥60 mmHg)
• Aortic valve calcification (severe)
• Rapid hemodynamic progression (increase in mean gradient >18-20 mmHg during exercise)
• Low flow (indexed stroke volume <35 mL/m²)
• Decreased longitudinal LV function (global strain <16%)
• Elevated BNP levels (>3 times normal)
• Abnormal exercise test (development of symptoms, abnormal BP response) 1

Monitoring and Follow-up

Follow-up intervals should be based on AS severity:

• Mild AS: Every 3-5 years
• Moderate AS: Every 1-2 years
• Severe asymptomatic AS: Every 6-12 months
• Very severe asymptomatic AS with risk factors: Every 3-6 months 1

During follow-up, it's essential to:

• Use consistent methods for measuring velocity/gradient and AVA
• Monitor for secondary changes (LV hypertrophy, decrease in LVEF, secondary MR/TR)
• Control blood pressure before echocardiographic evaluation 1
• Perform exercise testing in asymptomatic patients to unmask symptoms

Clinical Pitfalls and Caveats

1. Underestimation of symptoms: Patients may reduce their activity level to avoid symptoms. Careful questioning and exercise testing can unmask truly symptomatic patients.

2. Low-flow, low-gradient AS: Challenging to diagnose, especially with preserved LVEF. Multi-modality imaging approach is mandatory.

3. Rapid progression: Some patients may progress much faster than average. Close monitoring is essential in those with risk factors for rapid progression.

4. Concomitant conditions: Coronary artery disease, hypertension, and other valvular diseases may confound assessment and accelerate progression.

5. Aortic dilation: Patients with bicuspid aortic valves often have associated aortopathy. The aorta should be carefully evaluated during follow-up.