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Objective: To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals. Methods: The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H2O2, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts. Results: PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01). Conclusion: This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine. [ABSTRACT FROM AUTHOR]

Background: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. Methods: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). Results: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60–8.94); p = 0.003; univariate analysis] and [3.30 (1.11–9.82); p = 0.03]; multivariate logistic regression]. Conclusions: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses. [ABSTRACT FROM AUTHOR]

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Objective: Despite its widespread use and safety data, the cardiac safety of lamotrigine was brought into question in October 2020 when the U.S. Food and Drug Administration issued a safety warning about its cardiac side effects. Here, we investigated whether there are differences in electrocardiogram (ECG) findings between epilepsy cases receiving lamotrigine monotherapy and those receiving duotherapy. Methods: Patients older than 16 years who were followed up with a diagnosis of epilepsy and receiving lamotrigine were retrospectively identified. Those receiving only lamotrigine and any second anti-seizure medication (ASM) in addition to lamotrigine were included in the study, and those receiving more than two ASMs were excluded. Eligible patients were asked to apply to any health institution and have an ECG performed. Heart rate, PR distance, QRS duration, QT duration, corrected QT value, and Tp-Tend value were calculated manually, and ST-T changes were evaluated. Comparisons were made between patients receiving monotherapy and dootherapy and those receiving low-dose and high-dose lamotrigine. Results: There were 19 patients receiving monotherapy and 11 receiving duotherapy. The ECG parameters of all other patients were within normal values. When ECG parameters were compared between patients receiving monotherapy and those receiving duotherapy, no significant differences were found in heart rate, PR distance, QRS duration, QT duration, QTc duration, Tp-Tend duration, and presence of ST-T changes. When the patients were divided into low-dose and high-dose lamotrigine groups, there were no significant differences in the ECG parameters between these two groups. Conclusion: The relationship between the use of lamotrigine and cardiac conduction problems in patients with epilepsy has attracted the attention of physicians since its introduction into clinical practice. Although our results did not indicate a significant relationship, there is still a need to determine the risk groups and clarify the pathophysiology of lamotrigine-related arrhythmia through genotype- and phenotype-related studies. [ABSTRACT FROM AUTHOR]

Mexiletine, a class Ib antiarrhythmic drug, exhibits its major antiarrhythmic effect via inhibition of the fast and late Na+ currents in myocardial tissues that are dependent on the opening of Na+ channels for their excitation. Through a comprehensive examination of mexiletine's therapeutic benefits and potential risks, we aim to provide valuable insights that reinforce its role as a vital therapeutic option for patients with ventricular arrhythmias, long QT syndrome, and other heart rhythm disorders. This review will highlight the current understandings of the antiarrhythmic effects and rationales for recent off‐label use and address the mortality and proarrhythmic effects of mexiletine utilizing published basic and clinical studies over the past five decades. [ABSTRACT FROM AUTHOR]

Background. In the present work, we investigated the effect of exogenous glutathione in old rats on the expression of ATP-sensitive potassium (KATP) channels, the mitochondrial permeability transition pore (mPTP) opening in the heart, and the vasorelaxation responses of isolated aortic rings to activation of KATP channels. Methods. Experiments were performed on adult (6 months) and old (24 months) male Wistar rats, which were divided into three groups: adult, old, and glutathione-treated old rats. Glutathione was injected intraperitoneally at a dose of 52 mg/kg 1 hour before the studies. The mRNA expression of KATP channels was determined using reverse transcription and real-time polymerase chain reaction analysis. The effect of glutathione administration on mPTP opening, relaxation responses of isolated aortic rings, and oxidative stress markers was studied. Results. It was shown that the expression levels of Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and levels of reduced glutathione were significantly increased in glutathione-treated old rats (by 8.3, 2.8, 13.1, and 1.5-fold, respectively), whereas the levels of oxidative stress markers (hydrogen peroxide, diene conjugates, malondialdehyde, and rate of superoxide generation) in heart mitochondria and mPTP opening were significantly reduced. Relaxation of aortic rings was significantly increased in response to the actions of KATP channel openers flocalin and pinacidil in glutathione-treated animals, which was prevented by glibenclamide. Conclusions. Thus, the administration of exogenous glutathione to old rats resulted in a significant increase in the expression levels of the Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and a decrease in oxidative stress. This was accompanied by inhibition of mPTP opening and enhancement of vasorelaxation responses to activation of KATP channels. [ABSTRACT FROM AUTHOR]

Objective: Cardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4. Methods: CRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining. Results: PNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05). Conclusion: PNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4. Highlights: PNS improved cardiac function and suppressed pyroptosis in CRS4 rats. PNS inhibited cardiomyocyte injury and NLRP3 inflammasome-mediated pyroptosis. PNS inhibited cardiomyocyte pyroptosis by downregulating lncRNA-ANRIL. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease remains the leading cause of death worldwide and brings a heavy burden. However, the development of cardiovascular drug clinical trials in China remains unclear. The purpose of this study was to identify the status of clinical trials of cardiovascular drugs in China and provide a reference for stakeholders' decisions. Methods: Data were collected from the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Trials before July 1, 2021. We collected all information about clinical trials, including study design, and leading unit. The landscape of cardiovascular drug clinical trials was analyzed by the characteristics, time trends, indications, and geographical distribution. Results: A total of 1666 cardiovascular drug clinical trials were launched from 2009 to 2021 in China. Bioequivalence/bioavailability studies accounted for the most significant proportion (1099 [65.97%]), followed by phase I (296 [17.77%]), phase III (135 [8.10%]), phase II (118 [7.08%]), and phase IV trials (18 [1.08%]). Initiated trials increased by 23.45% annually from 2009 to 2020. Trials of hypertension accounted for the most significant number, followed by coronary heart disease, dyslipidemia, and heart failure. Most trials (66.68%) were conducted in eastern China, followed by the central and western regions, showing a regional disparity as leading units. Conclusion: Despite the significant progress of cardiovascular drug clinical trials in China, there is still a long way to innovative drug research and development, requiring persistent policy support and more investment. Innovation, quality, efficiency, and equity need to be carefully considered by all stakeholders in clinical trials. [ABSTRACT FROM AUTHOR]

