**4. Etiopathogenesis**

retrospective study, during which 16,185 echocardiograms were analyzed, performed according to clinical indications in the Consultative-Diagnostic Center of National Medical Research Center of V.A. Almazov (St. Petersburg, Russia) from 2008 to 2011, also showed a low preva-

There are multiple ways of classifying MVP, underscoring the heterogeneity of this disorder:

• Etiologically, MVP is classified as primary (degenerative disease in the absence of identifiable connective tissue disease, sporadic, or familial) versus secondary MVP (associated

• Clinically, MVP can be classified as syndromic when extracardiac manifestations are pres-

• MVP is also classified by the severity of the abnormal movement of the valve. The leaflets are described as billowing when the tips of leaflets remain in the left ventricle (LV) versus

• Morphologically, MVP is classified as classic (also known as Barlow's syndrome with markedly and diffusely thickened leaflets (≥5 mm) with bileaflet prolapse) versus nonclassic (with limited or absent thickening (thickness <5 mm) and segmental prolapse).

• Doppler echocardiography can also distinguish MVP without mitral regurgitation (MR)

The 2014 American Heart Association/American College of Cardiology guidelines for the management of patients with valvular heart disease separate mitral regurgitation by a mechanism into primary (disease of one or more valve components including leaflets, chordae tendineae, papillary muscles, or annulus) and secondary (disease of the left ventricle) [22]. In this classification, primary disease includes all forms of MVP along with other causes of MR involving the components of the valve (e.g., calcific degeneration, cleft mitral valve, leaflet perforations, etc.). Isolate primary (congenital, idiopathic) and secondary prolapse develops against the background of the already existing diseases of the cardiovascular system. Primary prolapse of the mitral valve is a hereditary violation of the formation of the connective tissue [6, 7, 10, 11]. It should be noted that in the MVP structure, the primary occurs much more often. The share of the secondary accounts for only 5% of the total number of observations. Clinically anatomically, MVP is a syndrome that accompanies many nosologi-

**1.** pleiotropic manifestation of some classified hereditary disorders of the connective tissue (syndromes Marfan, Ehlers-Danlo, etc.). Thus, the combination of MVP with aortic

flail when the tip(s) of one (or both) leaflets prolapses into the left atrium (LA).

For the first time, mitral valve prolapse was described by J.B. Barlow et al. in 1963.

lence of MVP and in the Russian population—1.3% [21].

82 Structural Insufficiency Anomalies in Cardiac Valves

with an identifiable disorder such as Marfan syndrome).

ent (e.g., pectus excavatum) versus non-syndromic, isolated MVP.

**3. Classification**

from MVP with MR.

cal forms [10, 15, 16].

Currently, there are several MVP variants [23]:

To explain the causes of primary prolapse of the mitral valve, several theories have been proposed. Proponents of the "myocardial" theory in the histological study of the myocardium found interstitial fibrosis and hypertrophy of myofibrils in patients with mitral valve prolapse and in electron microscopy—degenerative changes in mitochondria, endocardium thickening [25, 26].

The revealed changes allowed to make an assumption about the similarity of morphological changes with mitral valve prolapse and dilated cardiomyopathy. However, after conducting a complex echocardiographic, radionuclide, and angiographic study, the hypothesis of the cardiomyopathic etiology of the primary prolapse of the mitral valve has not been confirm [6, 26]. The theory of the "rheumatic" nature of the prolapse of the mitral valve was also common. This point of view is confirmed by information about a greater frequency of prolapse in patients with rheumatism. Supporters of this theory explained the mechanism of prolapse of the valves with partial chord separation as a result of inflammatory changes in the endocardium [5, 27]. There are also data indicating the possible involvement of a viral infection in the development and progression of mitral valve prolapse [28]. However, modern protocols for management of patients with MVP do not provide for antibiotic prophylaxis [3].

An association between panic disorder and MVP has also been suggested by several studies, including a meta-analysis [6]. However, these studies have been criticized because of inconsistencies in the diagnostic criteria used for both panic disorder and MVP and the use of imperfectly matched controls. In addition, panic disorder and MVP are both common illnesses with similar age and gender distributions, suggesting that their association may only be a coincidence.

