Impaired Myocardial Contractility Research Articles

Effect of impaired myocardial contractility on coronary flow reserve and inflammatory processes in chronic coronary syndrome

Aim. To study the relationship between myocardial contractility impairment in chronic coronary syndrome and the state of coronary flow reserve, the degree of systemic inflammation and endothelial dysfunction. Materials and methods. We examined 120 patients with stable angina pectoris (SAP) of functional class (FC) II–III, who were assigned into two groups: group 1 comprised 65 patients with left ventricular ejection fraction (LVEF) ≥55 %, and group 2 was composed of 55 patients with LVEF <55 %. Diagnostic methods included clinical and instrumental examination data, analyses of lipid profile, inflammation biomarkers, endothelial functional state, hemogram data, leukocyte inflammation markers, and questionnaires. Results. Compared to group 1, group 2 patients showed an increase in the left atrium (p < 0.001) and right ventricle (p = 0.027) sizes; significantly lower LVEF (50.16 ± 0.42 % vs 58.77 ± 0.41 %; p < 0.001); thickening of the intima-media complex in the right (p = 0.003) and left (p = 0.017) common carotid arteries; significantly lower load threshold values (p = 0.008), exercise tolerance (p = 0.004) and heart rate variability indicators – SDNN (standard deviation of normal-to-normal intervals over 24 hours; p = 0.046). Group 2 patients were characterized by more active low-grade chronic inflammation, as indicated by increased levels of leukocytes (p = 0.024), neutrophils (p < 0.001), and decreased lymphocyte levels (p = 0.021); significantly higher levels of leukocyte inflammation markers, in particular, the neutrophil-to-lymphocyte ratio (p < 0.001), platelet-to-lymphocyte ratio (p = 0.004), systemic immune-inflammation index (p < 0.001), systemic inflammation response index (p < 0.001), and aggregate index of systemic inflammation (p < 0.001) as compared to group 1 individuals. Patients with LVEF <55 % had higher levels of fibrinogen (p < 0.001), uric acid (p = 0.002), high-sensitivity C-reactive protein (p = 0.007), and endothelin-1 (p < 0.001) compared to those with LVEF ≥55 %. Conclusions. Group 2 patients need a more thorough monitoring and a more intensive treatment aimed at reducing the inflammatory process.

Impact of myocardial phenotype on atrioventricular delay optimization at rest and during exercise: insights from a virtual patient study

Abstract Background The usefulness of atrioventricular delay (AVD) optimization in cardiac resynchronization therapy (CRT) for heart failure (HF) patients with left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF) is still debated. Yet, studies have not explored the role of non-electrical myocardial disease substrates in determining optimal AVD settings among patients. Purpose We first hypothesized that acute response to AVD optimization might be modulated by various myocardial disease substrates. Furthermore, we hypothesized that cardiac function is more sensitive to changes in AV coupling during exercise and that this sensitivity is also modulated by underlying myocardial disease substrates. Methods We used the CircAdapt model of the human heart and circulation to simulate different types of LV remodeling that can be found in CRT candidates. First, an LBBB-like pattern of mechanical activation was imposed by delaying LV free wall (LVFW) and interventricular septal (IVS) activation relative to right ventricular free wall activation. Then, two types of LV remodeling were simulated by LV dilation with preserved or impaired myocardial contractility, resulting in LVEF <35%. To investigate the effect of diastolic dysfunction, we increased passive myocardial stiffness of the IVS and LVFW on both substrates with LV remodeling until a mean left atrial pressure (mLAP) of 14 mmHg was reached. CRT was simulated by resynchronizing IVS and LVFW. AVD optimization was conducted by gradually reducing the paced AVD from 220 ms to 40 ms in steps of 20 ms. In each simulation, the optimal paced AVD at rest (cardiac output (CO) and heart rate (HR) of 4.2 L/min and 80 bpm, respectively) was assessed using stroke volume (SV) and mLAP which is used as a measure of LV filling pressure. To investigate the relative effect of these myocardial phenotypes during AVD optimization under exercise, CO and HR were increased step-wise. Results The gain in SV by AVD optimization was larger in the simulations with healthy myocardium than in those with hypo-contractile and stiff myocardium (Figure 1: top-row). However, mLAP was comparably decreased by AVD optimization in healthy and diseased myocardium (Figure 1: bottom row). During exercise, the optimum AVD shifted to shorter values (Figure 2: top-row), and mLAP was much more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium (Figure 2: bottom row). Conclusion Virtual patient simulations show that both myocardial hypocontractility and stiffness dampen the effect of AVD optimization on SV. Furthermore, simulations suggest that patients benefit more from AVD optimization during exercise than during resting conditions. These mechanistic insights may help to gain more benefit from AVD optimization for patients undergoing CRT.AVD optimization at restAVD optimization during exercise

