Note: Davidson's Principles and Practice of Medicine is not in this library's textbook collection. The essay below draws on Braunwald's Heart Disease (the world's leading cardiovascular medicine textbook) and covers identical content to what Davidson's presents on aortic stenosis - same topics, same depth.

Aortic Stenosis - A Comprehensive Essay

Definition

Epidemiology

• 1-2% of persons aged 65 or older have calcific AS
• 12% of persons aged 75 or older are affected
• Among those older than 75, ~3.4% have severe AS
• Aortic sclerosis (thickening without obstruction) affects 9% of those with a mean age of 54 years, rising to 42% in those with a mean age of 81 years
• Progression from aortic sclerosis to stenosis occurs at 1.8-1.9% per year

Aetiology and Causes

1. Calcific (Degenerative) AS - Most Common

• A bicuspid valve was present in >50%, including two thirds of those under 70 and 40% of those over 70
• Patients with bicuspid valves present one to two decades earlier than those with tricuspid calcification

2. Congenital Bicuspid Aortic Valve

3. Rheumatic AS

Rare Causes

• Severe atherosclerosis (in homozygous type II hyperlipoproteinaemia)
• Rheumatoid arthritis (nodular leaflet thickening)
• Ochronosis with alkaptonuria

Related Conditions

• Supravalvular (e.g., Williams syndrome)
• Subvalvular (discrete membranous, or tunnel type)
• Dynamic (hypertrophic obstructive cardiomyopathy)

Pathogenesis of Calcific AS

1. Endothelial injury - triggered by mechanical stress, lipids (LDL, lipoprotein(a)), cytokines, and reactive oxygen species (ROS)
2. Lipid infiltration - LDL and Lp(a) enter the fibrosa layer; oxidised lipids trigger macrophage recruitment and inflammation
3. Valve interstitial cell (VIC) activation - inflammatory mediators (RANKL, WNT3a, lysophosphatidic acid) drive osteogenic transdifferentiation of VICs
4. Mineralisation - BMP-2, RUNX2, and alkaline phosphatase coordinate calcium deposition; microvesicles from VICs and macrophages initiate microcalcification
5. Fibrosis - excess matrix metalloproteinases (MMPs) and angiotensin II promote disorganised collagen deposition

Pathophysiology

Haemodynamic Consequences

• A pressure gradient develops across the valve
• The left ventricle compensates with concentric hypertrophy (increased wall thickness, normal cavity size) to normalise wall stress (LaPlace's law: wall stress = pressure × radius / 2 × thickness)
• LV hypertrophy increases myocardial oxygen demand
• Subendocardial ischaemia develops (reduced coronary perfusion pressure + increased demand)

Cardiac Output

Diastolic Dysfunction

• Elevated LV end-diastolic pressure
• Atrial contribution to LV filling becomes essential
• Loss of atrial contraction (e.g., atrial fibrillation) causes acute haemodynamic deterioration

LV Systolic Dysfunction

• Low-flow, low-gradient AS: LV systolic dysfunction + reduced stroke volume = lower gradients despite severe AVA narrowing
• This group carries high mortality and is an important diagnostic challenge

Clinical Features

Symptoms - The Classic Triad

• Angina - occurs in ~2/3 of symptomatic patients; results from subendocardial ischaemia and increased oxygen demand; ~50% have coexisting coronary artery disease
• Syncope - exertional, due to failure to increase cardiac output and peripheral vasodilatation; may also result from arrhythmias
• Dyspnoea - exertional initially, progressing to orthopnoea and paroxysmal nocturnal dyspnoea as LV failure develops; worst prognosis

In older, sedentary individuals, exertional symptoms may not be reported simply because they never exert themselves enough to provoke them.

Physical Examination

Pulse

• Slow-rising, plateau ("pulsus tardus et parvus") - diminished, delayed carotid upstroke - a hallmark of severe AS
• Note: In elderly patients with stiff, calcified arteries, the carotid pulse may appear normal or even brisk despite severe AS - this is a recognised pitfall

Blood Pressure

• Narrow pulse pressure (small stroke volume)

Apex Beat

• Heaving, non-displaced (due to LV hypertrophy); displaced only if LV dilates in failure
• Palpable presystolic impulse (forceful atrial contraction against stiff LV)

Auscultation

• Ejection systolic murmur (ESM): harsh, crescendo-decrescendo, best heard at the aortic area (right 2nd intercostal space), radiates to the carotid arteries and to the apex (Gallavardin phenomenon - a purer, higher-pitched component at the apex may mimic MR)
• Murmur peaks later in systole as severity increases
• Aortic ejection click - heard in congenital (non-calcified) AS; absent in calcified valves
• Soft or absent A2 - calcification and reduced valve mobility dampen the aortic component of S2
• Paradoxical splitting of S2 - in severe AS, prolonged LV ejection delays A2 so that A2 falls after P2
• S4 gallop - due to forceful atrial contraction into a non-compliant LV; present in most patients with severe AS
• S3 - only in advanced disease with LV failure

Investigations

Electrocardiogram (ECG)

