[Matrix metalloproteinases and hypertrophic cardiomyopathy].

Prognosis of patients with hypertrophic cardiomyopathy (HCMP) to a great extent is determined by clinical variant of the disease. As the system of matrix metalloproteinases (MMPs) plays an important role in development and progression of the processes of fibroformation and tissue remodeling polymorphisms of modifier genes regulating its components can influence clinical course of HCMP. Among possible markers of prognostication of the course of cardiovascular diseases the role of MMPs and their tissue inhibitors has been discussed. With the aim of studying effects of MMPs on the course of HCMP we conducted this investigation in which we included 58 patients and a group of healthy volunteers (control group) with comparable sex and age. In all participants (n=112) we determined polymorphism of MMP-3 - rs3025058 and markers of fibroformation (MMP-3, TIMP-1, TIMP-2, and collagen IV). We found that unfavorable allele variant MMP-3 1171 was associated with hypertrophy of interventricular septum. We also established that levels of TIMP-1 in the group of patients with HCMP were significantly lowered in comparison with those in control group. Concentration of marker MMP-3 was elevated in the group of patients with variant "atrial fibrillation" compared with groups of stable course and progressing course. We revealed medium degree reverse correlation between MMP-3 marker and thickness of left ventricular posterior wall and direct correlation of this parameter with coefficient of asymmetry. Polymorphism MMP-3 - 1171 produced an impact on the level of TIMP-1 marker. The data obtained by us confirm effect of the system of MMPs on formation of hypertrophic remodeling of the heart in HCMP.

[Renin-angiotensin-aldosterone system in hypertrophic cardiomyopathy].

Keeping in mind an important role of renin-angiotensin aldosterone system (RAS) in developing of cardiac remodeling and fibrosis, genetic polymorphisms coding its components could have influence with clinical variants of the course. Biomarkers could appear predictors of adverse. To examine the contribution of the RAS to developing of different hypertrophic cardiomyopathy (HCM) clinical variants of the course we studied 58 patients with HCM and controls comparable by age and gender. All patients were genotyped of gene polymorphisms CMA1 A(-1903)G rs1800875, AGTM235T rs699, AGTR1 A1166C rs5186, CYP11B2-344 T/C rs1799998. Angiotensin-converting enzyme (ACE) and angiotensin II (AII) levels were measured in 40 patients with HCM and 39 controls. We found out that AII were significantly decreased in patients with HCM than in healthy controls. The positive correlation between AII and left ventricle posterior wall (LVPW) were detected. Severity of heart hypertrophy were associated with pejorative genotype of AGT M235T polymorphism and CMA1 A(-1903) polymorphism. Significant association between the AG genotype of CMA1 A(-1903) polymorphism and angina class II-III and ventricular extrasystole of high gradation was observed. Our data not only support the hypothesis that RAAS polymorphisms may influence phenotype, but also allow for create new approaches to possible predicting adverse outcomes.

[Hypertrophic cardiomyopathy -- modern state of the problem. Issues of epidemiology and nomenclature, genetics and pathophysiology, variants of course and differential diagnosis].

The problem of the study of hypertrophic cardiomyopathy (HCM) has preserved its actuality because of high prevalence (1:500), risk of sudden cardiac death (SCD) in individuals of young able-bodied age. Subject of great interest appear problems of search for additional clinical, instrumental and genetic markers, environmental factors which are capable to influence formation of a clinical variant of HCM course, risk of SCD, and prognosis of HCM. Important problem requiring further study appears to be molecular genetic characteristic of the disease. Integrated nomenclature of various forms and variants of course of HCM is essential for elaboration of tactics of management of patients and assessment of results of multicenter trials.

[Contemporary trends of genetic analysis in hypertrophic cardiomyopathy].

Subject of great interest of contemporary scientific community is a search for additional genetic and environmental factors which are capable to influence formation of a clinical variant of the course of hypertrophic cardiomyopathy (HCMP). It has been shown by many works that besides mutations in genes of sarcomere proteins clinical course of HCMP is also affected by modifier genes of the cardiovascular system such as association of polymorphisms RAAS, sympathoadrenal system, NO-synthase, endothelin system, and system of blood coagulation. Attempts have been made to study effects of these polymorphisms on formation of clinical variant of HCMP course and to search for associations with development of unfavorable variants.

[Hypertrophic cardiomyopathy: course characteristics in long-term follow-up].

AIM: To detect relations between intracardiac hemodynamics and clinicoanamnestic features of patients with hypertrophic cardiomyopathy (HCMP). MATERIAL AND METHODS: We observed 84 patients with different clinical variants of a HCMP course. Of them, 15 patients were treated surgically. The patients were followed up from 3 to 24 years (mean 8.4 +/- 1.1 years). All the patients have undergone standard ECG, transthoracic echocardiography with doppler echocardiography, 24-h ECG monitoring, part of them--stress echocardiography (exercise and/or dobutamine), MRT of the heart, coronaroangiography and probing of the heart. RESULTS: The analysis of cardiac remodeling parameters in HCMP patients showed significance of diastolic disorders in development of basic clinical symptoms of the disease. A rise of atrial-ventricular index (AVI) reflects severity of a HCMP course. Patients with the most severe course of the disease had AVI equal or higher than 1.1. In obstructive and non-obstructive variants of HCMP time of the first symptoms onset did not differ significantly. In the disease onset the patients had asthenic syndrome, cardialgia, dyspnea. The disease ends with heart failure. CONCLUSION: Long-term follow-up of HCMP patients and comparison of clinico-morphological parameters revealed the role of diastolic dysfunction in formation of clinical symptoms.