Genetic variants of ABCB1 and CES1 genes on dabigatran metabolism in the Kazakh population.

Background: Allelic variants of genes encoding enzymes of the esterase system (CES1) and P-glycoprotein (ABCB1) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of ABCB1 (rs1045642, rs4148738, rs2032582, and rs1128503) and CES1 (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran. Methods: A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping. Results: Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the ABCB1 SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively). Conclusion: Our research demonstrates that the CES1 polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.

Gut Microbiome and Cytokine Profiles in Post-COVID Syndrome.

Recent studies highlight the crucial role of the gut microbiome in post-infectious complications, especially in patients recovering from severe COVID-19. Our research aimed to explore the connection between gut microbiome changes and the cytokine profile of patients with post-COVID syndrome. Using 16S rRNA amplicon sequencing, we analyzed the composition of the gut microbiome in 60 COVID-19 patients over the course of one year. We also measured the levels of serum cytokines and chemokines using the Milliplex system. Our results showed that severe SARS-CoV-2 infection cases, especially those complicated by pneumonia, induce a pro-inflammatory microbial milieu with heightened presence of Bacteroides, Faecalibacterium, and Prevotella_9. Furthermore, we found that post-COVID syndrome is characterized by a cross-correlation of various cytokines and chemokines MDC, IL-1b, Fractalkine, TNFa, FGF-2, EGF, IL-1RA, IFN-a2, IL-10, sCD40L, IL-8, Eotaxin, IL-12p40, and MIP-1b as well as a shift in the gut microbiome towards a pro-inflammatory profile. At the functional level, our analysis revealed associations with post-COVID-19 in homolactic fermentation, pentose phosphate, NAD salvage, and flavin biosynthesis. These findings highlight the intricate interplay between the gut microbiota, their metabolites, and systemic cytokines in shaping post-COVID symptoms. Unraveling the gut microbiome's role in post-infectious complications opens avenues for new treatments for those patients with prolonged symptoms.

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants.

Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', 'ABCB1', 'CES1', 'SULT1A', 'ABCG2', and 'CYP3A4'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulantsAtrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs.

Role of Genetic Polymorphisms in the Development of Complications in Patients with Implanted Left Ventricular Assist Devices: HeartWare, HeartMate II, and HeartMate 3.

Left ventricular assist device (LVAD) implantation is one of the mechanical circulatory support (MCS) treatments for advanced heart failure (HF) patients. MCS has emerged as a lifesaving therapy that improves patients' quality of life. However, MCS remains limited by a paradoxical coagulopathy accompanied by thrombosis and bleeding. The mechanisms of MCS thrombosis are increasingly being defined, but MCS-related bleeding, which is related to shear-mediated alteration of platelet function, remains poorly understood. Complications might develop due to the high non-physiological shear stress in the device and as a consequence of individual variability in response to the antithrombotic therapy. Thromboelastography (TEG) and genotyping of gene polymorphisms that are involved in the coagulation cascade and in the metabolism of the antithrombotic therapy might be valuable sources of information for the reduction of complication development. The aim of the study was to identify genetic factors related to the development of device complications according to the implanted LVAD type. We compared the clinical and genetic data of HF patients (n = 98) with/without complications with three types of implanted devices: HeartWare HVAD (HW), HeartMate II (HMII), and HeartMate 3 (HM3). rs9923231 in VKORC1 (95%CI -6.28-0.22, p = 0.04) and rs5918 in ITGB3 genes (95%CI 0.003-4.36, p = 0.05) showed significant association with the TEG coagulation index parameter, which identified hyper- and hypo-coagulation states. The wild genotype of rs5918 in the ITGB3 gene prevailed in patients implanted with HM3 devices, which developed fewer complications than with HMII (p = 0.04). Individual genetic information could be useful in the management of patients with HF and the implantation of MCS to reduce the development of complications.

Cardiac imaging in athlete's heart: current status and future prospects.

