Aortic Stenosis

Degenerative calcification and fibrosis of trileaflet valves

• The most frequent cause of aortic stenosis (AS) in adults, accounting for up to 80% of cases in developed nations.
• Represents a spectrum from aortic sclerosis (leaflet thickening without obstruction) to severe AS.
• Risk factors associated with progression include ageing, hypertension, diabetes mellitus, hypercholesterolaemia, smoking, elevated C-reactive protein, and raised lipoprotein(a).
• The disease process resembles atherosclerosis, involving endothelial dysfunction, inflammation, and ultimately calcification.
• Calcification may extend into the conduction system, predisposing to conduction defects, or affect adjacent structures such as the mitral annulus.

Congenital aortic valve disease

• Bicuspid aortic valve is the most common cause of AS in patients younger than 70 years.
• Altered leaflet architecture leads to turbulent flow, trauma, fibrosis, and accelerated calcification.
• Patients with coarctation of the aorta or Turner syndrome have a higher incidence of bicuspid valves.
• Other congenital variants include unicuspid, tricuspid with unequal cusps, and quadricuspid valves, all of which may predispose to stenosis.
• In neonates, a unicuspid valve is the most common anomaly causing fatal obstruction.
• A long-term cohort of adults with bicuspid valves demonstrated overall survival similar to the general population, but a high likelihood of eventual valve intervention.

Rheumatic heart disease

• Historically a major cause of AS, now rare in industrialised countries due to improved treatment of streptococcal infections.
• Remains prevalent in developing regions.
• The pathological process involves fibrosis, commissural fusion, leaflet retraction, and variable calcification.
• Rheumatic AS frequently coexists with mitral valve disease.

Chronic kidney disease (CKD)

• Associated with abnormal calcium-phosphate metabolism.
• Patients with CKD, particularly those on dialysis, develop AS more frequently and experience faster progression due to disordered mineral metabolism.

Other acquired and rare causes

• Metabolic and systemic disorders such as Fabry disease, homozygous type II hypercholesterolaemia, ochronosis, systemic lupus erythematosus, and alkaptonuria have been implicated.
• Radiotherapy, particularly as a late complication of mediastinal irradiation, may lead to AS.
• Paget disease of bone is occasionally a contributing factor.
• Rarely, obstructive vegetations or sequelae of infective endocarditis can cause stenosis.
• Obstruction can also occur outside the valve: dynamic subvalvular stenosis in hypertrophic cardiomyopathy, or congenital supravalvular stenosis as seen in Williams syndrome.

Age-related distribution

• In patients under 70 years requiring surgery, bicuspid valves are the predominant cause, whereas degenerative calcific disease predominates in those over 70.
• Rheumatic disease and post-inflammatory aetiologies also contribute across age groups.
• Differentiating bicuspid from tricuspid stenosis can be difficult even on surgical inspection, with frequent discordance between clinical and pathological assessments.

Active process of calcification

• Calcification of the aortic valve is now understood to be an active biological process, not a passive result of ageing.
• Endothelial injury, triggered by turbulent blood flow (as in bicuspid valves) or by other mechanisms in trileaflet valves, initiates an inflammatory cascade similar to atherosclerosis.
• This leads to infiltration of inflammatory cells, fibrosis, and progressive calcium deposition, which gradually stiffen valve leaflets and restrict their mobility.

Congenital valves and mechanical stress

• Unicuspid and bicuspid valves experience abnormal haemodynamic forces from birth, accelerating degeneration.
• Structural abnormalities induce turbulent flow and repeated mechanical stress, causing fibrosis and premature calcification compared with trileaflet valves.

Rheumatic involvement

• Rheumatic aortic stenosis develops after autoimmune cross-reactivity from prior Streptococcus infection.
• The pathological process includes leaflet inflammation, commissural fusion, fibrosis, and calcification, often accompanied by mitral valve involvement.

Left ventricular hypertrophy and adaptive changes

• Progressive outflow obstruction creates a pressure gradient between the left ventricle (LV) and aorta.
• The LV adapts by concentric hypertrophy to maintain wall stress, initially preserving systolic function but reducing diastolic compliance.
• As stenosis worsens, LV end-diastolic pressure rises, pulmonary venous pressure increases, and cardiac output falls due to diastolic dysfunction.
• Eventual loss of myocardial contractility leads to systolic dysfunction and heart failure.

Contribution of concentric LV hypertrophy to symptoms

• Hypertrophy reduces chamber compliance, increasing LV filling pressures, particularly during exertion, and producing exertional dyspnoea.
• Oxygen demand rises due to increased muscle mass, while coronary perfusion is compromised by elevated LV diastolic pressures and reduced coronary reserve.
• This imbalance explains the frequent occurrence of angina even in patients without coronary artery disease.

