Aortic stenosis

Article written and reviewed by Dr Luca Moretti

Aortic stenosis is characterized by reduced systolic opening of the valve, which obstructs ejection from the left ventricle, accelerates transvalvular flow and generates a pressure difference between the ventricle and aorta. In most adult forms the obstruction progresses slowly and imposes chronic pressure overload: hypertrophy, diastolic dysfunction and increased filling pressures initially maintain output, but over time promote ischemia, fibrosis and heart failure.

In high-income countries, the predominant cause is fibrocalcific degeneration of the tricuspid valve in older adults or of the bicuspid aortic valve, which becomes dysfunctional earlier. In low- and middle-income countries, rheumatic disease remains important and is often associated with mitral valve disease. Less common causes include a unicuspid valve, radiotherapy, severe mineral abnormalities in kidney disease, and inflammatory or fibrotic processes.

Calcific stenosis is the primary valve disease most frequently treated in Europe and North America. A meta-analysis in older adults estimated the prevalence of any aortic stenosis at 12.4% and severe disease at 3.4% in people older than 75 years, although with wide variability among studies. Population aging is rapidly increasing the absolute number of patients and also increases the frequency of frailty, coronary artery disease, kidney disease, amyloidosis and multiple valve lesions.

The term aortic stenosis should be reserved for true valvular obstruction. Sclerosis describes thickening or calcification without significant obstruction, whereas subaortic stenosis, dynamic obstruction in hypertrophic cardiomyopathy and supravalvular stenosis have different anatomy and treatment; correct localization by imaging and Doppler should therefore precede grading of severity.

Etiology, pathogenesis and pathophysiology

Calcific disease begins on the aortic side of the cusps, where oscillatory flow and mechanical stress favor endothelial dysfunction. ApoB-containing lipoproteins, including lipoprotein(a), enter the matrix and undergo oxidative and enzymatic modification. The innate response recruits monocytes and macrophages and activates mediators that alter the biology of valvular interstitial cells.

During the course of disease, interstitial cells can acquire myofibroblast-like and osteoblast-like phenotypes, while BMP, Wnt/β-catenin and Runx2 pathways, phosphate-mediated signaling, oxidative stress and oxidized phospholipid products promote deposition of mineralized matrix. Early microcalcifications increase stiffness and local stress and, as they coalesce into nodules, restrict cusp excursion and further alter force distribution, thereby sustaining progression.

The propagation phase shares factors with atherosclerosis, but the propagation phase has an autonomous osteogenic component. This explains why statins reduce atherosclerotic events but have not slowed progression of stenosis in randomized trials. Epidemiologic association does not imply that a treatment effective for coronary disease necessarily modifies established calcific valve tissue.

Lipoprotein(a) carries oxidized phospholipids, and genetic variants at the LPA locus are associated with calcification and stenosis. These data support a causal role in early disease, but do not yet demonstrate that pharmacologic lowering of Lp(a) arrests established clinical stenosis. Dedicated studies are required before the molecular rationale can be translated into therapy.

In chronic kidney disease, hyperphosphatemia, abnormalities of FGF23, parathyroid hormone and calcium-phosphate metabolism, inflammation and oxidative stress accelerate mineralization. Progression may be rapid, and calcification may involve the annulus and mitral apparatus. Treatment of mineral abnormalities is essential for general health, but is not a proven valve-specific therapy.

In bicuspid aortic valve, the raphe and asymmetric geometry produce eccentric jets and nonuniform stress. High mechanical load and tissue predisposition lead to fibrosis and calcium decades earlier than in a tricuspid valve. Coexisting dilation of the root or ascending aorta requires a decision that integrates both valve and aorta, not TAVI based on the gradient alone.

Rheumatic stenosis results from immune-mediated valvulitis followed by scarring. Commissural fusion, thickening and retraction produce morphology different from the degenerative calcific mass; associated regurgitation and mitral involvement are frequent. Aortic valvuloplasty does not provide the durability achieved in pulmonary stenosis or rheumatic mitral stenosis.

