Vol 49, No 2 (2021)

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Full Issue


Soluble suppression of tumorigenesis-2 (sST2), a new potential biomarker of response to cardiac resynchronization therapy and cardiac contractility modulation in patients with chronic heart failure

Shlevkov N.B., Gasparyan A.Z., Zhambeev A.A., Salami H.F., Guseva E.V., Tarasovskiy G.S., Sharf T.V., Stukalova O.V., Gupalo E.M., Mironova N.A., Skvortsov A.A., Golitsyn S.P.


Background: According to numerous studies, from 30% to 50% of patients with chronic heart failure (CHF) are resistant to cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM), despite their careful selection in accordance with current guidelines. It is of interest to study neurohormones characterizing myocardial (NT-proBNP) and fibrosis (sST2) as potential additional markers of CHF patients' “response” to CRT and CCM.

Aim: To evaluate the potential to use NT-proBNP and sST2 biomarkers in CHF patients combined with transthoracic echocardiography (Echo) and contrast magnetic resonance imaging (MRI) parameters of the heart to predict a positive response to CRT and CCM devices.

Materials and methods: The study included 51 patients (41 men, 10 women) aged 58 ± 12 years (26 to 79 years) with ischemic heart disease post acute myocardial infarction (n = 22) or non-ischemic cardiomyopathy (n = 29), left ventricle (LV) ejection fraction (EF) < 35%, and CHF II–III NYHA functional class despite ≥ 3 months of optimized medical therapy. The patients were assessed by serum biomarkers NT-proBNP and sST2 measurements, transthoracic Echo, and contrast- enhanced cardiac MRI. After the diagnostic assessment, CRT defibrillators (CRT-D) were implanted to 39 patients and CCM to 12 patients. After prospective follow-up of the patients for 18 to 24 months, predictors of the response to each device type were analyzed in univariate, multivariate, and ROC analysis.

Results: The response to CRT-D was found in 21 (54%) patients, to CCM in 7 (58%) patients. Multivariate analysis showed the following predictors of the response of patients to CRT-D were: 1) sST2 < 50 ng/mL, 2) NT-proBNP < 3900 pg/mL, 3) < 3 LV segments with fibrosis (by MRI) and 4) anteroposterior dimension of the left atrium < 4.8 cm (by Echo). Any 2 of these 4 characteristics made it possible to predict the response to CRT with an accuracy of 87% (sensitivity 90%, specificity 83%). The predictors of the response to CCM were: 1) sST2 < 30 ng/ml, 2) LV end diastolic diameter < 78 mm (Echo), 3) age < 56 years, 4) body mass index < 27 kg/m2. Any 2 of these 4 characteristics predicted the positive response to CCM with an accuracy of 92% (sensitivity 86%, specificity 100%).

Conclusion: The preoperative sST2 level was the only universal marker of the response to either CRT (< 50 ng/mL) or CCM (< 30 ng/mL) devices in CHF patients with reduced LVEF. The results indicate the potential for improved efficacy of these devices with their earlier implantation after the onset of the heart disease, as well as provided that maximal control CHF in these patients has been achieved.

Almanac of Clinical Medicine. 2021;49(2):99-112
pages 99-112 views

The new Russian language version of the DS14-RU questionnaire: reliability and validity assessment

Pushkarev G.S., Matskeplishvili S.T., Kuznetsov V.A.


Aim: To select new items for a  new Russian language version of the DS14-RU scale and to assess the reliability and validity of the new Russian-language version of the questionnaire.

Materials and methods: A  total of 929  subjects were recruited into the study, including 496 (53.4%) patients with coronary heart disease, 195  (21.0%) patients with chronic heart failure, 84 (9.0%) patients with arterial hypertension, and 154 (16.6%) healthy volunteers. 565 (60.8%) of the participants were men and 364  (39.2%) women. Their age ranged from 21 to 90  years (mean±SD 57.5±12.7 years). The respondents completed the extended and the new DS version, as well as the HADS, MSPSS, RSI, and STPI questionnaires.

