[Genetic predictors of myocardial infarction in subjects of young age].

AIM OF THE STUDY: to investigate associations of single nucleotide polymorphisms (SNP) rs499818 (6p24.1), rs619203 of ROS1 gene (6q22), rs10757278 rs1333049 (9p21.3), rs2549513 (16q23.1), rs4804611 of ZNF627 gene (19p13.2) with myocardial infarction in subjects of young age. The group of patients with MI (n=99) aged less than 45 years and the control group (n=111) did not differ significantly by sex (=0,617), age (=0.291), arterial hypertension (=0.766), diabetes mellitus (=0.395), hypercholestolemia (=0.696), excessive body mass and obesity (=0.361), abdominal obesity (=0.831) and history of smoking (=0.400). There was significant difference between groups by burdened heredity (<0.001). Genomic DNA was obtained from venous blood by phenol-chloroform extraction. Genetic testing was performed by real time polymerase chain reaction using 7900HT Fast Real-Time PCR System according to manufacturers protocol. We found significant association between rs1333049 and rs10757278 and myocardial infarction (MI). Odds ratio (OR) of development of MI in carriers of risk allele rs1333049 was 2.4 (95% confidence interval [CI] 1.24 to 4.65), in carriers of G rs10757278 allele - 2.00 (95%CI 1.05 to 3.80). Association of risk alleles rs 1333049 and G rs10757278 with MI remained significant after adjustment for burdened family history (OR 4.25, 95%CI 1.39 to 12.99, and OR 3.04, 95%CI 1.09 to 8.52, respectively). Presence in the genotype of both risk alleles rs1333049 and G rs10757278 was associated with OR of MI development 2.40 (95%CI 1.20 to 4.82) which was not different from that associated with carriage of allele rs1333049 only. Possibly in our population both SNPs belong to one linkage block and correspondingly it is sufficient to genotype one SNP. No significant associations with MI were found for variants rs4804611, rs2549513, rs499818, rs619203. SNPs rs1333049 and rs10757278 of 9p21.3 locus are predictors of MI in young individuals not dependent on both traditional risk factors and presence of burdened family history.

[Interrelationship between polymorphic markers of methylenetetrahydrofolate reductase gene and development of acute disturbance of brain circulation in families of patients with atrial fibrillation].

In the present work we for the first time on the clinic-genetic material revealed genetic predictors of development of acute disturbance of brain circulation (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was significantly more often found among patients with AF and ADBC compared with controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of probands compared with the control group (59.3 and 35.2%, respectively, p=0.008). With this in relatives with revealed paroxysmal AF and ADBC we also noted presence of CC genotype. Taking into consideration the relationship obtained between polymorphysms of MTHFR gene and AF it was possible to assume that polymorphic marker CC appeared to be a predictor of ADBC in these families.

[Association of 2B-adrenergic receptor gene polymorphism with disturbances of cardiac conduction].

In this work we for the first time revealed on clinical - genetic material association between hereditary disturbances of cardiac conduction and polymorphism of 2-adrenergic receptor gene.

[Polymorphisms of 2B-adrenergic receptor and endothelial NO-Synthase genes in genesis of the hereditary sick sinus node syndrome].

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome (SSNS) ADRA2B and eNOS genes polymorphisms. We have established predominance of homozygote genotype of more rare DD allele in patients with SSNS (28%) compared with subjects of control group (8.99%). We have found predominance of heterozygote genotype 4a/4b in patients with SSNS compared with subjects of control group (41.8 and 25.39%, respectively). The data obtained allow to suggest that eNOS gene polymorphism might be associated with SSNS.

[Polymorphism of connexin 40 gene-- a novel genetic marker of the sick sinus node syndrome].

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

[Ser49gly polymorphism as predictor of development of hereditary sick sinus node syndrome].

We demonstrated for the first time on clinico-genetic material an association of hereditary sick sinus node syndrome (SSNS) with polymorphism of beta-adrenorecetor gene. We found that heterozygous variant of Ser49gly of beta-adrenoreceptor gene was significantly more often met in patients with SSNS and their healthy relatives than in subjects of control group. In the group of patients with SSNS contrary to control group we noted statistically significant preponderance of carriers of mutant Gly49 allele of.

