Left Ventricular Myocardial Hypertrophy Research Articles

Transcatheter transfemoral aortic valve replacement in a patient with acromegaly and severe left ventricular myocardial hypertrophy. Case report

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

ELECTROCARDIOGRAPHIC DIAGNOSIS OF LEFT VENTRICULAR MYOCARDIAL HYPERTROPHY (LITERATURE REVIEW)

Left ventricular hypertrophy (LVH) is one of the most important predictors of cardiovascular events in patients with arterial hypertension (AH). Literature data on the role of electrocardiography (ECG) in diagnosing left ventricular (LV) myocardial hypertrophy are presented. Recommendations of the European Society of Cardiology and the European Society of Hypertension from 2018 and International Clinical Protocols "Duodecim" state the following LVH criteria: Sokolov-Lyon criteria: SV1 + RV5 > 35 mm; wave R in lead aVL > 11 mm; SV1 ≥ 25 mm, RV5–V6 > 25 mm; Cornell voltage index: SV3 + RaVL >20 mm in women and >28 mm in men; Cornell product: the product of the Cornell voltage index and the duration of the QRS complex (RaVL + SV3) × QRS – for men and (RaVL + SV3 + 8) × QRS – for women. The criteria of LVH is the value of the Cornell product > 2440 mm×ms. However, ECG criteria for detecting LVH are not sensitive enough. Peguero JG, Lo Presti S, et al. (2017) developed a more accurate method of diagnosing LVH by measuring the amplitude of the deepest S wave (SD) in any individual lead and adding it to the amplitude of the S wave in lead V4 (SV4) [SD+ SV4]. When the sum of [SD+ SV4] exceeds 28 mm in men or 23 mm in women (Peguero-Lo Presti criteria), LVH can be diagnosed.Objective: to systematize modern literary data on electrocardiographic diagnosis of left ventricular myocardial hypertrophy. Conclusion. Due to its low cost, easy availability, reproducibility and high specificity, electrocardiography remains the simplest and most common method of diagnosing myocardial hypertrophy. The Peguero-Lo Presti criteria for diagnosing left ventricular hypertrophy are more sensitive and specific than the voltage criteria of Sokolov-Lyon and Cornell.

Biomarkers and subclinical left ventricular dysfunction in patients with type 2 diabetes without clinical manifestations of cardiovascular diseases

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p<0,001). A higher level of NT-proBNP was associated with hypertension — odds ratio (OR) 3,64 [1,02-13,04] (p=0,005), a decrease in LV ejection fraction — OR 1,25 [1,06-1 ,47] (p=0,007), concentric hypertrophy — OR 4,84 [1,43-16,41] (p=0,011) and decreased GLS — OR 1,85 [1,62-2,06] (p=0,005), an increase in the ratio of early and late diastolic transmitral flow (E/A) — OR 0,01 [0,008-0,416] (p=0,024) and isovolumic relaxation time (IVRT) — OR 1,08 [1,03-1,14] (p=0,03). The sensitivity and specificity of NT-proBNP as a test for predicting GLS reduction <-18% were 86 and 27%, respectively. The hsCRP level, within the reference values, was significantly higher in the T2D and prediabetes groups compared to the control group (p<0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p<0,05). A higher level of hsCRP was significantly associated with diastolic dysfunction — OR 1,16 [1,02-1,32] (p=0,023), as well as with a GLS decrease <-18% — OR 1,58 [1,12-4,65] (p=0,03).Conclusion. In patients with T2D without clinical manifestations of cardiovascular disease, the presence of concentric LV myocardial hypertrophy, LV diastolic dysfunction and decreased GLS (<-18%) is associated with higher blood levels of NT-proBNP and hsCRP. However, in all cases, the levels of biomarkers do not exceed the reference values, which does not allow their use in the early diagnosis of subclinical LV dysfunction in T2D.

INFLUENCE OF LGALS-3 GENE POLYMORPHISM (rs2274273) ON THE PLASMA LEVELS OF GALECTIN-3 IN WOMEN WITH ESSENTIAL HYPERTENSION AND CHRONIC HEART FAILURE IN RESIDENTS OF THE PODILLYA REGION OF UKRAINE