During menopause, the sharp decline in estrogen levels leads to an increased risk of cardiovascular disease in women. The inflammatory response and oxidative stress are reportedly involved in the development of cardiovascular disorders postmenopause. In this study, we evaluated the cardioprotective effects of puerarin, a phytoestrogen derived from the root of Pueraria lobate, and investigated its underlying molecular mechanisms. Puerarin alleviated cytotoxicity and the production of reactive oxygen species (ROS) in lipopolysaccharide (LPS)- and hydrogen peroxide-stimulated H9c2 cardiomyoblasts. Puerarin scavenges free radicals and reduces apoptosis, thereby suppressing NADPH oxidase-1 and Bax activation to attenuate the production of ROS and restore Bcl-2 expression. Additionally, puerarin inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nitric oxide production and decreased the hypertrophic phenotype under LPS stimulation. Treatment with puerarin reduced the levels of malondialdehyde and restored glutathione levels when facing oxidative stress. Mechanistically, puerarin inhibited both the LPS-induced Toll-like receptor 4/NF- κ B and mitogen-activated protein kinase signaling pathways. Furthermore, it reversed both the LPS-mediated downregulation of Akt activation and heme oxygenase-1 (HO-1) expression. The cardioprotective effects of puerarin were abolished by inhibitors of Akt and HO-1 and the estrogen receptor antagonist fulvestrant (ICI). This indicated that the estrogen receptor mediated by these two molecules plays important roles in conferring the anti-inflammatory and anti-oxidative functions of puerarin. These results demonstrate the therapeutic potential of puerarin for treating heart disease in postmenopausal women through Akt and HO-1 activation. [ABSTRACT FROM AUTHOR]

Cardio-oncology is a subspecialty that provides cardiac care for patients with cancer. Newer oncological agents have not only increased survivorship, but also sprouted novel cardiovascular toxicity (CVT) involving any component of the cardiovascular system, albeit with some preferential targets. Patients with cancer should undergo a baseline cardiovascular risk assessment and have individualised surveillance planned during cancer therapy and post treatment. The early diagnosis of CVT, by clinical history and examination along with imaging and laboratory analysis, is paramount. Management includes cardioprotective strategies and multidisciplinary decision-making regarding the risk--benefit ratio of oncological treatment based on CVT. [ABSTRACT FROM AUTHOR]

Codonopsis Radix , commonly known as Dangshen in Chinese, is frequently used to treat deficiencies of spleen and lung Qi, gastrointestinal discomfort, fatigue, asthmatic breathing, sallow complexion, lack of strength, shortness of breath, deficiencies of both Qi and blood, as well as impairments to both Qi and body fluids in suboptimal health status. This review systematically expounds on the modern pharmacological studies related to the use of Codonopsis Radix in invigorating Qi and nourishing the body in recent years. The aim is to provide theoretical research and reference for the in-depth and systematic exploration and development of the applications of Codonopsis Radix in the fields of food and medicine. This study employs " Codonopsis Radix ," " Codonopsis ," and "Dangshen" as keywords to gather pertinent information on Codonopsis Radix medicine through electronic searches of classical literature and databases such as PubMed, Elsevier, Google Scholar, Wiley, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Baidu Scholar. From previous studies, activities such as immune system modulation, gastrointestinal motility regulation, cardiac function revitalization, lung function improvement, blood circulation enhancement, aging process deceleration, learning and memory augmentation, fatigue resistance enhancement, and liver and kidney damage protection of Codonopsis Radix have been reported. Recognized as an important medicine and food homologous traditional Chinese herbal remedy for supplementing deficiencies, its mode of action is multi-elemental, multi-systemic, multi-organ, multi-mechanistic, and multi-targeted. Furthermore, the benefits of its tonic surpass its therapeutic value, establishing it as an extraordinary preventive and therapeutic medicine. With its long history of traditional applications and the revelations of contemporary pharmacological research, Codonopsis Radix exhibits great potential as both a therapeutic agent and a dietary supplement for further research in medicine, nutrition, and healthcare. [Display omitted] • Codonopsis Radix (CR): A food-medicine homology and immune booster for all ages. • CR's dual-use in medicine and food enhances body systems via multiple paths. • CR: Potential treatment for heart disease, COPD, Alzheimer's, and more. • CR improves spleen, gut flora, potentially treating spleen-stomach issues. • CR displays anti-inflammatory, antioxidant, anti-aging and neuroprotective properties. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of Shenfu Injection (参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance (LC) in patients with post cardiac arrest syndrome (PCAS). Methods: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group (486 cases) and SFI (492 cases) group, receiving standardized post-resuscitation care bundle (PRCB) treatment or PRCB combined with SFI (100 mL/d), respectively. Patients' serum lactate was measured simultaneously with artery blood gas, lactate clearance (LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. Results: In both groups, compared with pre-treatment levels, mean arterial pressure (MAP) and PaO2 were significantly improved on 1, 3, 7 d after treatment (P<0.05), while heart rate (HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment (P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO2 (P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment (P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d (P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group (P<0.05). Compared with survivors, non-survivors had higher admission lactate levels (7.3 ±1.1 mmol/L vs. 5.5 ±2.3 mmol/L; P<0.01), higher lactate levels on days 1, 3 and 7 (P<0.05), and LC were decreased significantly on 3 and 7 d after treatment (P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. Conclusion: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients. [ABSTRACT FROM AUTHOR]

Objective. To analyze and evaluate the effectiveness of traditional Chinese medicine decoction (TCMD) in the treatment of cardiac neurosis (CN) complicated with depression and anxiety. Methods. Relevant literature on TCMD in the treatment of CN complicated with depression and anxiety was retrieved from Chinese and English databases, and the retrieved literature was included and excluded. The quality of the retrieved literature was evaluated according to the Cochrane system, and the meta-analysis was undertaken with RevMan5.3 software. Results. A total of 10 papers were included, including 686 patients and 349 patients in the treatment group (131 males and 218 females), and there were 337 cases in the control group (131 males and 206 females). The results of the meta-analysis showed that compared with the control group, TCMD could significantly improve palpitation (MD = 0.78, 95% CI = 0.55–1.01, P < 0.00001), chest tightness/chest pain (MD = 0.53, 95% CI = 0.10–0.97, P < 0.05), shortness of breath (MD = 0.60, 95% CI = 0.26–0.93, P = 0.0005), and TCM syndrome score (MD = 5.91, 95% CI = 4.32–7.49, P < 0.00001), reduce resting heart rate (MD = 13.21, 95% CI = 9.01–17.40, P < 0.00001), and could reduce psychological scale scores, such as Zung's self-rating Depression Scale (MD = 7.90, 95% CI = 4.98–10.83, P < 0.00001), Zung's self-rating Anxiety Scale (MD = 6.55, 95% CI = 4.25–8.86, P < 0.00001), Hamilton Depression Scale (MD = 4.46, 95% CI = 3.00–5.92, P < 0.00001), and Hamilton Anxiety Scale (MD = 3.35, 95% CI = 1.85–4.85, P < 0.0001). The differences were statistically significant. Tonic drugs were commonly used; Angelica sinensis, Poria cocos, Polygala tenuifolia, Wild jujube kernel, and Bupleurum were the most frequently used traditional Chinese medicines. Conclusion. TCMD mainly composed of tonic and tranquilizing herbs could significantly improve the clinical symptoms of patients with CN and reduce heart rate, anxiety, and depression scores. However, the evidence grade of the clinical research was limited by the quality of the included literature, and more high-quality clinical trials are still needed for further verification. This trial was registered with PROSPERO: CRD42022312164 [ABSTRACT FROM AUTHOR]