[Genetics of atrial fibrillation].

We carried out examination of 103 probands with atrial fibrillation (AF) and 301 their 1st, 2nd, and 3rd degree relatives (main group). In addition we examined 82 probands without clinical electrocardiographic signs of heart disease and 163 their 1st and 2nd degree relatives (control group). We found accumulation of AF in families of probands with this pathology. Segregation analysis of idiopathic forms of AF allowed to reveal autosomal dominant type of inheritance of this pathology. Heterozygous variant of Ser49Gly of betai-adrenoreceptor gene can be considered as one of genetic predictors of development of how primary and secondary AF.

[Peculiarities of cardiac involvement in patients with dystrophic myotonia].

Dystrophic myotonia is a widespread hereditary disease. Pathological process touches development and functioning of various organs and tissues: smooth and skeletal muscular tissue, the heart, organ of vision, brain. Pathology of the heart serves as one of frequent manyfestations of dystrophic myotonia. Degenerative changes and fatty infiltration of myocardium not infrequently leads to dilated cardiomyopathy. Involvement of the heart in such patients is represented mainly by disturbance of cardiac rhythm and conduction. Course of the disease is progressive.

Apoptosis of leukocytes as a marker of neutrophil-endotheliocyte interaction in coronary heart disease.

We studied the mechanism of interaction of peripheral blood neutrophils with endothelial cells (expression of cell adhesion molecules and production of NO) and the role of neutrophil apoptosis in the development of endothelial dysfunction. The effects of mitochondrial dysfunction of neutrophils on the development of apoptosis of these cells after their interaction with endothelial cells were analyzed.

[Comparative assessment of efficacy of tissue plasminogen activator and streptokinase in the treatment of patients with acute myocardial infarction]. / Sravnitel'naia otsenka éffektivnosti tkanevogo aktivatora plazminogena i streptokinazy v lechenii bol'nykh ostrym infarktom miokarda.

AIM: To compare results of treatment of patients with acute myocardial infarction with tissue plasminogen activator (TPA) and streptokinase. MATERIAL AND METHODS: TPA (100 mg intravenously) and streptokinase (1500000 U intravenously) were used for thrombolytic therapy of acute myocardial infarction in 114 and 118 patients, respectively. RESULTS: TPA treated compared with streptokinase treated patients were characterized by less frequent serious cardiac rhythm and conduction disturbances and hypotension during thrombolysis (p<0.05), as well as less frequent pathological Q-waves formation (p<0.001). More than 50% lowering of initially elevated ST-segment by 90-th minute occurred more often in TPA treated patients (p<0.001). Differences between TPA and streptokinase treated patients in mortality (3.5 and 7.6%, respectively), reinfarction rate during first 24 hours (3.5 and 5.1%, respectively), aneurysm formation (9.1 and 14.7%, respectively), and heart failure development (4.5 and 11.0%, respectively) were not significant. CONCLUSION: The use of TPA for thrombolytic therapy of patients with acute myocardial infarction gave better results than the use of streptokinase.

[Relationship between polymorphism of non-coding regions of human mitochondrial genome and primary cardiac conduction disorders]. / Sviaz' polimorfizma nekodiruiushchikh oblastei mitokhondrial'nogo genoma cheloveka s pervichnymi narusheniiami serdechnoi provodimosti.

