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Dmitry Shchekochikhin,1 Tatiana Nikiforova,1 Alexandra Shilova,2 Alexey Nesterov,2 Olga Baturina,1 Daria Gognieva,1 Natalia Kozlovskaya,3 Abram Syrkin,1 Philipp Kopylov11Department of Preventive and Emergency Cardiology of the Faculty of Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia; 2Department of Interventional Cardiology and Cardiac Rehabilitation, Pirogov Russian National Research Medical University (RNRMU), Moscow 117997, Russia; 3Department of Internal Medicine and Occupational Medicine, Eramishancev Moscow Clinical Hospital, Moscow 129327, RussiaBackground: Determining the prognosis of heart failure with preserved ejection fraction (HFpEF) is problematic, as the ejection fraction cannot be used. Formulae that estimate glomerular filtration rate (eGFR) may be potential prognosticators for this condition, since renal dysfunction is a well-known predictor of poor outcomes of all forms of heart failure.Methods: A prospective observational study of 117 HFpEF patients (average age 71.6±9.1 years; 65.8% women) who had eGFR determined after their first episode of cardiac decompensation by two different chronic kidney disease epidemiology collaboration (CKD-EPI) equations. The ability to predict hospitalizations and mortality over 24 months by the two equations were compared.Results: The CKD-EPI formula based on serum creatinine only performed poorly. However, the CKD-EPI equation that used both serum creatinine and serum cystatin C was associated with unfavorable outcome: eGFR 2, predicted 24-month mortality (HR=4.21 [1.32;13.43], p=0.02) and the combined endpoint of mortality and hospitalization (HR 2.45 [1.42;4.22], p=0.001). .Conclusions: eGFR by the CKD-EPI equation based on serum creatinine and cystatin C levels, but not by the CKD-EPI creatinine only equation, predicts the outcome of HFpEF patients.Keywords: cystatin C, CKD-EPI equation, heart failure with preserved left ventricle ejection fraction, estimated glomerular filtration rate

Mikhail Brovko,1 Lidia Kozlovskaya,1 Andrey Pulin,1,2 Sergey Moiseev,1 Victoria Sholomova,1 Dmitry Shchekochikhin,1 Daria Gognieva,1 Ludmila Milovanova,1 Victor Fomin1 1Sechenov First Moscow State Medical University, Moscow, Russia; 2Laboratory for Cell Technologies and Developmental Pathology, Federal State Budgetary Scientific Institution “Institute of General Pathology and Pathophysiology,” Moscow, Russia Purpose: Experimental studies suggest that the nephrotic syndrome is associated with “vasopressin escape”, characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome. Patients and methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA. Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all P

Background: The venous excess ultrasound score (VExUS) is used to objectify systemic venous congestion. The aim of the paper was to determine the association between VExUS grades and worsening renal function (WRF), reduced natriuretic response, diuretics resistance, and mortality in patients with acute heart failure (AHF). Methods: One hundred patients were included, and Doppler ultrasound of hepatic, portal, and renal veins was performed. Severity of congestion was graded using the VExUS score (grade 0, 1, 2, or 3). Sodium concentration in a spot urine sample was assessed in 2 h after the first loop diuretic administration and was adjusted for the prescribed dose of furosemide (31 mmol/40 mg). Diuretics resistance was defined as the need to double the starting dose of intravenous furosemide in 6 h. Results: Patients with VExUS grade 3 showed a higher incidence of WRF (OR: 11.17; 95% CI: 3.86-32.29; p < 0.001) and a decreased natriuretic response: a spot urine sodium content of <50 mmol/L (OR: 21.53; 95% CI: 5.32-87.06; p < 0.001) and an adjusted spot urine sodium content of <31 mmol/40 mg (OR: 9.05; 95% CI: 3.15-25.96; p < 0.001). The risk of diuretic resistance (OR: 15.31; 95% CI: 5.05-46.43; p < 0.001), as well as the need for inotropic and/or vasopressor support (OR: 11.82; 95% CI: 3.59-38.92; p < 0.001), was higher in patients with severe congestion. The hospital mortality rate increased in patients with VExUS grade 3 compared to in patients with other grades (OR: 26.4; 95% CI: 5.29-131.55; p < 0.001). Conclusions: Patients with AHF and VExUS grade 3 showed a higher risk of developing WRF, a decreased diuretic and natriuretic response, a need for inotropic and/or vasopressor support, and a poor prognosis during their hospital stay.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg -1 ·d -1 , i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 μM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

