What causes aortic stenosis?

Over the past 30 years, the etiology of aortic valve defects has changed. While the prevalence of postrheumatic aortic valve lesions has decreased from 30 to 18%, and the frequency of surgical correction of bicuspid aortic valve - from 37 to 33%, an increase in calcific aortic stenosis has been noted from 30 to 46%, especially in individuals over 65 years of age.

Congenital aortic stenosis

Congenital malformations of the aortic valve may include: unicuspid, bicuspid or tricuspid valves or the presence of a domed diaphragm.

A unicuspid valve causes severe obstruction already in infancy and is the cause of death in children under 1 year of age.

Stenosis of the congenital bicuspid valve leads to the appearance of turbulent blood flow, traumatizing the valve cusps, which subsequently leads to fibrosis, increased rigidity and calcification of the cusps, and narrowing of the aortic orifice in adults.

Congenitally malformed tricuspid valve is characterized by the presence of unevenly sized leaflets with evidence of fusion at the commissures, while turbulent blood flow caused by a moderate congenital defect can lead to fibrosis and ultimately to calcification and aortic stenosis.

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Acquired aortic stenosis

Rheumatic aortic stenosis occurs as a result of the inflammatory process, accompanied by the fusion of commissures, vascularization of the cusps and fibrous ring, which leads to the development of marginal fibrosis. Subsequently, calcifications appear on both surfaces (ventricular and aortic) of the cusps, and the opening of the aortic valve 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 damage to the mitral valve.

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

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

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Pathophysiology of aortic stenosis

In response to mechanical obstruction, expulsion of blood and increase in systolic tension of the left ventricle wall, its concentric hypertrophy develops, creating an additional pressure gradient on the aortic valve without reducing cardiac output, expanding the left ventricular cavity and not accompanied by clinical symptoms. Over time, given the heterogeneous nature of hypertrophied myocytes and the increase in the severity of mechanical obstruction, left ventricular failure occurs, caused by expansion of the chambers of the left sections of the heart and the development of venous congestion in the pulmonary circulation. In the late stages of the disease, cardiac output, stroke volume and, accordingly, the pressure gradient decrease.

Patients with aortic stenosis are characterized by a negative correlation between systolic wall stress and ejection fraction (EF), which causes a reflex decrease in the latter in some patients due to “uncoordinated afterload”. In other cases, the cause of the decrease in EF is a decrease in the contractility of the left ventricle. Thus, increased afterload and altered contractility contribute to the deterioration of the systolic function of the left ventricle.

Along with the increase in collagen content in the myocardium, characteristic of many cardiac diseases, aortic stenosis is accompanied by a change in the transverse striation, which leads to an increase in myocardial mass, an increase in diastolic stiffness and a violation of diastolic function, as a result of which a higher intracavitary pressure is required for full filling of the left ventricle chambers. Clinically, in patients with aortic stenosis, this is associated with the sudden development of episodes of pulmonary edema without obvious provoking factors.

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

• unusually large cell nuclei;
• loss of myofibrils;
• mitochondrial clusters;
• the presence of cytoplasmic regions 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, absolute values of coronary blood flow are increased, but when recalculated for the mass of the hypertrophied left ventricle, they can be considered normal. Further progression of left ventricular hypertrophy can lead to impaired myocardial oxygenation in patients with critical aortic stenosis even in the absence of significant changes in the coronary arteries. The substrate of myocardial ischemia in aortic stenosis, as in other heart diseases, is an imbalance between oxygen consumption and the ability to deliver it.

The increase in myocardial oxygen demand is due to:

• an increase in myocardial mass due to left ventricular hypertrophy;
• increased systolic tension of the left ventricular wall;
• prolongation of the time it takes for blood to be expelled from the left ventricular cavity.

Impaired oxygen delivery through the coronary arteries is caused by:

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

Additional factors that reduce left ventricular myocardial perfusion:

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