Haemodynamic and perfusion consequences

• Outflow obstruction increases LV systolic pressure and prolongs ejection time while systemic aortic pressure falls.
• Coronary perfusion time shortens, especially in diastole, limiting oxygen delivery.
• Reduced myocardial capillary density further predisposes the subendocardium to underperfusion and ischaemia.
• Angina arises from increased oxygen demand coupled with restricted supply.

Atrial contribution and arrhythmia

• In advanced AS, atrial contraction becomes critical for LV filling.
• Onset of atrial fibrillation compromises this mechanism, often leading to acute decompensated heart failure.

Genetic and metabolic influences

• Population-based studies suggest that genetic predisposition to elevated LDL cholesterol is associated with increased valve calcification and incident AS.
• Mineral metabolism abnormalities, such as those in chronic kidney disease, accelerate calcification and worsen disease progression.

Global burden and demographics

• Aortic stenosis (AS) is the most common valvular disease requiring treatment in North America and Europe, and the second leading indication for cardiac surgery.
• Prevalence rises sharply with age: approximately 5% of individuals aged 65 years and 12–13% of those aged ≥75 years are affected.
• In population studies, the prevalence of AS diagnosed by echocardiography in adults aged 45–84 years without established cardiovascular disease is about 1%.
• In the UK, estimates from 2019 indicated nearly 291,500 people aged ≥55 years living with symptomatic severe AS, with an additional 92,000 having severe but asymptomatic disease.
• Mortality impact is substantial: in the United States, aortic valve disorders accounted for over 15,800 deaths in 2022. Between 2010 and 2018, the incidence of AS rose from 13.5 to 17.0 cases per 1000.

Aortic sclerosis as a precursor

• Aortic sclerosis, defined as thickening or calcification of the valve leaflets without obstruction, is a precursor to calcific AS.
• Its prevalence increases with age, present in about 25% of people over 65 years and in more than a third of those older than 75.
• Reported rates vary between 9% and 45% depending on the studied population (mean age 54–81 years).

Severe disease prevalence

• Among elderly individuals, severe AS is present in 2–9% of those older than 75.
• Degenerative calcific AS typically manifests after the age of 75, with a higher prevalence in men.
• With global ageing, the number of cases is expected to rise two- to threefold in coming decades.

Congenital and early-life presentations

• Severe AS is rare in infancy, occurring in about 0.33% of live births, usually related to unicuspid or bicuspid valves.
• Adults with congenital bicuspid valves often remain asymptomatic until middle age or later.
• Bicuspid aortic valves occur in roughly 0.9–1.4% of the population, with a male predominance (2:1).
• Patients with bicuspid valves typically present with symptomatic disease around two decades earlier than those with trileaflet valves.

Geographic variation

• In high-income regions, degenerative calcific AS is the dominant cause.
• In contrast, rheumatic heart disease remains a more common cause in developing countries, with patients often presenting in later decades of life.

Latent period and early progression

• Aortic stenosis (AS) often remains silent for 10–20 years, during which the left ventricle adapts to rising outflow obstruction.
• Patients typically stay asymptomatic until diastolic dysfunction or flow limitation develops.
• The earliest symptoms are usually exertional dyspnoea, fatigue, reduced exercise tolerance, light-headedness, or dizziness with effort.
• Over time, activity becomes progressively limited, leading to presentation with the classic triad of angina, syncope, and heart failure.

Chest pain (angina pectoris)

• Classically exertional, relieved by rest, and similar to angina from coronary artery disease.
• May occur even in the absence of coronary atherosclerosis due to increased myocardial oxygen demand from hypertrophy and reduced coronary flow reserve.

Heart failure symptoms

• Patients may develop dyspnoea on exertion, orthopnoea, or paroxysmal nocturnal dyspnoea.
• These may arise from systolic dysfunction related to afterload mismatch or from diastolic dysfunction caused by hypertrophy and impaired relaxation.
• Later stages are marked by pulmonary oedema, progressive fatigue, and declining exercise capacity.

Syncope

• Often exertional, resulting from systemic vasodilatation in the presence of a fixed stroke volume, producing a fall in systolic blood pressure.
• May also be due to atrial fibrillation, ventricular tachyarrhythmias, or atrioventricular block from calcific extension into the conduction system.
• Vasodepressor reflexes from increased intracavitary pressure can contribute.
• Convulsions can accompany syncopal episodes, and nitroglycerin use may precipitate syncope due to haemodynamic sensitivity.