BACKGROUND: Physical activity contributes to changes in cardiac morphology, which are known as "athlete's heart". Therefore, these modifications can be characterized using different imaging modalities such as echocardiography, including Doppler (flow Doppler and Doppler myocardial imaging) and speckle-tracking, along with cardiac magnetic resonance, and cardiac computed tomography. MAIN TEXT: Echocardiography is the most common method for assessing cardiac structure and function in athletes due to its availability, repeatability, versatility, and low cost. It allows the measurement of parameters like left ventricular wall thickness, cavity dimensions, and mass. Left ventricular myocardial strain can be measured by tissue Doppler (using the pulse wave Doppler principle) or speckle tracking echocardiography (using the two-dimensional grayscale B-mode images), which provide information on the deformation of the myocardium. Cardiac magnetic resonance provides a comprehensive evaluation of cardiac morphology and function with superior accuracy compared to echocardiography. With the addition of contrast agents, myocardial state can be characterized. Thus, it is particularly effective in differentiating an athlete's heart from pathological conditions, however, is less accessible and more expensive compared to other techniques. Coronary computed tomography is used to assess coronary artery anatomy and identify anomalies or diseases, but its use is limited due to radiation exposure and cost, making it less suitable for young athletes. A novel approach, hemodynamic forces analysis, uses feature tracking to quantify intraventricular pressure gradients responsible for blood flow. Hemodynamic forces analysis has the potential for studying blood flow within the heart and assessing cardiac function. CONCLUSIONS: In conclusion, each diagnostic technique has its own advantages and limitations for assessing cardiac adaptations in athletes. Examining and comparing the cardiac adaptations resulting from physical activity with the structural cardiac changes identified through different diagnostic modalities is a pivotal focus in the field of sports medicine.

Unraveling Acute and Post-COVID Cytokine Patterns to Anticipate Future Challenges.

The aims of this study were to analyze cytokine profiles in patients with COVID-19, gain insights into the immune response during acute infection, identify cytokines associated with disease severity and post-COVID complications, and explore potential biomarkers for prognosis and therapeutic targets. Using a multiplex analysis, we studied the cytokine pattern in 294 acute COVID-19 and post-COVID patients with varying severities of infection. Our findings revealed that disease severity was associated with elevated levels of IL-15, IL-8, and fractalkine. Severe/extremely severe forms in comparison with mild/moderate disease were associated with MCP-1, IFNa2, IL-7, IL-15, EGF, IP-10, IL-8, Eotaxin, FGF-2, GROa, sCD40L, and IL-10. The key cytokines of post-COVID are FGF-2, VEGF-A, EGF, IL-12(p70), IL-13, and IL-6. By the sixth month after recovering from a coronavirus infection, regardless of disease severity, some patients may develop complications such as arterial hypertension, type 2 diabetes mellitus, glucose intolerance, thyrotoxicosis, atherosclerosis, and rapid progression of previously diagnosed conditions. Each complication is characterized by distinct cytokine profiles. Importantly, these complications can also be predicted during the acute phase of the coronavirus infection. Understanding cytokine patterns can aid in predicting disease progression, identifying high-risk patients, and developing targeted interventions to improve the outcomes of COVID-19.

Incidence, mortality and disability-adjusted life years of acute myocardial infarction in Kazakhstan: data from unified national electronic healthcare system 2014-2019.

Background: Cardiovascular diseases contribute to premature mortality globally, resulting in substantial social and economic burdens. The Global Burden of Disease (GBD) Study reported that in 2019 alone, heart attack and strokes accounted for the deaths of 18.6 million individuals. Ischemic heart diseases, including acute myocardial infarction (AMI), accounted for 182 million disability-adjusted life years (DALYs) and it is leading cause of death worldwide. Aim: The aim of this study is to present the burden of AMI in Kazakhstan and describe the outcome of hospitalized patients. Methods: The data of 79,172 people admitted to hospital with ICD-10 diagnosis I21 between 2014 and 2019 was derived from the Unified National Electronic Health System and retrospectively analyzed. Results: The majority of the cohort (53,285, 67%) were men, with an average age of 63 (±12) years, predominantly of Kazakh (38,057, 48%) and Russian (24,583, 31%) ethnicities. Hypertension was the most common comorbidity (61,972, 78%). In males, a sharp increase in incidence is present after 40 years, while for females, the morbidity increases gradually after 55. Throughout the observation period, all-cause mortality rose from 101 to 210 people per million population (PMP). In 2019, AMI account for 169,862 DALYs in Kazakhstan, with a significant proportion (79%) attributed to years of life lost due to premature death (YLDs). Approximately half of disease burden due to AMI (80,794 DALYs) was in age group 55-69 years. Although incidence is higher for men, they have better survival rates than women. In terms of revascularization procedures, coronary artery bypass grafting yielded higher survival rates compared to percutaneous coronary intervention (86.3% and 80.9% respectively) during the 5-year follow-up. Conclusion: This research evaluated the burden and disability-adjusted life years of AMI in Kazakhstan, the largest Central Asian country. The results show that more effective disease management systems and preventive measures at earlier ages are needed.