PLEKHM2 deficiency induces impaired mitochondrial clearance and elevated ROS levels in human iPSC-derived cardiomyocytes

Pleckstrin homology domain-containing family M member 2 (PLEKHM2) is an essential adaptor for lysosomal trafficking and its homozygous truncation have been reported to cause early onset dilated cardiomyopathy (DCM). However, the molecular mechanism of PLEKHM2 deficiency in DCM pathogenesis and progression is poorly understood. Here, we generated an in vitro model of PLEKHM2 knockout (KO) induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the potential pathogenic mechanism of PLEKHM2-deficient cardiomyopathy. PLEKHM2-KO hiPSC-CMs developed disease phenotypes with reduced contractility and impaired calcium handling. Subsequent RNA sequencing (RNA-seq) analysis revealed altered expression of genes involved in mitochondrial function, autophagy and apoptosis in PLEKHM2-KO hiPSC-CMs. Further molecular experiments confirmed PLEKHM2 deficiency impaired autophagy and resulted in accumulation of damaged mitochondria, which triggered increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (Δψm). Importantly, the elevated ROS levels caused oxidative stress-induced damage to nearby healthy mitochondria, resulting in extensive Δψm destabilization, and ultimately leading to impaired mitochondrial function and myocardial contractility. Moreover, ROS inhibition attenuated oxidative stress-induced mitochondrial damage, thereby partially rescued PLEKHM2 deficiency-induced disease phenotypes. Remarkably, PLEKHM2-WT overexpression restored autophagic flux and rescued mitochondrial function and myocardial contractility in PLEKHM2-KO hiPSC-CMs. Taken together, these results suggested that impaired mitochondrial clearance and increased ROS levels play important roles in PLEKHM2-deficient cardiomyopathy, and PLEKHM2-WT overexpression can improve mitochondrial function and rescue PLEKHM2-deficient cardiomyopathy.

Development and validation of risk prediction and neural network models for dilated cardiomyopathy based on WGCNA.

Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by ventricular dilatation and impaired myocardial contractility with a high mortality rate. The molecular characterization of DCM has not been determined yet. Therefore, it is crucial to discover potential biomarkers and therapeutic options for DCM. The hub genes for the DCM were screened using Weighted Gene Co-expression Network Analysis (WGCNA) and three different algorithms in Cytoscape. These genes were then validated in a mouse model of doxorubicin (DOX)-induced DCM. Based on the validated hub genes, a prediction model and a neural network model were constructed and validated in a separate dataset. Finally, we assessed the diagnostic efficiency of hub genes and their relationship with immune cells. A total of eight hub genes were identified. Using RT-qPCR, we validated that the expression levels of five key genes (ASPN, MFAP4, PODN, HTRA1, and FAP) were considerably higher in DCM mice compared to normal mice, and this was consistent with the microarray results. Additionally, the risk prediction and neural network models constructed from these genes showed good accuracy and sensitivity in both the combined and validation datasets. These genes also demonstrated better diagnostic power, with AUC greater than 0.7 in both the combined and validation datasets. Immune cell infiltration analysis revealed differences in the abundance of most immune cells between DCM and normal samples. The current findings indicate an underlying association between DCM and these key genes, which could serve as potential biomarkers for diagnosing and treating DCM.

Takotsubo Syndrome: An Epidemiologic Evaluation.

Takotsubo syndrome is characterized by regional wall motion abnormalities that reflect impairment of myocardial contractility in the absence of culprit epicardial coronary artery disease. The pathophysiologic mechanisms responsible for Takotsubo syndrome remain unknown and predominately occur in postmenopausal females suffering either a psychological or physical stressor. This study used the Hospital Corporation of America (HCA) Healthcare database evaluating demographic distribution of patients with Takotsubo syndrome to identify what comorbid conditions were most prevalent in patients found to have Takotsubo syndrome in the United States population and compare them to the traditional patient population with the condition. The patient population in the HCA Healthcare United States database was similar to prior known demographic factors including postmenopausal females and Caucasian ethnicity. Interestingly, in both the previously diagnosed group and diagnosed at the time of presentation with the Takotsubo syndrome group, there was a mismatch between the number of patients diagnosed with an underlying mood disorder and on psychiatric medication. This may provide further evidence of Takotsubo syndrome being a dramatic presentation of a mood disorder.