Gastrointestinal bleeding

• Patients may present with recurrent or chronic gastrointestinal blood loss.
• Frequently linked to angiodysplasia and associated with acquired von Willebrand factor deficiency (Heyde’s syndrome).
• Symptoms often improve following aortic valve replacement.

Infective endocarditis

• Can present with fever, malaise, anorexia, back pain, or weight loss.
• Younger patients with bicuspid valves are at greater risk, but endocarditis may occur at any age, including in those with heavily calcified valves.
• Aortic stenosis increases susceptibility, especially in the context of Staphylococcus aureus bacteraemia.

Systemic embolisation

• Calcific or thrombotic emboli may dislodge from the diseased valve.
• Embolic events can affect the brain (cerebral emboli), kidneys, or coronary arteries, causing corresponding end-organ manifestations.

Bicuspid valves

• Symptoms often develop earlier, typically between 50–70 years.
• Up to 25–40% of patients also have aortic root dilatation, predisposing to aortic dissection.
• Cerebral embolisation from microthrombi is more frequently reported in this group.
• Lifetime risk of infective endocarditis is higher compared with trileaflet valves.

Tricuspid (degenerative) valves

• Calcific AS of trileaflet valves presents later, usually after age 70.
• The disease progresses insidiously until patients develop the triad of angina, syncope, and heart failure, which signals a poor prognosis without valve intervention.

Carotid pulse and peripheral signs

• A slow-rising, delayed, and low-amplitude carotid upstroke (pulsus parvus et tardus) is a classic finding in severe AS, though it may be absent in elderly patients with stiff arterial walls.
• A palpable delay between the apical impulse and the carotid pulse may be noted.
• Pulsus alternans may occur in the presence of left ventricular systolic dysfunction.
• Jugular venous pressure may show prominent a waves due to reduced right ventricular compliance from septal hypertrophy.

Blood pressure

• Systolic hypertension may coexist with AS, but readings above 200 mmHg are unusual in critical disease.

Apex beat and precordial findings

• The left ventricular apex may show a sustained, heaving impulse, reflecting pressure overload.
• A hyperdynamic apex suggests concomitant aortic or mitral regurgitation.
• A forceful S4 may be detected due to atrial contraction against a hypertrophied ventricle, though in elderly patients its presence is less specific.

Heart sounds

• S1 is usually normal or soft.
• A2 (aortic component of the second heart sound) is often diminished or absent due to calcified, immobile cusps and prolonged ejection. A normal or accentuated A2 argues against severe AS.
• Paradoxical splitting of S2 may occur due to delayed aortic valve closure. P2 may be accentuated if pulmonary hypertension is present.
• An ejection click may be heard in children and young adults with congenital AS and mobile leaflets, but it is rare in elderly patients with calcific stenosis.

Murmurs

• The hallmark finding is a crescendo–decrescendo systolic ejection murmur, beginning shortly after S1, peaking in mid-to-late systole, and ending before S2.
• Best heard at the right second intercostal space, radiating to the carotid arteries.
• In elderly patients with calcific AS, high-frequency components may radiate to the apex (Gallavardin phenomenon), mimicking mitral regurgitation.
• The murmur intensifies after long diastolic filling intervals (e.g., following a premature beat) and with squatting, and softens during Valsalva strain—helping to distinguish it from hypertrophic obstructive cardiomyopathy.
• Murmur intensity does not directly reflect severity; rather, late peaking and prolonged duration suggest more advanced disease.
• In advanced LV failure with reduced stroke volume, the murmur may become softer or even inaudible.

Additional auscultatory findings

• A single or diminished second heart sound is common in severe disease.
• A high-pitched diastolic blowing murmur may be present if there is associated aortic regurgitation.

Electrocardiogram (ECG)

• Abnormal in more than 90% of patients with AS.
• Most common finding is left ventricular hypertrophy (LVH) due to pressure overload.
• May also reveal conduction disturbances such as atrioventricular block, hemiblock, or bundle branch block.
• Presence of LVH with absent Q waves can help distinguish AS from aortic sclerosis with coexistent ischaemic heart disease.

Transthoracic Echocardiography (TTE)

• First-line investigation and the gold standard for diagnosis and follow-up.
• Confirms valve anatomy, degree of calcification, and haemodynamic severity using Doppler-derived gradients and valve area.
• Assesses left ventricular systolic function, hypertrophy, and concomitant valve lesions.
• Guidelines recommend TTE for unexplained systolic murmurs, abnormal second heart sounds, bicuspid valve suspicion, or typical symptoms.
• In the UK, NICE advises echocardiography in all patients with suspected valve disease and urgent referral for severe symptoms such as exertional syncope or angina.