Background. Individual genetic features can influence to formation of structural and functional changes in organs during EH and encourage the search for biological markers of the state of the myocardium and conclusions about their diagnostic effectiveness.
 Aim: to improve the early diagnosis of changes in the structure and function of the myocardium and the formation of prerequisites for chronic heart failure (CHF) in women with EH carriers of various polymorphic variants of the LGALS-3 gene (rs2274273), based on galectin-3 plasma level.
 Materials and methods. 180 postmenopausal women, average age 57,34±0,45, residents of the Podillya region of Ukraine were examined. The main group included 113 women with EH, of which 62 people had EH II, 51 people - EH with CHF C stage according to the ESH 2023 classification. The control group included 67 women without signs of cardiovascular pathology. In addition to the general clinical examination, the research used the enzyme immunoassay method to determine the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene (rs2274273) by means of polymerase chain reaction, and ultrasound of the heart. The statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. Using the MedCalc Software Ltd. Odds ratio calculator (https://www.medcalc.org/calc/odds_ratio.php) the conformity of the frequency distribution of genotypes in the studied population to the Hardy-Weinberg equilibrium was checked and calculated the odds ratio (OR) of the development of left ventricular myocardial hypertrophy (LVH) and CHF on the background of EH. The threshold levels of galectin-3 in blood plasma for the diagnosis of LVH and CHF were calculated using the ROC analysis method.
 Results. During study the frequency distribution of genotype variants of the galectin-3 gene (rs2274273) among women residents of the Podillya region of Ukraine, it was found that both in people without cardiovascular pathology and in patients with EH II and EH III, the GA genotype predominates, although there is a significant difference between the frequency of occurrence genotypes GA and GG are not noted (p>0.05). The AA genotype variant is significantly less frequent than both the GA and GG genotypes (p<0.01). The frequency distribution of genotype variants corresponds to the Hardy-Weinberg equilibrium. Moreover, the ratio between genotypes in patients of different stages of EH does not reliably differ from that in the control group. However, in EH complicated by CHF among patients with LVEF < 50% A allele carriers significantly predominate compared to GG homozygotes (79.31%, n=23 vs. 20.69%, n=6). In patients with EH, it was found that the concentration of galectin-3 in blood plasma in carriers of the A allele is significantly higher than in carriers of the GG genotype: EH without CHF - 16.82±0.54 ng/ml vs. 12.82±0.54 ng/ml (p<0.01); EH with CHF – 35.70±1.53 ng/ml vs. 25.39±1.38 ng/ml (p<0.001). The threshold levels of galectin-3 plasma concentrations, which indicate the presence of LVH and CHF, are significantly higher in carriers of the A allele than in carriers of the GG genotype.
 Conclusion. The carriers of the A allele of the LGALS3 gene (rs2274273) have a greater chance of developing CHF with a LVEF < 50% (OR 4.60; 95% CI 1.35 - 15.73 z statistic 2.43 p<0.01 χ2=6 .28; p=0.0122) and correspondingly higher levels of galectin-3 in blood plasma compared to carriers of the GG genotype.

АТИПИЧНЫЙ ГЕМОЛИТИКО-УРЕМИЧЕСКИЙ СИНДРОМ У ДЕТЕЙ, АССОЦИИРОВАННЫЙ С АНТИТЕЛАМИ К ФАКТОРУ Н: КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ, ДИАГНОСТИКА И ЛЕЧЕНИЕ

Atypical hemolytic uremic syndrome (aHUS) refers to one of the forms of thrombotic microangiopathy occurring with preferred damage to the kidneys. About 10% of all cases of aHUS in children are aHUS associated with antibodies to complement factor H (CFH-Ab-aHUS). In 90% of cases CFH-Ab-aHUS is represented by DEAP-HUS (Deficiency of Complement Factor H Related (CFHR) plasma proteins and Autoantibody Positive Hemolytic Uremic Syndrome) with a predominant deficiency of CFHR1, most often due to a homozygous deletion of CFHR3/CFHR1. CFH-Ab-aHUS is characterized by the age of onset of the disease of 4 to 12 years old; the presence of a prodrome, more often associated with gastrointestinal disorders such as vomiting and abdominal pain, less often diarrhea; relapsing course with a high risk in the first 6 months from the onset of the disease, a high proportion of adverse outcomes: death of the patient or development of end stage chronic kidney disease (CKD). Determination of the CFH-Ab titer should be performed in all children with HUS, and in case of their increase, regularly monitored during treatment. Treatment begins with eculizumab or its biosimilar until a CFH-Ab titer is obtained and, if CFH-Ab-aHUS is confirmed, it is necessary to switch to intensive plasma exchanges in combination with immunosuppressive therapy. If there are contraindications to immunosuppressive therapy or if there is no effect from it, if plasma exchanges are impossible or ineffective, if significant mutations in complement regulator genes are detected, it is necessary to continue or return to complement blocking therapy. After achieving remission of the disease, long-term monitoring of patients is required to control residual effects on the kidneys (hematuria, proteinuria, CKD) and the cardiovascular system (arterial hypertension, left ventricular myocardial hypertrophy). In patients who have reached the end stage of CKD, it is mandatory to determine the anti-CFH titer and conduct a molecular genetic research in order to determine the risks of the disease returning to the kidney graft and the need for prophylactic therapy with eculizumab or its biosimilar before and after the surgical intervention.

Origin of stage I-II retinopathy

Aim – to study the causes of retinopathy (RP) formation and progression at the initial stages.
 Material and methods. The data of a 6-year prospective follow-up of a natural group of initially healthy male workers aged 18-66 years (n = 7,959) were used to determine the predictors of stage I-II RP. For this purpose, a 2×2 confusion matrix and a multivariate regression model were used, and the relative risk factors were assessed.
 Results. Stage I-II retinopathy was caused by such factors as age from 26 to 66 years, arterial hypertension, smoking, dyslipidemia, hyperglycemia, family history of early cardiovascular diseases, degree I-III obesity, left ventricular myocardial hypertrophy, microalbuminuria, type 2 diabetes mellitus, creatininemia, atherosclerotic plaque / thickening of the intima-media complex, aortic atherosclerosis. All predictors except for smoking, degree I-III obesity and aortic atherosclerosis had a statistically significant result in the applied mathematical models.
 Conclusion. Statistical heterogeneity of the stage I-II RP predictors is likely to be related to the qualitative specific characteristics of RP predictors and their unique damage effect in the development of stage I-II RP.

