Aortic Stenosis

Background #

Aortic stenosis (AS) is the narrowing of the aortic valve orifice, obstructing blood flow from the left ventricle into the aorta during systole. This results in increased left ventricular pressure, concentric hypertrophy, and eventually left ventricular dysfunction. If untreated, AS can lead to syncope, angina, heart failure, and sudden cardiac death.

Classification/Types

By Etiology:

• Calcific (Degenerative) AS: Most common in the elderly due to progressive calcium deposition on a trileaflet valve
• Bicuspid Aortic Valve (Congenital): Predisposes to early calcification and stenosis; often presents before age 65. Bicuspid aortic valve is the most common congenital heart disease, affecting 0.5-2% of the general population [1,2]
• Rheumatic AS: Rare in high-income countries; commissural fusion from rheumatic fever
• Radiation-Induced AS: Post-mediastinal radiation leading to fibrosis and calcification

By Severity (Based on Echocardiographic Criteria):

Severity	Aortic Valve Area	Mean Gradient	Peak Velocity
Mild	>1.5 cm²	<20 mmHg	<3.0 m/s
Moderate	1.0–1.5 cm²	20–39 mmHg	3.0–4.0 m/s
Severe	<1.0 cm²	≥40 mmHg	>4.0 m/s

Epidemiology

Aortic stenosis is currently recognized as the third most frequent cardiovascular disease in persons aged above 60 years, after atherosclerotic disease and hypertension [3]. The prevalence of AS is 2-3% in individuals aged over 65 years, and with an aging global population, the prevalence is anticipated to double by 2050 [4].

The pooled prevalence of all AS in the elderly (≥75 years) is 12.4%, and the prevalence of severe AS is 3.4% [5]. Over a 20-year period, the population incidence of severe AS remained stable at approximately 52 per 100,000 patient-years, though the absolute case burden increased due to population growth [6]. The age-standardized AS prevalence increased from 589 to 754 cases per 100,000 during a recent seven-year study period [7].

Sex: More common in males, especially with bicuspid valve disease [1]

Age: Degenerative AS typically manifests >65 years old; bicuspid valve disease presents earlier, typically at age 50-70 years

Geography: Degenerative AS is common in high-income countries; rheumatic causes still present in low- and middle-income regions [8]

Comorbidities: Often coexists with hypertension, coronary artery disease, and diabetes

Pathophysiology

Calcific aortic stenosis is an active multifactorial process characterized by progressive fibro-calcific remodeling and thickening of the aortic valve leaflets [3]. The disease process shares similarities with atherosclerosis, involving hemodynamic flow factors, genetic factors, lipoprotein deposition (particularly Lp(a)), oxidation, chronic inflammation, and immunomodulators leading to osteoblastic transformation of valvular interstitial cells [3,9].

The pathophysiological cascade begins with endothelial damage and lipoprotein deposition on the valve leaflets, triggering inflammatory responses and oxidative stress [9]. This leads to myofibroblast differentiation and activation of key signaling pathways including NOTCH, Wnt/β-catenin, BMP2/4, and RANK/RANKL/OPG, along with increased expression of transcription factors Runx2 and Msx2, which drive osteoblast-like differentiation of valvular interstitial cells [4,9].

Increased valvular resistance in progressive AS causes left ventricular (LV) pressure overload, initially leading to compensatory increase in LV wall thickness to normalize systolic wall stress [10]. However, LV hypertrophy is associated with maladaptive remodeling changes that ultimately diminish LV performance. A combination of increased myocardial oxygen demand, reduced coronary flow reserve, and microvascular dysfunction leads to subendocardial ischemia and interstitial fibrosis, potentiating increased LV stiffness and impaired relaxation [10,11].

With disease progression and persistently elevated left-sided heart pressures, pulmonary vascular changes precipitate pulmonary hypertension. Progressive right ventricle-pulmonary artery uncoupling and right ventricular dysfunction can occur, with right ventricular failure marked by symptoms related to elevated right-sided filling pressures [10].