Reduction in valve area accelerates blood flow and generates a gradient whose magnitude depends simultaneously on the orifice and flow; the simplified Bernoulli equation expresses the instantaneous gradient as four times the square of velocity. Consequently, severe stenosis may produce a modest gradient in low-flow states, whereas moderate stenosis may show high velocities and gradients when cardiac output is increased.

The left ventricle must develop a systolic pressure greater than aortic pressure. According to Laplace's law, concentric hypertrophy initially normalizes wall stress, but it increases stiffness, impairs relaxation and makes filling more dependent on atrial contraction. Elevated end-diastolic pressure is transmitted to the atrium and pulmonary veins, causing dyspnea especially during exertion.

Myocardial mass and intracavitary pressure increase oxygen demand, while diastolic time, subendocardial perfusion pressure and relative capillary density may decrease. Subendocardial ischemia may therefore cause angina even in the absence of epicardial coronary stenoses. Concomitant coronary artery disease amplifies the imbalance and should be investigated before intervention according to the patient's profile.

Diffuse interstitial fibrosis and replacement scar mark the transition from compensation to myocardial damage. Replacement fibrosis visualized by late gadolinium enhancement tends to persist after valve replacement and is associated with worse prognosis. Ejection fraction may remain normal despite reduced longitudinal strain and contractile reserve.

When contractility declines, stroke volume falls and the gradient may decrease, producing low-flow, low-gradient aortic stenosis. Similar physiology may occur with preserved ejection fraction in a small, concentrically remodeled, restrictive ventricle. A low gradient therefore does not mean nonsevere disease.

As stenosis progresses, damage is no longer confined to the left ventricle but progressively involves the left atrium, pulmonary circulation, tricuspid valve and right ventricle. The extent of this extravalvular involvement is associated with higher mortality after replacement and, despite variability introduced by comorbidities, supports the rationale for recognizing and treating the disease before it reaches a multichamber stage.

Clinical manifestations

The functional history should seek a change in performance rather than simply ask whether symptoms are present. Many older adults gradually reduce activity and no longer expose themselves to the level of exertion that would produce dyspnea, angina or presyncope. Number of flights of stairs climbed, walking pace, need for pauses and comparison with activities in the previous year provide concrete measures.

Exertional dyspnea is often the first symptom. It results from increased filling pressure, reduced ability to augment output and impaired diastolic function. With progression, orthopnea, paroxysmal nocturnal dyspnea and pulmonary edema develop. Anemia, lung disease and deconditioning should be assessed because they may coexist.

Angina affects a proportion of symptomatic patients. It may result from coronary artery disease, but also from increased demand by the hypertrophied myocardium and reduced coronary reserve. Its relationship to exertion and relief with rest resemble atherosclerotic angina; absence of coronary artery disease does not reduce the prognostic significance of the symptom.

Exertional presyncope and syncope may occur when cardiac output cannot increase despite peripheral vasodilation or when a vasodepressor response is present. Syncope at rest requires evaluation for arrhythmias, conduction disorders and nonvalvular causes. Automatically attributing it to stenosis risks missing a treatable mechanism.

Fatigue, weakness and reduced cognitive function may reflect low output. Palpitations may indicate atrial fibrillation, which removes the atrial contribution to filling of a stiff ventricle and may precipitate heart failure, or ventricular arrhythmias. Sudden death is uncommon in a truly asymptomatic patient under surveillance, but risk increases with symptoms and advanced disease.

On inspection, a compensated patient may have no obvious signs. The classic carotid pulse is low-amplitude and delayed, but arterial stiffness, hypertension and concomitant aortic regurgitation may modify it. A narrow pulse pressure and low systolic pressure suggest reduced output in advanced stages.

Palpation may reveal a sustained apical impulse, reflecting pressure hypertrophy, and a systolic thrill at the base or suprasternal notch. A displaced impulse indicates dilation or associated disease and is not typical of compensated disease. A parasternal impulse suggests right-sided involvement or pulmonary hypertension.