The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC.

Nowadays, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). We aimed to identify the influence of polymorphisms of the genes encoding P-glycoprotein (ABCB1) and carboxylesterase 1 (CES1) on the variability of plasma concentrations of DOACs in Kazakhstani patients with NVAF. We analyzed polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes and measured the plasma concentrations of dabigatran/apixaban and biochemical parameters in 150 Kazakhstani NVAF patients. Polymorphism rs8192935 in the CES1 gene (p = 0.04), BMI (p = 0.01) and APTT level (p = 0.01) were statistically significant independent factors of trough plasma concentration of dabigatran. In contrast, polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes did not show significant influence on plasma concentrations of dabigatran/apixaban drugs (p > 0.05). Patients with GG genotype (138.8 ± 100.1 ng/mL) had higher peak plasma concentration of dabigatran than with AA genotype (100.9 ± 59.6 ng/mL) and AG genotype (98.7 ± 72.3 ng/mL) (Kruskal-Wallis test, p = 0.25). Thus, CES1 rs8192935 is significantly associated with plasma concentrations of dabigatran in Kazakhstani NVAF patients (p < 0.05). The level of the plasma concentration shows that biotransformation of the dabigatran processed faster in individual carriers of GG genotype rs8192935 in the CES1 gene than with AA genotype.

Case report: A novel surgical technique for rapid valve-in-ring implantation into the native aortic annulus during left ventricular assist device implantation.

The implantation of a left ventricular assist device (LVAD) has become an essential requirement for managing patients with end-stage heart failure. However, aortic valve insufficiency is a contraindication for LVAD implantation in patients with end-stage heart failure, partly because of the decreasing efficiency of mechanical circulatory support and the eventual development of right ventricular failure. Herein, we present the first case of performing transcatheter aortic valve replacement in valve-in-ring along with LVAD implantation for the treatment of a 60-year-old male suffering from refractory heart failure due to dilated cardiomyopathy and pure aortic insufficiency in need of a new aortic bioprosthesis. A balloon-expandable bioprosthetic transcatheter heart valve was implanted into a previously sewn annulus ring into the aortic root via transaortic access. Subsequently, a centrifugal-flow LVAD was implanted. Postoperatively, the patient was in New York Heart Association Functional Class (NYHA) II with 6-min walk test of 310 m. The patient has completed 6 months of follow-up with no events. This novel and feasible surgical technique reduced the cardiopulmonary bypass time and duration of surgery. Furthermore, it avoids the risk of redo sternotomy and decreases the chances of paravalvular leakage and worsening of aortic regurgitation.

Association of Lung Fibrotic Changes and Cardiological Dysfunction with Comorbidities in Long COVID-19 Cohort.

Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID-19 and its comorbidities have not been established. Methods. In total, 312 patients with long COVID-19 from 21 primary care centers were included in the study. At the six-month follow-up, their lung function was assessed by computerized tomography (CT) and spirometry, whereas cardiac function was assessed by elec-trocardiogram (ECG), Holter ECG, echocardiography, 24 h blood pressure monitoring, and a six-minute walk test (6MWT). Results. Of the 312 persons investigated, significantly higher sys-tolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP were revealed in participants with hypertension or type 2 diabetes. Left ventricular diastolic dysfunc-tion was more frequently present in patients with hypertension. The most common registered CT abnormalities were fibrotic changes (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Among the tested biochemical parameters, three associations were found in long COVID-19 patients with hypertension but not diabetes: increased hemoglobin, fibrinogen, and ferritin. Nine patients had persisting IgM antibodies to SARS-CoV-2. Conclusions. We demon-strated a strong association between signs of cardiac dysfunction and lung fibrotic changes with comorbidities in a cohort of long COVID-19 subjects.

Central and effector memory T cells in peripheral blood of patients with interstitial pneumonia: preliminary clues from a COVID-19 study.