Results: The prevalence of type D personality by the DS14-RU scale among the patients with cardiovascular diseases was 21.4%  and among healthy participants 20.0%. The new DS14-RU version had high internal consistency, with the Cronbach's alpha for the negative affectivity (NA) and social inhibition (SI) subscales of 0.80. The twofactor structure of the DS14-RU was confirmed by and exploratory and confirmatory factor analysis, with χ2 /df, CFI, TLI, IFI, and RMSEA indices for the two-factor solution being 4.7, 0.90, 0.88, 0.90 and 0.069, respectively. It was found that the NA scale was positively correlated with HADS anxiety score, STPI trait anxiety score, HADS depression and STPI depression scores, as well as with RSI psychosocial stress score. Similar but less strong correlations were found for the SI scale. There was also a negative correlation with curiosity and a positive correlation with aggressiveness, as personality traits assessed by STPI.

Conclusion: The new Russian-language version of the DS14-RU questionnaire generally corresponds to the English-language version in terms of the reliability and internal structure of the scale. The construct validity of the questionnaire has been confirmed by the results of correlation analysis. Thus, the technique can be used to identify the type D personality.

Almanac of Clinical Medicine. 2021;49(2):113-124
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Clinical characteristics and treatment of outpatients with chronic heart failure in the Moscow Region

Chernyavskaya T.K., Glezer M.G.


Aim: To perform clinical characterization of patients with chronic heart failure (CHF) in the Moscow Region and to assess if their current treatments meet the current clinical guidelines.

Materials and methods: Based on the information submitted from 11  outpatient clinics in the Moscow Region in December 2019, we analyzed retrospective data on 286  patients with CHF, including their concomitant diseases, types of assessments and their results, as well as current treatments.

Results: The most common concomitant disease was arterial hypertension (95.1%  of the patients). 53.8% of the patients had previous myocardial infarction, 37.8%, diabetes mellitus, and 34.6%, atrial fibrillation. Chronic kidney disease was present in 18.5% of the patients, valvular heart disease in 11.9%, and past stroke in 10.5%. Of non-cardiovascular diseases, the most common were gastrointestinal disorders (25.2%), chronic obstructive pulmonary disease or asthma (9.8%), and anemia (5.2%). Only 8% of the patients had one concomitant disease, whereas 72%  had 2  to 3  diseases, and 20%  had at least 4  concomitant diseases. Mean number of comorbidities per patient was 2.7. Echocardiography had been performed in 82.9% of the cases. Mean left ventricular ejection fraction was 51.0±10.11%; in 11.5% of the patients it was≤40%. Glomerular filtration rate (GFR) was calculated in 58.7%  of the patients. 35.9%  of the patients had a GFR of less than 60 mL/min/1.73 m2 , in  3.6% it was≤30  mL/min/1.73  m2 . 83.2% of the patients were treated with renin angiotensin aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, sacubitril/valsartan), 79.0% with beta-blockers, 53.1% with mineralocorticoid receptor antagonists. Glycosides had been administered to 6.9% of the patients, and diuretics, to 51.1%. In most cases, the doses administered were below those recommended by the international clinical guidelines.

Conclusion: We have confirmed the need to increase the adherence of doctors to the clinical guidelines on assessment and management of CHF patients.

Almanac of Clinical Medicine. 2021;49(2):125-131
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The role of thyrostatic agents in the treatment of chronic heart failure patients with comorbid coronary artery disease and thyrotoxicosis

Pashchenko E.V., Chesnikova A.I., Terentyev V.P., Kudinov V.I., Lankina M.S., Matveychuk L.S.


Background: Thyroid dysfunction exerts a  pronounced effect on the cardiovascular system, and, if comorbid with an existing cardiovascular disorder, may lead to a significant deterioration in the outcome, thus obviating the need for timely diagnosis and therapy optimization.

Aim: To evaluate the effect of combination therapy, including thyrostatics, on the clinical symptoms of chronic heart failure (CHF), heart rate variability, NT-proBNP concentration, and structural and functional parameters of the left heart in patients with comorbid coronary artery disease (CAD) and thyrotoxicosis.

