Aortic Stenosis

Aortic stenosis is a valvular heart disease characterized by a narrowing of the aortic valve orifice, causing an obstruction to blood flow from the left ventricle to the aorta during systole. This impediment to normal blood ejection leads to pressure overload upstream of the valve—i.e., in the left ventricle—resulting in progressive hemodynamic and structural changes in the heart and, in advanced stages, throughout the cardiovascular system.

Etiology, Pathogenesis and Pathophysiology

Aortic stenosis can be congenital or acquired. The acquired forms are the most frequent and include three main causes:

• Senile fibrocalcific degeneration: the most common cause in industrialized countries, especially in individuals over 65–70 years. It involves an active calcification process of the valve cusps, progressively reducing mobility and valve area. It is often considered a form of “valvular atherosclerosis.”
• Bicuspid aortic valve: the most common congenital valvular anomaly, present in 1–2% of the population. It predisposes to early valve stenosis due to turbulent flow and increased mechanical stress on the leaflets, with symptom onset between ages 40 and 60.
• Rheumatic heart disease: now rare in Western countries but still common in some regions, causing commissural fusion, leaflet retraction, and secondary calcification.

Other less common causes include: post-endocarditic stenosis, congenital valvular dysplasia, Paget's disease, chronic kidney disease with secondary hyperparathyroidism (favoring valve calcification), and prior chest radiation therapy.

Narrowing of the aortic valve orifice causes a fixed systolic ejection obstruction, increasing the pressure gradient between the left ventricle and aorta. This pressure overload initially leads to a compensatory process: concentric left ventricular hypertrophy.

This hypertrophy results from increased myofibrils in parallel, allowing the maintenance of stroke volume and aortic pressure despite the obstruction. Over time, this adaptation leads to diastolic dysfunction, reducing ventricular compliance and impeding filling.

Major pathophysiological consequences include:

• Increased filling pressure: the left atrium must exert more pressure to fill a less compliant ventricle, raising atrial and pulmonary venous pressures;
• Reduced coronary reserve: hypertrophied myocardium requires more oxygen, but coronary perfusion is impaired due to shortened diastole, reduced diastolic aortic pressure, and subendocardial vessel compression;
• Subendocardial ischemia: may occur even without obstructive coronary artery disease, causing angina due to oxygen supply-demand mismatch;
• Progressive systolic dysfunction: in advanced stages, the ventricle can no longer sustain effective output, leading to decreased ejection fraction and heart failure.

Aortic stenosis is generally a progressive condition: gradual cusp calcification leads to continuous narrowing of the valve area and rising transvalvular gradients. The onset of symptoms in a previously asymptomatic patient marks a significant prognostic turning point and requires evaluation for surgical or transcatheter intervention.

Clinical Manifestations

Aortic stenosis often has a silent course for many years, until symptoms appear—indicating hemodynamic compromise and the need for valve intervention.

The classic symptomatic triad includes:

• Angina pectoris: can occur even in the absence of coronary artery disease, due to subendocardial ischemia from oxygen supply-demand mismatch. Present in 30–40% of symptomatic patients.
• Syncope: typically exertional, due to inadequate cardiac output in response to peripheral vasodilation or due to arrhythmias and acute systolic dysfunction. Present in 15–20% of patients.
• Dyspnea on exertion: reflects onset of diastolic or systolic heart failure with elevated pulmonary capillary pressure. It is the most frequent and late symptom.

Other clinical signs include fatigue, orthopnea, paroxysmal nocturnal dyspnea, and in advanced stages, low-output signs like peripheral cyanosis, hypotension, and oliguria.

Physical examination findings can be very telling:

• Pulsus parvus et tardus: weak, delayed carotid pulse with low amplitude;
• Systolic thrill: palpable at the right second intercostal space and over the carotids;
• Apical impulse: sustained, localized in the fifth intercostal space at the midclavicular line, often displaced inferiorly in advanced stages;
• Diamond-shaped midsystolic murmur: harsh, peaking in mid-systole, radiating to the neck vessels and sometimes to the apex (Gallavardin phenomenon);
• Paradoxical splitting of the second heart sound: due to delayed aortic valve closure;
• Ejection click: heard in moderate stenosis with still-mobile valves.