The escalating prevalence of obesity presents formidable challenges, necessitating the development of effective therapeutic strategies. In this study, we aimed to elucidate the preventive effects on obesity of tetrahydroberberrubine (THBru), a derivative of berberine (BBR) and to unravel its underlying mechanism. Using an obese mouse model induced by a high-fat diet (HFD), THBru was found to markedly ameliorate obesity, as evidenced by reduced body weight, decreased Lee's index, diminished fat mass in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT), alongside improved dyslipidemia. Notably, at the same dose, THBru exhibited superior efficacy compared to BBR. RNA-sequencing and gene set enrichment analysis indicated THBru activated thermogenesis, which was further confirmed in WAT, BAT, and 3T3-L1 cells. Bioinformatics analysis of RNA-sequencing data revealed the candidate gene Pgc1α, a key regulator involved in thermogenesis. Moreover, THBru was demonstrated to elevate the expression of PGC1α by stabilizing its mRNA in WAT, BAT and 3T3-L1 cells. Furthermore, PGC1α knockdown blocked the pro-thermogenic and anti-obesity action of THBru both in vivo and in vitro. This study unravels the preventive effects of THBru on obesity through the activation of PGC1α-mediated thermogenesis, thereby delineating its potential therapeutic implications for obesity and associated disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent endeavors have led to the exploration of Machine Learning (ML) to enhance the detection and accurate diagnosis of heart pathologies. This is due to the growing need to improve efficiency in diagnostics and hasten the process of delivering treatment. Several institutions have actively assessed the possibility of creating algorithms for advancing our understanding of atrial fibrillation (AF), a common form of sustained arrhythmia. This means that artificial intelligence is now being used to analyze electrocardiogram (ECG) data. The data is typically extracted from large patient databases and then subsequently used to train and test the algorithm with the help of neural networks. Machine learning has been used to effectively detect atrial fibrillation with more accuracy than clinical experts, and if applied to clinical practice, it will aid in early diagnosis and management of the condition and thus reduce thromboembolic complications of the disease. In this text, a review of the application of machine learning in the analysis and detection of atrial fibrillation, a comparison of the outcomes (sensitivity, specificity, and accuracy), and the framework and methods of the studies conducted have been presented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

According to the World Health Organization, ischemic stroke is the second leading cause of death in the world. Frequently, it is caused by brachiocephalic artery (BCA) atherosclerosis. Timely detection of atherosclerosis and its unstable course can allow for a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. This research included 90 blood plasma samples. The study group comprised 52 patients with severe atherosclerotic lesions BCA, and the control group comprised 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of their blood plasma was carried out. There was a statistically significant difference ( p < 0.05) in the values of the indices saturated fatty acids (FAs), unsaturated FAs, monounsaturated FAs, omega-3, and omega-6. Based on the results on the blood plasma lipidome, we formed models that have a fairly good ability to determine atherosclerotic lesions of the brachiocephalic arteries, as well as a model for identifying unstable atherosclerotic plaques. According only to the panoramic lipidome data, divided into groups according to stable and unstable atherosclerotic plaques, a significant difference was taken into account: p value < 0.05 and abs (fold change) > 2. Unfortunately, we did not observe significant differences according to the established plasma panoramic lipidome criteria between patients with stable and unstable plaques. Omics technologies allow us to obtain data about any changes in the body. According to our data, statistically significant differences in lipidomic profiling were obtained when comparing groups with or without BCA atherosclerosis.

State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. Objective : We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. Methods : the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). Results: In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. Conclusions: The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.

Tachycardia-induced cardiomyopathy (TIC) is a reversible subtype of dilated cardiomyopathy (DCM) resulting from sustained supraventricular or ventricular tachycardia and diagnosed by the normalization of left ventricular ejection fraction (LVEF) after stable sinus rhythm restoration. The aim of this study was to determine the contribution of cardiac magnetic resonance (CMR) to the differential diagnosis of TIC and DCM with persistent atrial arrythmias in patients hospitalized for the first time with heart failure (HF) with reduced LVEF of nonischemic origin. A total of 29 patients (age: 58.2 ± 16.9 years; males: 65.5%; average EF: 37.0 ± 9.5%) with persistent atrial tachyarrhythmia and first decompensation of HF without known coronary artery diseases were included in this study. The patients successfully underwent cardioversion and were observed for 30 days. The study population was divided into groups of responders (TIC patients; N = 16), which implies achieving FF > 50% or its increase > 10% in 30 days of TIC, and non-responders (N = 13). The increase in left ventricle (LV) volumes measured using CMR was significantly higher in the non-responder group when compared with the responders (114.8 mL ± 25.1 vs. 68.1 mL ± 10.5, respectively, p < 0.05). Non-responders also demonstrated decreased interventricular septum thickness (9.1 ± 0.8 vs.11.5 ± 1.3, respectively, p < 0.05). Late gadolinium enhancement (LGE) was observed in 12 patients (41.4%). The prevalence of LGE was increased in the non-responder group (25.0% vs. 65.1%, respectively, p = 0.046). Notably, a septal mid-wall LGE pattern was found exclusively in the non-responders. Epicardial adipose tissue thickness was decreased in the non-responder group versus the TIC patients. Conclusion: Patients with TIC were found to have smaller atrial and ventricular dimensions in comparison to patients with DCM. In addition, LGE was more common in DCM patients.