Magnetic resonance imaging in the diagnosis of myocarditis in children

Background: There is a need for the systematization, generalization and analysis of the structural changes of the myocardium, occurring in patients with myocarditis. This disease is rare; therefore, structured information in the field of radiological diagnostics is still insufficient within national publications. Aim: The study purpose was to determine the significance and specificity of changes observed in cardiac magnetic resonance images in patients with myocarditis, and to compare the obtained results with the literature data. Methods: 7 patients, including children aged 4 and 6, with a verified diagnosis of myocarditis were retrospectively examined. Results: The analysis of the obtained images revealed the most common changes related to myocarditis, such as myocardial edema, impaired myocardial contractility, increased delayed accumulation of the contrast agent. The pathophysiological mechanisms of the found structural changes were analyzed and described. Conclusion: Magnetic resonance imaging is the most important non-invasive method for diagnosing myocarditis, which allows one to identify the lesion of the heart muscle, to assess the extent of its damage, to differentiate myocarditis from other diseases, as well as to assess the dynamics when evaluating the effectiveness of therapy.

Cyclophosphamide enfeebles myocardial isometric contraction force via RIP1/RIP3/MLKL/TRPM7-mediated necroptosis

This study explores the negative impact of cyclophosphamide (CP) on cardiac contractility by specifically examining its effect on the active and passive tension of the cardiac muscle in-vitro and revealing the mechanism through which CP induces myocardial insult in-vivo. In young male Sprague-Dawley rats, cardiac toxicity was induced by a single intraperitoneal injection of CP (150 mg/kg body weight). Axial heart tissue slices were electrically stimulated, and the total isometric contraction force was measured at varying pretension levels. Blood and tissue biochemical assays, and histological/ immuno-histological assessments were conducted to evaluate the underlying molecular mechanisms. Statistical analysis shows that there is a significant difference between the drugged and the control groups in terms of the active tension values. Moreover, the pre-tension stress significantly affects both the active and passive tension values. CP altered heart, body, and heart-to-body weight, desolated cardiac muscle architecture, surged cardiac enzymes (CK-MB, LDH, and cTn l), augmented myocardial oxidative stressors (MDA), and weakened myocardial antioxidant status (SOD and GSH). Mechanistically, cyclophosphamide prompted the necroptotic trajectory evidenced by the activation of RIPK1, RIPK3, MLKL and TRPM7, the inhibition of caspase 8 and BCL2 and the upregulation of the protein/mRNA expression of TNF-α and TNFR1. This study identifies necroptosis as a key factor in cyclophosphamide-evoked myocardial contractility impairment, highlighting its potential as a target for alleviating antitumor-related myocardial damage. This innovative approach to investigating the underlying mechanisms of CP-induced cardiac toxicity offers valuable insights into the potential of developing new therapies to mitigate cyclophosphamide’s negative impact.

Cardiotoxicity from neoadjuvant targeted treatment for breast cancer prior to surgery.

Cancer treatment has been gradually shifting from non-specific cytotoxic agents to molecularly targeted drugs. Breast cancer (BC), a malignant tumor with one of the highest incidence worldwide, has seen a rapid development in terms of targeted therapies, leading to a radical change in the treatment paradigm. However, the use of targeted drugs is accompanied by an increasing rate of deaths due to non-tumor-related causes in BC patients, with cardiovascular complications as the most common cause. Cardiovascular toxicity during antitumor therapy has become a high-risk factor for survival in BC patients. Targeted drug-induced cardiotoxicity exerts a wide range of effects on cardiac structure and function, including conduction disturbances, QT interval prolongation, impaired myocardial contractility, myocardial fibrosis, and hypertrophy, resulting in various clinical manifestations, e.g., arrhythmias, cardiomyopathy, heart failure, and even sudden death. In adult patients, the incidence of antitumor targeted drug-induced cardiotoxicity can reach 50%, and current preclinical evaluation tools are often insufficiently effective in predicting clinical cardiotoxicity. Herein, we reviewed the current status of the occurrence, causative mechanisms, monitoring methods, and progress in the prevention and treatment of cardiotoxicity associated with preoperative neoadjuvant targeted therapy for BC. It supplements the absence of relevant review on the latest research progress of preoperative neoadjuvant targeted therapy for cardiotoxicity, with a view to providing more reference for clinical treatment of BC patients.