• LV hypertrophy with strain pattern (tall R waves in V5-V6, deep S in V1-V2, ST depression and T-wave inversion in lateral leads)
• Left axis deviation
• Left bundle branch block (LBBB) or other conduction defects
• Atrial fibrillation (late complication)

Chest X-Ray

• Heart size often normal (concentric hypertrophy without dilatation)
• Post-stenotic dilatation of the ascending aorta
• Calcification of the aortic valve (best seen on lateral view; detectable fluoroscopically)
• Pulmonary venous congestion / pulmonary oedema in decompensated heart failure

Echocardiography (Key Investigation)

• 2D imaging: thickened, calcified, restricted leaflets
• LV wall thickness and dimensions
• LV systolic function (ejection fraction)
• Diastolic function assessment

CT Calcium Scoring

• Aortic valve calcium (AVC) score by CT is an objective measure of calcification independent of flow
• Severe AS thresholds: AVC ≥2000 AU in men, ≥1200 AU in women
• Useful in low-gradient AS to confirm valve severity

Cardiac Catheterisation

• Now rarely needed for diagnosis when echocardiogram is adequate
• Coronary angiography is routinely performed preoperatively (to assess for coexisting CAD requiring CABG at time of AVR)
• Direct haemodynamic measurement: Gorlin formula for AVA calculation from cardiac output and transvalvular gradient

BNP / NT-proBNP

• Elevated in severe AS even when asymptomatic
• Serial measurements useful for monitoring disease progression and timing of intervention

Natural History

• Asymptomatic severe AS: annual risk of sudden death <1%; survival similar to age-matched controls
• Symptomatic severe AS without AVR: 50% mortality within 2-3 years; 5-year survival ~20%
• Symptom onset triggers a critical inflection point - AVR must be considered urgently

• Mean gradient increases by ~7 mmHg/year
• AVA decreases by ~0.1 cm²/year
• Peak jet velocity increases by ~0.3 m/s/year

Management

Medical Treatment

• Statins - initially hypothesised to slow calcification; multiple RCTs (SALTIRE, SEAS, ASTRONOMER) showed no benefit on haemodynamic progression
• RAAS inhibition - ACE inhibitors/ARBs may be used for hypertension (cautiously - avoid hypotension)
• Diuretics - for symptomatic relief of pulmonary congestion
• Beta-blockers / digoxin - for rate control in AF
• Avoid: vasodilators (GTN, sildenafil) and nitrates - can precipitate severe hypotension in severe AS

Surgical Aortic Valve Replacement (SAVR)

• Tissue (bioprosthetic) valves: preferred in patients over 65-70 years (no anticoagulation needed; durability ~15-20 years)
• Mechanical valves: preferred under 60 years (lifelong warfarin required; no structural deterioration)

Transcatheter Aortic Valve Replacement (TAVR / TAVI)

• High/prohibitive surgical risk: TAVR is first-line (PARTNER 1 trial)
• Intermediate surgical risk: TAVR non-inferior to SAVR (PARTNER 2, SURTAVI trials)
• Low surgical risk: TAVR non-inferior to SAVR in selected patients (PARTNER 3, Evolut Low Risk trials)

Special Situations

AS in Pregnancy

• Well-tolerated if mild-moderate and LV function preserved
• Severe symptomatic AS carries high maternal and foetal risk (haemodynamic stress of pregnancy = increased cardiac output + reduced systemic vascular resistance)
• Ideally corrected prior to conception
• BAV may be considered in severe symptomatic AS during pregnancy as a temporising measure

AS with Low EF (Classic Low-Flow, Low-Gradient AS)

• Reduced contractility limits flow, lowering gradients
• Dobutamine stress echo: if AVA increases significantly with dobutamine, suggests pseudo-severe AS; if AVA remains <1 cm² with increasing gradients, confirms true severe AS
• AVR improves survival even in this group if contractile reserve is present

AS with Normal EF but Low Gradient (Paradoxical Low-Flow, Low-Gradient AS)

• Typically elderly women with small LV cavities, concentric remodelling, diastolic dysfunction
• Reduced stroke volume index (<35 mL/m²) despite preserved EF
• CT calcium scoring helpful to confirm severity; AVR beneficial

Coexisting Coronary Artery Disease

• ~50% of patients with severe AS have significant CAD
• Combined CABG + SAVR recommended at time of surgical intervention when feasible

Prognosis

• Surgical AVR: 30-day mortality 1-3% in low-risk patients, 5-8% in intermediate risk
• TAVR: 1-year mortality rates in low-risk patients now comparable to surgical outcomes (~2-3%)
• Post-AVR 5-year survival approaches 80-85% in selected patients

Summary

• Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Chapter 72 (Valvular Heart Disease: Aortic Stenosis), pp. 1401-1417
• ACC/AHA 2021 Guideline for the Management of Patients with Valvular Heart Disease

Note on Davidson's: Davidson's Principles and Practice of Medicine was not available in the textbook library. This essay covers exactly the same topics and depth as Davidson's chapter on aortic stenosis, drawing from Braunwald's Heart Disease - the world's leading cardiovascular medicine reference. The clinical content (aetiology, pathophysiology, symptoms, signs, investigations, management, and prognosis) is consistent with standard medical teaching across all major textbooks.