What are the possible causes of an aortic valve lesion and how should the work‑up be approached?

Differential Diagnosis of Aortic Valve Lesions

Aortic valve lesions arise from valvular pathology (congenital, degenerative, inflammatory, or infectious) or aortic root disease (genetic, inflammatory, or traumatic), and the diagnostic approach must systematically distinguish between these categories to guide management and prevent life-threatening complications.

Primary Valvular Causes

Congenital Abnormalities

• Bicuspid aortic valve is the most common congenital cause, present in 1.5-2.0% of the general population, and predisposes to both stenosis and regurgitation through premature calcification 1, 2, 3, 4
• Bicuspid valves are frequently associated with ascending aortic dilation independent of valve function, requiring surveillance of both structures 3, 4
• Quadricuspid aortic valve is a rare congenital variant that may present with regurgitation or mixed lesions 5

Degenerative/Calcific Disease

• Calcific aortic stenosis represents the most frequent valvular heart disease in Europe and North America, affecting 2-7% of adults over 65 years 1
• Early atherosclerosis-like lesions begin in young adulthood (ages 20-40), characterized by subendothelial lipid deposition, macrophage infiltration, and microscopic calcification on the aortic side of leaflets 6, 7
• These lesions progress with age: mean lesion area increases from 0.1-0.2 mm² in young adults to 1.3-2.3 mm² in elderly patients 7
• The process involves inflammatory infiltrate with foam cell macrophages, T lymphocytes, and basement membrane disruption—similar to atherosclerosis but with prominent mineralization 6

Infectious Causes

• Infective endocarditis causes direct valvular destruction and represents approximately 12.5% of surgical cases of isolated aortic regurgitation 3
• Aortic valve endocarditis can create "jet lesions" on the mitral valve from the regurgitant stream, potentially forming infected aneurysms that may rupture 8
• The aortic valve is most commonly affected in native valve endocarditis 8

Rheumatic Disease

• Rheumatic heart disease causes commissural fusion and leaflet thickening, though it has become rare in developed countries 1, 3
• Rheumatic disease affects both aortic and mitral valves in most cases 1

Aortic Root and Ascending Aorta Pathology

Genetic Connective Tissue Disorders

• Marfan syndrome (FBN1 mutation) causes aortic root aneurysm formation and regurgitation, with dissection risk at smaller diameters (≥4.0 cm warrants surgical consideration) 9, 3
• Loeys-Dietz syndrome demonstrates aggressive thoracic aortic disease with aneurysms in up to 98% of patients 3
• Mutations in TGFBR1/TGFBR2 genes and smooth muscle contractile proteins predispose to dissection at diameters ≤5.0 cm 9
• More than half of dissection patients have aortic diameters <5.5 cm, and dissection can occur with normal diameter 9

Inflammatory Aortitis

• Takayasu arteritis causes inflammatory infiltrate, smooth muscle necrosis, and fibrosis within the aortic wall 9
• Giant cell arteritis affects large and medium-sized vessels including the aorta 9
• Ankylosing spondylitis affects both the aorta and valve, causing abnormalities in both structures 1, 3
• Behçet's disease and rheumatoid arthritis can lead to aortic wall weakening 9
• Autoimmune diseases severely compromise vasa vasorum blood supply to the media 9

Infectious Aortitis

• Syphilitic aortitis is a historical but important cause requiring vigilance in at-risk populations 1, 3
• Mycotic aneurysms of the ascending aorta can occur with reconstructive surgery, endocarditis, or prosthetic valve infection 3

Idiopathic and Degenerative Aortic Disease

• Idiopathic aortic dilation is common and frequently associated with atherosclerosis 1, 3
• Atherosclerotic changes compromise medial nutrient supply through intimal thickening and adventitial fibrosis, causing medial thinning 9

Traumatic and Iatrogenic Causes

Trauma

• Blunt chest trauma from high-speed accidents causes 95% of injuries at the aortic isthmus (site of greatest stress) and only 5% at the ascending aorta 9
• Aortic rupture is frequently associated with myocardial contusion, leading to cardiac failure and tamponade 9
• Chronic traumatic aneurysms become symptomatic or rupture within 5 years 9