Background: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.Objectives: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.Methods: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.Results: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.Conclusions: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082). [ABSTRACT FROM AUTHOR]

Left ventricular (LV) thrombus is a potentially serious complication affecting males and females with ischemic and nonischemic cardiomyopathy-specifically, after acute myocardial infarctions of the anterior left ventricular wall and long-standing tachyarrhythmias, respectively. LV thrombi pose significant risks for systemic embolization and devastating stroke events, while also demanding a treatment carrying inherent risks of its own. It is therefore imperative to have accurate detection of these ventricular thrombi and an appropriate understanding of the risks and benefits regarding management. Anticoagulation using warfarin has long been established as the gold-standard level of care in the current guidelines of the American College of Cardiology but the advent of direct oral anticoagulants (DOACs) prompts a re-examination of the literature. The particular question we seek to answer lies in the efficacy of these drugs and the safety and outcomes when used to treat LV thrombi. Recent case reports, meta-analyses, and most recently, the breakthrough of 2 novel randomized controlled trials have shown DOACs to be a promising treatment for LV thrombus. Contrarily, some retrospective cohort reviews suggest less-than-promising outcomes. This meta-analysis hopes to provide a current, curated review of up-to-date safety and efficacy in the documented tales of DOACs and LV thrombi that has been published since early 2020-by selecting these curated case studies, and analyzing the most recent randomized controlled trials, we hope to engage the reader with clearer illustrations of the key components of both the advocacy and warning of this pharmaceutical intervention. [ABSTRACT FROM AUTHOR]

Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP). Methods: The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated. Results: AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05). Conclusions: AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients. [ABSTRACT FROM AUTHOR]

Background: Pleuroparenchymal fibroelastosis (PPFE) has a variable disease course with dismal prognosis in the majority of patients with no validated drug therapy. This study is to evaluate the effect of nintedanib in patients with idiopathic and secondary PPFE. Patients admitted to a tertiary care center (2010-2019) were included into this retrospective analysis if they had a multidisciplinary diagnosis of PPFE, had been followed-up for 3 months or more, and had lung function tests and chest CTs available for review. Changes in pulmonary function tests were assessed using non-parametric tests and linear mixed effect model. Lung volumes were measured with lobar segmentation using chest CT.Results: Out of 21 patients with PPFE, nine had received nintedanib, six had received another treatment and another six patients were monitored without drug therapy. Annual FVC (% of predicted) relative decline was - 13.6 ± 13.4%/year before nintedanib and - 1.6 ± 6.02%/year during nintedanib treatment (p = 0.014), whereas no significant change in FVC% relative decline was found in patients receiving another treatment (- 13.25 ± 34 before vs - 16.61 ± 36.2%/year during treatment; p = 0.343). Using linear mixed effect model, the slope in FVC was - 0.97%/month (95% CI: - 1.42; - 0.52) before treatment and - 0.50%/month (95% CI: - 0.88; 0.13) on nintedanib, with a difference between groups of + 0.47%/month (95% CI: 0.16; 0.78), p = 0.004. The decline in the upper lung volumes measured by CT was - 233 mL/year ± 387 mL/year before nintedanib and - 149 mL/year ± 173 mL/year on nintedanib (p = 0.327). Nintedanib tolerability was unremarkable.Conclusion: In patients with PPFE, nintedanib treatment might be associated with slower decline in lung function, paving the way for prospective, controlled studies. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI.Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments.Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment.Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02610283. [ABSTRACT FROM AUTHOR]

Background: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with reduced ejection fraction. Its interplay with systolic blood pressure (SBP) is not known.Objectives: The goal of this study was to evaluate the interplay of SBP and the effects of empagliflozin in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).Methods: Study patients (N = 3,730) were randomly assigned to groups according to SBP at baseline (<110 mm Hg, n = 928; 110-130 mm Hg, n = 1,755; >130 mm Hg, n = 1,047). This study explored the influence of SBP on the effects of empagliflozin on cardiovascular death or HF hospitalization (primary outcome), as well as on total HF hospitalizations, rate of decline in estimated glomerular filtration rate, renal outcomes, and empagliflozin's effects and significance on SBP.Results: Over a median of 16 months considering only patients receiving placebo, baseline SBP and the risk of cardiovascular death or hospitalization for HF (P trend = 0.0015) were inversely related. Corrected for placebo, a slight early increase was observed in SBP at <110 mm Hg, no change at 110-130 mm Hg, and a slight reduction at >130 mm Hg. These between-group differences were of borderline significance (P for interaction trend = 0.05-0.10) after 4 and 12 weeks but were not significant later. SBP at baseline did not influence the effect of empagliflozin to reduce the risk of HF events or renal endpoints. When treated with empagliflozin, patients with SBP <110 mm Hg did not have an increased rate of symptomatic hypotension.Conclusions: Empagliflozin was effective and safe, with no meaningful interaction between SBP and the effects of empagliflozin in the EMPEROR-Reduced trial. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977). [ABSTRACT FROM AUTHOR]