In some patients with concomitant aortic regurgitation, a decrescendo diastolic murmur may also be heard.

Diagnosis and Investigations

The diagnostic approach to aortic stenosis involves clinical and instrumental assessment.

The ECG may be normal in early stages but shows signs of left ventricular hypertrophy in advanced cases (tall R in V5–V6, deep S in V1–V2, Sokolow-Lyon index >35 mm), ST-T abnormalities (ST depression, T inversion), and sometimes arrhythmias.

The chest X-ray is often normal in mild forms; in advanced disease, it shows cardiomegaly due to hypertrophy, valvular calcifications, and signs of pulmonary hypertension.

Transthoracic echocardiography is the mainstay of diagnosis and follow-up, allowing:

• Evaluation of leaflet thickness and mobility, presence of calcifications, dome-shaped systolic appearance;
• Measurement of transvalvular velocity (via continuous-wave Doppler), from which are derived:
• Mean gradient: average systolic pressure difference between the ventricle and the aorta;
• Aortic valve area (AVA): calculated by the continuity equation;
• Stroke volume index: useful in low-flow patients.

Based on valve area, aortic stenosis is classified as:

• Mild: AVA >1.5 cm², mean gradient <25 mmHg;
• Moderate: AVA 1–1.5 cm², gradient 25–40 mmHg;
• Severe: AVA <1 cm², gradient >40 mmHg or velocity >4 m/s.

If symptoms and echocardiographic data are discordant, dobutamine stress echocardiography is used (to evaluate low-flow, low-gradient stenosis with reduced EF), or cardiac MRI (to assess myocardial fibrosis), or multislice CT to quantify valve calcification (Agatston score).

Cardiac catheterization is reserved for preoperative coronary assessment or in uncertain cases. It allows direct measurement of the transvalvular gradient and pulmonary pressures. Often combined with coronary angiography to detect coexisting coronary artery disease.

Treatment and Prognosis

Therapeutic management of aortic stenosis depends on anatomic severity, presence of symptoms, and left ventricular function. The only definitive treatment is valve replacement.

In asymptomatic patients with mild or moderate stenosis, periodic echocardiographic monitoring is indicated:

• Every 3–5 years if AVA >1.5 cm²;
• Every 1–2 years if AVA between 1 and 1.5 cm²;
• Every 6–12 months if AVA <1 cm² but asymptomatic.

Symptom onset, even with preserved systolic function, is an absolute indication for surgery. ACC/AHA and ESC guidelines recommend valve replacement (Class I) in the presence of:

• Severe stenosis (AVA <1 cm² or gradient >40 mmHg) with symptoms;
• Severe stenosis in asymptomatic patients with EF <50% or positive stress test (hypotension, dyspnea);
• Severe stenosis in patients undergoing other cardiac surgery (e.g., coronary bypass).

Types of interventional treatment:

• Surgical aortic valve replacement (SAVR): standard for patients at low to intermediate surgical risk;
• Transcatheter aortic valve implantation (TAVI): indicated for high-risk or inoperable patients. Now also recommended for low-risk patients in experienced centers, based on the PARTNER 3 and EVOLUT Low Risk trials;
• Percutaneous balloon aortic valvuloplasty: only as a bridge for unstable patients awaiting TAVI/SAVR.

Medical therapy: no drugs are currently available to alter the progression of stenosis. It is useful to treat comorbidities (hypertension, dyslipidemia), and in cases of heart failure, diuretics may be used with caution. Nitrates are contraindicated due to the risk of severe hypotension.

Complications

The main complications of aortic stenosis include:

• Congestive heart failure, due to diastolic or systolic dysfunction;
• Myocardial ischemia, even in the absence of obstructive coronary artery disease;
• Syncope and sudden cardiac death, due to reduced output, ventricular arrhythmias, or AV blocks;
• Infective endocarditis, more frequent in patients with calcified valves;
• Hemolysis in patients with mechanical valves or paravalvular regurgitation after implantation;
• Prosthetic valve dysfunction (stenosis or regurgitation, endocarditis, thrombosis).

References
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