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Aortic Stenosis

Chapter 272 | Part 6: Disorders of the Cardiovascular System

KEY CLINICAL POINTS

  • Aortic stenosis (AS) is the most common valve lesion in adults with chronic valvular heart disease, with severe AS affecting ~3.5% of individuals >75 years.
  • Degenerative calcification of the aortic cusps is the primary cause in developed countries, while rheumatic fever is the leading cause in low- and middle-income countries.
  • Severe AS is defined by an aortic valve area <1 cm², mean pressure gradient >40 mmHg, or peak velocity >4 m/s. Low-flow, low-gradient AS with preserved EF is a diagnostic challenge.
  • Transcatheter aortic valve implantation (TAVI) has surpassed surgical aortic valve replacement (SAVR) for treating severe AS in high-risk patients, with 8-year survival rates of ~95% for low-risk SAVR.
  • Bicuspid aortic valve disease (BAV) affects 0.5–1.4% of the population and is associated with aortic aneurysms, coarctation, and accelerated calcification.

1. DEFINITION & OVERVIEW

Aortic stenosis is a valvular heart disease characterized by narrowing of the aortic valve, leading to impaired left ventricular (LV) outflow. It is classified as congenital, degenerative, or rheumatic in origin. Severe AS is defined by a valve area <1 cm², mean pressure gradient >40 mmHg, or peak velocity >4 m/s.

Table 272-1: Major Causes of Aortic Stenosis

VALVE LESION ETIOLOGIES
Aortic stenosis Congenital (bicuspid, unicuspid)
Degenerative calcific disease
Rheumatic fever
Radiation

1.1 Global Burden

Valvular heart disease ranks below ischemic heart disease, stroke, hypertension, obesity, and diabetes as a public health threat. Rheumatic heart disease (RHD) accounts for 12–65% of cardiovascular hospital admissions in endemic regions. The global prevalence of RHD is 150 per 100,000 in some areas, with highest rates in sub-Saharan Africa, South Asia, and Oceania.

1.2 Pathophysiology

AS causes a systolic pressure gradient between LV and aorta, leading to LV hypertrophy, diastolic dysfunction, and eventual heart failure. In severe cases, LV dilation and reduced ejection fraction (EF) occur, with symptoms including dyspnea, angina, and syncope.

2. EPIDEMIOLOGY

The incidence of newly diagnosed valvular heart disease is 64 per 100,000 person-years, with ~70% of cases in individuals ≥ 65 years. Severe AS affects 3.5% of those >75 years. Rheumatic heart disease (RHD) is the leading cause in low- and middle-income countries, with prevalence ranging from 1/100,000 in Costa Rica to 150/100,000 in China.

2.1 Risk Factors

Age, hypertension, diabetes, hyperlipidemia, smoking, and chronic kidney disease are major risk factors. Bicuspid aortic valve (BAV) disease is associated with aortic aneurysms and accelerated calcification.

2.2 Demographics

RHD is more prevalent in females and individuals aged 20–40 years. In the U.S., 3876 deaths from RHD were reported in 2020, with a 50% decline in age-standardized mortality rates (1990–2022).

3. ETIOLOGY & PATHOPHYSIOLOGY

Degenerative calcification of the aortic cusps is the primary cause in developed countries, while rheumatic fever is the leading cause in low- and middle-income countries. Pathogenesis involves lipid infiltration, inflammation, and fibro-calcific response, with endothelial dysfunction and vascular inflammation playing key roles.

Table 272-2: Frequency of Follow-Up Echocardiography in Aortic Stenosis

STAGE OF DISEASE FREQUENCY OF ECHOCARDIOGRAPHY
Progressive (stage B) Every 3–5 years (mild severity, V 2.0–2.9 m/s)
Every 1–2 years (moderate severity, V 3.0–3.9 m/s)
Severe asymptomatic (stage C1) Every 6–12 months (V >4 m/s)

3.1 Bicuspid Aortic Valve Disease

BAV affects 0.5–1.3% of the population and is associated with aortic aneurysms, coarctation, and accelerated calcification. It is linked to NOTCH1, GATA5, and GATA4 gene mutations.

3.2 Pathogenesis

Calcific AS involves lipid infiltration, inflammatory cell activation, and fibro-calcific response. Valvular interstitial cells (VICs) drive collagen deposition and calcium hydroxyapatite crystal formation. Genetic polymorphisms (e.g., vitamin D receptor, interleukin 10) and traditional atherosclerotic risk factors contribute to disease progression.

4. CLINICAL FEATURES

Symptoms include exertional dyspnea, angina, and syncope. Physical findings include a harsh, ejection systolic murmur, delayed carotid pulse (pulsus parvus et tardus), and a double apical impulse. In severe cases, signs of LV failure (pulmonary congestion, hepatomegaly) and right ventricular (RV) hypertrophy may develop.

4.1 Symptomatology

Exertional dyspnea, angina pectoris, and syncope are cardinal symptoms. Fatigue and reduced exercise tolerance are common. Sudden death occurs in ~10–20% of patients with severe AS, often in previously asymptomatic individuals.

4.2 Physical Examination

Early systolic ejection murmur, delayed carotid pulse, and a double apical impulse are characteristic. In advanced stages, signs of LV failure (pulmonary congestion, hepatomegaly) and RV hypertrophy may be present.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include hypertrophic cardiomyopathy, subaortic stenosis, and supravalvular aortic stenosis. Echocardiography and Doppler studies help distinguish valvular from non-valvular causes of LV outflow obstruction.