The systolic ejection murmur has a crescendo-decrescendo configuration, is loudest at the aortic area and radiates to the carotids. The aortic component of the second heart sound may be reduced; an ejection click is more consistent with a congenital valve that remains mobile. Murmur intensity depends on flow and may decrease in end-stage low-output stenosis.

The Valsalva maneuver generally reduces the valvular murmur by decreasing flow and increases the murmur of dynamic hypertrophic obstruction. Squatting increases venous return and systemic resistance and can modify murmurs. These maneuvers are suggestive, but echocardiography and Doppler localize the obstruction more reliably.

Crackles, a third heart sound, elevated jugular venous pressure, hepatomegaly and edema indicate advanced heart failure. Hypotension, cool skin, oliguria and altered mental status identify shock. In this setting evaluation must be urgent and distinguish critical stenosis, ischemia, arrhythmia, infection and other precipitating causes.

Older adults may present with frailty, falls or loss of independence rather than typical symptoms. Stenosis may coexist with transthyretin amyloidosis, suggested by a history of bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, ventricular thickening and discordance between myocardial mass and electrocardiographic voltages. Coexistence does not exclude benefit from replacement, but influences prognosis and overall treatment.

Symptom severity does not vary linearly with the gradient. A patient with very severe stenosis may limit activity and report little, whereas anemia, atrial fibrillation or lung disease may make less advanced stenosis symptomatic. The clinical task is to establish a plausible relationship and not wait for the full classic triad.

Frailty and cognitive impairment alter presentation: falls, loss of autonomy, delirium during congestion and reduced appetite may replace the usual description of dyspnea. Involving family members and caregivers helps reconstruct decline and estimate whether correcting the valve can restore meaningful function.

Investigations and diagnosis

The electrocardiogram may show left ventricular hypertrophy, strain, ST-T abnormalities, left atrial enlargement, atrial fibrillation or conduction disturbances. A normal ECG does not exclude severe stenosis. Chest radiography may show calcification, post-stenotic aortic dilation, congestion and late cardiomegaly, but does not quantify obstruction.

Transthoracic echocardiography is the fundamental test. Morphology defines the number of cusps, mobility, calcification and other lesions; chamber assessment documents hypertrophy, function, volumes, atrial size, pulmonary pressure and associated valve disease. Blood pressure should be controlled and recorded because elevated afterload alters flow and assessment.

Continuous-wave Doppler should interrogate the jet from apical, right parasternal, suprasternal and, when necessary, subcostal windows, using a nonimaging probe for optimal alignment. The highest peak velocity, not an average among windows, represents the jet. Misalignment clinically significantly underestimates velocity and gradient.

The peak Doppler gradient is derived from 4V²; the mean gradient is the integral of pressure differences during ejection and is more useful. It is not the same as the peak-to-peak gradient measured invasively at different times. Pressure recovery can explain differences between Doppler and invasive measurements, especially in small aortas.

Valve area is calculated by applying conservation of stroke volume between the left ventricular outflow tract and the valve. Outflow tract area depends on the square of the diameter and is the principal source of error; the pulsed-wave Doppler sampling site should correspond to the diameter measurement. CT and 3D imaging show that the tract is often elliptical, potentially leading to underestimation of area when a circular cross-section is assumed.

The dimensionless index is the ratio of the velocity-time integral in the outflow tract to the aortic velocity-time integral and does not require measurement of diameter. A value below 0.25 makes severe stenosis highly likely. It does not replace valve area and gradients, but is useful when the diameter is uncertain or parameters are discordant.

According to the 2025 ESC/EACTS guidelines, severe high-gradient aortic stenosis is confirmed by concordance of the following parameters:

• Mean transaortic gradient at least 40 mmHg.
• Peak aortic jet velocity at least 4.0 m/s.
• Valve area no greater than 1.0 cm², or indexed valve area no greater than 0.6 cm²/m².