Materials and methods: This open-label comparative study included 77 patients aged 45–65 years. The study group consisted of 36  patients with thyrotoxicosis, CAD and CHF II–III functional class, whereas the comparison group consisted of 41 patients with thyrotoxicosis without cardiovascular diseases. The patients were assessed clinically at baseline and after 6 months of therapy with addition of a thyrostatic, with tolerance to physical activity, measurements of NT-proBNP levels, 24-hour Holter monitoring, and echocardiography.

Results: At 6 months of the combination therapy including a  thyrostatic, with stable drug-induced euthyroidism, the patients in the group 1 showed an increase in the distance of a 6-minute walking test (p<0.001) and a decrease in CHF clinical symptoms. The incidence of heart rhythm disorders decreased (supraventricular extra systoles from 31% to 16%, ventricular extra systoles from 21% to 4%, atrial fibrillation from 32% to 23%; p<0.05), with a positive trend for spectral and temporal parameters of heart rate variability. The NT-proBNP level in patients with CAD, CHF and thyrotoxicosis decreased by 42.9% (p=0.001). During euthyrosis, echocardiography in the patients with ischemic CHF and concomitant thyrotoxicosis showed a significant increase in stroke volume (p=0.03), stroke ejection index (p=0.04), left ventricular ejection fraction (p=0.01), a decrease in the value of myocardial stress (p=0.02), and transmitral blood flow parameters (E/A, p<0.05). This indicates an improvement in systolic and diastolic left ventricular function after normalization of thyroid function.

Conclusion: The inclusion of thyreostatics to the combination therapy and the achievement of euthyrosis have contributed to increased tolerance to physical activity, reduction of sympathetic activity level of the autonomic nervous system and frequency of heart rhythm disorders, reduced the NT-proBNP levels, improved systolic and diastolic left ventricular function in patients with ischemic CHF and concomitant thyrotoxicosis

Almanac of Clinical Medicine. 2021;49(2):132-141
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The contribution of the AGT, GNB3, MTHFR, MTRR, ApoE, and PPARα polymorphisms to the development of masked arterial hypertension in patients with low and moderate cardiovascular risk

Koziolova N.A., Chernyavina A.I.


Aim: To assess the probability of masked arterial hypertension (MAH) in patients with low and moderate cardiovascular risk depending on polymorphisms in selected genes.

Materials and methods: Ninety two (92) patients (mean age, 41.93±8.92 years) with low and moderate cardiovascular risk without any documented cardiovascular disorders were assessed clinically and had 24-hour ECG monitoring performed, as well as genotyping on the following markers: AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, and PPARα G/C rs4253778. Depending on the presence of MAH, the patients were divided into two groups: with newly diagnosed arterial hypertension corresponding to the MAH criteria (n=58, 63%) and with normal office-based and ambulatory blood pressure and normal blood pressure according to the results of 24-hour ECG monitoring (n=34, 37%).

Results: Two groups were not different by their age, cardiovascular risk factors, concomitant diseases and clinical characteristics. There were more men than women in the MAH group (р=0.028). In MAH patients, the most prevalent was Ile22Met rs1801394 A/G polymorphism of the MTRR gene (the odds ratio (OR) and relative risk (RR) for MAH were 4.23 [95% сonfidence interval (CI) 1.56–11.72] and 2.17  [1.25–4.12], respectively). The Cys130Arg rs 429358 Т/С genotype polymorphism of the АроЕ gene was also significant. The probability of MAH in the patients with АроЕ Т/С genotype was more than 3-fold higher: OR 3.67  [95%  CI 1.34–10.28], RR 2.15  [95%  CI 1.17–4.36]. The correlation analysis showed a moderate association between MAH and MTRR and АроЕ gene polymorphisms (Q=0.62 and Q=0.57, respectively).