Left ventricular myocardial hypertrophy and strain changes in children with hypertrophic cardiomyopathy

Introduction. An assessment of the relationship between the severity of hypertrophy and changes in the myocardial strain at which systolic disfunction is detected in children with hypertrophic cardiomyopathy (HCM) is clearly essential.Aim. To assess the relationship between hypertrophy and the myocardial strain in children with hypertrophic cardiomyopathy (HCM).Materials and methods. 61 patients aged between 7 and 17 years with a primary form of HCM underwent an ultrasound examination of the heart using standard techniques. An assessment of the left ventricular systolic function performed using of-line the two-dimensional (2D) speckle-tracking mode with analysis parameters that included global and segmental longitudinal, circumferential, and radial myocardial strains. The analysis of hypertrophy of myocardial segments carried out taking into account the absolute values of the thickness of the left ventricular myocardium in systole and diastole, depending on age, in terms of standard deviation units in the population (Z-score factor).Results. A decrease in longitudinal strain below the relevant values, an increase in radial strain, and no changes in circular strain were observed when the thickness of the left ventricular myocardium increased over 2.48Z. A further decrease in radial strain was observed when myocardial thickness was over 4.24Z, and circular strain was over 3.16Z. The relationship between myocardial hypertrophy and longitudinal strain had an inverse linear relationship: the lower the strain values, the greater the thickness of the myocardium. With increasing thickness of the myocardium, the radial strain first tended to increase in a compensatory manner, but it decreased when myocardial thickness increased over 4.24Z. The circular strain, as well as longitudinal one, has an inverse linear relationship, but with longer preservation of normal values when myocardial hypertrophy increases.Conclusion. Children with HCM demonstrate various types of relationships between hypertrophy and myocardial strain, which detection is important for the assessment of the left ventricular systolic function to improve the prognosis and therapeutic approach to the disease. A comprehensive approach to the assessment of myocardial strain in children with HCM should include not only a routine identification of global strain, but also assessment of the segmental strain to detect early signs of myocardial dysfunction. Comparison of measures of various types of strain and the thickness of the left ventricular myocardium has a very important diagnostic value for understanding the degree of changes in its kinetics.

Prevalence of myocarditis and its contribution to the course of primary myocardial hypertrophy

Aim. To assess the incidence of myocarditis in patients with primary myocardial hypertrophy and to study its contribution to the disease course.Material and methods. The study included 100 patients with primary left ventricular myocardial hypertrophy, 52 men and 48 women (mean age, 51,5±15,7 years; followup period 10,4 [2,1; 36,1] months). All patients underwent electrocardiography, 24-hour electrocardiographic monitoring, echocardiography, as well as DNA analysis (n=96), myocardium pathological study (n=29), cardiac magnetic resonance imaging (n=31), cardiac multislice computed tomography (n=26), assessment of anti-cardiac antibodies (n=43), free light chain level in serum and urine by immunofixation method (n=10); 99mTc-pyrophosphate myocardial scintigraphy (n=5); biopsy of the rectal mucosa and/or subcutaneous fat for amyloid (n=9).Results. In 68%, true (sarcomeric) hypertrophic cardiomyopathy (HCM) was diagnosed, in 16% — amyloidosis with cardiac involvement, in 10% — storage diseases, in 3% — neuromuscular diseases, in 2% — myocardial hypertrophy was combined with severe restriction (mixed phenotype), and in 1% — LEOPARD syndrome. Concomitant myocarditis was diagnosed in 30% of patients. In HCM, myocarditis was detected in 31% of cases. These patients had a significantly higher heart failure class (heart failure class 3 [2; 3] vs 2 [1; 3], p=0,026) and mortality (33,3% vs 6,4%, p=0,01). In amyloidosis, the incidence of myocarditis was 31,3%. In these patients, ventricular tachycardia was observed significantly more often: 80,0% vs 18,2% (p=0,036). The prevalence of concomitant myocarditis in the subgroup of storage diseases was 30%: 2 patients with Fabry disease and 1 patient with Danon disease. Of the three patients with neuromuscular diseases, myocarditis was diagnosed in 1. In the subgroups with the restrictive phenotype and LEOPARD syndrome, no cases of myocarditis were recorded. Treatment of myocarditis made it possible to stabilize the patients' condition.Conclusion. Concomitant myocarditis led to heart failure progression, worsening ventricular arrhythmias and, as a consequence, an increased risk of sudden cardiac death. It is necessary to actively diagnose and treat myocarditis in patients with primary myocardial hypertrophy.

