Increase In Ejection Fraction Research Articles

Comparison of carvedilol vs. bisoprolol for heart failure with reduced ejection fraction (HFrEF): A systematic review and meta-analysis from the Asian population

China, Indonesia, and Malaysia have the highest age-standardized rates of heart failure in Asia, according to the Global Burden of Disease study. While numerous systematic reviews and meta-analyses have compared bisoprolol and carvedilol in HFrEF, most have focused on Western populations. To address this gap, we conducted a meta-analysis of RCTs and cohort studies involving Asian patients with HFrEF from PubMed and Cochrane databases that reported all-cause mortality, hospital admission, and left ventricular ejection fraction (LVEF) increase. The search result identified five eligible studies, primarily from Taiwan, Japan, and South Korea, with a total of 11,577 participants. The meta-analysis revealed no significant difference between bisoprolol and carvedilol in terms of all-cause mortality (RR 1.04, p 0.62, I2 = 0%), hospitalization (RR 1.23, p. 0.23, I2 = 0%), and LVEF increase (RR -1.40, p. 0.50, I2 = 0%). These findings suggest that both drugs have comparable efficacy in the Asian population.

Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer

IntroductionDoxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.ObjectivesThis study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment.MethodsFemale FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5 mg/kg/week). Mice underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed.ResultsDOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. DOX-treated exercised mice did not differ from tumor-bearing group without DOX in LVGU or from the tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight.ConclusionIn a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity.

Cardiovascular effects of lactate in healthy adults

BackgroundLow-volume hypertonic solutions, such as half-molar lactate (LAC), may be a potential treatment used for fluid resuscitation. This study aimed to evaluate the underlying cardiovascular effects and mechanisms of LAC infusion compared to sodium-matched hypertonic sodium chloride (SAL).MethodsEight healthy male participants were randomized in a controlled, single-blinded, crossover study. Each participant received a four-hour infusion of LAC and SAL in a randomized order. Assessor-blinded echocardiography and blood samples were performed. The primary endpoint was cardiac output (CO) measured by echocardiography.ResultsDuring LAC infusion, circulating lactate levels increased by 1.9 mmol/L (95% CI 1.8–2.0 mmol/L, P < 0.001) compared with SAL. CO increased by 1.0 L/min (95% CI 0.5–1.4 L/min, P < 0.001), driven primarily by a significant increase in stroke volume of 11 mL (95% CI 4–17 mL, P = 0.002), with no significant change in heart rate. Additionally, left ventricular ejection fraction improved by 5 percentage points (P < 0.001) and global longitudinal strain by 1.5 percentage points (P < 0.001). Preload indicators were elevated during SAL infusion compared with LAC infusion. Concomitantly, afterload parameters, including systemic vascular resistance and effective arterial elastance, were significantly decreased with LAC infusion compared with SAL, while mean arterial pressure remained similar. Indicators of contractility improved during LAC infusion.ConclusionsIn healthy participants, LAC infusion enhanced cardiac function, evidenced by increases in CO, stroke volume, and left ventricular ejection fraction compared with SAL. Indicators of contractility improved, afterload decreased, and preload remained stable. Therefore, LAC infusion may be an advantageous resuscitation fluid, particularly in patients with cardiac dysfunction.Clinical trial registrationshttps://clinicaltrials.gov/ct2/show/NCT04710875. Registered 1 December 2020.

The impact of combination of zofenopril and different diuretics on regression of myocardial reperfusion injury and oxidative status in spontaneously hypertensive rats.

As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20min of ischemia followed by 30min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.

Left Bundle Branch Area Pacing Versus Right Ventricular Pacing in Patients With Atrioventricular Block: A Systematic Review and Meta-Analysis.