Etiology #

• Calcific degeneration of a normal or bicuspid valve
• Congenital bicuspid aortic valve (0.5-2% of population) [1,2]
• Rheumatic heart disease
• Prior chest radiation
• Rare: systemic conditions (e.g., Paget disease, end-stage renal disease with hyperparathyroidism)

Risk Factors

• Age >65 years
• Congenital bicuspid aortic valve
• Rheumatic fever history
• Male sex
• Hyperlipidemia, particularly elevated Lp(a) [3]
• Smoking
• Hypertension
• Chronic kidney disease

Clinical Presentation #

I) History (Symptoms)

Often asymptomatic until severe. Classic triad when symptomatic:

• Angina: Due to increased myocardial oxygen demand and decreased perfusion
• Syncope: Especially on exertion from fixed cardiac output
• Dyspnea/Heart failure symptoms: From elevated LVEDP and pulmonary congestion

Other symptoms:

• Fatigue
• Dizziness
• Decreased exercise tolerance
• Sudden cardiac death (in rare, advanced cases)

II) Physical Exam (Signs)

General Exam:

• Patients may appear well-compensated in early stages
• In advanced disease, patients may show signs of heart failure and decreased functional capacity

Vital Signs:

• Narrow pulse pressure
• Delayed and diminished carotid upstroke (pulsus parvus et tardus)

Cardiac Exam:

• Harsh crescendo-decrescendo systolic murmur at right upper sternal border, radiating to the carotids
• S4 gallop (due to stiff LV)
• Soft or absent A2 (delayed aortic valve closure)
• Paradoxical splitting of S2

Pulmonary:

• Rales in advanced heart failure

Peripheral:

• Cool extremities, signs of low output
• Peripheral edema (late)

Differential Diagnosis (DDx) #

• Hypertrophic obstructive cardiomyopathy (HOCM)
• Subaortic stenosis
• Mitral regurgitation
• Aortic sclerosis (no obstruction)
• Pulmonary embolism (if presenting with syncope)
• Anemia (if exertional symptoms are out of proportion)

Diagnostic Testing #

Initial Tests:

Transthoracic Echocardiogram (TTE):

• Determines severity (valve area, gradients, velocity)
• Assesses LV function, wall thickness, and aortic root
• Global longitudinal strain imaging can detect occult myocardial dysfunction [11]

Electrocardiogram (ECG):

• LV hypertrophy (LVH)
• Left atrial enlargement
• Possible conduction abnormalities (e.g., LBBB)

Chest X-ray:

• Post-stenotic dilation of the ascending aorta
• Pulmonary congestion in decompensated heart failure

BNP/NT-proBNP:

• Elevated in symptomatic or decompensated patients

Cardiac CT (Calcium Scoring):

• Used if echo inconclusive, especially for valve morphology
• Useful for risk stratification

Cardiac MRI:

• Evidence of focal myocardial fibrosis (using late gadolinium enhancement) or diffuse interstitial myocardial fibrosis (using T1 mapping and myocardial extracellular volume quantitation) [11]

Cardiac Catheterization:

• Confirms severity if noninvasive data is conflicting
• Assesses coronary anatomy preoperatively

Treatment #

There is no medical therapy proven to halt disease progression; management focuses on timely intervention and symptom control.

I) Medical Management

Conservative Measures:

• Diuretics for pulmonary congestion (use cautiously to avoid hypotension)
• Beta-blockers or ACE inhibitors for comorbid conditions (e.g., hypertension, CAD) but used cautiously in severe AS
• Statins for concomitant atherosclerotic disease (not shown to slow AS progression)
• Hypertension should be treated in patients with asymptomatic AS [12]

II) Interventional/Surgical

Surgical Aortic Valve Replacement (SAVR):

According to current ACC/AHA guidelines [12,13], SAVR is recommended for:

• Symptomatic patients with severe high-gradient AS (Class I)
• Asymptomatic patients with severe AS and LVEF <50% without another cause (Class I)
• Patients undergoing other cardiac surgery (Class I)
• Patients <65 years of age or life expectancy >20 years (preferred over TAVR) [13]

Transcatheter Aortic Valve Replacement (TAVR):

TAVR indications have expanded significantly based on landmark trials including PARTNER 3 and Evolut Low Risk [14,15,16]:

• Symptomatic severe AS across all surgical risk categories [12,13]
• Age >80 years or life expectancy <10 years (preferred over SAVR) [13]
• Age 65-80 years: either TAVR or SAVR based on shared decision-making, anatomic suitability, and patient preference (Class I) [12,13]
• The PARTNER 3 trial demonstrated that TAVR with the balloon-expandable SAPIEN 3 valve was non-inferior to SAVR at 5 years for the composite endpoint of death, stroke, or rehospitalization in low-risk patients [14]
• The Evolut Low Risk trial showed that TAVR with self-expanding valves resulted in sustained non-inferiority to SAVR for all-cause mortality or disabling stroke at 5 years (15.5% vs 16.4%) [16]

Important Considerations:

• All patients with severe AS being considered for valve intervention should be evaluated by a multidisciplinary Heart Team [12,13]
• The choice between TAVR and SAVR should involve shared decision-making considering lifetime risks, benefits, valve type, valve durability, and procedural approach [12]
• For bicuspid aortic valve, current guidelines suggest SAVR may be more appropriate, though recent data supports TAVR as a viable option in selected low-risk patients [17]

Balloon Aortic Valvuloplasty:

• Temporary measure in select non-surgical patients (e.g., bridge to TAVR or destination therapy in prohibitive-risk patients)

Consults #

• Cardiology: All moderate to severe AS, or symptomatic patients
• Cardiothoracic Surgery: For SAVR evaluation
• Interventional Cardiology: For TAVR eligibility
• Anesthesiology: If surgery planned (pre-op evaluation)
• Primary Care: For comorbidity optimization

Patient Education #

Counseling

• Educate on symptoms that warrant urgent evaluation: syncope, worsening dyspnea, chest pain
• Emphasize need for regular follow-up and imaging
• Avoid strenuous activity in symptomatic patients
• Limit salt intake if volume overload present
• Maintain good dental hygiene to reduce endocarditis risk

Screening

The U.S. Preventive Services Task Force (USPSTF) does not have specific recommendations for screening asymptomatic adults for aortic stenosis. However, the USPSTF recommends:

• Hypertension Screening: Recommended for all adults 18 years or older [18]
• Cardiovascular Disease Risk Assessment: Using the Pooled Cohort Equations to assess CVD risk [19]
• Statin Use: For primary prevention in adults aged 40-75 years with 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater (Grade B recommendation) [20]
• Screening with ECG: Recommended against routine screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at low risk (Grade D) [19]

Vaccinations

The USPSTF defers to the CDC Advisory Committee on Immunization Practices (ACIP) for immunization recommendations [21]. Based on current CDC/ACIP guidelines, patients with aortic stenosis should receive:

• Annual Influenza Vaccine: Recommended for all adults ≥6 months of age
• Pneumococcal Vaccination:
  • Adults ≥65 years: PCV20 or PCV21 (single dose), or PCV15 followed by PPSV23 [22]
  • Adults 19-64 years with cardiovascular disease or risk factors: PCV15 followed by PPSV23, or PCV20/PCV21 [22]
• COVID-19 Vaccination: Age-appropriate vaccination as per current CDC recommendations
• Tdap/Td: Tdap once, then Td booster every 10 years

Follow-Up #

Echocardiography:

• Mild AS: every 3–5 years
• Moderate AS: every 1–2 years
• Severe AS: every 6–12 months (or sooner if symptomatic)

Monitoring:

• Monitor for symptom development (dyspnea, angina, syncope)
• Assess LV function and new conduction abnormalities
• Reevaluate for valve intervention as disease progresses
• Cardiac damage staging based on extent of cardiac remodeling can predict outcomes and guide timing of intervention [23]

Optimization:

• Optimize cardiovascular risk factors (e.g., BP, lipids, diabetes)
• Regular assessment of functional status and quality of life