Chest X-ray

• May be normal or show features such as pulmonary congestion, post-stenotic aortic dilatation, or calcification of the valve.
• Used to exclude other pulmonary causes of breathlessness.

Cardiac Computed Tomography (CT)

• Provides quantitative assessment of valve calcification.
• Agatston aortic valve calcium score can confirm severe AS, especially in low-flow, low-gradient cases where echocardiographic findings are inconclusive.
• Also useful in anatomical assessment before transcatheter aortic valve implantation (TAVI).

Cardiac Magnetic Resonance Imaging (MRI)

• Offers accurate evaluation of LV function, hypertrophy, and myocardial fibrosis (via late gadolinium enhancement).
• Helpful when echocardiographic images are poor or when subvalvular stenosis is suspected.
• Presence of mid-wall fibrosis has prognostic implications and may guide follow-up intensity.

CT Angiography (CTA) and MR Angiography (MRA)

• Provide detailed 3D images of the aortic valve and root morphology.
• CTA also screens for coronary artery disease in patients considered for valve surgery.
• MRA is useful for aortic annulus and ascending aorta measurements, but technical limitations (artefacts, arrhythmias, device incompatibility) reduce its routine use.

Exercise Testing

• Contraindicated in symptomatic severe AS due to risk of collapse.
• In asymptomatic patients, exercise stress testing helps unmask symptoms and assess prognosis.
• A positive test may show reduced exercise tolerance or a drop in systolic blood pressure ≥10 mmHg.
• Exercise echocardiography may provide additional haemodynamic information.

Dobutamine Stress Echocardiography

• Used in patients with low-flow, low-gradient AS and reduced LV ejection fraction to differentiate true severe stenosis from pseudostenosis.
• Demonstrates contractile reserve if stroke volume increases by ≥20% with dobutamine, which is associated with better surgical outcomes.

Transoesophageal Echocardiography (TOE)

• Provides detailed imaging when TTE windows are poor.
• Used in pre-surgical planning, intraoperative guidance, and in evaluation of bicuspid valves or sub-/supravalvular stenosis.

Cardiac Catheterisation

• Gold standard for direct measurement of aortic pressure gradients.
• Now reserved for cases where echocardiographic and clinical findings are discrepant.
• Also performed to assess for concomitant coronary artery disease in patients undergoing surgical valve replacement.

Biomarkers

• B-type natriuretic peptide (BNP) or NT-proBNP may help risk-stratify patients with severe AS, particularly those who are asymptomatic.
• Persistently high or rising levels predict adverse outcomes and earlier need for valve intervention.

Additional/Research Imaging

3D CT

• Precise quantification of valve calcification burden, correlating with disease severity.

Positron Emission Tomography (PET-CT)

• Emerging tool to detect active mineralisation and inflammation in the aortic valve, still investigational.

Acute Coronary Syndrome (ACS) and Myocardial Infarction

• Chest pain in aortic stenosis (AS) may closely mimic angina due to coronary artery disease.
• AS and coronary artery disease frequently coexist, complicating interpretation of symptoms.
• In isolated AS, Q waves are usually absent on ECG and regional wall motion abnormalities are not seen on echocardiography.
• In myocardial infarction or ACS, Q waves may be present, and echocardiography typically reveals wall motion abnormalities corresponding to ischaemic territories.
• Coronary angiography can help distinguish pure AS from concomitant coronary disease.

Hypovolaemic Shock

• Both hypovolaemia and severe AS may present with hypotension, syncope, or collapse.
• Clinical context and rapid response to fluid resuscitation help differentiate hypovolaemia from fixed outflow obstruction due to AS.

Mitral Regurgitation (MR)

• MR produces a pansystolic murmur, best heard at the apex, often radiating to the axilla, in contrast to the ejection systolic murmur of AS which radiates to the carotids.
• Murmur intensity in MR does not vary with R–R interval, whereas in AS it may be accentuated following a long diastolic filling interval.
• Echocardiography is definitive, showing regurgitant flow into the left atrium and normal aortic valve morphology.

Mitral Stenosis (MS)

• MS presents with exertional dyspnoea and fatigue, similar to AS, but is distinguished by its diastolic rumbling murmur and presence of an opening snap.
• Echocardiography shows restricted mitral leaflet opening and transmitral diastolic gradients, without outflow obstruction at the aortic valve.