Severe high-gradient stenosis is considered severe regardless of ejection fraction and flow status. If velocity, gradient and area are discordant, the diagnosis should not be assigned by selecting the most severe value: measurements, stroke volume index, blood pressure, ejection time, high or low output and morphology should be reviewed.

A stroke volume index no greater than 35 mL/m² conventionally defines low flow. With valve area no greater than 1.0 cm² and gradient below 40 mmHg, one distinguishes the classical form with ejection fraction below 50%, the paradoxical form with preserved ejection fraction and low flow, and the normal-flow form with preserved ejection fraction. The dedicated page on low-flow, low-gradient aortic stenosis describes confirmation of these patterns.

In the classical form, low-dose dobutamine echocardiography assesses increases in stroke volume, gradient and valve area. An increase in stroke volume of at least 20% traditionally defines flow reserve. If flow increases and valve area remains no greater than 1.0 cm² while the gradient reaches the severe range, obstruction is truly severe; if the area increases above 1.0 cm², stenosis is pseudo-severe. Projected valve area at normalized flow helps when the increase in flow is incomplete.

The CT calcium score is independent of flow. Values above 2000 Agatston units in men and 1200 in women support severe stenosis with good sensitivity and specificity; values above 3000 and 1600 are highly specific, whereas below 1600 and 800 severe stenosis is unlikely. Bicuspid valves, amyloidosis and predominantly fibrotic forms require caution because severe disease may occur with less calcium.

Exercise testing is recommended to clarify symptom status in apparently asymptomatic patients with severe stenosis when it is safe and feasible. Attributable symptoms or an abnormal blood-pressure response reclassify risk. The test is not indicated to provoke ischemia in a patient who is already symptomatic with severe stenosis.

BNP or NT-proBNP above three times the age- and sex-corrected upper limit of normal, rapid velocity progression, severe calcification, very high velocity, ejection fraction below 55% and reduced longitudinal strain are prognostic markers. They do not replace the diagnosis, but contribute to decision-making in asymptomatic patients.

Magnetic resonance imaging characterizes myocardial mass, volumes and fibrosis. CT angiography is mandatory for TAVI planning to assess the annulus, coronary ostia, sinuses, sinotubular junction, outflow tract calcium and vascular access. CT coronary angiography or invasive angiography assesses coronary disease according to probability and planned procedure; invasive hemodynamic catheterization is reserved for persistent discordance that remains unresolved.

Differential diagnoses include sclerosis without stenosis, dynamic obstruction or a subaortic membrane, supravalvular stenosis, high-output states and prosthesis-patient mismatch after replacement. Amyloidosis, hypertension and cardiomyopathy may also explain symptoms and wall thickening. The final assessment requires consistency between severity and clinical presentation, or explicit resolution of any discordance.

Treatment and prognosis

No pharmacologic treatment has changed the natural history of calcific stenosis. Statins do not slow obstruction in clinical trials and should not be prescribed for this purpose, although they remain indicated for atherosclerotic risk. Drugs targeting calcification pathways have not yet produced a validated therapy.

Hypertension should be treated to reduce additional arterial afterload, with cautious titration; the 2025 guidelines generally favor renin-angiotensin system blockers. Diuretics may relieve congestion, but excessive reduction of preload causes hypotension and low output. In heart failure with reduced ejection fraction, standard therapy is initiated and optimized without delaying valve replacement.

Valve replacement is the only treatment capable of removing the obstruction. It is recommended in all eligible patients with symptomatic severe high-gradient stenosis when life expectancy exceeds one year and expected benefit is not futile. In low-gradient forms, intervention first requires confirmation that obstruction is truly severe.

In asymptomatic patients, an ejection fraction below 50% without another cause is an indication for intervention. An exercise test that provokes symptoms means the patient should be treated as symptomatic. Very high velocity, rapid progression, heavy calcification, elevated natriuretic peptides and ejection fraction below 55% strengthen the case for early intervention.