AIM: Analysis of associations between idiopathic disturbances of cardiac conduction (DCC) and polymorphism of mitochondrial genome. MATERIAL AND METHODS: A family examination was performed in 431 probands with various DCC and 1347 relatives of the first, second and third degree of kinship (the study group). All the examinees were divided into four subgroups. These included 158 probands with atrioventricular block (AVB) of various degree and their 518 relatives (subgroup 1); 50 probands with a complete right bundle-branch block (BBB) and their 161 relatives (subgroup 2); 108 probands with a complete left BBB and left anterior branch of the His bundle and their 152 relatives (subgroup 3); 115 probands with sick sinus syndrome (SSS) and their 327 relatives (subgroup 4). The control group consisted of 104 probands without clinical ECG manifestations of cardiac diseases and their 321 relatives. All the examinees have undergone ECG, atropin test, echocardioscopy, electrophysiological examination of the heart and mitochondrial DNA (mDNA). RESULTS: Comparison of the incidence of mDNA D-loop restriction sites in the group of patients with idiopathic DCC and controls has found higher frequency of the Hae III 16517 site in the group of the patients (p = 0.0480). By location of the blocks (atrioventricular and intraventricular), the site occurred more frequently in patients with AVB (86.36%). The variant "+" by the site of Hae III 16517 mDNA was found to associate with disturbances of cardiac conduction, more closely in AVB. CONCLUSION: Variability of mDNA may be an etiological factor of idiopathic DCC pathogenesis.

[Angiotensin-converting enzyme gene polymorphism in patients with primary disturbances of cardiac conduction]. / Polimorfizm gena angiotenzinprevrashchaiushchego fermenta u bol'nykh s narusheniiami serdechnoi provodimosti.

Increased frequencies of angiotensin-converting enzyme (ACE) D-allele and ID-genotype among patients with idiopathic atrioventricular blocks and I allele and II genotype among patients with idiopathic intraventricular blocks allow to consider these genotypes risk factors of corresponding disturbances of cardiac conduction. Decreased frequency of ACE I allele and II genotype among patients with idiopathic atrioventricular blocks is indicative of a possible protective role of II genotype against development of this type of cardiac conduction defect. Low frequency of D allele and genotype D prevents derangements of conduction in His-Purkinje system.

[New data on etiology of heart conduction disturbances]. / Novoe ob étiologii narushenii vnutriserdechnoi provodimosti.

AIM: To make a clinicogenealogical analysis of different types of heart conduction disturbances in families of Krasnoyarsk city. MATERIALS AND METHODS: 104 probands with ECG-verified idiopathic forms of atrioventricular and intraventricular blocks of different severity and 331 their close relatives (kinship degree I and II) were examined using standard clinical investigations, ECG, echocardioscopy, electrophysical investigations in some cases and coronarography. RESULTS: All the observed 104 families were divided into 3 groups according to the type of heart conduction in proband. Group 1 consisted of 24 probands with atrioventricular block and 80 their relatives. The sick relatives had for the most part atrioventricular blocks (31.2%). 26 probands of group 2 had complete right bundle branch blocks. Of their 81 relatives, the sick ones had primarily conduction disturbances in right bundle branch (incomplete block--44.7%, a complete block--5.2%). Group 3 consisted of 54 probands with left bundle branch block and 170 relatives. The left bundle branch block was present in 27.4% of the relatives. CONCLUSION: A definite family aggregation of heart conduction disturbances was found. This proves genetic determination of this pathology.

[Combined use of left atrial transesophageal pacing and cordarone in atrial flutter]. / Sochetannoe primenenie chrezpishchevodnoi stimuliatsii levogo predserdiia i kordarona pri lechenii trepetaniia preserdii.

AIM: To investigate the effectiveness of superfrequent transesophageal left atrial stimulation (TLAS) and its combination with cordarone in management of atrial flutter (AF). MATERIALS AND METHODS: 650 patients with paroxysmal AF underwent TLAS. The paroxysm duration varied from 1 hour to 1 month. In 312 patients TLAS was performed prior to treatment with antiarrhythmic drugs (group 1), in 338 patients--after intravenous administration of cordarone (group 2). RESULTS: Superfrequent TLAS has restored sinus rhythm (SR) in 85(27.2%) and 169(50%) patients of groups 1 and 2, respectively (p < 0.001). TLAS promoted conversion of AF in atrial fibrillation (AFi) in 185(59.3%) and 159(47.1%) patients of groups 1 and 2, respectively (p < 0.01). Moreover, SR recovered 24-48 hours after TLAS in 87(27.9%) and 64(18.9%) patients of groups 1 and 2 respectively (p < 0.01). Sinus rhythm recovered in a total of 172(55.1%) and 233(69.0%) patients, AF was converted to AFi in a total of 88(31.4%) and 95(28.1%) patients (p > 0.05) of groups 1 and 2, respectively. TLAS was uneffective in 42(13.5%) and 10(2.9%) patients of groups 1 and 2, respectively. CONCLUSION: Superfrequent TLAS is a highly effective and non-invasive modality in the treatment of paroxysmal AF. It promotes recovery of SR. In some patients TLAS induces AFi which is more controllable by medication as regards the heart rate. Cordarone contributes to the response to TLAS in patients with paroxysmal AF.