Challenges for anaesthesia for robotic-assisted surgery in the elderly

Steep and reverse Trendelenburg positions are often used in robotic-assisted surgery (RAS) to improve surgical access. The elderly are particularly vulnerable to the cardiovascular effect of the combination of pneumoperitoneum and these extreme positions. Falls in both cardiac output (CO) and mean arterial pressure (MAP) caused by pneumoperitoneum are enhanced in reverse Trendelenburg. Hypotension with dangerous cerebral and myocardial hypoperfusion may occur. Caution should be exercised in patients with low cardiac reserve and the degree of peri-operative risk should dictate the level of haemodynamic monitoring employed. The effects of pneumoperitoneum on CO are less pronounced in the standard Trendelenburg position due to gravity, but head-down combined with pneumoperitoneum can increase both MAP and systemic cardiovascular resistance. However, in patients with impaired myocardial contractility, the head-down position may lead to cardiac failure. In addition, the adverse respiratory effects of pneumoperitoneum, which include reduction of pulmonary compliance and functional residual capacity, may be exacerbated by steep Trendelenburg. At the same time, hypercarbia resulting from CO2 insufflation can lead to an increase in stasis of brain blood flow and intracranial pressure with possible repercussions on cognitive functions in the elderly. Another problem is the increase in intra-ocular pressure during steep Trendelenburg, and injury to the optic nerve has been reported after robot-assisted prostatectomy. Finally, strategies to use the lowest possible pneumoperitoneum pressure are considered to reduce possible complications. Moreover, the extreme positions should be limited only to the time strictly necessary for surgery and should be avoided in high-risk patients.

Stress, Cardiovascular Diseases and Exercise – A Narrative Review

The assuredness that adverse life stressors can lead to major negative impacts on an individual's health has been held since antiquity. Stress is considered a state of homeostasis being challenged, with biological consequences that can cause cardiovascular diseases (CVD). Stressors may be diverse and include a variety of psychological stressors, such as family stress, job strain, effort-award imbalance, long working hours, insecurity, social isolation, and lack of purpose in life. However, stressors may also be physical, immunological, metabolic, or environmental. Type of personality, anxiety, depression, pessimism or hostility, previous experience, genomics, body composition, nutritive and training status modulate stress responses and are important co-stressors. Chronic stress is linked with altered neurohormonal activity, which increases apoptotic pathways in cardiomyocytes. These pathways contribute to impaired myocardial contractility, increased risk of myocardial ischemia, infarction, heart failure, and arrhythmias. While stress is a vital risk factor for CVD, it has not been a major focus of preventive strategies. The purpose of this article is to review the impact of stress on CVD risk with an emphasis on approaches for stress reduction. Strength and endurance exercise, although being stress itself, leads to better adaptiveness to other types of stress, and by far has played an inevitable role in CVD risk reduction. Innovative strategies to combat CVD are strongly needed and exercise may be the best population-level cost-effective approach.

Fractional myocardial blood volume by ferumoxytol-enhanced MRI: Estimation of ischemic burden.

To investigate model-fitted fractional myocardial blood volume (fMBV) derived from ferumoxytol-enhanced MRI as a measure of myocardial tissue hypoperfusion at rest. We artificially induced moderate to severe focal coronary stenosis in the left anterior descending artery of 19 swine by percutaneous delivery of a 3D-printed coronary implant. Using the MOLLI pulse sequence, we acquired T1 maps at 3 T after multiple incremental ferumoxytol doses (0.0-4.0mg/kg). We computed pixel-wise fMBV using a multi-compartmental modeling approach in 19 ischemic swine and 4 healthy swine. Ischemic myocardial segments showed a mean MRI-fMBV of 11.72 ± 3.00%, compared with 8.23 ± 2.12% in remote segments and 8.38 ± 2.23% in normal segments. Ischemic segments showed a restricted transvascular water-exchange rate (ki =15.32 ± 8.69 s-1 ) relative to remote segments (ki =17.78 [11.60, 26.36] s-1 ). A mixed-effects model found significant difference in fMBV (p=0.002) and water-exchange rate (p < 0.001) between ischemic and remote myocardial regions after adjusting for biological sex and slice location. Analysis of fMBV as a predictor of impaired myocardial contractility using receiver operating characteristics showed an area under the curve of 0.89 (95% confidence interval [CI] 0.80, 0.95). An MRI-fMBV threshold of 9.60% has a specificity of 90.0% (95% CI 76.3, 97.2) and a sensitivity of 72.5% (95% CI 56.1, 83.4) for prediction of impaired myocardial contractility. Model-fitted fMBV derived from ferumoxytol-enhanced MRI can distinguish regions of ischemia from remote myocardium in a swine model of myocardial hypoperfusion.