The RECOVERY and AVATAR trials showed benefits of early surgery in selected low-risk populations; EARLY TAVR reduced the composite of death, stroke or cardiovascular hospitalization compared with surveillance, mainly by reducing hospitalizations and urgent conversion to intervention, whereas the individual components of death and stroke did not differ significantly in the published follow-up, whose median was 3.8 years. The 10-year follow-up of RECOVERY published in 2026 confirmed a survival benefit in relatively young patients with very severe stenosis.

The 2025 ESC/EACTS guidelines therefore consider early intervention an alternative to surveillance in asymptomatic patients with severe high-gradient stenosis and low procedural risk, after exercise testing and shared decision-making. Generalization requires caution: the trials selected specific anatomies, ages and risk profiles, and earlier prosthesis implantation prolongs exposure to structural deterioration and reintervention.

SAVR removes the diseased valve, permits implantation of a mechanical or biological prosthesis, and allows concomitant CABG, aortic surgery and treatment of other valves. According to the 2025 ESC/EACTS guidelines, it is preferred in low-risk patients younger than 70 years, in younger patients with bicuspid valves, in aortopathy, complex coronary artery disease, endocarditis, anatomy unfavorable for TAVI, and when a mechanical prosthesis is required.

TAVI implants a bioprosthesis by a transcatheter approach. It is recommended as the primary modality in patients aged at least 70 years with a tricuspid valve, suitable anatomy and transfemoral access. Compared with surgery, it provides faster recovery and less severe bleeding, atrial fibrillation and kidney injury, but more vascular complications, paravalvular leak and pacemaker implantation, with differences depending on the device.

In the age range not defined by these cutoffs, Heart Team selection considers risk, life expectancy, frailty, access, annular size, calcium distribution, coronary ostia, need for revascularization, risk of prosthesis-patient mismatch and future coronary access. Durability through 10 years appears favorable for studied devices, but lifetime data in younger adults remain limited.

Bicuspid valves were excluded from most trials. A calcified raphe, asymmetric calcium, a dilated root and an elliptical annulus increase the risks of leak, rupture and sizing difficulty. Surgery remains the primary approach in younger patients or when aortopathy is present; TAVI may be considered in patients at increased risk with selected anatomy and at an experienced center.

Selection between a mechanical and biological prosthesis after SAVR balances anticoagulation and durability. The 2025 European guidelines generally favor a mechanical prosthesis below age 60 and a biological prosthesis above age 65 in the aortic position, leaving the intermediate range to individual decision-making. Pregnancy plans, bleeding risk, adherence and valve-in-valve strategy modify the choice.

The Ross procedure uses the pulmonary autograft and may provide excellent survival in selected young patients at experienced centers while avoiding anticoagulation, but it converts single-valve disease into a condition in which two valves may ultimately require reintervention. It is not a routine procedure and requires dedicated expertise.

Balloon valvuloplasty produces temporary fracture or separation of calcium and a limited increase in valve area. Restenosis is rapid and risks include severe regurgitation, stroke and vascular complications. It is reserved as a bridge to TAVI or SAVR in selected unstable patients or before urgent high-risk noncardiac surgery.

In asymptomatic severe stenosis managed with surveillance, follow-up should occur at least every six months and include education about symptom recognition, clinical examination and echocardiography; serial BNP may help. Moderate stenosis is reassessed at least annually, especially when heavily calcified, whereas mild forms in younger patients without significant calcium may be checked every two or three years.

After replacement, an early baseline echocardiogram and subsequent surveillance are performed. Rehabilitation improves exercise capacity and independence, particularly after surgery and in older adults. Atrial fibrillation, heart failure and coronary artery disease continue to require treatment even after the gradient has been corrected.

The prognosis of untreated symptomatic stenosis is poor. Replacement markedly improves survival and quality of life, but benefit is smaller in the presence of fibrosis, multichamber cardiac damage, right ventricular dysfunction, pulmonary hypertension, frailty and end-stage noncardiac disease. Assessment of futility should be individualized and not based on age alone.