Background: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported.Objectives: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).Methods: Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP.Results: Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs <1,115 pg/mL). Study participants with higher NT-proBNP had 2- to 3-fold total hospitalizations higher than the lowest NT-proBNP quartile. Empagliflozin reduced risk for major cardiorenal events without heterogeneity across NT-proBNP quartiles (primary endpoint Pinteraction = 0.94; renal composite endpoint Pinteraction = 0.71). Empagliflozin treatment significantly reduced NT-proBNP at all timepoints examined; by 52 weeks, the adjusted mean difference from placebo was 13% (P < 0.001). An NT-proBNP in the lowest quartile (<1,115 pg/mL) 12 weeks after randomization was associated with lower risk for subsequent cardiovascular death or heart failure hospitalization regardless of baseline concentration. Treatment with empagliflozin resulted in 27% higher adjusted odds of an NT-proBNP concentration of <1,115 pg/mL by 12 weeks compared with placebo (P = 0.01).Conclusions: In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977). [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF), as a serious health condition, is characterised by the decreasing ability of the heart to pump enough blood around the body. This study compared the effects of spironolactone and eplerenone on the echocardiographic variables of the left ventricular (LV) function in symptomatic patients diagnosed with new-onset systolic HF.Method: This study was a randomised controlled trial, including 85 symptomatic patients with new-onset systolic HF (namely, dilated cardiomyopathy). The patients were then randomly assigned to two groups in a 1:1 ratio and received either spironolactone or eplerenone in addition to optimal HF therapy for 6 months. Echocardiography was performed to visualise alterations in two-dimensional, pulse Doppler, tissue Doppler, and deformation indices of LV function.Results: The results revealed that the group receiving eplerenone had a significantly greater increase in LV ejection fraction (LVEF) and a decrease in end-systolic LV internal diameter compared with the group receiving spironolactone (intergroup p=0.002 and p=0.006, respectively). There was a significant reduction in the end-diastolic LV internal diameter and the left atrial diameter, and a significant rise in tissue Doppler peak systolic mitral annular velocity in the group taking eplerenone; there were no significant changes in these variables in the group receiving spironolactone (intergroup p=0.006 and p=0.049, respectively). Accordingly, eplerenone had greater favourable effects on LVEF and the global longitudinal strain than spironolactone (B=5.207 [p<0.001] and B= -2.072 [p=0.044]), respectively.Conclusions: This study established that adding eplerenone to optimal HF therapy might be associated with more improvements in echocardiographic variables of LV function than spironolactone in symptomatic patients with new-onset systolic HF. [ABSTRACT FROM AUTHOR]

Tournefortia sarmentosa is a traditional Chinese medicine used to reduce tissue swelling, to exert the antioxidant effect, and to detoxify tissue. T. sarmentosa is also used to promote development in children and treat heart dysfunction. However, many of the mechanisms underlying the effects of T. sarmentosa in the treatment of disease remain unexplored. In this study, we investigated the antioxidant effect of T. sarmentosa on rat H9c2 cardiomyocytes treated with hydrogen peroxide (H2O2). T. sarmentosa reduced the cell death induced by H2O2. T. sarmentosa inhibited H2O2-induced changes in cell morphology, activation of cell death-related caspases, and production of reactive oxygen species. In addition, we further analyzed the potential active components of T. sarmentosa and found that the compounds present in the T. sarmentosa extract, including caffeic acid, rosmarinic acid, salvianolic acid A, and salvianolic acid B, exert effects similar to those of the T. sarmentosa extract in inhibiting H2O2-induced H9c2 cell death. Therefore, according to the results of this study, the ability of the T. sarmentosa extract to treat heart disease may be related to its antioxidant activity and its ability to reduce the cellular damage caused by free radicals. [ABSTRACT FROM AUTHOR]

New recommendations call for lowering LDL-C < 55 mg/dL and non-HDL-C < 85 mg/dL in very-high cardiovascular risk (VH-CVR) patients with type 2 diabetes (T2DM). This study assessed the proportion of VH-CVR diabetics currently meeting these primary and secondary lipid targets, and which therapies/phenotypes predict combined goals achievement. We analysed the cardiometabolic phenotype, use of lipid-modulatind drugs (LMD), pre- and post-LMD lipids levels, and CV complications among 1196 T2DM with high (n = 221; 18%) or VH-CVR (n = 975; 82%). Among the latter, the characteristics of combined lipid goal-achievers (n = 158) were compared to those of non-achievers (n = 817), with subgroup analyses of on-statin patients (n = 732) and those with established CVD taking statins (n = 362). Presence of statin-associated muscle symptoms (SAMS) was also recorded. 75% of VH-CVR patients were on statins. Both LDL-C and non-HDL-C goals were achieved by 16.2% of all VH-CVR, 19.3% of on-statin VH-CVR, and 24.3% of patients with established CVD taking statins. Achieving both targets was associated with high-intensity statins, specifically rosuvastatin, [statin + ezetimibe] combination, lower baseline LDL-C, smaller LDLs, lower TG and lipoprotein(a), and reduced metabolic syndrome frequency. SAMS reporting did not differ between achievers and non-achievers. More than 80% of patients are above targets. To bridge this gap, apart from treating more LMD-naive/refractory diabetics, one should consider for LDL-C to put most patients on high-intensity statins, more often with ezetimibe and, within statins, to switch preferably to rosuvastatin. As regards non-HDL-C, the off-target patients' phenotype suggests that intensifying lifestyle measures against metabolic syndrome should supplement current therapies. [ABSTRACT FROM AUTHOR]

Previous studies have found that Salvia miltiorrhiza (SM) injection have a protective effect on the iron overloaded (IO) heart. However, the mechanisms are not completely known. In the present study, we investigated the underlying mechanisms based on the iron transport-related proteins. The rats were randomly divided into five groups: control, IO group, low-dose SM group, high-dose SM group, and deferoxamine control group. Iron dextran was injected to establish the IO model. After 14 days of treatment, cardiac histological changes were observed by hematoxylin and eosin (H&E) staining. Iron uptake-related proteins divalent metal transporter-1 (DMT-1), transferrin receptor-1 (TfR-1), and iron export-related proteins ferroportin1 (FP1) in the heart were detected by Western blotting. The results showed that SM injection decreased cardiac iron deposition, ameliorated cardiac function, and inhibited cardiac oxidation. Most important of all, SM injection downregulated the expression of DMT-1 and TfR-1 and upregulated FP1 protein levels compared with the IO group. Our results indicated that reducing cardiac iron uptake and increasing iron excretion may be one of the important mechanisms of SM injection reducing cardiac iron deposition and improving cardiac function under the conditions of IO. [ABSTRACT FROM AUTHOR]