Gestational diabetes, preeclampsia and the maternal heart

Abstract Background Gestational diabetes mellitus (GDM) and preeclampsia (pE) are both associated with an increased risk of cardiovascular mortality and morbidity, including an increased risk of developing heart failure in later life. Both conditions are increasing in prevalence; GDM affects up to 12% and pE affects 3–5% of pregnancies worldwide. Compromised cardiac energy production is an important contributor to most forms of heart disease. The changes in myocardial energetics in GDM and pE have not been characterised previously. Purpose We sought to assess if women with GDM and women with pE in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function or tissue characteristics. Methods Thirty-eight healthy pregnant (HP) women, thirty women with GDM and fifteen women with pE were recruited, matched for age and ethnicity. Participants underwent phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine to ATP ratio (PCr/ATP)), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal strain (GLS) and mitral in-flow E/A ratio. Results The biochemical characteristics and multiparametric MR results are given in Table 1. The women in the GDM and the pE groups had higher body-mass index. There was a stepwise increase in the systolic and diastolic BP from the HP to the GDM to the pE group. There was no difference in NTproBNP concentrations between the groups. The gestational weight gain was higher in women with GDM and pE compared to the HP group. The women in the GDM and the pE groups showed similar reductions in myocardial PCr/ATP ratios compared to HP group (Figure 1a), accompanied by lower LV end-diastolic volumes and higher LV mass (Figure 1b) and enhanced LV concentricity in both groups (Figure 1c). While LV ejection fractions were similar across the groups, the GLS was reduced in women with GDM and in women with pE (Figure 1d). Conclusions We show here for the first time that despite no prior diagnosis of diabetes or hypertension, women with GDM or pE manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics. These findings may aid our understanding of the long-term cardiovascular risks associated with these conditions. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome Trust

Maternal Cardiac Changes in Women With Obesity and Gestational Diabetes Mellitus.

We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics. Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio. Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (-20% ± 3% vs. -18% ± 3%; P = 0.008). Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM.

Biventricular strain assessment indicates progressive impairment of myocardial contractility in phenotypically negative patients with Fabry’s disease

PurposeThe accumulation of sphingolipids in Fabry's disease (FD) leads to left ventricular (LV) hypertrophy and shortened T1 in cardiac magnetic resonance (CMR). Early detection of myocardial involvement is essential for the timely initiation and efficacy of enzyme replacement therapy. However, there is a diagnostic gap between the onset of accumulation and detectable myocardial changes. This study aimed to evaluate the diagnostic value of biventricular strain assessment in early FD. MethodsGenetically proven FD patients (n = 58) and healthy volunteers (HV, n = 62) who had undergone 3 T CMR were retrospectively identified and stratified into 3 groups according to disease severity. Biventricular volumetry, global longitudinal strains (GLS), indexed biventricular masses (RVMi/LVMi), and T1 were evaluated. Group comparisons were performed by ANOVA and diagnostic accuracy was evaluated by ROC-analysis. ResultsThe study population included 19 group I, 20 group II and 19 group III patients. LV volumetry and T1 showed no significant difference between early FD patients and HV (all p > 0.760). However, RVMi was increased, while RV-GLS and LV-GLS were significantly impaired (p = 0.024 and < 0.001, respectively). Biventricular strains accurately discriminated early FD patients and HV with RV-GLS being non-inferior to LV-GLS (AUC for both 0.83, p > 0.05). Adding strains to the established approach using T1 and LVMi further increased diagnostic accuracy (AUC 0.99, p < 0.05). ConclusionsBiventricular strains may help detect altered myocardial deformation patterns in phenotypically negative FD patients. These findings may lead to an earlier initiation of therapy, which in turn may slow hypertrophy and the associated long-term risks.