Polymorphism of the coding gene LGALS-3 rs2274273 as an endogenous factor of the predictive effectiveness of the plasma concentration of galectin-3 in relation to the risk of development of chf on the background of eh in women

Objective. The purpose of the study is to improve the early diagnosis of the development of left ventricular myocardial hypertrophy (LVH) and the formation of prerequisites for chronic heart failure (CHF) in women with essential hypertension, residents of the Podillya region of Ukraine by determining the plasma concentration of galectin-3 in carriers of different polymorphic variants of the LGALS-3 (rs2274273) gene. Material and methods. 180 women of postmenopausal age, average age of 57.34±0.45, residents of the Podillya region of Ukraine, who lived in this territory in the third generation, were examined. The control group consisted of 67 women, average age of 56.43±0.64 years, without signs of cardiovascular pathology and signs of left ventricular hypertrophy (LVH) for other reasons were detected. The main group included 113 women with essential hypertension, of which 62 had essential hypertension with LVH without heart failure (EH II), 51 had essential hypertension with chronic heart failure stage C according to the ESH/ESC 2023 classification. General clinical examination, enzyme immunoassay method for determining the level of galectin-3 in blood plasma, genotyping of the LGALS3 (rs2274273) gene using polymerase chain reaction, and ultrasound of the heart were performed. The statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. Mathematical methods were used: multiple regression stepwise analysis of proportional risks with 95% CI confidence interval, Fisher's linear discriminant analysis with the creation of a mathematical prognostic model, and cluster analysis. Compliance of the frequency distribution of genotypes in the studied populations to the Hardy-Weinberg equilibrium was checked using the MedCalc Software Ltd. Odds ratio calculator. https://www.medcalc.org/calc/odds_ratio.php and calculated the odds ratio (OR) of developing left ventricular myocardial hypertrophy (LVH) and chronic heart failure (CHF).Results. In patients with EH and CHF, carrying the A allele of the LGALS-3 (rs2274273) gene was associated with a more severe degree of diastolic dysfunction and reduced LVEF compared with carriers of the GG genotype, and higher plasma levels of galectin-3 were also recorded, which were associated with a more significant deterioration structural and functional indicators of the myocardium. With the help of cluster analysis, it was found that carriers of the A allele of the LGALS-3 (rs2274273) gene are more likely to be included in unfavorable cluster 1. In contrast, in cluster 2, with a more favorable course of the disease, carriers of the GG genotype and carriers of the A allele occur with almost the same frequency. Conclusions. In postmenopausal women, residents of the Podillya region of Ukraine, carrying the A allele of the LGALS-3 (rs2274273) gene is associated with a more severe course of EH with the development of LVH, a higher concentration of galectin-3 in the blood plasma, and the formation of CHF with reduced LVEF when compared with carriers of the genotype GG.

New-onset atrial fibrillation in patients with SARS-CoV-2 pneumonia as a manifestation of acute myocardial injury

BACKGROUND: Over the past 3 years, the prevalence of atrial fibrillation (AF) has increased significantly worldwide, which was associated with the pandemic caused by SARS-CoV-2. It is accompanied by an increase in the cases of ischemic stroke, myocardial infarction, and development of heart failure due to acute myocardial injury. Given the high lethality of SARS-CoV-2 infection (COVID-19), studying the characteristics of new-onset AF is essential.
 AIM: The study aims at determining the predictors of new-onset AF in patients with COVID-19 pneumonia and at analyzing the clinical and pathophysiological characteristics of acute myocardial injury.
 MATERIALS AND METHODS: In 36 patients aged 4482 years (average 68.0) with COVID-19 pneumonia, AF paroxysms were recorded for the first time. All of them underwent computed tomography of the chest, electrocardiography, and echocardiography. The left ventricular ejection fraction was calculated using the Simpson method. Oxygen saturation was determined as blood oxygen saturation. Clinical blood tests were performed, C-reactive protein (CRP), ferritin, D-dimer, fibrinogen, and troponin I levels were measured.
 RESULTS: Along with the well-known predictors of AF development (arterial hypertension, coronary heart disease, left ventricular myocardial hypertrophy, and left atrial dilatation), with COVID-19 pneumonia, new-onset AF paroxysms were recorded in patients of the middle, elderly, and late-life age. In 44.4% of patients with AF, cardiomegaly occurred with dilatation of both atria and ventricles. With decreased left ventricular ejection fraction, the incidence of AF paroxysms reached 61.5%. With preserved ejection fraction, AF paroxysms occurred much less frequently (27%). In patients with AF, the extent of lung damage is on average 62.5% (2080%) with oxygen support saturation of 93% (7697%). Serum troponin I levels of 2000 ng/L indicated acute myocardial injury. CRP and blood ferritin values confirmed the presence of a pronounced inflammatory component in myocardial injury. High concentrations of blood fibrinogen and D-dimer, reaching 16,301 ng/mL, were associated with a tendency to hypercoagulation in patients with AF and COVID-19 pneumonia.
 CONCLUSIONS: COVID-19 has a direct damaging effect on the myocardium and probably persists for a long time, which may induce AF in patients with acute pneumonia.

#6067 GUT MICROBE-DERIVED UREMIC TOXIN TRIMETHYLAMINE N-OXIDE CONTRIBUTES TO CARDIAC REMODELING IN PATIENTS ON HEMODIALYSIS