Described as the 'single largest unmet need in cardiovascular medicine', heart failure with preserved ejection fraction (HFpEF) remains an untreatable disease currently representing 65% of new heart failure diagnoses. HFpEF is more frequent among women and associates with a poor prognosis and unsustainable healthcare costs. Moreover, the variability in HFpEF phenotypes amplifies complexity and difficulties in the approach. In this perspective, unveiling novel molecular targets is imperative. Epigenetic modifications—defined as changes of DNA, histones, and non-coding RNAs (ncRNAs)—represent a molecular framework through which the environment modulates gene expression. Epigenetic signals acquired over the lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative stress, inflammation, dysmetabolism, and maladaptive left ventricular remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, and machine learning have enabled the identification of reliable epigenetic biomarkers in cardiovascular patients. Contrary to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNAs biology has led to the development of several Food and Drug Administration approved 'epidrugs' (chromatin modifiers, mimics, anti-miRs) able to prevent transcriptional alterations underpinning left ventricular remodelling and HFpEF. In the present review, we discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF. [ABSTRACT FROM AUTHOR]

Introduction: A multinational post-authorization safety study assessed cardiovascular safety in initiators of prucalopride for chronic constipation compared with a matched cohort of polyethylene glycol 3350 initiators. The primary safety outcome was major adverse cardiovascular events (MACE), a composite of hospitalization for acute myocardial infarction, stroke, or in-hospital cardiovascular death. We report the validation process for MACE endpoints in United Kingdom (UK) data sources: Clinical Practice Research Datalink (CPRD GOLD), The Health Improvement Network (THIN), and the Information Services Division (ISD) Scotland. Methods: Modified electronic algorithms from prior research identified potential MACE cases. Validation followed a common protocol, adapted for each database, with all information anonymized: (1) direct confirmation via linkage to hospital records (CPRD GOLD); (2) requests for additional clinical information through questionnaires (CPRD GOLD), free-text (THIN), or abstraction of hospital records (ISD); (3) manual review of electronic records of potential events retrieved by the algorithm (CPRD GOLD/THIN); and (4) event adjudication by three clinicians, blinded to exposure, for all remaining events. Results: Electronic algorithms identified 260 potential MACE cases: 38 confirmed via linkage to hospital records (CPRD GOLD), 56 ruled out as non-cardiovascular death cases (THIN), and three unavailable for review (ISD), leaving 163 potential cases. After manual review with additional information (steps 2 and 3), 45 were considered noncases (CPRD GOLD/THIN). Upon final adjudication (step 4), remaining potential events were adjudicated as definite (n = 62), probable (n = 10), possible (n = 13), or noncases (n = 33). Conclusions: Given the limitations of relying solely on computer algorithms to identify cardiovascular outcomes, validation with clinical review is essential to guide interpretation. [ABSTRACT FROM AUTHOR]

Background: One of the diagnostic criteria of low cardiac output syndrome (LOS) is a cardiac index of less than 1.8 l/min/m2. However, recognition of this syndrome differs among intensivists as to whether or not LOS is synonymous with cardiogenic shock. Case reports: Here, we present two cases of heart failure who were initially treated with diuretics and subsequently fell into a state of low cardiac output. We treated the patient with low blood pressure with inotropes and the patient with high blood pressure with a vasodilator according to their hemodynamics. We observed that cardiac power was the most significant hemodynamic change in response to these treatments. In this paper, we discuss the definition of LOS and show several criteria for determining LOS. Conclusions: Broadly, there are several conditions of determining LOS. Even with those conditions, we should still be aware of the pathophysiology of each patient with heart failure. We propose that the definition of LOS should be a state of low cardiac output with corresponding symptoms, even if their blood pressure is high. [ABSTRACT FROM AUTHOR]

Background: Prophylactic milrinone is commonly used to prevent Low Cardiac Output Syndrome (LCOS) after pediatric cardiac surgery. This study compares the use of levosimendan with milrinone when used as the primary inotrope following pediatric cardiac surgery. Subjects and Methods: Forty infants undergoing corrective surgery for congenital heart disease were recruited during the study and randomized into two groups (group L and group M). During rewarming, a loading dose of levosimendan or milrinone was administered followed by a 24-hour infusion of the chosen inotrope. Echocardiographic variables were measured postoperatively. Statistical analysis was done with SPSS-20 computer package. Association between the variables was found by independent t test. P < 0.05 was considered statistically significant. Results: Mean age and weight of the patient in Group L was 8.55 ± 5.83 months and 6.05 ± 2.09 kgs, while that in group M was 6.85 ± 3.57 months and 5.26 ± 2.11 kgs. 4 patients (20%) treated with levosimendan had LCOS in comparison with 6 (30%) patients in those treated with milrinone. Echocardiographic parameters in both groups L and M were comparable (cardiac index 3.47 ± 0.76 vs 3.72 ± 1.05 L/min/m², EF 66.10 ± 7.82% vs 59.34 ± 10.74%, stroke volume index 25.4 ± 6.3 vs 27.74 ± 10.35 mL/m²). The duration of ventilation, ICU stay and hospital stay were lesser in group L (12.75 ± 9.69, 35.95 ± 12.11, 119.10 ± 46.397 vs 23.60 ± 22.03, 51.20 ± 29.92, 140.20 ± 52.65 hours). Conclusions: The incidence of LCOS was lesser in those patients treated with levosimendan, when compared with those treated with milrinone. Cardiac index and stroke volume index were comparable between the two groups. Thus, levosimendan provides a non-inferior alternative to milrinone when used as the primary inotrope following pediatric cardiac surgery. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of bempedoic acid for low-density lipoprotein cholesterol (LDL-C) reduction. Data Sources: A PubMed search was conducted from January 2000 to June 15, 2020, using the keyword bempedoic acid for phase III clinical trials published in the English language. Study Selection and Data Extraction: Articles related to the Food and Drug Administration (FDA) approval of bempedoic acid and other trials relating to the safety and efficacy of this drug were included. Data Synthesis: The findings from this review show that bempedoic acid is a safe and effective option for lowering LDL-C levels in patients requiring LDL-C lowering for primary or secondary prevention of cardiovascular events. Relevance to Patient Care and Clinical Practice: Statin therapy remains the mainstay of treatment for both primary and secondary prevention. However, many patients cannot tolerate statin therapy because of statin-associated muscle symptoms. Bempedoic acid may be a reasonable adjunct for LDL-C reduction, though further evaluation of cardiovascular outcomes with bempedoic acid in this population is needed. Conclusions: The recent FDA approval of bempedoic acid offers an additional option for lowering LDL-C levels in patients with atherosclerotic cardiovascular disease or heterozygous familial hyperlipidemia. Additional data regarding effect on long-term cardiovascular outcomes with bempedoic acid are currently being studied. [ABSTRACT FROM AUTHOR]

