Vol 11, No 3 (2020)

Genetics and Heart Diseases

Association of polymorphism -1171 5A/6A of the matrix metalloproteinase gene type 3 (rs35068180) with dilated cardiomyopathy

Kuznetsova O.O., Nikulina S.Y., Chernova A.A., Maksimov V.N.


The paper describes the investigation of matrix metalloproteinase type 3 (MMP-3) -1171 5A/6A gene polymorphic allele’s variants (rs35068180) in patients with dilated cardiomyopathy. A allele and 6А6А genotype of MMP-3 -1171 5A/6A gene (rs35068180) were determined as new genetic predictors of dilated cardiomyopathy development.

Aim. To study the association of polymorphism -1171 5A/ of the MMP-3 gene with dilated cardiomyopathy of various origins.

Material and methods. The main study group comprised 221 patients with dilated cardiomyopathy (DCM) of different origin. Their average age was 55.30±9.69 years. Among them there were 111 persons with DCM of ischemic origin, including 99 (89.2%) men and 12 (10.8%) women. The average age of the subjects with DCM was 51.73±9.74 years, the age of the male subgroup was 51.00±8.96 years, and the age of the female subgroup was 57.75±3.71 years. A total of 110 patients with idiopathic cardiomyopathy were included in the study. Among 221 patients, 110 persons did not demonstrated idiopathic dilated cardiomyopathy as the cause of myocardium dilation. This group comprised 100 (91.5%) male patients and 10 (8.5%) female patients. The control group of subjects (221 persons) was represented by healthy people without diseases of the cardiovascular system. The average age of control subjects was 53.6±4.8 years. We examined all patients in the main group using routine laboratory and instrumental methods, as well as coronary angiography. If myocarditis was suspected, we did an MRI of the heart. Genotyping of polymorphism -1171 5A/6A (rs35068180) of the MMP-3 gene was performed using PCR.

Results. Among patients of the main group with dilated myocardial remodeling of various Genesis, the allele was documented in 65.8% of cases against 59.3% among the control group, p=0.044. The homozygous genotype of the MMP-3 gene in patients of the main group was verified in 42.1% of patients against 32.6% of cases in relatively healthy individuals (p=0.099).

Conclusion. We have proved the predominance of 6A allele and 6А6А genotype of the MMP-3 gene in the group of patients with DCM. It seems that it is homozygous 6A allele that causes a decrease in the activity of the transcription process and change in the level of stromelysin in arterial walls. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.

CardioSomatics. 2020;11(3):6-9
pages 6-9 views

Invasive Interventions and Acute Myocardial Infraction

Terms of admission to the hospital and performing endovascular procedures in patients with acute myocardial infarction without ST segment elevation in real clinical practice

Rafaeli I.R., Kireeva A.I., Chernysheva I.E., Kostyanov I.Y., Tsereteli N.V., Azarov A.V., Stepanov A.V., Semitko S.P.


Aim. To find out the relationship of the severity of patients condition, with acute myocardial infarction without ST segment elevation (NSTEMI), upon admission to the hospital on the basis of the Global Registry of Acute Coronary Events (GRACE) scale with the time interval between the onset of the disease and up to hospitalization (“pain–hospitalization”), and to clarify the effect of the GRACE score on the time interval to endovascular procedures (EVP) – “door–balloon”, in real clinical practice.

Material and methods. The study included 421 NSTEMI patients. Patients were admitted between 2000 and 2017. All patients underwent coronary angiography followed by EVP. Depending on the clinical condition, at admitted to the hospital, patients were divided into risk groups on the GRACE scale. According to the indicators – “pain–hospitalization” and “door–balloon” – 3 time intervals were allocated: ≤6 hours, 6–24 and >24 hours.

Results. At admission, 73.9% (311) patients had an average and high risk on the GRACE scale. Patients with high risk were significantly more often (49.6%) hospitalized during the first 6 hours after onset of the disease than later (p<0.05). 2/3 of all patients and 3/4 of patients with high risk had the time interval of “pain–hospitalization” up to 24 hours. 51.8% patients in the total group and 65.8% among high-risk patients had a “door–balloon” interval up to 6 hours. During first 24 hours after hospitalization EVP was successfully completed on 90.7% of patients. One patient had a fatal outcome. At discharge none of the patients were observed the symptoms of angina pectoris and congestive heart failure.