BACKGROUND: SARS-CoV-2 pre-existing T-cell immune reactivity can be present in some people. A general perturbation of the main peripheral lymphocyte subsets has been described in severe COVID-19 patients, but very few studies assessed the general memory T-cell homeostasis in the acute phase of COVID-19. Here, we performed a general analysis of the main memory T cell populations in the peripheral blood of patients admitted to the hospital for a confirmed or probable COVID-19 diagnosis. METHODS: In this cross-sectional study, adult patients (aged ≥ 18 years) needing hospital admission for respiratory disease due to confirmed or probable COVID-19, were recruited before starting the therapeutic protocol for this disease. In addition to the assessment of the general lymphocyte subpopulations in the early phase of COVID-19, central memory T cells (Tmcentr cells: CD45RO+CCR7+) and effector memory T cells (Tmeff cells: CD45RO+CCR7-) were assessed by multi-color flow cytometry, in comparison to a control group. RESULTS: During the study period, 148 study participants were recruited. Among them, 58 patients turned out positive for SARS-CoV-2 PCR (including both patients with interstitial pneumonia [PCR+Pn+] and without this complication [PCR+Pn-]), whereas the remaining 90 patients resulted to be SARS-CoV-2 PCR negative, even though all were affected with interstitial pneumonia [PCR-Pn+]. Additionally, 28 control patients without any ongoing respiratory disease were recruited. A clear unbalance in the T memory compartment emerged from this analysis on the whole pool of T cells (CD3+ cells), showing a significant increase in Tmcentr cells and, conversely, a significant decrease in Tmeff cells in both pneumonia groups (PCR+Pn+ and PCR-Pn+) compared to the controls; PCR+Pn- group showed trends comprised between patients with pneumonia (from one side) and the control group (from the other side). This perturbation inside the memory T cell compartment was also observed in the individual analysis of the four main T cell subpopulations, based upon the differential expression of CD4 and/or CD8 markers. CONCLUSION: Overall, we observed both absolute and relative increases of Tmcentr cells and decrease of Tmeff cells in patients affected with interstitial pneumonia (regardless of the positive or negative results of SARS-CoV-2 PCR), compared to controls. These results need confirmation from additional research, in order to consider this finding as a potential biological marker of interstitial lung involvement in patients affected with viral respiratory infections.

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study.

The left ventricular assist device (LVAD) is one of the alternative treatments for heart failure (HF) patients. However, LVAD support is followed by thrombosis, and bleeding complications which are caused by high non-physiologic shear stress and antithrombotic/anticoagulant therapy. A high risk of complications occurs in the presence of the genotype polymorphisms which are involved in the coagulation system, hemostasis function and in the metabolism of the therapy. The aim of the study was to investigate the influence of single-nucleotide polymorphisms (SNP) in HF patients with LVAD complications. We analyzed 21 SNPs in HF patients (n = 98) with/without complications, and healthy controls (n = 95). SNPs rs9934438; rs9923231 in VKORC1, rs5918 in ITGB3 and rs2070959 in UGT1A6 demonstrated significant association with HF patients' complications (OR (95% CI): 3.96 (1.42-11.02), p = 0.0057), (OR (95% CI): 3.55 (1.28-9.86), p = 0.011), (OR (95% CI): 5.37 (1.79-16.16), p = 0.0056) and OR (95% CI): 4.40 (1.06-18.20), p = 0.044]. Genotype polymorphisms could help to predict complications at pre- and post-LVAD implantation period, which will reduce mortality rate. Our research showed that patients can receive treatment with warfarin and aspirin with a personalized dosage and LVAD complications can be predicted by reference to their genotype polymorphisms in VKORC1, ITGB3 and UGT1A6 genes.

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients.

Introduction: Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity. Methods: Electronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies. Results: Overall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD -0.1684 with 95%CI (-0.2826; -0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias. Conclusions: The hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.

Epidemiology of Arterial Hypertension in Kazakhstan: Data from Unified Nationwide Electronic Healthcare System 2014-2019.

The in-depth epidemiology of hypertension has not been studied in Kazakhstan (KZ) yet. We aimed to investigate the crude; age and sex standardized prevalence, incidence, and all-cause mortality rate among hypertensive patients in Kazakhstan using a large-scale Unified National Electronic Health System (UNEHS) for the period 2014-2019. Hypertension was defined based on the ICD-10 codes (ICD-code: I10; I11; I12; I13). Of 1,908,419 patients, 1,186,706 (62.18%) were females and 721,713 (37.82%) were males. The majority of the patients (56.3%) were ethnic Kazakhs, 26.6% were Russians, and 16.2% were of other ethnicities. In 2014, the crude rates of prevalence, incidence, and mortality were 3661, 1396.1, and 33.1 per 100,000 population, respectively. The overall prevalence, incidence, and mortality rates among hypertension patients had a gradual increase over the period 2014-2019. The sex and age adjusted rates demonstrate the same trend throughout the entire period. We observed 71% higher risk of crude death in males comparing to females (Hazard ratio (HR): 1.71 [95%CI: 1.69-1.72]); Russian and other ethnicities had 1.56-fold (95%CI: 1.54-1.58 and 1.43-fold (95%CI: 1.41-1.45) higher risk of all-cause death compared to Kazakhs, and the elderly group had the highest risk of death (Hazard ratio (HR): 35.68 [95%CI: 28.11-45.31]) comparing to the younger generation, which remained significant after adjustment to age and sex. Overall, these findings show statistically significant lower survival probability in male patients compared to female, in older patients compared to younger ones, and in patients of Russian and other ethnicities compared to Kazakh.