Complications

The most common complication of progression is heart failure. Diastolic dysfunction and rising filling pressures initially cause exertional dyspnea; with fibrosis and loss of contractility, output falls and congestion becomes persistent. An episode of atrial fibrillation, infection, anemia or hypertension can precipitate pulmonary edema.

Myocardial ischemia results from mismatch between supply and demand. Hypertrophy, high intracavitary pressure and reduced capillary density increase demand and compress the microcirculation; elevated end-diastolic pressure reduces the subendocardial perfusion gradient. Concomitant coronary stenosis adds an epicardial limitation.

Syncope can cause trauma and loss of independence. The exertional mechanism is hemodynamic, but conduction block, tachyarrhythmias and a vasodepressor response are possible. Calcium may extend into the fibrous skeleton and contribute to conduction disorders, especially after intervention.

Atrial fibrillation removes the atrial contribution to filling, shortens diastole and can precipitate low output and congestion in a stiff ventricle. Atrial dilation and elevated pressure favor its development. Thromboembolic risk is managed according to atrial fibrillation guidance and the presence of a prosthetic valve.

Ventricular arrhythmias may arise from ischemia and fibrosis. Sudden death in asymptomatic patients is less frequent than historically feared, but the risk is not zero and increases with severity, symptoms and dysfunction. Syncope and palpitations require appropriate monitoring and should not be considered inevitable.

Pulmonary hypertension is initially post-capillary; vascular remodeling may make it combined pre- and post-capillary. The right ventricle dilates and fails, the tricuspid annulus enlarges and regurgitation develops. This stage is associated with worse prognosis even after replacement.

Cardiogenic shock may occur in end-stage stenosis or following a precipitating event. The ventricle cannot increase output through the fixed orifice, while tachycardia and hypotension reduce filling and coronary perfusion. Stabilization, urgent assessment and a replacement or bridging strategy are essential.

Endocarditis may affect the stenotic valve and cause acute regurgitation, abscesses and emboli. Transition from chronic stenosis to an acute mixed lesion produces disproportionate deterioration. Fever and new instability require blood cultures, echocardiography and a dedicated diagnostic and therapeutic pathway.

Calcific material may very rarely embolize spontaneously or during procedures. TAVI carries a risk of clinical stroke and silent cerebral lesions; embolic protection does not replace careful selection and technique. Antithrombotic treatment should balance ischemic and bleeding risk according to prosthesis type and concomitant indications.

Complications of TAVI include vascular injury, bleeding, paravalvular leak, annular rupture, coronary obstruction, pacemaker implantation, thrombosis and kidney injury. Complications of surgery include bleeding, atrial fibrillation, stroke, kidney injury, infection, prosthetic dysfunction and sternotomy-related complications. Individual probability depends on anatomy and comorbidities.

Prosthesis-patient mismatch leaves an effective orifice area that is too small for body surface area and a residual gradient. A small annulus requires planning among surgical enlargement, a supra-annular prosthesis and TAVI. Severe mismatch limits regression of hypertrophy and may worsen outcomes.

Paravalvular leak is more common after TAVI and results from incomplete apposition, calcium or sizing. Significant regurgitation increases volume overload and mortality and may require closure or reintervention. Small leaks should be followed and interpreted together with hemolysis, symptoms and remodeling.

Bioprostheses may deteriorate through calcification, tearing or fibrosis; thrombosis and endocarditis may mimic degeneration. Valve-in-valve strategies reduce the risk of redo surgery in selected patients, but may cause mismatch and coronary obstruction. Coronary access after TAVI and after a future TAV-in-TAV procedure should be considered from the first implantation.

Irreversible damage is the most underestimated complication of waiting. Fibrosis, right ventricular dysfunction, pulmonary hypertension, renal and hepatic damage and frailty may persist after a technically successful procedure. Structured follow-up aims to correct the valve before stenosis becomes a systemic disease.