Lily disease was first recorded in Synopsis of the Golden Chamber by Zhang Zhongjing. It is a disease of heart and lung internal heat by Yin deficiency, which belongs to the category of emotion disease in Chinese medicine. In recent years, researchers believe that lily disease and depression syndrome of Yin deficiency and internal heat have many similarities in etiology, pathogenesis, and clinical manifestations. This review summarizes the clinical symptoms, etiology, pathogenesis, and therapeutic medication of lily disease and modern Yin-deficient internal heat depression and discusses the relationship between them. Furthermore, the relationship between coronavirus disease 2019 (COVID-19) and lily disease was discussed from the etiology, pathogenesis, and treatment. It provides new ideas for the treatment of COVID-19 and the treatment of psychological problems after recovery. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a risk factor for cardiac damage and cardiovascular disease. Increasing evidence has shown that dyslipidemia-related cardiac damage is associated with lipid accumulation, oxidative stress, and inflammation. Thymoquinone (TQ) is the major constituent of Nigella sativa, commonly known as black seed or black cumin, and is globally used in folk (herbal) medicine for treating and preventing a number of diseases and conditions. Several studies have shown that TQ can protect against cardiac damage. This study is aimed at investigating the possible protective effects of TQ on hyperlipidemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R-/-) mice. Eight-week-old male LDL-R-/- mice were randomly divided into normal diet (ND), high-fat diet (HFD), and HFD and TQ (HFD+TQ) groups and were fed the different diets for eight weeks. Blood samples were obtained from the inferior vena cava in serum tubes and stored at -80°C until use. Some cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap-frozen in liquid nitrogen for mRNA preparation or immunoblotting. The levels of metabolism-related factors, such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP), were decreased in the HFD+TQ group compared with those in the HFD group. Periodic acid-Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than in the HFD group. The expression of pyroptosis indicators (NOD-like receptor 3 (NLRP3), interleukin- (IL-) 1β, IL-18, and caspase-1), proinflammatory factors (IL-6 and tumor necrosis factor alpha (TNF-α)), and macrophage markers (cluster of differentiation (CD) 68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group. Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipidemia-induced cardiac damage. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (SC) is reported to improve myocardial ischemia. Velocity vector imaging (VVI) is a noninvasive technique for evaluating myocardial function in humans, while few reported on the application in animals. In this study, we aimed to evaluate the improved effects of SC on the myocardium of Sprague Dawley rats having hyperthyroid heart disease (HHD) using VVI technique. HHD models were established by injecting daily with subcutaneous levothyroxine (0.5 mg/kg). Then, the SC group was administered the aqueous extract of SC (2 g/kg) once daily, while the HHD and control (CON) groups were administered the same amount of distilled water daily. All the rats were provided the same amount of food and water daily, and the intervention was stopped after 28 days. The efficacy of SC in HHD rats was evaluated by ultrasound VVI. The serum total triiodothyronine level, total thyroxine level, N-terminal pro-brain natriuretic peptide expression, p53 expression, and calmodulin (CaM) activity were assessed by western blotting, Hematoxylin-Eosin and Masson staining, and electron microscopy. The results indicated that SC significantly improved the systolic velocity, diastolic velocity, strain, systolic strain rate, and diastolic strain rate of the heart by significantly reducing p53 expression and CaM activity (P < 0.05), improving myocardial fibrosis in HHD rats. Also, VVI can be a valuable tool for the evaluation of myocardial function in HHD rats. [ABSTRACT FROM AUTHOR]

Background: Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients.Methods: We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility.Results: We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min-1; 95% CI, -13.3 to -5.8). Risk of bradycardia was not different between ivabradine and control (five RCTs, 434 patients; OR=1.2; 95% CI, 0.60-2.38). Risk of bias was overall high or unclear.Conclusions: Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted.Clinical Trial Registration: Prospero CRD42018086109. [ABSTRACT FROM AUTHOR]

Background Patients with cardiometabolic disease, specifically, stroke, heart disease and diabetes have a high prevalence of polypharmacy. Interventions to better manage or reduce polypharmacy in these populations may help improve patient outcomes. However, there is a paucity of data in this area, which needs to be investigated. Aim of the review The purpose of this scoping review was to identify and synthesize the available evidence pertaining to polypharmacy interventions in patients with cardiometabolic disease(s) and to determine what outcomes measures are assessed in these studies. Methods We followed an evidence-based scoping review guiding framework to address our study objectives. Three electronic databases (MEDLINE, EMBASE, CINAHL) were searched for all relevant studies up to May 2019. The Cochrane Library was also searched; studies included in relevant reviews were screened for inclusion. Reference lists of all included papers were also manually reviewed to identify additional articles. Polypharmacy interventions and measures used to assess efficacy were qualitatively described. Results Overall, six studies met the inclusion criteria. The majority of interventions were clinical pharmacist interventions reporting on a variety of outcomes including surrogate markers, quality of life and patient satisfaction, drug-related problems, and healthcare utilization and costs. The findings from the included studies generally indicated positive effects but had high risk of bias. Conclusions Existing polypharmacy interventions have some efficacy at improving a variety of patient and healthcare system outcomes. Increased frequency and duration of follow-up with patients led to significant improvements in quality of life, disease control and cost-savings in outpatient and in-patient settings. However, our analysis of the identified studies suggests low-quality evidence and significant knowledge gaps regarding patients with stroke and cardiometabolic multimorbidity. This signals a need for further high-quality research to both confirm these findings and include these other high-risk patient populations to validate these findings. [ABSTRACT FROM AUTHOR]

Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-β superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT). [ABSTRACT FROM AUTHOR]