5.1 Non-Valvular Causes

Hypertrophic obstructive cardiomyopathy, discrete fibromuscular subaortic stenosis, and supravalvular aortic stenosis must be differentiated from valvular AS using imaging and hemodynamic studies.

6. INVESTIGATIONS & DIAGNOSIS

Echocardiography is the primary diagnostic tool, assessing valve morphology, LV hypertrophy, and transvalvular gradients. Doppler measurements estimate valve area and pressure gradients. Cardiac catheterization may be used for hemodynamic assessment in complex cases.

Table 272-3: Factors Favoring SAVR, TAVI, or Palliative Care

FAVORS SAVR FAVORS TAVI FAVORS PALLIATION
Age/life expectancya Younger age/longer life expectancy Older age/fewer expected remaining years of life
Valve anatomy Bicuspid aortic valve Calcific trileaflet AS
Prosthetic valve preference Mechanical or surgical bioprosthetic valve preferred Bioprosthetic valve preferred
Concurrent conditions Aortic dilationc Severe calcification of the ascending aorta
Noncardiac conditions Severe lung, liver, or renal disease
Estimated risk of SAVR or TAVI SAVR risk low TAVI risk low to medium
Goals of care Life prolongation Avoid futile or unnecessary procedures

6.1 Echocardiography

Transthoracic echocardiography identifies valve calcification, LV hypertrophy, and eccentric closure. Doppler velocity measurements estimate valve area and pressure gradients. Transesophageal echocardiography provides detailed imaging of the valve orifice.

6.2 Cardiac Catheterization

Right- and left-sided catheterization may be used to measure LV pressures and assess coronary artery disease. It is particularly useful in patients with discordant clinical and noninvasive findings.

7. MANAGEMENT & TREATMENT

Medical management includes control of hypertension and CAD. Surgical aortic valve replacement (SAVR) is indicated for severe AS with symptoms or LV dysfunction. Transcatheter aortic valve implantation (TAVI) is preferred for high-risk patients. Low-flow, low-gradient AS with preserved EF requires careful evaluation with dobutamine stress echocardiography.

Table 272-3: Factors Favoring SAVR, TAVI, or Palliative Care (continued)

FAVORS SAVR FAVORS TAVI FAVORS PALLIATION
Procedure-specific impediments Valve anatomy, annular size, or low coronary ostial height precludes TAVI Vascular access does not allow transfemoral TAVI
Goals of care Lower risk of permanent pacer Avoid procedural stroke risk
Improved long-term exercise capacity and QOL Avoid possibility of cardiac pacer

7.1 Medical Therapy

Control of hypertension and CAD is critical. Beta-blockers, ACE inhibitors, and statins are generally safe for asymptomatic patients. Nitroglycerin may relieve angina in patients with CAD.

7.2 Surgical Management

SAVR is recommended for severe AS with symptoms or LV dysfunction. Bioprosthetic valves are preferred for older patients, while mechanical valves are used in younger patients with higher life expectancy. TAVI is preferred for high-risk patients, with 8-year survival rates of ~95% for low-risk patients.

7.3 Percutaneous Intervention

TAVI is most commonly performed via transfemoral access. It is preferred for high-risk patients, with lower complication rates compared to SAVR. TAVI is increasingly used for valve-in-valve replacement in bioprosthetic valve failure.

8. PROGNOSIS & COMPLICATIONS

The average time to death after symptom onset is 3 years for angina, 2 years for dyspnea, and 1.5–2 years for heart failure. Sudden death occurs in ~10–20% of patients with severe AS. Complications include heart failure, arrhythmias, and embolic events.

8.1 Natural History

Death in severe AS occurs most commonly in the 7th and 8th decades. The average time to death after symptom onset is 3 years for angina, 2 years for dyspnea, and 1.5–2 years for heart failure. Sudden death occurs in ~10–20% of patients.

8.2 Complications

Complications include heart failure, arrhythmias (e.g., atrial fibrillation), embolic events, and valve-related complications (e.g., paravalvular leak, thrombosis).

9. SPECIAL CONSIDERATIONS

In pregnancy, AS management focuses on monitoring for maternal and fetal complications. In pediatric patients, congenital AS requires early intervention. In the elderly, careful evaluation of surgical risk and comorbidities is essential. Patients with BAV disease require close monitoring for aortic aneurysms and dissection.

9.1 Pregnancy

AS in pregnancy requires close monitoring for maternal heart failure and fetal complications. Valve replacement may be considered in severe cases to prevent maternal mortality. Congenital AS in children requires early intervention, with surgical or percutaneous valve replacement depending on severity. BAV disease in children is associated with aortic aneurysms and requires regular imaging follow-up.

10. KEY POINTS & CLINICAL PEARLS

  • Severe AS is defined by valve area <1 cm², mean gradient >40 mmHg, or peak velocity >4 m/s.
  • TAVI is preferred for high-risk patients, with 8-year survival rates of ~95% for low-risk patients.
  • Bicuspid aortic valve disease is associated with aortic aneurysms and accelerated calcification.
  • Low-flow, low-gradient AS with preserved EF requires dobutamine stress echocardiography for accurate assessment.
  • Management of AS involves a multidisciplinary approach, with careful consideration of surgical risk, valve durability, and patient preferences.