What causes aortic stenosis?

Over the past 30 years, the aetiology of aortic valve defects has changed. While the prevalence of postoperative aortic valve lesions decreased from 30 to 18%, and the frequency of operative correction of a two-leaved aortic valve from 37 to 33%, an increase in calcified aortic stenosis from 30 to 46% was noted, especially in persons older than 65 years.

Congenital aortic stenosis

Congenital malformations of the aortic valve can be: single-leafed, bivalve or tricuspid valves or the presence of a domed diaphragm.

Single-leaf valve causes severe obstruction already in infancy and causes death of children under 1 year.

Stenosis of the congenital bivalve valve leads to the appearance of turbulent blood flow, traumatic valve flaps, which subsequently leads to fibrosis, increased stiffness and calcification of the valves, to a narrowing of the aortic aperture in adults.

The congenital-altered tricuspid valve is characterized by the presence of irregularly sized flaps with signs of fusion along the commissures, and the turbulent blood flow caused by a mild birth defect can lead to fibrosis and eventually to calcification and aortic stenosis.

[1], [2], [3], [4], [5], [6], [7]

Acquired aortic stenosis

Rheumatic aortic stenosis occurs due to the inflammatory process, accompanied by fusion of the commissure, vascularization of the valves and the fibrous ring, which leads to the development of marginal fibrosis. Calculations appear on both surfaces (ventricular and aortic) on the both surfaces, and the aortic valve aperture decreases and acquires a round or triangular shape. Rheumatic valve damage is characterized by both aortic stenosis and regurgitation. Other signs of the rheumatic process are often diagnosed in the heart, in particular, the damage to the m of the valve

Calcified aortic stenosis (CAS) developing in elderly patients is due to both mechanical wear of the valve and long-term inflammation with the infiltration of the valves with macrophages and T-lymphocytes, followed by deposition of calcium pyrophosphate crystals in the fibrous ring, leading to a narrowing of the aortic orifice and spreading to the valves aortic valve. Among the causes of the inflammatory reaction most commonly called oxidized LPGT (by analogy with atherosclerosis) and infectious agents (Chlamydia pneumoniae), which can serve as triggers for "damage response" and form primary "calcification nests". Under the influence of the activation of markers of osteogenesis (expressed constitutionally) and remodeling of collagen in the valves of the aortic valve, myofibroblasts acquire osteoblastic functions. Another source of osteogenesis by the endochondral type may be polytotic mesenchymal cells circulating in the blood stream and penetrating into the thickness of the aortic valve flaps through damage in the endothelial layer. Under these conditions, macrophages and T-lymphocytes serve as factors of neoosteoclastic resorption. Additional regulators of the ongoing processes are vitamin D, parathyroid hormone and bone metabolism, which undergo significant changes in the elderly, leading to D-deficiency, hyperparathyroidism and osteoporosis. All of the above contributes to the formation of mature bone tissue with the presence of micro-fractures, the functioning bone marrow and signs of bone remodeling in the thickness of the aortic valve flaps, which allows us to consider the calcification of the aortic valve in CAS patients as a regenerative rather than degenerative process.

Other causes of calcified aortic stenosis are diseases accompanied by a systemic calcium metabolism disorder, in particular Paget's disease (bone form), terminal stage of chronic renal failure and alkaponuria.

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Pathophysiology of aortic stenosis

In response to mechanical obstruction, ejection of blood and an increase in the systolic tension of the left ventricular wall, its concentric hypertrophy develops, creating an additional pressure gradient on the aortic valve without reducing cardiac output, widening the left ventricular cavity, and not accompanied by clinical symptoms. With the passage of time, taking into account the heterogeneous nature of hypertrophied myocytes and the increase in the severity of mechanical obstruction, left ventricular failure is associated with the expansion of the chambers of the left heart and the development of venous plethora in the small circulation. In the late stages of the disease, cardiac output, stroke volume and, correspondingly, the pressure gradient decrease.

Patients with aortic stenosis are characterized by a negative correlation between systolic wall tension and ejection fraction (EF), which causes a reflex decrease in the latter in some patients due to "uncoordinated afterload". In other cases, the reason for the decrease in PV also consists in a decrease in the contractility of the left ventricle. Thus, increased afterload and altered contractility contribute to a deterioration in the systolic function of the left ventricle.

Along with the increase in collagen content in the myocardium, characteristic of many cardiac diseases, a transverse striation changes in aortic stenosis, which leads to an increase in myocardial mass, an increase in diastolic stiffness and a diastolic dysfunction, as a result of which a larger interior cavity pressure. Clinically, in patients with aortic stenosis, this is associated with the sudden development of episodes of pulmonary edema without apparent provoking factors.

Other features of the structure of the myocardium in patients with severe aortic stenosis:

• unusually large nuclei of cells;
• loss of myofibrils;
• accumulations of mitochondria;
• presence of cytoplasmic areas in cells without contractile elements;
• proliferation of fibroblasts and collagen fibers in the interstitial space.

Ischemia

In patients with aortic stenosis, in contrast to patients without heart disease, the absolute values of coronary blood flow are increased, but when recalculating to the weight of the hypertrophied left ventricle, they can be considered normal. Further progression of left ventricular hypertrophy can lead to disturbance of myocardial oxygenation in patients with critical aortic stenosis even in the absence of pronounced changes in the coronary arteries. The substrate of myocardial ischemia in aortic stenosis, as well as in other heart diseases, is the imbalance between oxygen consumption and the possibility of its delivery.

The increase in myocardial oxygen demand is due to:

• an increase in the mass of the myocardium due to hypertrophy of the left ventricle;
• increased systolic stress of the left ventricular wall;
• lengthening the time of expulsion of blood from the cavity of the left ventricle.

Disruption of oxygen delivery through the coronary arteries is caused by:

• excess pressure compressing the coronary arteries from the outside, above the perfusion pressure inside the coronary vessels;
• shortening of diastole.

Additional factors that reduce myocardial perfusion of the left ventricle:

• relative decrease in the density of capillaries;
• an increase in the end-diastolic pressure in the cavity of the left ventricle, leading to a decrease in perfusion pressure in the coronary arteries.