Abstract Background and Aims It is well established that cardiovascular pathology is the leading cause of increased morbidity and mortality in chronic kidney disease patients, especially in the terminal stage. This is explained by high prevalence of both traditional and non-traditional cardiovascular risk factors, among which inflammation, intestinal dysbiosis and microbe-derived uremic toxins such as indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide (TMAO) are recently considered the most significant. However, the potential underlying mechanisms of these findings have not been fully elucidated. Here we aimed to investigate the association of serum TMAO with echocardiographic parameters of cardiac remodeling in patients receiving hemodialysis treatment. Method One hundred and forty (85M, 55F) clinically stable patients on dialysis were studied. The median (interquartile range) age was 56,5 (46,2-60,5) years, median duration of dialysis treatment – 48 (14,5-97) months, 39 (27,9%) were diabetic, 109 (77,9%) had high blood pressure, 39 (27,9%) – previous history of ischemic heart disease, including 8 (5,7%) suffered a myocardial infarction. All patients underwent transthoracic echocardiography (General Electric Vivid E95 device) with the registration of standard parameters. The determination of TMAO in serum was performed by LC/MS using a Shimadzu-8060 system combined with a Shimadzu LC-20AD liquid chromatograph. Statistical analysis was performed with STATISTICA 14.0 program. Non-parametric Spearman's rank correlation method was used to evaluate the associations between serum TMAO level and echocardiographic parameters. Value of p<0.05 was considered statistically significant in all analyses. Results Median serum TMAO was 5244 (3588-8701) ng/ml. Echocardiography data: end-systolic left ventricular (LV) size is 38,2±0,6 mm, end-systolic LV volume – 62,0±4,4 ml, end-diastolic LV size – 55,8 ±1,3 mm, end-diastolic LV volume – 111,5±19,7 ml, ejection fraction (according to Simpson method) – 53,2±7,2%, shortening fraction – 28,9±4,4%, inter-ventricular septum thickness – 11,6±0,2 mm, posterior wall thickness – 11,9 ± 0,1 mm, LV mass index – 142,8±4,6 g/m2, LV mass – 298,6±8,8 g, relative wall thickness – 0,43±0,3, number of patients with LV remodeling or hypertrophy – 98 (70%). LV diastolic function parameters (n = 113): E – 0,69±0,2 m/s, A – 0,79±0,2 m/s, E/A (early (E) to late (A) ventricular filling ratio) – 0,89±0,2, deceleration time (DT) – 211±52 ms, number of patients with diastolic disfunction – 104 (74,3%). Statistically significant correlation was fount between TMAO concentration and end-diastolic LV volume (r = 0,315; р = 0,028), LV mass (r = 0,409; р = 0,011) and DT (r = 0,272; р = 0,041). TMAO levels in individuals with LV myocardial hypertrophy and diastolic dysfunction was significantly higher than without these abnormalities (Mann–Whitney U-test р = 0,037 and р = 0,043, correspondingly). Conclusion Our results suggest that elevated TMAO may contribute to cardiac remodeling in hemodialysis patients through the myocardial fibrosis and hypertrophy. The pathophysiological mechanisms of TMAO must be investigated further for a better understanding of its role in cardiovascular disease progression and to develop therapeutic interventions against uremic toxicity.

Parameters of intra-cardiac hemodynamics in women with essential hypertension and heart failure, carriers of different polymorphic variants of the galectin-3 gene (LGALS-3, rs 2274273)

Annotation. The study aims to improve the prediction and diagnostics of cardiac remodeling, specifically left ventricular myocardial hypertrophy (LVH) in essential hypertension and the development of chronic heart failure (CHF) in carriers of polymorphic variants of the galectin-3 gene (LGALS-3, rs2274273). 180 postmenopausal women, on average aged 58.51±0.45, residents of the Podillya region of Ukraine, were examined. The main group consisted of 113 women with EH, of which 62 had EH II, and 51 had EH III with CHF II A stage. The control group included 67 women without signs of cardiovascular pathology. General clinical examination, enzyme immunoassay method for determining the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene (rs2274273) using polymerase chain reaction, and ultrasound of the heart were performed. Compliance of the frequency distribution of genotypes in the studied populations to the Hardy-Weinberg equilibrium was checked using the MedCalc Software Ltd. Odds ratio calculator. https://www.medcalc.org/calc/odds_ratio.php and calculated the odds ratio (OR) of developing left ventricular myocardial hypertrophy (LVH) and chronic heart failure (CHF). OR = 1 was considered as no association, OR>1 – as a positive association (increased risk of pathology), and OR<1 – as a negative association (reduced risk of pathology). The results were considered reliable at p<0.05. Statistical processing of the obtained results was performed using the SPSS statistical program package, STATISTICA v. 10.0. The reliability of the difference in percentages of quantitative values between groups was calculated according to the χ2 criterion. In postmenopausal women, residents of the Podillya region of Ukraine, without signs of cardiovascular pathology, the following frequency distribution of galectin-3 gene genotype variants (rs2274273) was found: GA – 49.25%, GG – 40.30%, AA – 10.45%, which corresponds to the Hardy-Weinberg equilibrium. The specified ratio does not reliably differ from that in women with EH of different stages. Therefore, the galectin-3 gene polymorphism (rs2274273) is not associated with the risk of EH: OR =0.88; 95% CI 0.47 – 1.63; z statistic 0.417; χ2 =0.1744, p=0.6763. Analysis of the structural and functional parameters of the myocardium in carriers of the A allele shows more pronounced remodeling of the myocardium with eccentric LVH, a more advanced diastolic dysfunction (DD), and lower left ventricular ejection fraction than in GG homozygotes (LVEF 47.63±0.49% vs. 50.61±0.63%, p<0.05). Therefore, the GG genotype of the galectin-3 gene (rs2274273) is a marker of limited changes in the structure of the myocardium in EH.