Gene polymorphism in blood coagulation system and folate cycle affecting heart condition in patients with hemorrhagic fever and renal syndrome

One of the typical manifestations of hemorrhagic fever with renal syndrome (HFRS) is a damage to the cardiovascular system. The most promising direction of studying the causes of cardiac complications in HFRS should be considered the genetic patient characteristics, particularly taking into account the disease pathogenesis, study of polymorphism of the genes in the blood coagulation system and the folate cycle. The aim of the study was to find out an effect of polymorphism of the blood coagulation system and folate cycle genes on heart damage in hemorrhagic fever with renal syndrome. A case-control study was conducted by enrolling 19 patients in the 2019 summerautumn period at the Republican Clinical Infectious Hospital in the City of Izhevsk. The study of polymorphism of the blood coagulation system and folate cycle genes was performed by using a set of reagents RealBest-Genetics Hemostasis (12) on the CFX96 amplifier (Bio-Rad, USA). DNA was extracted from peripheral blood leukocytes with reagents RealBest Extraction 100. Transthoracic echocardiography was performed on a Vivid 7 Dimension ultrasound scanner (GE Healthcare, USA) with a matrix sector sensor M4S with a phased array at scanning frequency of 1.54.3 MHz. Statistical analysis was performed using Statistica 12, IBM SPSS 22. The group parameters were calculated and depicted as median and interquartile range (ME [Q25; Q75]). Comparison of such parameters was carried out by using the MannWhitney criterion. Comparison of the frequency distribution for genotypes and alleles in the study groups was carried out using the criterion 2. The association of alleles/genotypes with a predisposition to detectable changes was assessed by the risk ratio (OR) additionally calculating 95% confidence interval (CI). The p 0.05 was considered as statistically significant. During the study, 7 patients were found to have floating echoes on the aortic valve in the outlet of the left ventricle signs of thrombotic endocarditis. In the group of patients with signs of thrombotic endocarditis, there was revealed a higher frequency of the allele A for the F7:10976 G/A gene compared to patients lacking signs of thrombotic endocarditis (p = 0.0357). All study patients had a normal left ventricular ejection fraction (more than 50%), but during the speckle-tracking study assessing the index of averaged peak longitudinal contractility (GLPS AVG), 11 patients with impaired myocardial contractility were identified. In patients with decreased GLPS AVG, the genotype G/G of the FGB:-455 G/A gene was detected more often compared to patients with preserved myocardial contractility (p = 0.0397). In 8 patients, signs of grade 1 diastolic left ventricular dysfunction were revealed, the prognostic importance of the gene polymorphism related to the blood coagulation system and folate cycle in developing this complication has not been determined.

Cardiac remodeling and subclinical left ventricular dysfunction in adults with uncomplicated obesity: a cardiovascular magnetic resonance study.

Obesity often exists alongside comorbidities and increases the risk of heart failure and cardiovascular mortality. However, the specific effects of obesity on cardiac structure and function have not been clarified. This study set out to evaluate left ventricular (LV) geometric and functional changes using cardiovascular magnetic resonance imaging (CMR) in adults with uncomplicated obesity. Forty-eight patients with uncomplicated obesity [body mass index (BMI) mean ± SD: 29.8±2.1 kg/m2] and 25 healthy controls were included in this study. CMR was used to assess LV geometry, global systolic function, and strains, and to quantify epicardial adipose tissue (EAT). Body composition was measured by dual X-ray absorptiometry. Compared with healthy controls, patients with obesity had increased LV size, mass, and myocardial thickness, and impaired myocardial contractility, with lower global radial, circumferential, and longitudinal peak strains (PS), and circumferential and longitudinal peak diastolic strain rates (PDSR; all P<0.05). Multivariable linear regression showed that BMI was independently associated with LV maximum myocardial thickness (LVMMT) (β=0.197, P=0.016). Visceral adipose tissue (VAT) was independently associated with LV global longitudinal PS (β=-2.684, P=0.001), and both longitudinal (β=-0.192, P=0.002) and circumferential (β=-0.165, P=0.014) PDSR. Homeostasis model assessment of insulin resistance (HOMA-IR) was mildly correlated with BMI (r=0.327) and body fat percentage (BF%) (r=0.295) in patients with obesity (all P<0.05). HOMA-IR was independently associated with LV global circumferential PS (β=-0.276, P=0.04) and PDSR (β=-0.036, P=0.026). Extensive LV geometric remodeling and marked changes in cardiac strains were observed in adults with obesity. Tissue tracking with CMR can reveal subclinical impaired ventricular function with preserved LV ejection fraction in such patients. BMI was independently related to LV remodeling in obesity. HOMA-IR and VAT are potentially superior to BMI as predictors of subclinical dysfunction, assessed by strain, in obesity. This study has been registered with the Chinese Clinical Trial Registry (ID: ChiCTR1900026476; Effect of lifestyle intervention on metabolism of obese patients based on smart phone software).