Conclusion: In patients with low and moderate cardiovascular risk, the probability of MAH depends not only from their gender, but also from their genetic background. The candidate genes for MAH in such patients are Ile22Met rs1801394 A/G polymorphism of the MTRR gene and Cys130Arg rs 429358 Т/С polymorphism of the АроЕ gene.

Almanac of Clinical Medicine. 2021;49(2):142-148
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Cardiac causes of death in Moscow and Moscow Region

Samorodskaya I.V., Kakorina E.P.


Rationale: Cardiovascular disorders play a leading role in populational mortality, but they are not synonymous to cardiac pathology. The city of Moscow and the Moscow Region are one of the biggest urban agglomeration worldwide.

Aim: Analysis of cardiac-related mortality in Moscow and the Moscow Region.

Materials and methods: We calculated standardized mortality coefficients (SMC) for 23  death causes given as separate lines in the Short List of Death Causes by the Russian Agency of Statistics (Rosstat) in 2019.

Results: In 2019, SMC for cardiac causes was 171.2 per 100 000 of the population in Moscow (27.6% of all causes) and 248.7 per 100 000 of the population in the Moscow Region (26.9% of all causes). More than 60% of deaths both in Moscow and in the Moscow Region were caused by chronic variants of ischemic heart diseases, whose criteria are not well-defined or are absent. In Moscow, SMC for myocardial infarction is significantly lower, whereas that for unspecified cardiomyopathy (the code by International Classification of Diseases and Health-related Conditions, version 10 (ICD10) I42.9) is higher. SMC from the groups of death causes related to chronic illness possibly unrelated to atherosclerosis, are comparable: 29.64 in Moscow and 24.59 in the Moscow Region. SMC from arterial hypertension (ICD10 I10-13) are 8.7 and 5.6 per 100000 of the population, respectively.

Conclusion: Despite higher total cardiac mortality in the Moscow Region, SMCs for individual death causes in Moscow are significantly higher. SMC variability is mostly related to different algorithms for determination of primary death cause. ICD10 and the Rosstat the Short List of Death Causes seem to be suboptimal sources to understand the contribution of cardiac causes into the mortality structure. Any correct comparison would become possible after a consensus of expert positions by specialists in Moscow and Moscow Region on the criteria of diagnosis, choice of primary death cause and corresponding disease code.

Almanac of Clinical Medicine. 2021;49(2):149-156
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Orthostatic hypotension in patients of 60 years and older with arterial hypertension: an association between arterial stiffness and frailty

Luzina A.V., Runikhina N.K., Tkacheva O.N., Lysenkov S.N., Kotovskaya Y.V., Eruslanova K.A.


Aim: To assess an association between orthostatic hypotension and arterial stiffness, measured by the cardio-ankle vascular index (CAVI), in a group of patients≥60 years of age with arterial hypertension and frailty.

Materials and methods: The study included 160 patients aged 60 to 101 years with confirmed arterial hypertension without severe concomitant physical disorders. Compliance to the previously prescribed medications was assessed. A  short questionnaire, "Age is not a  hindrance," was used to identify patients with frailty. According to the current diagnostic algorithm for frailty, the patients were categorized into three groups: group 1, frail, group 2, pre-frail, group 3, healthy. Arterial stiffness was assessed by volumetric sphygmometry (VaSera-VS-1500, Fukuda Denshi, Japan) with the measurement of CAVI. The orthostatic test was considered positive if blood pressure falls by≥20/10 mm Hg after changing from supine to standing position.

Results: The mean age of the study patients was 77.2±8.1 years (n=160), being 72.4±6.9 years in the healthy patients (n=50), 76.6±8.1 years in the pre-frail (n=50) and 81.7±6.6 years in the frail patients (n=60). Orthostatic hypotension was identified in total of 53 (33%) patients, with marginally significant difference between the pre-frail and healthy groups (44 and 20% of the patients, respectively, p=0.053). The CAVI values were higher in frail patients, compared to healthy ones (p=0.0005). Orthostatic hypotension was associated with a  higher CAVI, irrespective of the patients’ age and frailty (р=0.0067). The association between orthostatic hypotension and CAVI in frail patients was found only with unifactor analysis, but became non-significant with the additional analysis.

