[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.

[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.

[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.

[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.

[Comparative analysis of the significance of transesophageal stimulation of the left atrium and bicycle ergometry in the detection of residual myocardial ischemia during the early period of myocardial infarct]. / Sravnitel'nyi analiz znachimosti chrespishchevodnoi stimuliatsii levogo predserdiia i veloérgometrii v vyiavlenii rezidual'noi ishemii miokarda v rannie sroki infarkta miokarda.

The study was undertaken to compare transesophageal left atrial pacing (TLAP) and bicycle ergometry (BE) in the detection of residual myocardial ischemia (RMI) in 187 patients with myocardial infarction in the early periods of the disease (on days 20 to 26). The intensity of TLAP and BE was increased up to the threshold and submaximal levels according to the conventional criteria. Among the patients, RMI was detected in 71% with TLAP and in 55% with BE (p less than greater than 0.01). Thus, this suggests that TLAP has advantages over BE in the detection of RMI in patients with myocardial infarction in the early periods of the disease.

[Sinus node function of ischemic heart disease patients with chronotropic incompetence]. / Funktsional'noe sostoianie sinusnogo uzla u bol'nykh ishemicheskoi bolezn'iu serdtsa s "khronotropnoi nekompetentnost'iu".

Forty-five (17.6%) of 256 coronary patients showed inadequately small heart rate augmentation in response to rationed exercise ("chronotropic incompetence"). To assess their sinoatrial node function, esophageal atrial stimulation was done in all patients before and after drug-induced vegetative block, and the adjusted sinoatrial node function time and sinoatrial conduction time were determined. Electrophysiological evidence suggests that "chronotropic incompetence" is in most cases determined by abnormal sinoatrial rhythm. Rationed exercise testing can be used as a screening test for latent weak sinoatrial node syndrome in coronary patients.

[Clinico-electrocardiographic variants of combined lesions of the sinoatrial and atrioventricular nodes]. / Kliniko-elektrokardiograficheskie varianty pri sochetannom porazhenii sinusovogo i atrioventrikuliarnogo uzlov.

A study of 71 patients with atrioventricular blocks and 57 patients with the sick-sinus syndrome (SSS) revealed electrophysiologic evidence of sinus dysfunction in 38 (53.5%) patients with atrioventricular blocks. Sinus dysfunction was due to pathologic vegetative effects in 15 (21.1%) patients with AV blocks, and a pathology of the sinus node itself in 23 (32.4%). Impaired atrioventricular conductivity, was registered in 29 (38.7%) patients with the SSS. A disorder of atrioventricular automatism was detected in 38 patients, and was combined with impaired AV conductivity in 19 of those. Five clinico-electrocardiographic variants of binodal heart disease have been identified, and possible therapies are discussed for each of those.

[Auricular fibrillation in myocardial infarct]. / Mertsatel'naia aritmiia pri infarkte miokarda

Auricular fibrillation was observed in 17.8% of patients with large-focal myocardial infarction, mainly in females (p 0.01). The localization of myocardial infarction had no impact on the incidence of auricular fibrillation. The precursors of auricular fibrillation included atrial extrasystoli and an elevated electrolyte coefficient of the blood NaeKe. In the group of patients with myocardial infarction and auricular fibrillation mortality was more common among the females. Auricular fibrillation developing beyond the first postinfarction day worsened the prognosis considerably. The outcome of myocardial infarction did not much depend on the duration of auricular fibrillation and on the cardiac contraction frequency.

[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.

[Prognostic evaluation of sick sinus syndrome]. / Prognosticheskaia otsenka sindroma slabosti sinusovogo uzla.

Altogether 114 patients with sick sinus syndrome (SSS) were followed up for 2-10 yrs. They were divided into 3 groups: the 1st group (33 patients) with the latent SSS, the 2nd group (44 patients) with the compensated SSS, and the 3rd group (37 patients) with the decompensated SSS. The lethality rate in the 1st group was 6.1%, in the 2nd group--9.1%, in the 3rd group--13.5% (statistically insignificant difference). Paroxysms of atrial fibrillation/flutter were observed in 36.4% of the patients of the 1st group, in 36.4% of the patients of the 2nd group, and in 37.8% of the patients of the 3rd group. Persistent atrial fibrillation/flutter was observed in the 1st group (9.1%), in the 2nd group (11.4%), and in the 3rd group (27%) (p1 = 3 less than 0.05; p2 = 3 less than 0.05). The lethality rate among the SSS patients with persistent atrial fibrillation/flutter was 38.9%, among the rest of the SSS patients--4.2% (p less than 0.01). The lethality rate among the decompensated SSS patients with cardiac pacemakers was 10.5%, without them--16.6% (p greater than 0.1).

[Significance of autonomic block by drugs for the diagnosis and evaluation of the pathogenesis of the sick sinus syndrome]. / Znachenie medikamentoznoi vegetativnoi blokady dlia diagnostiki i otsenki patogeneza sindroma slabosti sinusovogo uzla.

Altogether 65 patients with the sinoatrial node weakness syndrome (SANWS) and 48 patients with the heart pain syndrome (control group) were examined for a study of the corrected time of sinoatrial node function recovery (CTSNFR) and the time of sinoatrial conduction (TSAC) before and after medicamentous vegetative blockade (MVB). A considerable increase in CTSNFR and TSAC sensitivity after MVB was noted. In most of the SANWS patients CTSNFR after MVB was increased, TSAC was decreased. Elevated CTSNFR in the SANWS patients was determined by the effect of propranolol and atropine and was noted mainly during atrial stimulation with a high frequency (over 160 imp/min).

[Work capacity evaluation of patients with sick sinus syndrome]. / Otsenka fizicheskoi rabotosposobnosti bol'nykh s sindromom slabosti sinusovogo uzla.

Thirty-four normal subjects, 30 patients with sinoatrial node weakness (SANW), and 129 patients with coronary heart disease (CHD) without the signs of sinoatrial node involvement were examined. The work fitness was studied with the aid of indirect estimates (PWC 170, maximal oxygen consumption per kg bw, double product), spiroergometry (oxygen pulse, rest quotient) and central hemodynamic data (cardiac and stroke indices). The work fitness in SANW patients was low, depending on the disease etiology and chronotropic reserves of the heart. PWC 170, maximal oxygen consumption per kg bw, oxygen pulse were found to overestimate the genuine level of the SANW patients' physical status. In view of this fact these estimates cannot be used for its evaluation. It is inferred that the power of the threshold loading, the rest quotient, the cardiac index, and double product adequately reflect the work fitness of SANW patients.

[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 a physical exertion test for the diagnosis of the sick sinus syndrome]. / Primenenie proby s fizicheskoi nagruzkoi dlia diagnostiki sindroma slabosti sinusovogo uzla.

Forty-three patients with the sick sinus syndrome (SSS) and 74 normal persons were examined. All the patients were subjected to bicycle ergometry. The lower limits of normal for the heart rate (HR) (in men and women separately) were established during exercise of varying intensity. In 66.7% of patients with the SSS, the HR during exercise was under normal. In a significant part of SSS patients, the reduction of the HR after exercise proceeded more rapidly than in normal subjects. The authors suggest a heart rate retardation index (HRRI) for recognizing the SSS, the diagnostic importance of which rises with an increase in the exercise intensity. The total sensitivity of both indices (the HR at the end of exercise and the HRRI) reaches 100%. It is concluded that the exercise test can be used for preliminary screening of patients with the SSS.