Mitral Valve Prolapse (MVP)

• MVP may present with atypical chest pain, palpitations, or syncope, overlapping with AS symptoms.
• The murmur in MVP is mid-systolic or late systolic, often preceded by a click, best heard at the apex.
• Echocardiography confirms leaflet prolapse and mitral regurgitation, but aortic valve morphology is normal.

Ischaemic Heart Disease (Stable Angina)

• Exertional angina occurs in both AS and coronary artery disease.
• ECG in stable ischaemic disease often shows Q waves in contiguous leads, whereas isolated AS usually lacks Q waves.
• Echocardiography may show preserved global systolic function in AS, versus regional wall motion abnormalities in ischaemic heart disease.

Hypertrophic Cardiomyopathy (HCM)

• Produces dynamic subvalvular obstruction and a systolic murmur that can mimic AS.
• Manoeuvres help distinguish the two: handgrip reduces the HCM murmur but does not significantly affect AS, while standing after squatting increases HCM murmur intensity.
• Echocardiography is diagnostic, showing asymmetric septal hypertrophy, dynamic LV outflow obstruction, and usually no calcification of the aortic cusps, particularly in younger patients.

Aortic Sclerosis

• Produces a systolic murmur without significant outflow obstruction.
• The murmur is typically softer, non-radiating, and the second heart sound (S2) remains normal and physiologically split.
• Doppler echocardiography demonstrates thickened valve leaflets but with minimal pressure gradient (<5 mmHg).

Subvalvular and Supravalvular Stenosis

Subvalvular stenosis 

• May result from fixed lesions (membranes, fibromuscular ridges) or dynamic obstruction (as in HCM).

Supravalvular stenosis 

• Most often congenital and occurs in syndromes such as Williams syndrome, where an hourglass narrowing of the ascending aorta above the sinuses of Valsalva is seen.

Pulmonary Disease

• Dyspnoea on exertion may arise from chronic pulmonary conditions rather than cardiac outflow obstruction.
• Pulmonary function tests and cardiopulmonary exercise testing are useful in distinguishing non-cardiac from valvular causes of breathlessness.

Indications for Aortic Valve Replacement

Symptomatic severe AS

• AVR is strongly recommended, including low-flow/low-gradient AS with reduced ejection fraction and evidence of persistent severe obstruction on dobutamine stress echocardiography.

Asymptomatic severe AS

• AVR is indicated if LVEF <50% or if the patient is undergoing cardiac surgery for another reason.
• AVR may be considered in asymptomatic patients with very severe AS, rapid progression, abnormal exercise testing, or markedly elevated B-type natriuretic peptide (BNP).

Choice of intervention

Surgical Aortic Valve Replacement (SAVR)

• Favoured in patients aged <65 years or with life expectancy >20 years, where long-term durability is critical.
• Prostheses:
  • Mechanical valves are suited for younger patients who can tolerate lifelong anticoagulation. They offer durability but require warfarin, as direct oral anticoagulants are not recommended.
  • Bioprosthetic valves are increasingly common, especially in patients >65 years, those who cannot take anticoagulation, or those preferring to avoid it. They have limited durability but avoid the risks of lifelong anticoagulation.

Transcatheter Aortic Valve Replacement (TAVR/TAVI)

• Now exceeds SAVR in many regions for isolated AS.
• Indicated in patients ≥80 years or with life expectancy <10 years, and those with prohibitive or high surgical risk.
• For patients aged 65–80 years, either SAVR or TAVR may be appropriate, based on patient preference, anatomical suitability, comorbidities, and surgical risk.
• Outcomes from large trials (e.g., PARTNER series) show TAVR is non-inferior to SAVR in high-, intermediate-, and selected low-risk patients, though long-term durability beyond 10 years remains under study.
• NICE and ESC recommend TAVR for patients ≥75 years, or those unsuitable for surgery, provided it is performed in specialised centres with experienced multidisciplinary teams.

Balloon Aortic Valvuloplasty

• Reserved as a bridge-to-definitive therapy or palliation in unstable patients, those requiring urgent non-cardiac surgery, or when prognosis is uncertain.
• Provides temporary haemodynamic relief but restenosis occurs within months and survival benefit is limited.

Medical Therapy

• Does not alter the natural history of AS but addresses comorbidities:
  • Diuretics: relieve pulmonary congestion in heart failure but must be used cautiously to avoid reducing preload.
  • Beta-blockers: may help with angina, but excessive bradycardia should be avoided.
  • Digoxin: may be used for atrial fibrillation with rapid ventricular response or heart failure.
  • ACE inhibitors/ARBs: safe in carefully monitored patients; observational data suggest possible benefit post-SAVR or TAVR.
  • Statins: reduce ischaemic events but do not slow AS progression.
  • Aspirin or clopidogrel: considered post-TAVR. NICE does not recommend anticoagulation for biological SAVR unless another indication exists.
• Morphine may be used acutely in severe decompensation to relieve dyspnoea and anxiety.
• Antibiotic prophylaxis for endocarditis is no longer routinely recommended.