Left bundle branch area pacing (LBBAP) is a new technique for patients with atrioventricular block (AVB) and preserved left ventricular ejection fraction (LVEF), potentially offering better cardiac function than right ventricular pacing (RVP). We searched databases and registries for studies that compared LBBAP with RVP in patients with AVB and preserved LVEF. We extracted data on various outcomes and pooled the effect estimates using random-effects models. Our meta-analysis included 14 studies (10 observational and 4 RCTs) involving 3062 patients with AVB. The analysis revealed that the QRS duration was significantly shorter in the LBBAP group compared to the RVP group [MD = -35.56 ms; 95% CI: (-39.27, -31.85), p < 0.00001]. Patients in the LBBAP group also exhibited a significant increase in left ventricular ejection fraction (LVEF) [MD = 5.48%; 95% CI: (4.07%, 6.89%), p < 0.00001], and a significant reduction in left ventricular end-diastolic diameter (LVEDD) compared to RVP [MD = -3.98 mm; 95% CI: (-5.88, -2.09 mm), p < 0.0001]. In terms of clinical outcomes, LBBAP was associated with a significantly lower risk of heart failure hospitalizations (HFHs) compared to RVP [OR = 0.26; 95% CI: (0.16, 0.44), p < 0.0001]. However, no significant differences were observed between the two groups in the implant success rate, pacing impedance, or pacing threshold. The RVP group demonstrated a significantly higher R-wave amplitude increase than the LBBAP group [MD = 0.85 mV; 95% CI: (0.23, 1.46), p = .007]. Lastly, there was no significant difference in the incidence of complications between the two groups [OR = 2.12; 95% CI: (0.29, 15.52), p = 0.46]. LBBAP outperforms RVP in several cardiac function indicators, suggesting it may be a superior pacing method for AVB patients with preserved LVEF. However, the small sample size in studies and the result in heterogeneity call for more research to validate these findings and assess LBBAP's long-term effects.

Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy.

Septic cardiomyopathy (SCM) is a severe cardiac complication of sepsis, characterized by cardiac dysfunction with limited effective treatments. This study aimed to identify repurposable drugs for SCM by integrated multi-omics and network analyses. We generated a mouse model of SCM induced by lipopolysaccharide (LPS) and then obtained comprehensive metabolic and genetic data from SCM mouse hearts using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and RNA sequencing (RNA-seq). Using network proximity analysis, we screened for FDA-approved drugs that interact with SCM-associated pathways. Additionally, we tested the cardioprotective effects of two drug candidates in the SCM mouse model and explored their mechanism-of-action in H9c2 cells. Network analysis identified 129 drugs associated with SCM, which were refined to 14 drug candidates based on strong network predictions, proven anti-infective effects, suitability for ICU use, and minimal side effects. Among them, acetaminophen and pyridoxal phosphate significantly improved cardiac function in SCM moues, as demonstrated by the increased ejection fraction (EF) and fractional shortening (FS), and the reduced levels of cardiac injury biomarkers: B-type natriuretic peptide (BNP) and cardiac troponin I (cTn-I). In vitro assays revealed that acetaminophen inhibited prostaglandin synthesis, reducing inflammation, while pyridoxal phosphate restored amino acid balance, supporting cellular function. These findings suggest that both drugs possess protective effects against SCM. This study provides a robust platform for drug repurposing in SCM, identifying acetaminophen and pyridoxal phosphate as promising candidates for clinical translation, with the potential to improve treatment outcomes in septic patients with cardiac complications.

Atractylenolide-III restrains cardiac fibrosis after myocardial infarction via suppression of the RhoA/ROCK1 and ERK1/2 pathway.