Background: Atherosclerosis is driven by synergistic interactions between pathological biomechanical and lipid metabolic factors. Long noncoding RNAs (LncRNAs) have been implicated in atherogenesis. The purpose of this study was to investigate the potential mechanism of lncRNA AI662270 on macrophage cholesterol transport in atherosclerosis., Methods: Apolipoprotein E deficiency (ApoE -/- ) mice were fed a high fat diet for 16 weeks to construct atherosclerotic model, and the mice were injected with recombinant lentivirus carrying AI662270 gene to overexpress AI662270. Macrophages were cleared by liposomal clondronate in vivo. Fundamental experiments and functional assays, hematoxylin and eosin staining, oil red O staining and others, were performed to evaluate the function of AI662270 on atherogenesis. Peritoneal macrophages were treated with oxidized low density lipoprotein (ox-LDL) to simulate in vitro model. Mechanism assays, RNA-interacting protein immunoprecipitation, RNA-protein pulldown and others, were performed to study the regulatory mechanism of AI662270 in macrophages., Results: The novel AI662270 was mainly enriched in macrophages, but not in endothelial cells, smooth muscle cells and fibroblasts of mouse atherosclerotic lesions and was upregulated by ox-LDL. Overexpression of AI662270 resulted in lipid accumulation, larger atherosclerotic plaques and cardiac dysfunction in vivo. After macrophages were removed, the pro-atherogenic effect of AI662270 disappeared. Downregulation of AI662270 in macrophages protected against foam cell formation by potentiating cholesterol efflux and reducing intracellular total cholesterol. The opposite effect was observed in macrophage-specific AI662270-overexpressed cells in vitro. AI662270 bound to adenosine triphosphate-binding cassette transporter A1 (Abca1) responsible for regulating cholesterol efflux in macrophages. Forced expression of AI662270 in macrophages decreased Abca1 expression. The reverse occurred when expression of AI662270 was repressed., Conclusion: These findings reveal an essential role for AI662270 in atherosclerosis progression by regulating cholesterol efflux from macrophages., (© 2023. The Author(s).)

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown., Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia., Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [-2; 4] mmol/L), as compared to the control group (-1 [-3.75; 2]); p &lt; 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [-3; 3.75] mmol/L vs. -2 [-4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008)., Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To determine the impact of sodium-dependent glucose type 2 cotransporter inhibitors on the renal function in acute heart failure., Methods: In a single-centre, controlled, randomised study, patients were prescribed dapagliflozin in addition to standard therapy, or were in receipt of standard therapy. The prespecified outcome was renal function deterioration; the secondary outcomes were the development of resistance to diuretics, weight loss, death during hospitalisation and the rehospitalisation or death for any reason within 30 days following discharge., Results: 102 patients were included (73.4±11.7 years, 57.8% men). The average left ventricular ejection fraction was 44.9%±14.7%, the average N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was 4706 (1757; 11 244) pg/mL, the average estimated glomerular filtration rate (eGFR) was 51.6±19.5 mL/min. eGFR decreased 48 hours after randomisation in the dapagliflozin group (-4.2 (-11.03; 2.28) mL/min vs 0.3 (-6; 6) mL/min; p=0.04) but did not differ between the groups on discharge (54.71±19.18 mL/min and 58.92±24.65 mL/min; p=0.36). The incidence of worsening renal function did not differ (34.4% vs 15.2%; p=0.07). In the dapagliflozin group, there was less tendency to increase the dose of loop diuretics (14% vs 30%; p=0.048), lower average doses of loop diuretics (78.46±38.95 mg/day vs 102.82±31.26 mg/day; p=0.001) and more significant weight loss (4100 (2950; 5750) g vs 3000 (1380; 4650) g; p=0.02). In-hospital mortality was 7.8% (4(8%) in the dapagliflozin and 4 (7.7%) in the control group (p=0.95). The number of deaths within 30 days following discharge in the dapagliflozin group and in the control group was 9 (19%) and 12 (25%), p=0.55; the number of rehospitalisations was 14 (29%) and 17 (35%), respectively (p=0.51)., Conclusion: The use of dapagliflozin was associated with a more pronounced weight loss and less need to increase diuretic therapy without significant deterioration of the renal function. Dapagliflozin did not improve the in-hospital and 30-day prognosis after discharge., Trial Registration Number: N04778787., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively., Methods and Results: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization., Conclusions: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)