Asymptomatic Aortic Stenosis

• Careful monitoring is crucial.
• ACC/AHA: serial echocardiography every 3–5 years for mild AS, 1–2 years for moderate, and every 6–12 months for severe disease.
• AVR is considered for:
  • LVEF <50% without other cause,
  • Very severe AS (Vmax >5 m/s or mean gradient ≥60 mmHg),
  • Rapid progression (Vmax increase ≥0.3 m/s per year),
  • Abnormal exercise test or markedly elevated BNP.
• ESC/European guidelines also emphasise intervention in asymptomatic severe AS with demonstrable systolic dysfunction or abnormal exercise response.
• NICE recommends regular clinical and echocardiographic review every 6–12 months in asymptomatic severe AS, with referral if progression or high-risk features emerge.

Risk Stratification and Shared Decision-Making

• STS-PROM or EuroSCORE II
  • Surgical risk is estimated using but must be complemented by frailty, comorbidity, and anatomical considerations.
  • Management decisions should involve a multidisciplinary heart team including cardiologists, surgeons, anaesthetists, imaging specialists, and geriatricians, ensuring individualised care.

Asymptomatic severe aortic stenosis

• Patients may remain without symptoms for many years despite severe left ventricular outflow tract obstruction.
• Annual mortality is less than 1%, and sudden cardiac death is relatively rare (~4% of cases).
• Risk stratification is improved by grading systems that integrate valve area, gradient, and flow patterns.
• Progression is more likely in older age, with severe leaflet calcification, hypertension, obesity, smoking, hyperlipidaemia, renal insufficiency, and raised lipoprotein(a).
• Doppler aortic jet velocity is the most reliable predictor of progression.
• Surveillance intervals: mild AS every 3–5 years, moderate AS every 1–2 years, and severe AS every 6–12 months.

Low-gradient aortic stenosis

• Up to 40% of patients with severe AS fall into this subgroup.
• Outcomes are generally worse compared with high-gradient AS, although the SEAS trial showed similarities to moderate AS in selected cases.
• Symptomatic paradoxical low-flow, low-gradient AS (with preserved LVEF) is associated with poor prognosis, potentially linked to heart failure with preserved ejection fraction.
• Prognostic markers include absence of contractile reserve, mean gradient <20 mmHg, very high BNP, and frailty.

Symptomatic severe aortic stenosis

• Prognosis is poor once symptoms occur unless valve replacement is performed.
• Median survival: 1.5–2 years with heart failure, ~3 years with syncope, ~5 years with angina.
• Mortality in untreated symptomatic disease is ~25% at 1 year and ~50% at 2 years, with more than half of deaths being sudden.
• Sudden death occurs in 8–34% of symptomatic patients without intervention.

Rate of haemodynamic progression

• Valve area narrows by ~0.1–0.3 cm²/year; mean gradient increases by 7–15 mmHg/year.
• Progression is faster in elderly patients and those with coronary artery disease or chronic kidney disease.

Surgical aortic valve replacement (SAVR)

• Remains the standard definitive treatment, with perioperative mortality now <3% overall and ~1% in patients <70 years.
• Long-term survival is excellent, with relative survival rates of 99% at 5 years, 85% at 10 years, and 82% at 15 years.
• Most patients demonstrate improvement in left ventricular function and heart failure symptoms.
• Poorer postoperative outcomes may result from prosthesis–patient mismatch, residual LV dysfunction, or significant comorbidities.

Transcatheter aortic valve replacement (TAVR)

• Comparable survival to SAVR in high- and intermediate-risk patients, and non-inferior or superior early outcomes in low-risk patients, although durability beyond 10 years is not yet established.
• In inoperable patients, TAVR provides a substantial survival benefit compared with medical therapy, with 1-year mortality reduction of ~20% and improved quality of life.
• Paravalvular regurgitation remains more common after TAVR than after surgery, though valve haemodynamics and symptom relief are similar.

Special populations

Bicuspid aortic valve disease

• Most patients eventually require intervention, often at a younger age than those with tricuspid valves.
• Post-AVR survival is significantly improved, but patients remain at risk for aortic root dilatation and dissection, requiring lifelong surveillance.