Cardiac fibrosis, a critical factor in myocardial remodeling post-myocardial infarction (MI), can advance heart failure progression. Atractylenolide III (ATL-III), derived from Atractylodes lancea, has recognized antioxidant and anti-inflammatory effects; however, its influence on cardiac fibrosis remains unclear. MI was induced in mice by permanent ligation of the left anterior descending (LAD) coronary artery, followed by 2weeks of ATL-III or dimethyl sulfoxide (DMSO) treatment. Cardiac fibrosis was assessed by echocardiography, tissue histology, and serum biomarkers of myocardial injury. In vitro, the effects of ATL-III on cardiac fibroblast (CF) proliferation and collagen deposition were evaluated using immunofluorescence, 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques. Network pharmacology and molecular docking identified potential ATL-III targets. ATL-III treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) and fractional shortening (FS) and reduced left ventricular dilation. Histological analysis revealed decreased fibrotic areas in ATL-III-treated mice, along with reduced expression of fibrosis markers α-SMA and Collagen I. ATL-III also alleviated oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing superoxide dismutase (SOD) activity. Furthermore, ATL-III suppressed inflammation, decreasing TNF-α, IL-6, and IL-1β protein and mRNA levels. In vitro, ATL-III inhibited TGF-β1-induced CF proliferation, migration, and differentiation, reducing the expression of fibrotic markers. Mechanistically, ATL-III suppressed the RhoA/ROCK1 and ERK1/2 signaling pathways, as confirmed by molecular docking and pathway analysis. ATL-III demonstrates therapeutic potential in mitigating post-MI cardiac fibrosis by reducing oxidative stress, inflammation, and CF activation. These findings highlight ATL-III as a promising candidate for the treatment of cardiac fibrosis and associated heart failure.

Effect of Compound Danshen Dripping Pills on cardiac function after acute anterior ST-segment elevation myocardial infarction: A randomized trial.

The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills (CDDP) in improving cardiac function among patients with acute anterior ST-segment elevation myocardial infarction (AAMI). Between February 2021 and February 2023, 247 eligible patients with AAMI after primary percutaneous coronary intervention (pPCI) were enrolled and randomly assigned (1∶1) to receive CDDP ( n = 126) or placebo ( n = 121), with a follow-up of 48 weeks. Compared with the placebo group, the CDDP group demonstrated a significant increase in left ventricular ejection fraction (LVEF) values after 24 weeks of the treatment (least squares mean: 3.31; 95% confidence interval [CI]: 1.72-4.90; P < 0.001) and at the 48-week follow-up (least squares mean: 4.35; 95% CI: 2.76-5.94; P < 0.001). Significant reductions of N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24- and 48-week visits without difference between the two groups ( P > 0.1 for all), and 6.35% and 5.79% of patients in the CDDP and placebo groups experienced major adverse cardiovascular and cerebrovascular events, respectively ( P = 0.822). Therefore, no serious adverse events were attributed to CDDP. These findings sugget that CDDP was well tolerated and improved LVEF of patients with AAMI in 24 and 48 weeks.

Comparison of Catheter Ablation in Patients with Paroxysmal Non-valvular Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction.

Background: The efficacy of radiofrequency ablation (RFA) in patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) has been established, but the efficacy and safety of cryoballoon ablation (CBA) and pulsed field ablation (PFA) remain unclear. Methods: This retrospective cohort study included 223 patients with paroxysmal non-valvular AF and HFpEF who underwent their first AF ablation between January 2017 and December 2021 and were divided into RFA (n = 77), CBA (n = 127), and PFA (n = 19) groups. Results: After a mean follow-up of 11.2 ± 1.8 months, no significant differences were observed in the rates of AF recurrence among the groups (P = 0.964). Both RFA and PFA were associated with a reduction in left atrial diameter and an increase in left ventricular ejection fraction (LVEF), whereas CBA showed no significant changes. The New York Heart Association (NYHA) functional classification and quality of life scores significantly improved across all groups (P < 0.01). No significant differences in the incidence of postprocedural complications were observed. Multivariate Cox regression analysis identified serum albumin (ALB) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) as independent predictors of AF recurrence post-ablation. Conclusion: RFA, CBA, and PFA are all effective in maintaining sinus rhythm in patients with paroxysmal non-valvular AF and HFpEF. RFA and PFA were associated with improved quality of life, improved NYHA functional classification, reversal of atrial remodeling, and increased LVEF. While CBA improved quality of life and NYHA functional status, it did not reverse atrial remodeling or increase LVEF. ALB and NT-pro BNP levels were identified as independent predictors of AF recurrence post-ablation in HFpEF patients.

Comparison of clinical results between transpulmonary thermodilution monitoring and conventional methods in cardiac surgery: An observational study.