Conclusion. In the all group, according to the allocated time intervals “pain–hospitalization”, patients were distributed practically equally. The severity of the condition of the studied patients is indicated by the fact that almost 3/4 of them had a high and average risk on the GRACE scale. It is encouraging that in the first 6 hours from the onset of the disease, high-risk patients were significantly more often hospitalized. Almost 2/3 of high-risk patients and more than half of all patients had a “door–balloon” indicator-up to 6 hours. It is important that in the first 24 hours, successful EVP was performed in 90.7% of patients. Thus, our results (low mortality, absence of angina and heart failure after EVP) indicate the correct management and treatment of NSTEMI patients, which is close to the latest world recommendations, comes from real life circumstances and can be recommended for real clinical practice.

CardioSomatics. 2020;11(3):10-15
pages 10-15 views

Pathogenetic Aspects of Cardiovascular Diseases

Relationship between the expression of angiotensin II receptors type 1 and vasoactive regulators in arterial hypertension

Logatkina A.V., Nikiforov V.S., Bondar' S.S., Terekhov I.V., Parfeniuk V.K.


In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task.

Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension.

Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators.

Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.

CardioSomatics. 2020;11(3):16-21
pages 16-21 views

The role of matrix metalloproteinases in the myocardial remodeling

Bazylev V.V., Kanaeva T.V.


The main structural event in the development of heart failure is the myocardial remodeling. The extracellular matrix, that was knows as, considered an inert framework of cardiomyocytes, plays an important role in cardiac remodeling. The enzyme system, primarily responsible for the degradation of the extracellular matrix, is a matrix metalloproteinases (MMP). This review examines the evidence for the participation of MMP in the myocardial remodeling and recent studies of MMP as prognostic markers. Regulation of induction and/or activation of MMP are potential therapeutic targets.

CardioSomatics. 2020;11(3):22-28
pages 22-28 views

Hemodialysis in Cardiology

The effect of hemodialysis on echocardiographic parameters and on supraventricular cardiac arrhythmias

Likhachev-Mishchenko O.V., Kornienko A.A., Khaisheva L.A., Duzhikova A.V., Kornienko N.A., Kadyan E.G., Dyuzhikov A.A., Shlyk S.V.


Relevance. Supraventricular arrhythmias are frequent comorbid conditions in patients with end-stage renal failure undergoing dialysis. The prevalence of atrial fibrillation (AF) in this group of patients is higher than in the general population and is associated with increased mortality.

Aim. To analyze the effect of a dialysis session on echocardiographic parameters and to assess their relationship with the occurrence of supraventricular arrhythmias and AF during hemodialysis.

Material and methods. The study included 78 patients on hemodialysis. All patients underwent Holter electrocardiography monitoring, taking into account the heart rate before and after dialysis, the number and duration of AF episodes associated with the dialysis session. Using echocardiography, which was performed before and after the dialysis procedure, all patients were also evaluated for the presence of left ventricular (LV) hypertrophy, impaired systolic and diastolic function, as well as LV myocardial mass, sizes of the left atrium, its volume, volume of the right atrium and LV ejection fraction.

Results. An analysis of the differences in echocardiographic parameters before and after dialysis showed a significantly larger volume of the left atrium, the volume of the right atrium, the width of the inferior vena cava, and the parameter P’(early transmitral velocity) before dialysis compared with the state after dialysis. Also, AF paroxysms were recorded much more frequently after dialysis. The volume of the left atrium >32 mm and the right atrium >30 mm (limit values) were observed much more often in patients before dialysis. A relationship was found between an increased number of paroxysms of atrial fibrillation and a decrease in the volume of the right atrium >5 mm and the left atrium >7 mm after dialysis. No correlation was found between the mass of the LV and the volume of the left atrium.

Conclusions. 1. The age and duration of dialysis therapy in hemodialysis patients are associated with an increased risk of atrial fibrillation. 2. A decrease in the volumes of the right and left atriums after the hemodialysis procedure has a positive correlation with paroxysmal AF. 3. The hemodialysis procedure leads to a decrease in the volumes of the right and left atriums, as well as the width of the inferior vena cava and a decrease in the speed of movement of the mitral valve in early diastole. 4. No relationship was found between the volume of the left atrium and the mass of the LV myocardium in patients on hemodialysis.

CardioSomatics. 2020;11(3):29-34
pages 29-34 views

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