Conclusion: Orthostatic hypotension can be found in 33% of the elderly patients with arterial hypertension. Arterial stiffness increases with increasing frailty, as well as with concomitant orthostatic hypotension in the group of the patients≥60 years of age. The progression of arterial stiffness in the elderly group is heterogeneous and depends on the presence of frailty.

Almanac of Clinical Medicine. 2021;49(2):157-164
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Ventricular arrhythmias in a patient with obstructive sleep apnea syndrome and its effective non-pharmaceutical treatment

Palman A.D., Akselrod A.S.


Patients with obstructive sleep apnea syndrome (OSAS) are characterized by various cardiac arrhythmias during sleep. However, while the association between OSAS and atrial fibrillation is considered proven, the presence of a  pathophysiological link between sleep apnea and ventricular arrhythmias remains a  matter of debate.

We present a  case of a  51-year old man with arterial hypertension and type 2 diabetes who was referred for sleep assessment after being diagnosed with predominantly nocturnal cardiac arrhythmias. Overnight cardiorespiratory monitoring showed that the patient had a severe OSAS with an apnea-hypopnea index of 57 per hour and a minimal SpO2 during sleep of 73%. On the channel of electrocardiogram (ECG) frequent single monomorphic ventricular extrasystoles, eventually of the bigeminal type, and one short paroxysm of a wide-complex regular rhythm of 60  beats per minute (accelerated idioventricular rhythm) associated with prolonged apnea were identified. Continuous airway positive pressure (CPAP) therapy was started which was able to control for breathing disorders during sleep. At the follow-up 24-hours Holter ECG monitoring, the numbers of ventricular extrasystoles during sleep decreased 2-fold, without any idioventricular rhythm episodes.

The clinical case clearly illustrates that in some patients with OSAS, first of all, in those with severe OSAS and comorbid cardiovascular disorders, breathing disorders during sleep can trigger ventricular arrhythmias. In such patients, CPAP therapy could both improves their quality of life and provide an indirect antiarrhythmic effect.

Almanac of Clinical Medicine. 2021;49(2):165-170
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Special Section: COVID-19

Evaluation of an association of radiological findings and severity of the disease in patients with the new coronavirus infection (COVID-19)

Strutynskaya A.D., Koshurnikov D.S., Tyurin I.E., Karnaushkina M.A.


Rationale: Interpretation of lung abnormalities identified by computed tomography (CT) in patients with COVID-19 could be controversial in some cases. At present, there is no highly reliable algorithm for assessment and prediction of the disease coursed based on CT findings.

Aim: To identify an association of the radiological findings in COVID-19 and its clinical manifestations.

Materials and methods: This observational retrospective cohort study included 92 patients, categorized into three groups according to their clinical severity (mild COVID-19 29 patients, moderate COVID-19 33 patients, and severe COVID-19 30 patients). Chest CT was performed in all patients at admittance to the hospital and at day 10 of their hospital stay.

Results: Almost all patients with severe COVID-19 (28 patients, 96.6%) demonstrated an increase in the damaged lung parenchyma volume at the second CT. The risk of clinical deterioration in these patients was 15.037-fold higher, compared to that in the patients with a  stable volume of lung lesions. The area of pulmonary lesions at the first CT demonstrated its good prognostic ability (ROC area under the curve 0.831, sensitivity 87.5%, specificity 70.0%, p<0.001) to predict clinical deterioration. The presence of bronchial dilation in the total patient group significantly (p<0.01) correlated with an increase of the pulmonary lesion area. Clinical deterioration was found in 5 patients (62.5%) with bronchial dilatation.

Conclusion: CT patterns in COVID-19 patients do not always correlate with clinical severity of the disease. Therefore, lung CT cannot be used for prediction of the COVID-19 course as a  single method without clinical and laboratory assessments.

Almanac of Clinical Medicine. 2021;49(2):171-178
pages 171-178 views

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