The Pulse Index Contour Continuous Cardiac Output (PICCO) module provides advanced and continuous monitoring of cardiac output through the use of arterial pulse contour analysis and transpulmonary thermodilution. The objective of this study was to compare the early postoperative outcomes of patients who were monitored using the conventional method and the pulse contour analysis method. A prospective observational study was conducted involving 45 patients who underwent cardiac surgery between 2020 and 2022. Patients were randomly assigned to either Group P (PICCO) or Group C (conventional). In the PICCO cohort, a femoral artery cannula was inserted for the continuous recording and management of hemodynamic data, in accordance with the decision-making algorithm of the module. In the conventional group, cannulation of the radial artery and jugular vein was performed. The postoperative hemodynamic and clinical data are subjected to analysis. The utilization of dopamine was markedly diminished in Group P at both the 0- and 6-hour postoperative intervals, whereas the administration of dobutamine was observed to be elevated (P = .008). The frequency of red packed cell transfusions was higher in Group C at postoperative hour 0. Hemodynamic data indicated a 42% increase in cardiac index and a 33% decrease in systemic vascular resistance, along with a 33% increase in global ejection fraction in patients monitored with PICCO. The mortality rates observed in the 2 groups were not statistically different. The implementation of advanced monitoring techniques, specifically the PICCO module, led to notable enhancements in hemodynamic parameters. The utilization of this technique may prove advantageous in guiding inotrope selection and transfusion decisions during the initial postoperative period. However, it is important to note that morbidity and mortality rates remain comparable.

An Alginate/Gelatin Injectable Hydrogel Containing Au Nanoparticles for Transplantation of Embryonic Mouse Cardiomyocytes in Myocardial Repair.

In advancing cardiac tissue engineering (CTE), the development of injectable hydrogels mirroring myocardial properties is pivotal. The designed hydrogels must not only support cardiac cell growth but also have to be conductive to properly promote the functionalities of cardiac cells. Here, a facile approach is developed to incorporate gold nanoparticles (AuNPs) into an injectable hydrogel composed of Alginate (Alg) and Gelatin (Gel). The resultant nanocomposite hydrogel boasts a porous interconnected network and superior conductivity (2.04 × 10-4 Scm-1) compared to the base Alg/Gel hydrogel. Hydrogel hydration and in vitro degradation profiles affirm their suitability as carriers for cardiac cells. Importantly, Alg/Gel+AuNPs hydrogels exhibit no toxicity to mouse Embryonic Cardiac Cells (mECCs) over 7 days, elevating connexin 43 (Cx43) and cardiac troponin T (CTnT) gene expression compared to controls. Then, the Alg/Gel+AuNPs hydrogel is used as a carrier for intramyocardial delivery of mECCs in rats with myocardial infarction. The significant increase in α-Smooth Muscle Actin (α-SMA) and cardiac troponin T (CTnT) expression along with the increase in ejection fraction (EF), smaller infarction size, less fibrosis area confirmed that the hydrogel efficiently promoted the transmission of mechanical and electrical signals between transplanted cells and surrounding tissue.

Low dose Adenoviral Vammin gene transfer induces myocardial angiogenesis and increases left ventricular ejection fraction in ischemic porcine heart

This preliminary study investigated if VEGFR-2 selective adenoviral Vammin (AdVammin) gene therapy could induce angiogenesis and increase perfusion in the healthy porcine myocardium. Also, we determined using a clinically relevant large animal model if AdVammin gene therapy could improve the function of a chronically ischemic heart. Low doses of AdVammin (dose range 2 × 109–2 × 1010 vp) gene transfers were performed into the porcine myocardium using an endovascular injection catheter. AdCMV was used as a control. The porcine model of chronic myocardial ischemia was used in the ischemic studies. The AdVammin enlarged the mean capillary area and stimulated pericyte coverage in the target area 6 days after the gene transfers. Using positron emission tomography 15O-radiowater imaging, we demonstrated that AdVammin gene therapy increased perfusion in healthy myocardium at rest. AdVammin treatment also increased ejection fraction at stress in the ischemic heart, as detected using left ventricular cine angiography. In addition, we demonstrated successful in vivo imaging of enhanced angiogenesis using [68Ga]NODAGA-RGD peptide. However, AdVammin also increased tissue permeability and was associated with significant pericardial fluid accumulation, limiting AdVammin’s therapeutic potential and emphasizing the importance of correct dosage.