Rationale: Brain death (BD) precipitates cardiac dysfunction impairing the ability to transplant hearts from eligible organ donors. Retrospective studies have suggested that thyroid hormone may enhance myocardial recovery and increase hearts transplanted. We performed a randomized trial evaluating whether intravenous thyroxine (T4) improves cardiac function in BD donors with impaired ejection fraction (EF). Methods: All heart-eligible donors managed at a single-organ procurement organization (OPO) underwent protocolized fluid resuscitation. Those weaned off vasopressors underwent transthoracic echocardiography (TTE) within 12 hours of BD and, if EF was below 60%, were randomized to T4 infusion or no T4 for 8 hours, after which TTE was repeated. Results: Of 77 heart-eligible donors, 36 were weaned off vasopressors. Ejection fraction was depressed in 30, of whom 28 were randomized to T4 (n = 17) vs control (n = 11). Baseline EF was comparable (45%, interquartile range [IQR] 42.5-47.5 vs 40%, 40-50, P =.32). Ejection fraction did not improve more with T4 (10%, IQR 5-15 vs 5%, 0-12.5, P =.24), although there was a trend to more hearts transplanted (59% vs 27%, P =.14). This difference appeared to be accounted for by more donors with a history of drug use in the T4 group, who exhibited greater improvements in EF (15% vs 0% without drug use, P =.01) and more often had hearts transplanted (12 of 19 vs 1 of 9, P =.01). Conclusions: In this small randomized study of BD donors with impaired cardiac function, T4 infusion did not result in greater cardiac recovery. A larger randomized trial comparing T4 to placebo appears warranted but would require collaboration across multiple OPOs. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs, originally termed "carcinoids") create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis. [ABSTRACT FROM AUTHOR]

Qing Gan Zi Shen Decoction (QGZS) is a traditional Chinese formula. It has been extensively used for decades in the treatment of hypertension combined with metabolic diseases, but its cardioprotective effects and underlying mechanisms are poorly understood. To explore the cardioprotective effects and potential mechanisms of QGZS in an animal model of obese hypertension. In this study, spontaneously hypertensive rats (SHRs) were utilized as an animal model to examine the effects of a high-fat diet and two concentrations of QGZS. Echocardiography, hematoxylin eosin (H&E) staining, and wheat germ agglutinin (WGA) staining were employed to assess the cardiac structure and function of the SHRs throughout a 16-week therapy period. Furthermore, Western blotting (WB) and immunofluorescence (IF) were employed to identify the levels of Nrf2 expression in the mitochondria, cytoplasm, and nucleus of the myocardium. Additionally, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to measure mitochondrial morphology and pro-inflammatory cytokine levels, respectively. Furthermore, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to quantify the levels of marker proteins associated with myocardial fibrosis, cardiac inflammation, oxidative stress, and mitochondrial dysfunction. QGZS inhibited weight gain and depressed systolic and mean arterial pressures in high-fat-fed SHRs. Echocardiographic results demonstrated that QGZS prevented the increase in left ventricular mass, restricted the growth of left ventricular diameter, and improved ejection fraction (EF), fractional shortening (FS), and the ratio of early diastolic peak velocity of transmitral flow (E) to late diastolic peak velocity (A) in high-fat-fed SHRs. This suggested that QGZS prevented ventricular remodeling and protected cardiac systolic and diastolic functions. H&E and WGA staining showed that QGZS improved cardiomyocyte disorders and restricted cardiomyocyte hypertrophy. The underlying mechanisms, QGZS attenuated the oxidative stress state, including reducing the generation of reactive oxygen species (ROS) in the myocardium, revitalizing the antioxidant enzyme system, and protecting mitochondrial function. Moreover, QGZS alleviated the pro-inflammatory state in high-fat-fed SHRs. What's more, QGZS significantly increased the expression level of Nrf2 in nuclei and mitochondria in rat heart tissues, exerting a proximate Nrf2 agonist effect. QGZS exerted cardioprotective effects, in part due to its increasing expression of Nrf2 protein in the heart, which promoted Nrf2 nuclear expression. [Display omitted] • In high-fat-induced obese SHRs, Qing Gan Zi Shen reversed ventricular remodeling and protected cardiac function. • In high-fat-induced obese SHRs, Qing Gan Zi Shen alleviated ventricular remodeling and myocardial fibrosis. • QGZS actived Nrf2 to play a role in reducing cardiac inflammation, inhibiting cardiac oxidative stress, and protecting mitochondrial function. [ABSTRACT FROM AUTHOR]

Commiphora mukul (Hook. ex Stocks) Engl. (also known as Guggulu) is one of the oldest and most prominent herb used in Ayurvedic medicine. Commiphora mukul plants have traditionally been used to treat inflammation, diabetes, rheumatism, arthritis, obesity, and hyperlipidemia. It has long been used in China, India, Greece, and other countries. Commiphora mukul is an over-the-counter dietary supplement in the United States and Western countries. Commiphora mukul has excellent medicinal and commercial value and deserves further investigation. This paper systematically reviews the historical records, application rules, phytochemistry, pharmacokinetics, pharmacology, clinical research, and adverse reactions of C. mukul and provides a reference for its comprehensive application in basic research, new drug development, and clinical treatment. Literature were collected from databases such as PubMed, CNKI, Web of Science, TBRC, and other sources such as ancient books on traditional medicine, classic books on herbal medicine, and modern monographs. In this study, the application history and modern pharmacological research on C. mukul in the medicine of all ethnic groups were comprehensively and systematically reviewed. According to the vast literature, the varieties, morphological characteristics, distribution, and description of C. mukul used in Unani medicine, Ayurveda, traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uygur medicine are highly consistent. Commiphora mukul is mainly used to treat rheumatoid arthritis, heart disease, obesity, hemorrhoids, urinary system diseases, skin diseases, inflammation, diabetes, hyperlipidemia, tumors, and other diseases. The core medicinal material combination in different ethnic medical preparations was C. mukul - Terminalia chebula Retz. (101 times), C. mukul -Moschus (55 times), C. mukul - Aucklandia lappa (Decne.) Decne. (52 times), and C. mukul - Acorus calamus L (27 times). Phytochemical studies confirmed that 150 components with different structures had been isolated and identified. Z-and E-guggulsterone are the main isomers in C. mukul. C. mukul has anti-cancer, anti-inflammatory, antioxidant, hypolipidemic, bone resorption, nervous system protection, myocardial protection, antibacterial, and other pharmacological properties. Clinical studies have only identified the role of C. mukul in treating hemorrhoids and lowering blood lipids. As an essential traditional medicine, C. mukul is widely used in the national traditional medicine system, and rich in chemical constituents and exhibit pharmacological activities. This study found that current research on C. mukul mainly focuses on its chemical composition and pharmacological properties. However, scientific research on the quality control of medicinal materials, identification of original plants, pharmacokinetics, and toxicology are relatively weak, and research in this area needs to be strengthened. [Display omitted] • The application of Commiphora mukul in Ayurveda and Tibetan medicine has a history of more than 2000 years. • The varieties of Commiphora mukul were roughly clarified based on five traditional medical texts. • The isomer Z and E-guggulsterones of Commiphora mukul have certain anti-inflammatory and hypolipidemic effects. • Commiphora mukul has main therapeutic diseases such as treating cancer, diabetes and obesity. [ABSTRACT FROM AUTHOR]