A clinical case of SARS-CoV-2 infection complicated by nephrogenic pulmonary edema and COVID-associated pneumonitis, alveolitis

COVID-19 is a highly transmissible disease with severe course especially in patients with nephrogenic hypertensive disease and chronic kidney disease due to a higher incidence of all-type infections than in the general population. The aim of the study is to describe a clinical case of SARS-CoV-2 infection complicated by nephrogenic pulmonary edema and COVID-associated pneumonitis, alveolitis. Description of the case. Patient K.S., born in 1975, was hospitalized 24 hours after symptom onset at emergency hospital due to complaints of increased blood pressure up to 180200/110120 mm Hg, temperature up to 38.7C, dry cough, feeling of heaviness in the chest, change in urine color. PCR smear for SARS-CoV-2 was positive. Computed tomography revealed a pattern of bilateral COVID-associated pneumonitis, alveolitis, with 75% involvement. The electrocardiogram revealed signs of left ventricular myocardial hypertrophy. Ultrasound examination showed numerous cysts in the kidneys. Urinalysis at admission: leukocytes 499, erythrocytes 386. Glomerular filtration rate (CKD-EPI: 29 ml/min/1.73 m2) and corresponds to stage IV of chronic kidney disease. Coagulogram: fibrinogen: 32.3 (1.64.0) g/l, D-dimer: 663 (0250). Despite the treatment, the patients condition worsened, the phenomena of cardiopulmonary and renal insufficiency increased, which led to a fatal outcome. During a virological study of sectional material: SARS-CoV-2 coronavirus RNA was found in the lung and kidneys. Signs of bilateral COVID-associated pneumonitis, alveolitis with diffuse cellular infiltrates in combination with changes in the alveolar apparatus, signs of pulmonary edema were revealed. Heart-related signs swelling of the interstitium, fragmented muscle fibers, some of them hypertrophied, a wave-like deformation of cardiomyocytes, blurring of the transverse striation. Arteries with thickened sclerosed walls. In the kidneys diffuse damage to the proximal tubules of the nephron with areas of cortical and proximal necronephrosis, areas of fibrinoid swelling. Conclusion. The cause of death of a 45-year-old patient was a severe course of bilateral COVID-associated pneumonitis, alveolitis, which contributed to the development of renal medullary hypoxia and type 1 cardiorenal syndrome, which led to early nephrogenic pulmonary edema.

Odnos varijabilnosti arterijskog pritiska iz ambulatornog 24-časovnog monitoringa arterijskog pritiska sa ehokardiografskim parametrima u bolesnika pod antihipertenzivnom terapijom

Introduction: Variability of systolic daytime arterial pressure was until recently a controversial parameter but is now recognized as an independent prognostic risk factor for stroke in hypertensive patients. Blood pressure variability is a quantitative index of spontaneous daily and nocturnal variations in systolic and diastolic arterial blood pressure and has been proposed as a risk factor for inducing subclinical damage to target organs in arterial hypertension. Besides varying degrees of left ventricular myocardial hypertrophy (LVH), patients with hypertension also exhibit accompanying diastolic dysfunction of the left ventricle as an early sign of hypertensive damage, even when myocardial hypertrophy does not develop. The variability of pressure over 24 hours in Ambulatory Blood Pressure Monitoring (ABPM) has not been sufficiently studied in terms of correlation with echocardiographic parameters in controlled hypertension. Methods: A total of 196 adequately treated patients with stage 2 hypertension, with a target of achieving normotension less than 140/90, were examined. The total of 196 patients, 109 males and 87 females, with a mean age of 49.3 ± 8.4 years, untreated or inadequately treated patients with stage 2 hypertension (mean BP before treatment 167/106 mmHg) were divided into three groups according to blood pressure variability parameters. Alongside standard methods: medical history, clinical examination, and electrocardiogram (ECG), 24-hour ambulatory arterial pressure monitoring (ABPM, so-called blood pressure holter) was performed with 24-hour, daytime, and nighttime variability of systolic and diastolic blood pressure as well as Color and Tissue Doppler echocardiography after adequate treatment. Results: Elevated blood pressure variability was observed in 66/196 patients (34%) in group V despite good pressure regulation, while 130/169 (66%) had normal variability - group C (control). A subgroup ExtV was particularly highlighted within group V with extreme variability of daytime systolic BP (SD>20 mmHg) - 15/66 patients (8%). Evaluation of left ventricular myocardial mass index (LVMI) showed no difference in the degree of LVH between groups C and V. In the subgroup ExtV (from group V with extreme blood pressure variability), comprising 15/66 patients (8%), a significant difference in the degree of left ventricular myocardial hypertrophy was found between groups C and V regarding extreme variability (p<0.01). There was no difference concerning gender and age structure. Statistical analysis of investigated 24-hour blood pressure parameters and echocardiographic parameters did not show significant correlation through calculation of the linear correlation coefficient between mean arterial pressure measured by 24-hour ambulatory pressure monitoring and standard deviations of daytime and nighttime pressure and the degree of left ventricular myocardial hypertrophy (linear correlation coefficients r <0.20), as expected. However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51. Conclusion: One-third of the examined patients, 66/196 patients (34%) in group V, had elevated blood pressure variability despite good pressure regulation. There was no significant difference in the degree of left ventricular myocardial hypertrophy between the investigated parameters of 24-hour blood pressure and echocardiographic indices, except in extreme variability ExtV (P<0.01). However, there is a moderate but significant correlation between the best echocardiographic parameter of diastolic function, E/E' ratio, and variability of daytime systolic pressure: r= 0.41. Only the subgroup with extreme variability ExtV in terms of daytime systolic pressure has a statistically significant correlation with the degree of LVMI myocardial hypertrophy, r=0.51.