TNF alpha Inhibitors in Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis.

Recent studies have focused on treating cardiac sarcoidosis (CS) with corticosteroids primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves tumor necrosis factor (TNF) alpha inhibitors. A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier's Science Direct databases to identify studies comparing TNF alpha inhibitors with other drugs in CS patients who had heart failure. The analyses were conducted using the random-effects model. The study's primary outcome is an increase in ejection fraction (EF), secondary outcomes include a reduction in the dose of prednisone at 6 and 12 months, maximum standardized uptake value by cardiac tissue, and fluorodeoxyglucose uptake by cardiac myocytes on positron emission tomography scan. The total number of pooled participants was 154 out of which 140 met the Heart Rhythm Society criteria for CS. The pooled analysis showed that treatment with the TNF alpha inhibitors was associated with a significant increase in EF [weighted mean difference (WMD), 46.272; 95% confidence interval (CI), 40.60-51.94, P < 0.001; I2, 75.74%], reduction in the dose of prednisone at 6 months (WMD, 9.20; 95% CI, 7.65-10.75; P < 0.001; I2, 13.33%) and at 12 months (WMD, 6.40; 95% CI, 4.74-8.07; P < 0.001; I2, 9.37%); decrease in myocardial maximum standardized uptake value (WMD, 1.99; 95% CI, 0.91-3.06; P < 0.001; I2: 97%) and reduction in fluorodeoxyglucose uptake by cardiac myocytes (WMD, 1.55; 95% CI, 1.09-2.00; P < 0.001; I2, 32.29) on positron emission tomography scans. The research findings suggest that TNF alpha inhibitors improve EF, reduce required steroid dosage, and improve clinical outcomes. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on patients with CS.

Catheter ablation for atrial tachycardia in pediatric patients: a single-center experience.

Atrial tachycardia is an uncommon supraventricular tachycardia in children. It is often drug-resistant and likely to occur concomitantly with tachycardia-induced cardiomyopathy, making radiofrequency catheter ablation the preferred treatment. The aim of this study was to assess the feasibility, safety, and effectiveness of radiofrequency catheter ablation for the treatment of different types of atrial tachycardia in children, particularly in those with drug-resistant and tachycardia-induced cardiomyopathy. A total of 28 children with atrial tachycardia (including focal atrial tachycardia and atrial flutter) who underwent atrial radiofrequency ablation at the Children's Hospital Affiliated to Chongqing Medical University from May 2018 to December 2023 were included. The baseline characteristics, preoperative medication, surgical information, and postoperative follow-up data of these children were analyzed statistically. The mean age patients at ablation was 10.24 ± 3.40 years. A total of 78.6% of the patients (22/28) who received preoperative pharmacological treatment had intermittent or persistent atrial tachycardia. Of the 28 children who underwent radiofrequency ablation, 24 (85.7%) were diagnosed with focal atrial tachycardia, three (10.7%) with atrial flutter, and one (3.6%) with both. No postoperative complications occurred in any patient. The immediate ablation success rate in the 25 patients with focal atrial tachycardia was 96.0% (24/25). After 26.89 ± 18.17 months of follow-up, only three patients had recurrence. The ablation difficulty of focal atrial tachycardia originating in the appendage was higher than that originating in the non-atrial appendage (44.4% vs. 6.3%, p = 0.01). The success rate of ablation for atrial flutter was 100%, except in one child with underlying cardiomyopathy who experienced recurrence. Final success was achieved in 25 of the 28 patients (89.2%) at the end of the follow-up period. In addition, eight children (28.6%) in this study were diagnosed with tachycardia-induced cardiomyopathy, with significantly increased ejection fraction and shortening rate after radiofrequency ablation (p < 0.01), whereas the left ventricular end-systolic diameter were not significantly reduced during the follow-up period (p > 0.05). Radiofrequency catheter ablation is safe and effective for the treatment of atrial tachycardia in children in the short- and long-term.It can be used as the first treatment option for children with medically refractory atrial tachycardia and tachycardia-induced cardiomyopathy.