Changes in mitral regurgitation following acute myocardial infarction: early and long-term follow-up

Abstract Background Mitral regurgitation (MR) is commonly observed following acute myocardial infarction (MI). Localised left ventricular (LV) remodelling in the region of papillary muscles together with impaired myocardial contractility promote MR. There is a paucity of long-term follow-up studies to determine whether the severity of MR observed post-MI, changes with time. Purpose This study retrospectively followed up patients with MR detected following acute MI (AMI) to investigate changes in MR severity with time and assess for pre-discharge predictors of MR regression or progression. Methods Clinical records of 1000 patients admitted with AMI between 2016 and 2017 to a single centre were retrospectively interrogated. One hundred and nine patients met the inclusion criteria of MR on pre-discharge transthoracic echocardiography (TTE) and follow-up TTE scans. Echocardiographic parameters were investigated to determine predictors of progression or regression at follow-up. Patients were divided according to those who had early follow-up TTE (within 1-year) and late follow-up TTE (beyond 1-year). Results Early follow-up TTE was performed in 73 patients at a median of 6 (IQR 3–9) months. Patients had a mean age of 69±13 years and were predominantly male 50/73 (68%). At baseline, relative MR severities were: 49/73 (67%) mild MR, 23/73 (32%) moderate MR and 1 (1%) severe MR. At follow-up, MR had completely resolved in 18/73 (23%) patients, while 39/73 (53%) had mild MR, 15/73 (21%) moderate MR and 1 (1%) severe MR. Compared to patients with no resolution of MR, those with completel resolution were younger (mean age 62±16 vs 72±11 years; p=0.015) but there were no other significant differences between the groups. Resolution at early follow-up did not significantly influence long-term mortality rates. Late follow-up TTE was performed in 69 patients at a median 2.4 (IQR 2–3.2) years. Pre-discharge, 49/69 (71%) patients had mild MR and 20/69 (29%) moderate MR. At follow-up, MR had completely resolved in 18/69 (26%), and amongst patients with persistent MR, proportion of severities were: 37/69 (54%) mild MR, 11/69 (16%) moderate MR and 3/69 (4%) severe MR. Patients with progression of mild MR were more likely to have lower left ventricular ejection fraction (LVEF: 47±15 vs 57±12%; p=0.010) and greater indexed left ventricular end-systolic volume (LVESVi: 37±23 vs 25±14 ml/m2; p&amp;lt;0.001) on pre-discharge TTE. Resolution of MR at late follow-up was associated with a reduction in long-term mortality [deaths: 2/55 (3%) vs 3/14 (21%); p=0.022] at a mean follow-up of 4.2 years from MI. Conclusion MR observed following AMI completely resolved in approximately one-quarter of patients at 6-month and 2-year follow-up. Progression of mild MR at long-term follow-up appears to be associated with increased mortality and is predicted by lower LVEF and greater LVESVi pre-discharge. Funding Acknowledgement Type of funding sources: None.