References #

1. Aschauer J, Zilberszac R, Gleiss A, et al. Long-term outcome of bicuspid aortic valve disease. Eur Heart J Cardiovasc Imaging. 2024;25(3):425-435. https://doi.org/10.1093/ehjci/jead312
2. Kostopoulou A, Karyofyllis P, Lipiecki J. Bicuspid Aortic Valve in Children and Young Adults for Cardiologists and Cardiac Surgeons: State-of-the-Art of Literature Review. J Clin Med. 2024;11(10):317. https://doi.org/10.3390/jcdd11100317
3. Halapas A, Cokkinos DV. Aortic Stenosis Prevention: Is a New Cardiovascular Disease Paradigm Coming of Age? J Clin Med. 2025;14(3):903. https://doi.org/10.3390/jcm14030903
4. Sato Y, Lee JJ, Joho A, et al. Age Differences in Aortic Stenosis. Rev Cardiovasc Med. 2025;26(4):28185. https://doi.org/10.31083/RCM28185
5. Osnabrugge RLJ, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013;62(11):1002-1012. https://doi.org/10.1016/j.jacc.2013.05.015
6. Benfari G, Essayagh B, Michelena HI, et al. Severe aortic stenosis: secular trends of incidence and outcomes. Eur Heart J. 2024;45(21):1877-1886. https://doi.org/10.1093/eurheartj/ehad887
7. Patel A, Swaminath A, Strom JB, et al. Temporal trends in the prevalence and severity of aortic stenosis within a contemporary and diverse community-based cohort. Am J Cardiol. 2023;203:188-195. https://doi.org/10.1016/j.amjcard.2023.06.082
8. Coffey S, Cairns BJ, Iung B. The modern epidemiology of heart valve disease. Heart. 2016;102(1):75-85. https://doi.org/10.1136/heartjnl-2014-307020
9. Nakagawa R, Lindman BR. Pathophysiology of aortic valve disease. Future Cardiol. 2011;7(5):629-642. https://doi.org/10.2217/fca.11.41
10. Androshchuk V, Chehab O, Wilcox J, et al. Evolving perspectives on aortic stenosis: the increasing importance of evaluating the right ventricle before aortic valve intervention. Front Cardiovasc Med. 2025;11:1506993. https://doi.org/10.3389/fcvm.2024.1506993
11. Mengi S, Januzzi JL, Cavalcante JL, et al. Aortic Stenosis, Heart Failure, and Aortic Valve Replacement. JAMA Cardiol. 2024;9(12):1159-1168. https://doi.org/10.1001/jamacardio.2024.3205
12. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;143(5):e72-e227. https://doi.org/10.1161/CIR.0000000000000923
13. Lee G, Chikwe J, Milojevic M, et al. ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis. Eur Heart J. 2023;44(10):796-812. https://doi.org/10.1093/eurheartj/ehac803
14. 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):1695-1705. https://doi.org/10.1056/NEJMoa1814052
15. Braghiroli J, Kapoor K, Thielhelm TP, et al. Transcatheter aortic valve replacement in low risk patients: a review of PARTNER 3 and Evolut low risk trials. Cardiovasc Diagn Ther. 2020;10(1):59-71. https://doi.org/10.21037/cdt.2019.09.12
16. Thyregod HGH, Ihlemann N, Jørgensen TH, et al. Five-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2025;85(15):1361-1373. https://doi.org/10.1016/j.jacc.2025.03.004
17. Zahr F, Ramlawi B, Reardon MJ, et al. 3-Year Outcomes From the Evolut Low Risk TAVR Bicuspid Study. JACC Cardiovasc Interv. 2024;17(14):1667-1675. https://doi.org/10.1016/j.jcin.2024.05.017
18. US Preventive Services Task Force. Screening for Hypertension in Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2021;325(16):1650-1656. https://doi.org/10.1001/jama.2021.4987
19. US Preventive Services Task Force. Screening for Cardiovascular Disease Risk With Electrocardiography: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319(22):2308-2314. https://doi.org/10.1001/jama.2018.6848
20. US Preventive Services Task Force. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;328(8):746-753. https://doi.org/10.1001/jama.2022.13044
21. US Preventive Services Task Force. Immunizations for Adults. Available at: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/immunizations-for-adults [Accessed November 22, 2025]
22. Centers for Disease Control and Prevention. Pneumococcal Vaccine Recommendations. Updated October 2024. Available at: https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html
23. Harmon E, Howard T, Tereshchenko L, et al. Cardiac Damage Staging, Moderate Aortic Stenosis, and the Impact of Aortic Valve Replacement. JACC Adv. 2025;4(12):102348. https://doi.org/10.1016/j.jacadv.2025.102348

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