THE EFFECT OF EMPAGLIFLOZIN AND RANOLAZINE ON THE DYNAMICS OF STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE HEART AND LEVELS OF BIOMARKERS NT-proBNP AND SOLUBLE (s)ST-2 IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE

Atrial fibrillation (AF) is the most common long-term arrhythmia worldwide and has a strong association with heart failure (HF).Aim. To investigate the effect of empagliflozin and ranolazine in addition to standard therapy on the dynamics of structural and functional parameters of the heart and levels of biomarkers NT-proBNP and soluble (s)ST-2 in patients with atrial fibrillation and heart failure.Materials and Methods. We examined 300 patients aged 45-65 years. All patients were divided into groups: Group I - patients with HF without AF (n=150). Group II - patients with HF and AF (permanent form) (n=150). Group of 136 practically healthy individuals. All patients underwent clinical examination, echocardiography (Echo), determination of NT-proBNP and (s)ST-2 levels by enzyme-linked immunosorbent assay.Results. The dynamics of parameters of the LV in the main group was more significant compared to the control group (p&lt;0.05). After treatment, the concentration of circulating NT-ProBNP in the control group decreased by an average of 26.2% (p&lt;0.05), and in the main group of patients - by 15.9% (p&lt;0.05). As for the blood levels of the (s)ST-2 biomarker, after treatment in the control group there was an average decrease of 13.1% (p&lt;0.05) compared with the dynamics in the main group of patients - by 38.8% (p&lt;0.05).Conclusions. The use of INSKTG-2 empagliflozin against the background of standard therapy of heart failure reduction of myocardial remodelling and increase ejection fraction. Complex treatment with empagliflozin and ranolazine as INZCTG-2 helps to reduce the level of NT-ProBNP and (s)ST-2 in the blood serum.

Elevated plasma progranulin levels in the acute phase are correlated with recovery of left ventricular function in the chronic phase in patients with acute myocardial infarction.

Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated. We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients. Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase. The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI.

Clinical Features and Outcomes of Pediatric MYH7-Related Dilated Cardiomyopathy.

Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

Horizontal QRS axis predicts response to cardiac resynchronization therapy in heart failure patients with left bundle branch block

Electrocardiogram criteria for left bundle branch block (LBBB) inadequately predict left ventricular electrical dyssynchrony, complicating cardiac resynchronization therapy (CRT) candidate selection. This study aimed to investigate the predictive value of the horizontal QRS axis for CRT response in heart failure (HF) patients with LBBB patterns. The direction and magnitude of the horizontal QRS axis were calculated using the net amplitudes in leads V2 and V6. CRT response was defined as a ≥10% increase in left ventricular ejection fraction and at least 1 New York Heart Association class reduction 1 year after CRT implantation. The composite end point included HF hospitalization or all-cause mortality. Of 244 consecutive CRT recipients, 156 (63.9%) responded favorably; 88 (36.1%) were nonresponders. The horizontal QRS axis demonstrated significant backward deviation (-75.5° [-79.7° to -69.0°] vs -65.0° [-73.0° to -46.5°]; P < .001) and larger magnitude (35.5 ± 10.9 mm vs 25.5 ± 10.5 mm; P < .001) in CRT responders compared with nonresponders. The direction and magnitude independently predicted CRT response with an area under the curve of 0.778 (95% confidence interval [CI], 0.717-0.839) and 0.749 (95% CI, 0.685-0.814), respectively. Combining both parameters increased the area under the curve to 0.814 (95% CI, 0.760-0.868). Moreover, the direction and magnitude of the horizontal QRS axis, or their combination, predicted the composite end point of HF hospitalization or all-cause mortality, with hazard ratios of 0.36 (95% CI, 0.22-0.60), 0.41 (95% CI, 0.25-0.67), and 0.25 (95% CI, 0.15-0.41), respectively. Horizontal QRS axis accurately predicts CRT response and prognosis in HF patients with LBBB.