Mitral Valve Prolapse in Pregnancy: Modern Concept http://dx.doi.org/10.5772/intechopen.76692 85

The clinical manifestations of prolapsus of the mitral valve differ in variety [5, 6]. At the same time, most researchers note the polymorphism of the clinical picture [3, 17]. Data on the frequency of clinical symptoms and the pathogenetic mechanisms of their formation are contradictory [3, 10, 11, 13]. However, the recognition of prolapsus is accompanied by a fairly clear and definite clinical picture. It is proposed to isolate clinically and morphologically significant MVP syndromes:

**1.** the pain syndrome in the left half of the chest (32.3–65%) [6, 10, 17]. At the same time, the mechanisms of the formation of the pain syndrome remain controversial. Currently, the most common explanations of pathogenetic mechanisms of pain syndrome are local myocardial ischemia as a result of tension of papillary muscles, microthrombemia in the zone located between the left atrium and the back wall of the mitral valve, a decrease in the diastole duration as a result of an increase in the heart rate, and sinus tachycardia in response

**2.** the syndrome of disturbance of vegetative regulation of heart rhythm (25.8–79%). The complaints about the heartbeat and interruptions in the work of the heart are noted in individuals in cases [30]. There was no consensus on the mechanism of cardiac rhythm disturbance and repolarization process disturbances in these patients, the role of abnormal traction of papillary muscles, the presence of late ventricular potentials, myxomatous degeneration of dilated valves, and dysfunction of the autonomic nervous system was discussed [10, 17]; **3.** the hyperventilation syndrome (dyspnea—15.6–31.5%). Domestic authors with mitral valve prolapse noted the presence of a feeling of lack of air and obstacles in the way of inhaled air, the need to periodically make deep sighs, and a feeling of dissatisfaction with

**4.** the hemorrhagic syndrome: nasal bleeding, tendency to easy formation of bruises, bleeding gums, prolonged bleeding after removal of the teeth, prolonged and (or) profuse menstruation. The tendency to easy bruising and nasal bleeding can be explained by the presence of disturbances in the hemostasis system in patients with MVP—a change in the aggregation function of platelets, a decrease in the activity of von Willebrand factor in the blood plasma, and a disruption of the final stage of blood coagulation [31]. As is known, hemorrhagic syndrome is one of the manifestations of mesenchymal dysplasia, which explains its presence

**5.** the vascular disorders in the limbs of persons with mitral valve prolapse (68.8%), which are presented in the form of vascular necklace, Raynaud's syndrome, changes in the color of the limbs, idiopathic pastosity, or swelling [6]. Lipothymia is a complex of sensations that preceded the loss of consciousness noted in the work of Т.М. Dominitskaya (1998) in 69.0% of patients with mitral valve prolapse in combination with abnormally located chord and in 51.0% of persons with abnormally located chord with orthostatic load, emo-

tional stress, prolonged stay in a vertical position, and in stuffy rooms [32];

inspiration [6]. The main pathogenetic mechanism is disautonomy [10];

to stress or physical exertion [3];

in patients with prolapse of the mitral valve;

At the basis of the development of secondary MVP lies the violation of myocardial contractility of the left ventricle and dysfunction of the papillary muscles. It develops under the following pathological conditions: inflammatory processes (myocarditis), cardiomyopathy, myocardial dystrophy [10, 16], ischemic heart disease, a decrease in tissue elasticity as a result of left ventricular contraction asymmetry and papillary muscle ischemia and tendon chords, violation of autonomic innervation and impulse conduction in myocarditis, extrasystole, WPW syndrome, with neuroses and hysteria. Also, the cause of secondary MVP can serve as a blunt trauma to the heart [22].

Most researchers are supporters of the "valve" theory. This theory presupposes the presence of a genetically determined collagen defect, which leads to the "weakness" of the connective tissue of the mitral valve flaps and their prolapse into the atrial cavity. Three gene loci are described on 16, 11, and 13 chromosomes, but the genetic defects underlying them are not known to date. The recessive form of MVP associated with the X chromosome is known as myxomatous dystrophy of the heart valves, and mutations of the gene for the pathogen have recently been identified [6].

There are several possible pathogenetic mechanisms that can explain the onset of MVP. According to some data, the role of magnesium deficiency in the development of MVP is great. The lack of magnesium reduces the activity of magnesium-dependent adenylate cyclase, which ensures the removal of defective collagen [29] and affects the ability of fibroblasts to produce collagen [16]. In addition to the direct participation of magnesium ions in the processes of collagen formation, the role of magnesium in the functioning of the vegetative nervous system is undoubtedly important, since a deficiency of magnesium ions promotes an increase in the level of catecholamines of the blood plasma, that is, the development of hypercatecholaminemia, changes in the tone of the papillary muscles, and the formation of MVP.