Efekat metaboličkog sindroma na incidencu i stepen hipertrofije miokarda leve komore kod hipertenzivnih pacijenata

Metabolic syndrome (MetS) is characterized by the simultaneous presence of obesity, hypertension, dyslipidemia and hyperglycemia in an individual, which leads to an increased risk of cardiovascular disease (CVD). Left ventricular hypertrophy (LVH) is thickening of the heart muscle wall -hypertrophy of cardiomyocytes in concentric and/or elongation of cardiomyocytes and hyperplasia of connective tissue in eccentric hypertrophy with the participation of hemodynamic and non-hemodynamic factors (genetics, stress, other external factors). MetS, which essentially includesinsulin resistance, hyperinsulinemia, and hyperglycemia, alters myocardial metabolism and promotes myocardial inflammation, fibrosis, hypertrophy, and left ventricular remodeling. OBJECTIVE: To determine the impact of MetS, that is, obesity to the incidence and degree of severity of LVH in hypertensive patients with metabolic syndrome in comparison with the control group -hypertensive patients without metabolic syndrome. PATIENTS AND METHODS: Consecutive patients of the Office of Internal Medicine "Dr. Bastać" were examined, a total of 55 patients with hypertension, who were divided into two groups: the first group with MetS, 22 people, average age 56±8.5 years with BMI>30kg /m 2 and waist circumference more than 80 cm for women and >94 cm for men, the second control group without MetS-33 people, average age 52±14 years, with BMI<30kg/m 2 . Echocardiography was done for all subjects on a Power Vision 6000 Toshiba echo camera with standard echocardiographic measurements in the M, B and Doppler technique, and the mass of the left ventricular myocardium was determined for them using the Devereux formula. RESULTS: The prevalence of LVH in group 1 with metabolic syndrome (MetS) was 64%, while in the control group without (MetS) it was 36%. There was a statistically significantly higher number of patients with LVH in hypertension with MetS compared to hypertensive patients of the control group without MetS (X2, p=0.027). In the group of hypertensive patients with MetS, the degree of severity of myocardial hypertrophy, that is, the myocardial mass , was statistically significantly higher compared to the control group (respectively 302±84g versus 224±89g, p=0.0002). Arterial pressure values were higher for both systolic and diastolic blood pressure 168/106 mmHg in hypertensive patients with MetS, but did not reach statistical significance in relation to blood pressure values in hypertensive patients without MetS (156/95 mmHg, p=0.16). CONCLUSION. Patients with metabolic syndrome and hypertension have a statistically significantly higher prevalence of left ventricular myocardial hypertrophy and a highly statistically significant degree of left ventricular hypertrophy compared to the control group of hypertensive individuals without MetS. Given that mean values of arterial pressure do not differ between groups, it can be concluded that non-hemodynamic factors for the development of LVH have an important role in the induction of a more severe degree of LVH in hypertensive patients with metabolic syndrome.

Insulin resistance and heart failure with preserved ejection fraction. Pathogenetic and therapeutic crossroads

Insulin resistance, which is a fundamental pathogenetic factor of prediabetes, is closely associated with abdominal obesity on the one hand and the development of cardiovascular diseases, heart failure (HF), on the other. The pathogenetic role of insulin resistance is multifaceted and consists in the acceleration of atherosclerosis, the formation of left ventricular myocardial hypertrophy, including through mechanisms that do not depend on blood pressure, as well as the development of its diastolic dysfunction. The latter is the starting point for starting HF with preserved ejection fraction (HFpEF).Compared with patients with HF with reduced ejection fraction, the presence of HFpEF determines a higher frequency of hospitalizations not due to decompensation of heart failure, but due to concomitant diseases, such as destabilization of the course of arterial hypertension, decompensation of type 2 diabetes mellitus, curation of which, in general, has a greater impact in terms of improving prognosis. Thus, in patients with prediabetes and HFpEF, the correction of insulin resistance as the underlying cause and trigger of cardiometabolic disorders can potentially improve not only insulin-glucose homeostasis, but also the parameters of myocardial diastolic function. This literature review is devoted to the accumulated experience of using metformin as a «strategic» antidiabetic drug in HFpEF and considering potential new points of its application as a protector of the cardiovascular system.