Metabolome and microbiome analyses reveal the efficacy of Shen-Fu formula in treating heart failure.

Improvement of strategies to treat heart failure (HF) has been a longstanding global goal and challenge. Shen-Fu formula (SF), as a classic herbal preparation, has demonstrated efficacy in treating HF in clinical settings. However, further understanding of the therapeutic mechanisms of SF is required. In this study, metabolomics and 16S rDNA sequencing were used to analyze the effects of SF on metabolic profiling and gut microbiota in HF rats. After 4 weeks of SF treatment, the cardiac function of HF rats showed improvement, with a significant increase in ejection fraction and fractional shortening, as well as a significant decrease in left ventricular volume and mass. Metabolomics study revealed that SF regulates the levels of substances related to energy metabolism, primarily involving lysophosphatidylcholines and polyunsaturated fatty acids. In addition, we found that SF regulates the structure of the microbial community in HF rats and modulates the balance between probiotic and pathogenic bacteria. Furthermore, the SF combination exhibited a superior effect that was better than the use of each herb separately. These results demonstrate the potential of SF therapy in the management of HF and highlight the role of SF in regulating fatty acid metabolism and gut microbiome during HF.

LV reverse remodeling after SAVR in patients with severe symptomatic aortic stenosis: impact on the clinical outcome

Abstract Introduction Surgical aortic valve replacement (SAVR) is the treatment of choice for young patients with severe aortic stenosis (AS) and low surgical risk. Left ventricular (LV) reverse remodeling (RR) after surgery is expected to occur. However, this is not always the case following afterload relief, and this may impact the prognosis. We aimed to assess the prognostic effect of distinct definitions of LV RR after SAVR in the long-term outcome of patients with severe AS. Methods Single-centre prospective study including patients referred for SAVR due to severe symptomatic AS, with no previous history of ischemic cardiomyopathy. Both pre- and post-operative transthoracic echocardiographic (TTE) and cardiac magnetic resonance (CMR) study (at the 3rd to 6th month after SAVR) were performed. LV RR was defined when in presence of at least one of the imaging criteria: &amp;gt;15% decrease in end-diastolic volume (EDV) by CMR; &amp;gt;15% decrease in LV indexed mass (LVM) by CMR; &amp;gt;10% decrease in geometric remodeling (LV mass/EDV ratio) by CMR; &amp;gt;10% increase in LV ejection fraction (LVEF) by CMR; &amp;gt;50% increase on global longitudinal strain (GLS) by TTE. We assess the prognostic value of RR definitions for the outcome after SAVR using Cox regression and Kaplan-Meier analysis. The primary endpoint was defined as all-cause mortality, heart failure (HF) hospitalization or worsening HF. Results We enrolled 140 patients – mean age 71±9 years-old, 49% male, predominantly high-gradient-normal flow AS (mean gradient 65±18mmHg, aortic valve area 0.7±0.2cm2, index stroke volume 47±11mL/m2) submitted to SAVR. At a mean follow-up (FUP) of 34±12 months, 23 (16%) patients met the primary endpoint: 4% (5 patients) died immediately after surgery; three patients died at the FUP (overall mortality rate of 6%). 12 patients (9%) were admitted for HF and 7 (5%) had at least one episode of worsening HF. 118 patients had complete pre and post-surgery imaging study (mean FUP: 36±10 months): 103 patients (87%) had at least one RR parameter (Table 1). Post-operative RR was not independently associated with the clinical outcome (Figure 1A). LVM was the sole independent predictor of the outcome at univariate analysis (Figure 1B–F). Conclusions LV RR after SAVR is highly prevalent in a cohort of patients with classical severe symptomatic AS. However, only LVM regression independently predicts the clinical outcome after surgery. This may stand the greater importance of structural reverse remodeling, rather than LV functional improvement, after pressure overload relief.