[Use of transesophageal left atrial cardiac pacing for assessment of cordarone effectiveness in patients with atrioventricular tachycardia]. / Primenenie chrezpishchevodnoi stimuliatsii levogo predserdiia dlia otsenki éffektivnosti lecheniia kordaronom patsientov s atrioventrikuliarnymi takhikardiiami.

AIM: To assess by means of transesophageal left atrial pacing the effectiveness of cordarone treatment for arrhythmias caused by re-entry mechanism. MATERIALS AND METHODS: Effectiveness of cordarone treatment was estimated in 25 patients with atrioventricular nodal tachycardia (AVNT) and in 33 patients with WPW syndrome and reciprocal atrioventricular tachycardia (RAVT) with frequent paroxysms of tachycardia 1-5 times per week. Transesophageal left atrial pacing (TELAP) was performed before antiarrhythmic treatment and on cordarone treatment day 14-18. Cordarone was given for two months in common regimen (the first 10 days--600 mg/day, the next 10 days--400 mg/day and then 200 mg/day). RESULTS: The first TELAP induced paroxysmal AVNT or RAVT in all the patients. According to the results of the second TELAP, all the patients were divided into three groups. Group 1 included 28 patients in whom the second TELAP was unable to induce tachycardia. All these patients had increased effective refractory period (ERP) of AV node and/or of accessory pathway (AP) values and a decreased Wenkebach point (WP) < 150/min during the second TELAP in comparison with the first TELAP. All these patients had no spontaneous paroxysms of T during the 3-month follow-up. Group 2 included 18 patients in whom the second TELAP induced AVT lasting < 30 seconds. 16 of these patients had tachycardia with less heart rate during the second TELAP in comparison with the first TELAP, 153 + (-) 8 bpm vs 188 + (-) 10 bpm, p < 0.001, respectively. Also, in these 16 patients we found an increase of values of ERP of AV node and/or AP > 360 ms and a decrease of WP < 150 bmp. 14 of these 16 patients had no spontaneous paroxysms of AVT and 2 patients had short episodes of AVT during the 3-month follow-up with effects of vagal manoeuvers. From 2 other patients of group 2 one had short episodes of spontaneous T and one had long episodes of tachycardia with effect of verapamil i.v. Group 3 included 12 patients in whom the second TELAP induced the same AVT as the first TELAP. Values of ERP of AV node and/or AP and WP during the first and second TELAP were not different. All of these patients had long spontaneous paroxysms of AVT during cordarone treatment day 14-18. The treatment was discontinued in all patients of group 3. CONCLUSION: Cordarone is effective in prevention of AVT. Negative results in provocation of AVT during TELAP after 14-18 days of cordarone treatment is a very specific predictor of cordarone treatment effectiveness. Provocation by TELAP of short episodes of AVT with reduced heart rate and higher values of ERP of AV node and AP and lowering of WP < 150 bpm may not predict ineffectiveness of cordarone in patients with AVT. Moreover, the majority of these patients had no spontaneous episodes of AVT. Provocation by TELAP during cordarone treatment of the same AVT episodes as before cordarone treatment is a very specific predictor of cordarone effectiveness.

[Prevalence of early repolarization syndrome]. / Rasprostranennost' sindroma prezhdevremennoi repoliarizatsii zheludochkov.

Early repolarization of the heart ventricles occurs in population over 13 years old rather evenly. In children it is encountered significantly more frequently than in adults, in males 2 times more often than in females, in inpatients, especially with gastrointestinal and nervous diseases, more frequently than in population. In patients with organic cardiovascular disorders the syndrome occurs less frequently.