Mortality predictors of hospitalized patients with COVID-19: Retrospective cohort study from Nur-Sultan, Kazakhstan.

BACKGROUND: First reported case of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in Kazakhstan was identified in March 2020. Many specialized tertiary hospitals in Kazakhstan including National Research Cardiac Surgery Center (NRCSC) were re-organized to accept coronavirus disease 2019 (COVID-19) infected patients during summer months of 2020. Although many studies from worldwide reported their experience in treating patients with COVID-19, there are limited data available from the Central Asia countries. The aim of this study is to identify predictors of mortality associated with COVID-19 in NRCSC tertiary hospital in Nur-Sultan, Kazakhstan. METHODS: This is a retrospective cohort study of patients admitted to the NRCSC between June 1st-August 31st 2020 with COVID-19. Demographic, clinical and laboratory data were collected from electronic records. In-hospital mortality was assessed as an outcome. Patients were followed-up until in-hospital death or discharge from the hospital. Descriptive statistics and factors associated with mortality were assessed using univariate and multivariate logistic regression models. RESULTS: Two hundred thirty-nine admissions were recorded during the follow-up period. Mean age was 57 years and 61% were males. Median duration of stay at the hospital was 8 days and 34 (14%) patients died during the hospitalization. Non-survivors were more likely to be admitted later from the disease onset, with higher fever, lower oxygen saturation and increased respiratory rate compared to survivors. Leukocytosis, lymphopenia, anemia, elevated liver and kidney function tests, hypoproteinemia, elevated inflammatory markers (C-reactive protein (CRP), ferritin, and lactate dehydrogenase (LDH)) and coagulation tests (fibrinogen, D-dimer, international normalized ratio (INR), and activated partial thromboplastin time (aPTT)) at admission were associated with mortality. Age (OR 1.2, CI:1.01-1.43), respiratory rate (OR 1.38, CI: 1.07-1.77), and CRP (OR 1.39, CI: 1.04-1.87) were determined to be independent predictors of mortality. CONCLUSION: This study describes 14% mortality rate from COVID-19 in the tertiary hospital. Many abnormal clinical and laboratory variables at admission were associated with poor outcome. Age, respiratory rate and CRP were found to be independent predictors of mortality. Our finding would help healthcare providers to predict the risk factors associated with high risk of mortality. Further investigations involving large cohorts should be provided to support our findings.

Hypertension as a manifestation of COVID-19 pneumonia.

Several factors such as hypertension, bile duct disease, and age can affect the duration of COVID, which can lead to long COVID. Any course of coronavirus infection could have a diverse nature of clinical forms and should have a personalized approach.

First Clinical Experience With the Pressure Sensor-Based Autoregulation of Blood Flow in an Artificial Heart.

The CARMAT-Total Artificial Heart (C-TAH) is designed to provide heart replacement therapy for patients with end-stage biventricular failure. This report details the reliability and efficacy of the autoregulation device control mechanism (auto-mode), designed to mimic normal physiologic responses to changing patient needs. Hemodynamic data from a continuous cohort of 10 patients implanted with the device, recorded over 1,842 support days in auto-mode, were analyzed with respect to daily changing physiologic needs. The C-TAH uses embedded pressure sensors to regulate the pump output. Right and left ventricular outputs are automatically balanced. The operator sets target values and the inbuilt algorithm adjusts the stroke volume and beat rate, and hence cardiac output, automatically. Auto-mode is set perioperatively after initial postcardiopulmonary bypass hemodynamic stabilization. All patients showed a range of average inflow pressures of between 5 and 20 mm Hg during their daily activities, resulting in cardiac output responses of between 4.3 and 7.3 L/min. Operator adjustments were cumulatively only required on 20 occasions. This report demonstrates that the C-TAH auto-mode effectively produces appropriate physiologic responses reflective of changing patients' daily needs and represents one of the unique characteristics of this device in providing almost physiologic heart replacement therapy.

