Cardial sympathic activity and acute left ventricle dysfunction in stress-induced cardiomyopathy

The term "hypertrophic cardiomyopathy" refers to myocardial disease with asymmetric or symmetric left ventricular myocardial hypertrophy and mandatory involvement in the hypertrophic, interventricular septum process. The true prevalence and frequency of hypertrophic cardiomyopathy is not exactly established.

Morphological substrate of the disease is asymmetric hypertrophy of various parts of the interventricular septum with possible concomitant hypertrophy of other parts of the left ventricular myocardium. Hypertrophic cardiomyopathy with involvement of the right ventricle in the myocardium process is extremely rare.

In accordance with the localization of myocardial hypertrophy, the following clinical hemodynamic variants of hypertrophic cardiomyopathy are distinguished.

• 1.    Idiopathic hypertrophic subaortal stenosis with disproportionate hypertrophy of the interventricular septum, obstruction of the left ventricular outflow tract, thickening of the endocardium under the aortic valve, thickening and paradoxical movement of the anterior mitral valve leaf to the septal partition.

• 2.    Asymmetric hypertrophy of the septum without changes in the aortic and mitral valves and without obstruction of the output tract of the left ventricle.

• 3.    Apical hypertrophic cardiomyopathy with zone limitation

• 4.    Symmetric hypertrophic cardiomyopathy with concentric hypertrophy of the left ventricular myocardium. Occasionally, asymmetric hypertrophic cardiomyopathy with mesoventricular obstruction is also isolated, and a form with biventricular obstruction is extremely rare.

With hypertrophic cardiomyopathy, disorganization of muscle fibers, their hypertrophy, fibrosis areas, glycogen accumulations, "perinuclear gloobes", extensive zones with increased number and degenerative changes of mitochondria are observed. At the same time, the quantitative ratio of mitochondria and myofibrils is disturbed.

A characteristic histological sign is the "disorder" of myocytes, which distinguishes myocardial state in hypertrophic cardiomyopathy from left ventricular hypertrophy due to hypertension or aortic stenosis. "Disorder" is manifested by the disorganization of the myofibrillar structure, with the predominance of intersections above the normal parallel arrangement and misposition of the myocytes relative to each other, with the formation of "curls" around the foci of connective tissue.

It should be remembered that the histological examination data are not strictly specific for hypertrophic cardiomyopathy and may, although to a lesser extent, be detected with hypertrophies of the myocardium of another etiology.

The etiology of hypertrophic cardiomyopathy is unknown. There is no doubt that in many cases (from 30 to 50%) the disease is hereditary (familial hypertrophic cardiomyopathy), and the remaining cases are regarded as sporadic (idiopathic hypertrophic cardiomyopathy). With hereditary hypertrophic cardiomyopathy, both autosomal dominant and autosomal recessive and mixed inheritance types are assumed. Numerous family cases are described.

With idiopathic hypertrophic subaortic stenosis and asymmetric hypertrophy of the septum, the family predisposition to the disease is much higher than in the apical and symmetrical forms, which occur mainly in the form of sporadic cases. The expected genetic factors include abnormal ratios of various components of the sarcolemmal membrane, enzyme and receptor anomalies.

In fact, in all cases of hypertrophic cardiomyopathy there is heterozygosity, and the gene is dominant negative.

Thus, the mutant myofibrillar protein "mixes" with the normal protein with the formation of the correct arrangement of myofibrils in the myocyte. In most families with so-called sporadic cases of hypertrophic cardiomyopathy, there are likely to be other asymptomatic carriers of the gene. In the past, studies in which carriage was determined only by clinical manifestations, did not lead to the detection of a large number of carriers.

Mutations of the beta-heavy chain of myosin caused about 35% of cases of hypertrophic cardiomyopathy, now more than 40 individual point mutations in this gene are known. Mutations in other genes are less common, each accounting for 515% of cases.

A wide range of phenotypes and the severity of clinical manifestations observed in individual patients raises the question of the relationship between phenotype and genotype in hypertrophic cardiomyopathy. In early observations, the diagnosis was made only in the phenotype associated with asymmetric thickening of the septum and obstruction of outflow from the left ventricle. It is now evident that the phenotype is highly variable. Hypertrophy may be symmetrical and asymmetric, concomitant right ventricular involvement may or may not be present, the extent of left ventricular mass increase may also be very different. In some cases, the thickening of the wall of the left ventricle is minimal.

To a certain extent, the variants of phenotypic manifestations and clinical outcome depend on the specificity of the gene and the mutation. Some specific mutations of the myosin heavy chain gene carry a very high risk of sudden death and cause a "malignant" family history. Mutations of troponin T lead to much less severe left ventricular hypertrophy compared with the mutation of the myosin heavy chain, but are associated with a high risk of sudden death. However, in many families with hypertrophic cardiomyopathy, a full spectrum of phenotypic manifestations is observed even when all members of the family are carriers of the same mutation.

The reason for such intrafamily variations is unknown. The ratio of normal and mutant protein in the myocardium, as well as whether it is the same for members of the same family, is also unknown. It also remains unclear why in some cases extensive regional involvement of the ventricles with histological changes in the septum occurs at the normal posterior wall. Local hemodynamic factors may influence the predominance of thickening of the septum, but a more acceptable explanation for individual variations is that other genes suppress the phenotypic expression of the gene for hypertrophic cardiomyopathy. Any gene that enhances hypertrophy can potentiate phenotypic expression of hypertrophic cardiomyopathy.