Epicardial adipose tissue (EAT)

• Increased EAT volume is associated with adverse outcomes after TAVR.
• Patients with higher EAT show greater all-cause mortality at 1, 2, and 3 years, highlighting its role as a prognostic marker.

Sudden cardiac death

• One of the most feared complications, occurring most frequently in symptomatic severe AS.
• Annual incidence is high in those with symptoms but remains low (~1%) in asymptomatic patients.
• Ventricular arrhythmias are the most common mechanism.
• Symptomatic patients should be urgently referred for valve replacement to reduce the risk.

Heart failure

• A frequent complication due to progressive left ventricular hypertrophy (LVH) and diastolic dysfunction.
• Diastolic dysfunction arises from hypertrophy and myocardial fibrosis, often persisting even after valve replacement.
• Systolic dysfunction may also occur, usually from afterload mismatch, leading to reduced ejection fraction and advanced symptoms.
• Pulmonary hypertension develops secondary to chronic elevation of left ventricular filling pressures.
• Medical therapy is limited; diuretics and cautious vasodilator use may provide relief, but definitive treatment requires valve replacement.

Conduction abnormalities

• Conduction disease may develop from calcification extending into the interventricular septum or due to long-standing LVH.
• Manifestations include atrioventricular block, bundle branch block, and the need for pacemaker implantation, particularly after valve replacement.

Infective endocarditis

• Patients with AS, especially those with bicuspid valves, have an increased risk of endocarditis.
• Prosthetic valves remain susceptible; any fever or new signs of valve dysfunction should prompt blood cultures and urgent assessment.

Bleeding complications

• Acquired von Willebrand syndrome is common due to high shear stress across the stenotic valve, leading to proteolysis of von Willebrand factor.
• This predisposes to mucocutaneous bleeding and gastrointestinal haemorrhage from angiodysplasia (Heyde’s syndrome).
• Bleeding risk often improves following valve replacement.

Embolic phenomena

• Calcific or thrombotic emboli from diseased valves may cause cerebral, coronary, or systemic embolisation.
• Risk is heightened in heavily calcified valves and in patients with mechanical prostheses if anticoagulation is suboptimal.

Complications of prosthetic valves

Infection

• Prosthetic valve endocarditis carries high morbidity and mortality.

Valve thrombosis

• Occurs primarily in mechanical valves without adequate anticoagulation, leading to obstruction or embolic events.

Re-stenosis

• May occur in bioprosthetic valves due to structural degeneration, presenting with recurrence of symptoms.

Valve dehiscence

• Suggested by new-onset heart failure or a diastolic murmur, indicating paravalvular leak.

1. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, Iung B, Otto CM, Pellikka PA, Quiñones M. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;22(1):1-23.
2. Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. 2008 ACC/AHA Guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol. 2008;52(13):e1-142.
3. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol. 2006;48(3):e1-148.
4. Braunwald E, Ross J, Morrow AG. Idiopathic hypertrophic subaortic stenosis: clinical, hemodynamic, and angiographic manifestations. Am J Med. 1960;29:924-45.
5. Brown JM, O'Brien SM, Wu C, et al. Isolated aortic valve replacement in North America comprising 108,687 patients: outcomes and temporal trends. J Thorac Cardiovasc Surg. 2009;137(1):82-90.
6. Brown JM, O'Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in Society of Thoracic Surgeons National Cardiac Database: outcomes and temporal trends. J Thorac Cardiovasc Surg. 2009;137(1):82-90.
7. Carabello BA. Clinical practice. Aortic stenosis. N Engl J Med. 2002;346(9):677-82.
8. Carabello BA, Paulus WJ. Aortic stenosis. Lancet. 2009;373(9667):956-66.
9. Clavel MA, Berthelot-Richer M, Capoulade R, et al. Impact of classic and paradoxical low flow on survival after aortic valve replacement for severe stenosis. J Am Coll Cardiol. 2015;65(7):645-53.
10. Coffey S, Cox B, Williams MJ. The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis. J Am Coll Cardiol. 2014;63(25 Pt A):2852-61.
11. Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352(23):2389-97.
12. Dahl JS, Videbæk L, Poulsen MK, Rudbæk TR, Pellikka PA, Møller JE. Global strain in severe aortic valve stenosis: relation to clinical outcome after aortic valve replacement. Circ Cardiovasc Imaging. 2012;5(5):613-20.
13. d’Arcy JL, Coffey S, Loudon MA, Kennedy A, Pearson-Stuttard J, Myerson SG, Prendergast BD. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J. 2016;37(47):3515-22.
14. Davies JE, Kaprielian R, Carabello BA. Pathophysiology of aortic valve stenosis: mechanisms and management. Heart. 2002;88(6):641-6.
15. Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol. 2012;60(19):1854-63.
16. Généreux P, Stone GW, O’Gara PT, et al. Natural history, diagnostic approaches, and therapeutic strategies for patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2016;67(19):2263-78.
17. Golia E, Limongelli G, Natale F, et al. Inflammatory and fibrotic pathways in aortic stenosis: a prospective study on epicardial adipose tissue volume and outcomes after TAVR. Int J Cardiol. 2019;274:139-45.
18. Kearney LG, Lu K, Ord M, et al. Global longitudinal strain is a strong independent predictor of all-cause mortality in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2012;13(10):827-33.
19. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-1607.
20. Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P. Calcific aortic stenosis. Nat Rev Dis Primers. 2016;2:16006.
21. Loscalzo J. From clinical observation to mechanism—Heyde’s syndrome. N Engl J Med. 2012;367(20):1954-6.
22. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380(18):1695-705.
23. Makkar RR, Thourani VH, Mack MJ, et al. Five-year outcomes of transcatheter or surgical aortic-valve replacement. N Engl J Med. 2020;382(9):799-809.
24. Magne J, Lancellotti P, Piérard LA. Exercise testing in asymptomatic severe aortic stenosis. JACC Cardiovasc Imaging. 2014;7(2):188-99.
25. Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014;64(1):83-99.
26. Mathieu P, Boulanger MC. Basic mechanisms of calcific aortic valve disease. Can J Cardiol. 2014;30(9):982-93.
27. National Institute for Health and Care Excellence (NICE). Heart valve disease presenting in adults: investigation and management. NICE Guideline NG208. 2021.
28. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease. Circulation. 2014;129(23):e521-643.
29. Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, Bogers AJ, Piazza N, Kappetein AP. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement. J Am Coll Cardiol. 2013;62(11):1002-12.
30. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease. J Am Coll Cardiol. 2021;77(4):e25-e197.
31. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Cardiol. 1989;13(3):545-50.
32. Otto CM, Prendergast B. Aortic-valve stenosis — from patients at risk to severe valve obstruction. N Engl J Med. 2014;371(8):744-56.
33. Pai RG, Kapoor N, Bansal RC, Varadarajan P. Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement. Ann Thorac Surg. 2006;82(6):2116-22.
34. Pellikka PA, Nishimura RA, Bailey KR, Tajik AJ. The natural history of adults with asymptomatic, haemodynamically significant aortic stenosis. J Am Coll Cardiol. 1990;15(5):1012-7.
35. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of adults with asymptomatic, haemodynamically significant aortic stenosis. Circulation. 2005;111(24):3290-5.
36. Rajamannan NM, Evans FJ, Aikawa E, et al. Calcific aortic valve disease: not simply a degenerative process. Circulation. 2011;124(16):1783-91.
37. Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis. Circulation. 2005;111(7):920-5.
38. Ross J, Braunwald E. Aortic stenosis. Circulation. 1968;38(1 Suppl):61-7.
39. Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis (SEAS study). N Engl J Med. 2008;359(13):1343-56.
40. Senechal M, Germain DP. Fabry disease: a functional and anatomical study of cardiac manifestations in 20 hemizygous male patients. Clin Genet. 2003;63(1):46-52.
41. Shah PM. Echocardiography in mitral valve disease. J Am Soc Echocardiogr. 2014;27(8):802-10.
42. Smith JG, Luk K, Schulz CA, et al. Association of low-density lipoprotein cholesterol–related genetic variants with aortic valve calcium and incident aortic stenosis. JAMA. 2014;312(17):1764-71.
43. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol. 1997;29(3):630-4.
44. Thaden JJ, Nkomo VT, Enriquez-Sarano M. The global burden of aortic stenosis. Prog Cardiovasc Dis. 2014;56(6):565-71.
45. Tzemos N, Therrien J, Yip J, et al. Outcomes in adults with bicuspid aortic valves. JAMA. 2008;300(11):1317-25.
46. Umana E, Ahmed W, Alpert MA. Valvular and perivalvular abnormalities in end-stage renal disease. Am J Med Sci. 2003;325(4):237-42.
47. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022;43(7):561-632.
48. Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82(6):2111-5.
49. Weber M, Arnold R, Rau M, et al. Relation of N-terminal pro–B-type natriuretic peptide to progression of aortic valve disease. Circulation. 2006;113(14):2064-70.
50. Williams RG, Pearson GD, Barst RJ, et al. Congenital heart disease in the adult: a new cardiovascular specialty. Circulation. 2006;114(18):1887-93.