Patients with coronary heart disease, dilated cardiomyopathy and idiopathic ventricular tachycardia share overlapping patterns of pathogenic variation in cardiac risk genes.

BACKGROUND: Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD). Clinical investigations can sometimes fail to identify the underlying cause of VT and the event is classified as idiopathic (iVT). VT contributes significantly to the morbidity and mortality in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility screening for disease-predisposing variants could improve VT diagnostics and prevent SCD in patients. METHODS: Ninety-two patients diagnosed with coronary heart disease (CHD), DCM, or iVT were included in our study. We evaluated genetic profiles and variants in known cardiac risk genes by targeted next generation sequencing (NGS) using a newly designed custom panel of 96 genes. We hypothesized that shared morphological and phenotypical features among these subgroups may have an overlapping molecular base. To our knowledge, this was the first study of the deep sequencing of 96 targeted cardiac genes in Kazakhstan. The clinical significance of the sequence variants was interpreted according to the guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015. The ClinVar and Varsome databases were used to determine the variant classifications. RESULTS: Targeted sequencing and stepwise filtering of the annotated variants identified a total of 307 unique variants in 74 genes, totally 456 variants in the overall study group. We found 168 mutations listed in the Human Genome Mutation Database (HGMD) and another 256 rare/unique variants with elevated pathogenic potential. There was a predominance of high- to intermediate pathogenicity variants in LAMA2, MYBPC3, MYH6, KCNQ1, GAA, and DSG2 in CHD VT patients. Similar frequencies were observed in DCM VT, and iVT patients, pointing to a common molecular disease association. TTN, GAA, LAMA2, and MYBPC3 contained the most variants in the three subgroups which confirm the impact of these genes in the complex pathogenesis of cardiomyopathies and VT. The classification of 307 variants according to ACMG guidelines showed that nine (2.9%) variants could be classified as pathogenic, nine (2.9%) were likely pathogenic, 98 (31.9%) were of uncertain significance, 73 (23.8%) were likely benign, and 118 (38.4%) were benign. CHD VT patients carry rare genetic variants with increased pathogenic potential at a comparable frequency to DCM VT and iVT patients in genes related to sarcomere function, nuclear function, ion flux, and metabolism. CONCLUSIONS: In this study we showed that in patients with VT secondary to coronary artery disease, DCM, or idiopathic etiology multiple rare mutations and clinically significant sequence variants in classic cardiac risk genes associated with cardiac channelopathies and cardiomyopathies were found in a similar pattern and at a comparable frequency.

Heart transplantation of patients with ventricular assist devices: impact of normothermic ex-vivo preservation using organ care system compared with cold storage.

BACKGROUND: Organ Care System (OCS) minimizes the cold ischemic time and allows for optimization of logistics and meticulous recipient preparation. Impact of normothermic ex-vivo preservation using OCS compared with cold storage (CS) for prolonged heart preservation especially beneficial for high-risk recipients bridged to transplantation with Mechanical Circulatory Support (MCS). METHODS: Between 2012 and 2018, we performed a retrospective single-center review of prospectively collected data. All patients who underwent heart transplantation with MCS using the OCS Heart (n = 25) versus standard cold storage (n = 10) were included in this study. RESULTS: During this period, 353 patients were implanted with left ventricular assisted device (LVAD) and 35 (10%) were bridged to heart transplantation. There was no significant difference in donor and recipient characteristics and risk factors. The Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was a trend towards higher estimated risk of death at 1y in the OCS group (14.2 vs. 10.8% p = 0.083). Mean total ischemic time during preservation was statistically significantly longer in CS vs OCS group (210 (23) Vs 74.6 (13) min p = 0.001). Median ex vivo normothermic heart perfusion time in OCS was 348.4(132; 955) min. There was significant difference in total out of body time between OCS group 423(67) Vs CS group 210(23) min p = 0.002). All patients were alive on the 30th days post implant in CS groups and 96% in OCS group (p = 0.5). CONCLUSION: Normothermic ex-vivo preservation of the allograft during transportation with the organ care system might be beneficial for long-time out of body organ preservation in comparison of cold storage especially for recipients on mechanical circulatory support.