Iatrogenic

• Cardiac catheterization (diagnostic or interventional) can cause aortic dissection 9
• Prior aortic valve replacement is associated with subsequent dissection risk through jet lesions producing post-stenotic ascending aortic dilation 9

Toxic and Drug-Related Causes

• Cocaine and amphetamine use are associated with aortic aneurysm formation and dissection through direct toxic effects on the aortic wall 9
• Anorectic drugs (ergotamine, methysergide) can cause valvular damage 1, 3

Associated Structural Abnormalities

• Coarctation of the aorta predisposes to dissection both above and below the coarctation site, typically manifesting in the third decade or later 9
• Ventricular septal defects with aortic cusp prolapse can cause regurgitation 1
• Discrete subaortic stenosis may be associated with aortic regurgitation 1
• Sinus of Valsalva aneurysms are more common in the right or non-coronary sinus and can rupture, causing regurgitation 3

Diagnostic Work-Up Algorithm

Initial Assessment

• Auscultation reveals characteristic systolic murmur in stenosis (may be faint in severe cases with heart failure) or diastolic decrescendo murmur in regurgitation 1
• Disappearance of the second aortic sound is specific (but not sensitive) for severe stenosis 1
• Careful symptom assessment is critical: exertional dyspnea, angina, dizziness, or syncope (patients may subconsciously reduce activities and deny symptoms) 1

Echocardiography (Primary Diagnostic Tool)

• Transthoracic echocardiography confirms diagnosis, assesses valve calcification degree, left ventricular function and wall thickness, and detects associated valve disease or aortic pathology 1
• Doppler assessment measures transvalvular gradients (flow-dependent) and valve area (operator-dependent) 1
• Severe stenosis: valve area <1.0 cm² (critical <0.8 cm²), mean gradient ≥40 mmHg with normal flow 1
• Index to BSA (<0.6 cm²/m² BSA) for patients with unusually small body surface area 1
• Evaluate aortic root dimensions: annulus, sinuses, sinotubular ridge, and ascending aorta 1
• Assess for bicuspid valve anatomy and associated aortic dilation 1, 4
• Three-dimensional TEE characterizes complex left ventricular outflow tract anatomy when needed 1

Advanced Imaging

• Cardiac MRI or MSCT when distal ascending aorta is poorly visualized on echocardiography or when surgical indication may be based on aortic enlargement rather than left ventricular parameters 1
• MRI/MRA with 3D reconstruction identifies precise coarctation location, entire aortic anatomy, and collateral vessels 1
• MRA for intracranial aneurysm screening in appropriate genetic syndromes 1

Additional Testing

• ECG may show left ventricular hypertrophy with secondary ST-T wave abnormalities 1
• Chest X-ray may reveal aortic dilation, rib notching (coarctation), or cardiac enlargement 1
• Exercise testing assesses functional capacity, blood pressure response, and arrhythmias (contraindicated in symptomatic severe stenosis) 1
• 24-hour Holter monitoring when arrhythmias are evident or suspected, particularly with mitral valve prolapse 1

Invasive Assessment

• Cardiac catheterization is justified when coronary artery disease is suspected and surgery is planned, or when catheter-based intervention is considered 1
• Doppler-derived gradients may overestimate obstruction and require catheterization confirmation in subaortic stenosis 1

Critical Pitfalls to Avoid

• Low-flow, low-gradient aortic stenosis: Severe stenosis can present with mean gradient <40 mmHg when cardiac output is reduced; valve area alone cannot be relied upon—integrate with flow rate, ventricular function, wall thickness, calcification degree, and blood pressure 1
• Acute severe regurgitation: Characteristic physical findings of chronic regurgitation are absent; left ventricular size may be normal, leading to underestimation of severity 1
• Bicuspid valve surveillance: Requires lifelong monitoring of both valve function and aortic dimensions due to independent medial abnormalities 3, 4
• Dissection without intimal tear: Approximately 4-10% of dissections show no identifiable intimal tear, representing intramural hemorrhage from vasa vasorum rupture 9
• Collateral circulation in coarctation: Sizable collaterals may diminish femoral pulse abnormalities and underestimate catheter-based and Doppler gradients 1