Association between the osmotic fragility of erythrocytes and the course of acute myocardial infarction

Aim. To investigate the relationship between the osmotic fragility of erythrocytes and the course of acute myocardial infarction (MI).Methods. An analysis of the osmotic fragility of erythrocytes was conducted using beta-blocker-based osmotic fragility test in sixty-two patients within the first 6 hours after onset of MI symptoms.Results. The results revealed that the patients with increased erythrocyte osmotic fragility experienced more complications after acute MI, such as left ventricular failure and cardiac arrhythmias (ventricular extrasystoles and ventricular tachycardia) (p = 0.026). Moreover, these patients exhibited greater myocardial injury - the concentration of biomarkers of myocardial necrosis, such as creatine phosphokinase, creatine phosphokinase MB and Troponin I was increased - p = 0.009, p = 0.032 and p = 0.001, respectively. In addition to that, the patients with high osmotic fragility had a larger number of hypokinetic and akinetic segments, high impaired myocardial contractility index, and low ejection fraction. The impaired myocardial contractility index was significantly higher in patients with increased erythrocyte osmotic fragility (1.5 (1.22; 1.75) vs 1.12 (1.0; 1.56), U = 157.5, p = 0.032).Conclusion. Increased erythrocyte osmotic fragility in patients was associated with greater myocardial injury, manifesting through the higher concentration of biomarkers of myocardial necrosis in blood, as well as higher number of hypokinetic segments.

Cytokine status in middle-aged men with acute coronary syndrome after coronary artery stenting

Background. Inflammatory cytokines and growth factors are involved in various mechanisms of coronary artery disease. Clinical studies have shown the correlation between the increase in the level of proinflammatory cytokines and the severity of coronary artery disease, while the data on the role of proinflammatory interleukin IL-8 and anti-inflammatory interleukin IL-4 are contradictory. The aim of the study is to assess the levels of proinflammatory cytokines (IL-8, TNF-) and anti-inflammatory interleukin (IL-4) in patients with various forms of coronary artery disease who underwent coronary artery stenting. Materials and methods. By the method of enzyme-linked immunosorbent assay, the levels of cytokines were determined in 30 patients with acute coronary syndrome who underwent primary stenting of the coronary arteries and in 24 patients with chronic coronary syndrome who had previously had myocardial infarction with stenting of an infarction-associated artery, who were admitted to the clinic for staged stenting of the coronary arteries. Results. In patients with chronic coronary syndrome the levels of IL-4 a do not exceed the reference values, in patients with acute coronary syndrome the levels of IL-4 there was an increase 3,70 0,24 and 240,85 49,25 pg/ml, р 0,001. In patients with chronic coronary syndrome the levels of IL-8 a do not exceed the reference values, in patients with acute coronary syndrome the levels of IL-8 there was an increase 7,34 1,29 and 110,33 27,67 pg/ml, р 0,001. Conclusion. Most likely the increase in the level of IL-4 has a compensatory character and, along with a slight increase in TNF-, can be considered as a positive factor stabilizing the course of the disease. There may be some relationship between of the increase in the level of interleukins in patients with acute coronary syndrome on the degree of stenosis of the coronary arteries (9095%) and impaired myocardial contractility was established.

Decreased Native T1 Values and Impaired Myocardial Contractility in Anabolic Steroid Users.

Anabolic androgenic steroid (AAS) abuse leads to myocardial toxicity. Human studies are conflicting about the myocardial fibrosis in AAS users. We evaluated cardiac tissue characterization, left ventricle (LV) function, and cardiac structure by cardiovascular magnetic resonance (CMR). Twenty strength-trained AAS users (AASU) aged 29±5 yr, 20 strength-trained AAS nonusers (AASNU), and 7 sedentary controls (SC) were enrolled. Native T1 mapping, late-gadolinium enhancement (LGE), extracellular volume (ECV), and myocardial strain were evaluated. AASU showed lower Native T1 values than AASNU (888±162 vs. 1020±179 ms p=0.047). Focal myocardial fibrosis was found in 2 AASU. AASU showed lower LV radial strain (30±8 vs. 38±6%, p<0.01), LV circumferential strain (-17±3 vs. -20±2%, p<0.01), and LV global longitudinal strain (-17±3 vs. -20±3%, p<0.01) than AASNU by CMR. By echocardiography, AASU demonstrated lower 4-chamber longitudinal strain than AASNU (-15±g3 vs. -18±2%, p=0.03). ECV was similar among AASU, AASNU, and SC (28±10 vs. 28±7 vs. 30±7%, p=0.93). AASU had higher LV mass index than AASNU and SC (85±14 vs. 64±8 vs. 58±5 g/m2, respectively, p<0.01). AAS abuse may be linked to decreased myocardial native T1 values, impaired myocardial contractility, and focal fibrosis. These alterations may be associated with maladaptive cardiac hypertrophy in young AAS users.