The role of clinical and genetic factors in the progression of hypertrophy of the left ventricular myocardial in arterial hypertension

Introduction. A special position among the structural changes of the heart is occupied by left ventricular myocardial hypertrophy (LVH), which refers to the subclinical signs of heart damage in arterial hypertension (AH). Currently, the role of not only demographic, neuroendocrine, but also genetic factors in the development and progression of LVH is no longer in doubt.Aim. To assess the role of clinical and genetic factors in the progression of LVH in patients with hypertension based on the results of a dynamic 5-year follow-up of a cohort of Shors.Materials and methods. The survey of the indigenous population in Gornaya Shoria was carried out in two time periods: onetime (from 2013 to 2017) and prospective (from 2018 to 2020). The study included the adult population (18 years and older) – a total of 901 people – by continuous method. A group of patients with hypertension was identified – 367 people (40.7%). LVH was assessed by electrocardiography and/or echocardiography. The prospective stage of the study included patients with hypertension who had not previously received antihypertensive therapy (263 people). The control and correction of blood pressure numbers was carried out annually, the dynamics of LVH was assessed after five years.Results. Clinical predictors of negative dynamics of LVH were established: obesity (OR = 3.61), abdominal obesity (OR = 4.11), impaired carbohydrate metabolism (OR = 2.83), low high-density lipoprotein cholesterol (OR = 2.05). Genetic markers also demonstrated their involvement in the progression of LVH: allele D of the ACE gene, allele C of the AGTR1 gene, and 4a of the eNOS gene (OR = 9.69; OR = 6.72; OR = 6.37, respectively).Conclusion. The associations of clinical and genetic factors with LVH identified in the Shor cohort can be considered as predictors of myocardial remodeling in hypertension. The data obtained support the hypothesis that polymorphisms of the renin-angiotensin-aldosterone system and endothelial function can influence the phenotype, creating new approaches to the possible prediction of unfavorable outcomes.

Proteomic analysis of exercise-induced hypertrophy reveals sex-related mitochondrial differences mediated by AMPK

Abstract Background Regular physical activity results in characteristic structural and functional changes in the heart, which are collectively referred to as the athlete's heart. However, the extent of exercise-induced left ventricular (LV) hypertrophy and functional changes show significant differences between men and women, the molecular background of which is not fully elucidated. Objective The aim of this study was to provide a proteomic characterization of long-term, intense exercise-induced LV myocardial hypertrophy in a rat model, with a focus on sex-related differences. Methods Our rats were divided into trained (FEx) and control female (FCo) as well as trained (MEx) and control male (MCo) groups. In the trained groups, athlete's heart was induced by a 12-week swimming protocol. Myocardial hypertrophy was confirmed by echocardiography and functional adaptation by pressure-volume analysis. Proteomic measurements based on liquid chromatograph-coupled mass spectrometry were performed on proteins isolated from our LV myocardial samples. Results Echocardiography and post-mortem myocardial mass showed significant LV hypertrophy in both sexes, which was more pronounced in female animals (tibial length normalized LV muscle mass: + 17.4% MEx vs. MCo, + 31.0% FEx vs. FCo). LV contractility increased to the same extent in both sexes. Relative expression of 3074 proteins were determined by proteomics. There was a significant change in expression of 229 proteins in males and 599 in females compared to the level of same-sex controls. Based on our gene ontological analysis, physiological LV remodeling in females is characterized by increased expression of proteins in mitochondrial function (cellular respiration and fatty acid oxidation) and biogenesis, whereas in males, proteins that bind to the actin cytoskeleton is primarily increased. Further investigation revealed that the quantity of AMP-activated protein kinase (AMPK) and sirtuin 3 (SIRT3) was increased only in female animals. Conclusions Our data suggests that physiological LV hypertrophy resulting from regular, balanced exercise is associated with sex-specific changes in the myocardial proteome. The main differences might be associated with different regulation of mitochondrial function and biogenesis, related to AMPK pathway. Our results contribute to the understanding of the development of physiological myocardial hypertrophy. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bolyai János Research Scholarship (BO/00837/21) to OANational Research, Development and Innovation Office (NKFIH) K135076 to B.M.

Diagnostics of Fabry disease in arrhythmology practice: a case report

Heart failure in Fabry disease (FD) is unfavorable prognostic manifestation and cause of death. Given that the disease is rare in clinical practice, the low awareness of physicians about this pathology leads to its late diagnosis and the lack of pathogenetic therapy.Aim. To present a clinical picture of the cardiovascular phenotype in FD in order to increase the awareness of doctors about this disease.Material and methods. In this clinical case, an asymptomatic FD course up to 46 years of age and mani festation in the form of arrhythmia were observed. According to echo car dio graphy, severe left ventricular hypertrophy (myocardial mass index, 214 g/m2) without signs of left ventricular (LV) outflow tract obstruction and left atrial (LA) dilatation were revealed (LA volume index — 47 ml/m2). Right ventricular (RV) and LV systolic function was assessed using two-dimensional speckletracking strain echocardiography. Latent subclinical RV and LV systolic dysfunction was established.Results. Tandem mass spectrometry revealed a sharp decrease in alphagalactosidase activity of 0,03 umol/L/h (norm range, 0,80-15,00 umol/L/h), as well as an in creased Lyso-GB3 concentration of 95,18 ng/ml (normal range, 0,05-3,0 ng/ ml). A molecular genetic study of blood samples was carried out. By direct automatic sequencing of the GLA gene, a variant of the c.1229 C>T nucleotide sequence was identified, leading to the replacement of p.Thr4101le in the hemizygous state.Conclusion. This case shows the possibility and expediency of diagnosing FD in cardiology practice in patients with LV myocardial hypertrophy of unclear etiology, while atypical variants can be diagnosed only by molecular genetic testing.

Cardioprotection effect of Yiqi-Huoxue-Jiangzhuo formula in a chronic kidney disease mouse model associated with gut microbiota modulation and NLRP3 inflammasome inhibition.

The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi-Huoxue-Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified. A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways. YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1β both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman's correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels. Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications.