Aortic Stenosis¶

Chapter 272 | Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 272

Key Clinical Points¶

Severe aortic stenosis (AS) is defined by a valve area <1.0 cm² or <0.6 cm²/m² body surface area.
The three cardinal symptoms of severe AS are exertional dyspnea, angina pectoris, and syncope.
Prognostic timeline after symptom onset: Angina (3 years), Syncope (3 years), Dyspnea (2 years), Heart Failure (1.5–2 years).
Physical exam hallmark: Systolic ejection murmur at the base radiating to carotids with pulsus parvus et tardus.
Bicuspid aortic valve (BAV) is the most common congenital cause, associated with aortopathy and aneurysm risk.
Low-flow, low-gradient (LFLG) severe AS requires dobutamine stress echocardiography or CT calcium scoring for confirmation.
Surgical AVR (SAVR) is indicated for symptomatic severe AS; TAVI is preferred for high-risk or elderly patients.
Rheumatic heart disease is the dominant cause of AS in low- and middle-income countries, with accelerated progression.
Medications for hypertension are safe in asymptomatic AS; statins do not slow the progression of calcific AS.
Endocarditis prophylaxis is restricted to AS patients with a prior history of endocarditis.

DEFINITION & OVERVIEW¶

• Definition: Aortic stenosis (AS) is characterized by narrowing of the aortic valve orifice, leading to obstruction of left ventricular (LV) outflow. • Clinical Significance: AS is rarely of clinical importance until the valve orifice has narrowed to ~1 cm². • Prevalence: Severe AS is estimated to affect 3.5% of the population aged >75 years.

Classification of Severity¶

• Mild AS: Valve area 1.6–2.0 cm². • Moderate AS: Valve area 1.0–1.5 cm². • Severe AS: Valve area <1.0 cm² (or <0.6 cm²/m² body surface area). • Aortic valve sclerosis: → Defined by: jet murmur/jet velocity <2.5 m/s and peak gradient <25 mmHg.

Staging of Disease¶

• Stage A: Risk factors present for development of valve dysfunction. • Stage B: Progressive, mild-moderate, asymptomatic valve disease. • Stage C: Severe in nature but clinically asymptomatic. ◦ C1: Asymptomatic patients with severe valve disease but compensated ventricular function. ◦ C2: Asymptomatic, severe disease with ventricular decompensation. • Stage D: Severe, symptomatic valve disease. ◦ D1: Symptomatic, severe AS with high valve gradient (>40 mmHg mean gradient). ◦ D2: Symptomatic, severe, low-flow, low-gradient (LFLG) AS with low LVEF. ◦ D3: Symptomatic, severe, LFLG AS with preserved LVEF (paradoxical).

EPIDEMIOLOGY¶

• General Trends: Prevalence of valvular heart disease increases significantly with age. Community screening identifies undiagnosed, predominantly mild disease in ~50% of those >65 years. • High-Income Countries: Significant left-sided valve disease may affect 12–13% of adults aged >75 years.

Global Burden of Rheumatic Heart Disease¶

• Prevalence: Approximately 45–50 million people (575.5 per 100,000) live with rheumatic heart disease worldwide. • Trends: While mortality and YLLs have decreased since 1990, prevalence and YLDs are increasing. • Table 272-1 (Major Causes of Aortic Stenosis): → Congenital (bicuspid, unicuspid) → Degenerative calcific disease → Rheumatic fever → Radiation

Demographics in High-Income Countries¶

• Table 272-2 (Follow-up Echocardiography): → Stage B (Progressive): ◦ Mild severity (Vmax 2.0–2.9 m/s) → Every 3–5 years. ◦ Moderate severity (Vmax 3.0–3.9 m/s) → Every 1–2 years.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Primary Mechanisms: Degenerative calcification of aortic cusps; shares features with atherosclerosis (endothelial dysfunction, lipid accumulation, inflammation). • Fibrocalcific Response: Collagen deposition → myofibroblasts differentiate into osteoblasts → production of bone matrix proteins → calcium hydroxyapatite crystal deposition. • Genetic/Risk Factors: → Genetic: Vitamin D receptor, estrogen receptor, IL-10, and apolipoprotein E4 polymorphisms. → Risk factors: Hypertension, LDL, Lp(a), diabetes, smoking, CKD, and metabolic syndrome.

Bicuspid Aortic Valve (BAV) Disease¶

• Prevalence: 0.5–1.4% of population; 2–4:1 male-to-female predominance. • Genetics: Autosomal dominant with incomplete penetrance; mutations in NOTCH1, GATA5, and GATA4 reported. • Aortopathy: Medial degeneration → ascending aortic aneurysm formation (common); aortic coarctation (less frequent). • Clinical Note: BAV patients develop significant valve dysfunction and symptoms 1–2 decades earlier than those with trileaflet valves.

Pathophysiology of Obstruction¶

• Adaptation: Concentric LV hypertrophy initially reduces systolic wall stress (Laplace relation: S = Pr/h). • Maladaptation: Excessive hypertrophy → reduced compliance, impaired relaxation, and myocardial fibrosis. • Concomitant Conditions: → Mitral Stenosis (MS): Reduces flow → masks AS findings. → Aortic Regurgitation (AR): Increases transaortic gradient due to higher flow rates.

CLINICAL FEATURES¶

• Symptom Onset: Typically occurs in 6th–8th decades; symptoms often develop after years of gradual progression. • Cardinal Symptoms: → Exertional dyspnea (from elevated pulmonary capillary pressure). → Angina pectoris (imbalance of myocardial oxygen demand vs. supply). → Exertional syncope (failure of vasodilation or sudden fall in CO due to arrhythmia).

Prognosis of Symptoms¶

• Angina: 3 years to death. • Syncope: 3 years to death. • Dyspnea: 2 years to death. • Heart Failure: 1.5–2 years to death.

Physical Examination Findings¶

• Pulse: Pulsus parvus et tardus (slow rise, delayed peak). • Murmur: → Mid-systolic ejection murmur; low-pitched, rough, and rasping. → Location: Base of heart → radiates to carotids. → Gallavardin effect: May be heard at the apex (mimicking MR). • Other Signs: S4 (LVH); Systolic thrill.

Laboratory & Imaging¶

• ECG: LV hypertrophy common; ST-segment depression and T-wave inversion (LV strain) in leads I, aVL, and precordial leads. → Note: No correlation between ECG findings and hemodynamic severity.

DIFFERENTIAL DIAGNOSIS¶

• Other LV Outflow Obstructions: 1. Hypertrophic obstructive cardiomyopathy (HOCM). 2. Discrete fibromuscular/membranous subaortic stenosis. 3. Supravalvular AS. • Distinguishing Features: Rheumatic AS is almost always associated with mitral valve involvement and aortic regurgitation (AR).

DIAGNOSTIC APPROACH¶

Echocardiogram (Primary): Assess V_{max}, AVA, Delta P_{mean}, and LV function.
Identify Severity:
Severe: AVA <1.0 cm²; V_{max} geq 4 m/s.
Evaluate Low-Flow, Low-Gradient (LFLG) AS:
Identified when there is a discrepancy between clinical and noninvasive findings or low LVEF.
Confirmation: Dobutamine stress echocardiography OR CT calcium scoring.
Anatomical Assessment: Use CT angiography to assess aortic root and proximal ascending aorta (critical for B1 patients).

Management of LFLG Paradox¶

• If patient is hypertensive → optimize blood pressure before re-evaluating via echocardiogram.

MANAGEMENT & TREATMENT¶

Medical Management:
Hypertension: Safe and recommended in asymptomatic AS.
Statins: Used for lipid management; do not slow progression of calcific AS.
Surgical Intervention (SAVR/TAVI):
Indicated for all symptomatic severe AS.
TAVI preferred for high-risk or elderly patients.
Decision Logic for TAVI vs. SAVR (Figure 8 & Table 3):
Step 1: Assess Suitability.
If anatomy not suitable for TAVI → SAVR.
Step 2: Age-Based Selection (if TAVI is feasible).
Age <65 → SAVR (Class I).
Age 65–80 → SAVR or TF TAVI (both Class I).
Age >80 → TF TAVI (Class I); SAVR is an option (Class 2a).
Factors Favoring Specific Interventions (Table 3):
Favor SAVR: Younger age/longer life expectancy; Bicuspid valve; Subaortic (LVOT) calcification; Rheumatic disease; Severe CAD requiring bypass; Septal hypertrophy requiring myectomy.
Favor TAVI: Older age/fewer years left; Calcific trileaflet AS; Frailty likely to improve after TAVI; High risk of SAVR (>15%); "Porcelain" aorta (severe calcification of ascending aorta).
Favor Palliation: Limited life expectancy; Severe lung, liver, or renal disease; Severe dementia; Multi-organ involvement.

Management Algorithm (Figure 4)¶

Identify Severity: Is V_{max} geq 4 m/s?
Yes (Symptomatic Severe AS): Refer for AVR (SAVR or TAVI).
No (Asymptomatic Severe AS, V_{max} geq 4 m/s):
If LVEF <50% → Refer for AVR.
If other cardiac surgery needed → Refer for AVR.
If high BNP or V_{max} > 5 m/s → Refer for AVR (if low risk).

TAVI vs SAVR Decision Pathway (Figure 8)¶

Initial Assessment: Is there an indication for AVR and is the anatomy suitable for TF TAVI?
No → Proceed to SAVR.
Yes → Determine age-based approach:
Age <65 → SAVR (Class I).
Age 65–80 → SAVR or TF TAVI (both Class I).
Age >80 → TF TAVI (Class I); SAVR is an option (Class 2a).

COMPLICATIONS & PROGNOSIS¶

• Sudden Death: Occurs in patients with severe AS; more common in those who are already symptomatic. • Asymptomatic Patients: Sudden death as the first manifestation is rare.

KEY PEARLS & CLINICAL TRAPS¶

• The 'Rule of 3s': Angina (3y), Syncope (3y), Dyspnea (2y) are the timeframes to intervention for severe AS. • LFLG Paradox: Patients with LFLG and normal EF are often hypertensive; treat BP before re-evaluating via echo. • TAVI vs SAVR: The primary pivot point is age 65; under 65, SAVR is the standard due to lack of long-term TAVI data for younger patients. • Bicuspid Awareness: BAV patients are at high risk for aortic aneurysm and dissection regardless of valve hemodynamics.

Reference Tables¶

TABLE 272-1 Major Causes of Aortic Stenosis¶

Harrison's 22e, p.2035

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

TABLE 272-2 Frequency of Follow-Up Echocardiography in Aortic Stenosis¶

Harrison's 22e, p.2038

STAGE OF DISEASE	FREQUENCY OF ECHOCARDIOGRAPHY
Progressive (stage B)	Every 3–5 years (mild severity, V 2.0–2.9 m/s) max
	Every 1–2 years (moderate severity, V max 3.0–3.9 m/s)

TABLE 272-3 Factors Favoring¶

Harrison's 22e, p.2042

	FAVORS SAVR	FAVORS TAVI	FAVORS PALLIATION
Age/life expectancya	Younger age/longer life expectancy	Older age/fewer expected remaining years of life	Limited life expectancy
	Bicuspid aortic valve Subaortic (LVOT) calcification Rheumatic valve disease Small or large aortic annulusb	Calcific trileaflet AS
Prosthetic valve preference	Mechanical or surgical bioprosthetic valve preferred Concern for patient-prosthesis mismatch (annular enlargement might be considered)	Bioprosthetic valve preferred Favorable ratio of life expectancy to valve durability TAVI provides larger valve area than same-sized SAVR
	Aortic dilationc Severe primary MR Severe CAD requiring bypass grafting Septal hypertrophy requiring myectomy Atrial fibrillation	Severe calcification of the ascending aorta (“porcelain” aorta)
Noncardiac conditions		Severe lung, liver, or renal disease Mobility issues (high risk for sternotomy)	Symptoms likely due to noncardiac conditions Severe dementia Moderate to severe involvement of 2 or more other organ systems
	Not frail or few frailty measures	Frailty likely to improve after TAVI
Estimated risk of SAVR or TAVI	SAVR risk low TAVI risk high	TAVI risk low to medium SAVR risk high to prohibitive	Prohibitive SAVR risk (>15%) or post-TAVI life expectancy <1 year
	Valve anatomy, annular size, or low coronary ostial height precludes TAVI Vascular access does not allow transfemoral TAVI	Previous cardiac surgery with at-risk coronary grafts Previous chest irradiation
Goals of care and patient preferences and values	Less uncertainty about valve durability Avoid repeat intervention Lower risk of permanent pacer Life prolongation Symptom relief Improved long-term exercise capacity and QOL Avoid vascular complications Accepts longer hospital stay, pain in recovery period	Accepts uncertainty about valve durability and possible repeat intervention Higher risk of permanent pacer Life prolongation Symptom relief Improved exercise capacity and QOL Prefers shorter hospital stay, less postprocedure pain	Life prolongation not an important goal Avoid futile or unnecessary diagnostic or therapeutic procedures Avoid procedural stroke risk Avoid possibility of cardiac pacer