Rationale: Right heart thrombi (RiHT) is characterized by the presence of thrombus within the right atrium or right ventricle (RV). Current literature suggests pulmonary embolism (PE) with RiHT carries a high mortality. Guidelines lack recommendations in managing RiHT. We created a pooled analysis on RiHT and report on our institutional experience in managing RiHT. We aimed to evaluate whether patient characteristics and differing treatment modalities predict mortality. Methods: We created a pooled analysis of case reports and series of patients with RiHT and PE between January 1956 and 2017. We also reviewed a series of consecutive patients with RiHT identified from our institutional PE registry. Age, shock, RV dysfunction, clot mobility, treatment modality, and hospital outcome had to be reported. Results: We identified 316 patients in our pooled analysis. Patients received the following therapies: no treatment 15 (5%), systemic anticoagulation 73 (23%), systemic thrombolysis 108 (34%), surgical embolectomy 101 (32%), catheter-directed therapy 11 (3%), and systemic thrombolysis with surgery 8 (3%). In-hospital mortality was 18.7%. Univariate analysis showed age and shock reduced odds of survival. Multivariate analysis showed shock reduced odds of survival (odds ratios [OR] 0.36, 95% confidence interval [CI]: 0.19-0.72, P ≤ .01) while age, RV dysfunction, and clot-mobility did not affect mortality. In a reduced multivariate analysis adjusting for shock, treatment modality, and clot location alone, systemic thrombolysis increased odds of survival when compared to systemic anticoagulation (OR 2.72, 95% CI: 1.11-6.64, P = .02). Our institutional series identified 18 patients, where in-hospital mortality was 22.2%, 18 (100%) had RV dysfunction, and 5 (28%) had shock. Patients received the following therapies: systemic anticoagulation 8 (44.4%), systemic thrombolysis 4 (22.2%), surgical embolectomy 4 (22.2%), and catheter-directed thrombolysis 2 (11.1%). Conclusion: Presence of shock in RiHT is an independent predictor of mortality. Systemic thrombolysis may offer increased odds of survival when compared to systemic anticoagulation. Our findings should be interpreted with caution as they derive from retrospective reports and subject to publication bias. [ABSTRACT FROM AUTHOR]

The cumulative incidence of systolic heart failure is similar in men and women. However, major prognostic differences exist between genders. We sought to measure gender differences in furosemide prescribing patterns for patients with preexisting heart failure with reduced ejection fraction (HFrEF) admitted with Stage C acute decompensation, regardless of the underlying cause. We conducted a single-center retrospective analysis of patients admitted between 2015 and 2018 for acute on chronic decompensated HFrEF. Primary outcomes were differences in initial furosemide dose, total dose over the first 24 hours of hospitalization, and total dose during the entire hospitalization between women and men. Secondary outcomes included acute kidney injury (AKI), intubation, noninvasive ventilation (NIV), and in-hospital 30-day and 1-year mortality. We studied 434 patients (31% female) with similar baseline characteristics. Females received significantly less furosemide compared to men for the initial dose, over the first 24 hours, and throughout their hospitalization. However, AKI was more prevalent in women versus men (p=0.008). Females admitted for acute on chronic decompensated HFrEF receive significantly less furosemide when compared to men, but developed more AKI prior to discharge. [ABSTRACT FROM AUTHOR]

The majority of patients with chronic heart failure (HF) receive long-term treatment with loop diuretics. The comparative effectiveness of different loop diuretics is unknown. We searched PubMed, clinicaltrials.gov , the Cochrane Central Register of Controlled Trials and the European Union Clinical Trials Register for randomised clinical trials exploring the efficacy of the loop diuretics azosemide, bumetanide, furosemide or torasemide in patients with HF. Comparators included placebo, standard medical care or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, HF-related hospitalisation and any combined endpoint thereof. Hypokalaemia and acute renal failure were defined as additional safety endpoints. Evidence was synthesised using network meta-analysis (NMA). Thirty-four trials reporting on 2647 patients were included. The overall quality of evidence was rated as moderate. NMA demonstrated no significant differences between loop diuretics with respect to all-cause mortality, cardiovascular mortality or hypokalaemia. In contrast, torasemide ranked best in terms of HF hospitalisation, and there was a trend towards benefits with torasemide with regard to occurrence of acute renal failure. Sensitivity analyses excluding trials with a follow-up < 6 months, trials with a cross-over design and those including < 25 patients confirmed the main results. We found no significant superiority of either loop diuretic with respect to mortality and safety endpoints. However, clinicians may prefer torasemide, as it was associated with fewer HF-related hospitalisations. [ABSTRACT FROM AUTHOR]

Purpose: Patients in cardiac intensive care units (ICU) are admitted with increasingly higher disease acuity and a larger burden of non-cardiac critical illness. Accordingly, positive inotropes are being used with increased frequency and little comparative data to support drug selection. We compared the effectiveness and safety of dobutamine and milrinone in low cardiac output states (LCOS) and/or cardiogenic shock (CS).Methods: We performed a systematic review comparing dobutamine to milrinone on all-cause mortality, length of stay in the ICU (LOS-ICU), length of stay in hospital (LOS-H) and significant arrhythmias in hospitalized patients with LCOS and/or CS.Results: We identified 11 studies that meet eligibility requirements and which were published between 2001 and 2016 and included 23,056 patients. Only one randomized clinical trial was identified, with the remaining studies comprising observational cohort studies. The primary outcome, all-cause mortality, trended towards a benefit with milrinone but did not meet pre-specified significance (OR 1.13, 95% CI 1.00-1.29, p=0.06). While LOS-ICU (mean difference -0.72, 95% CI -1.10- -0.34, p=0.0002) was shorter with dobutamine, there was no difference in LOS-H (mean difference -1.22, 95% CI -4.68 - 2.24, p=0.49). Significant arrhythmias, specifically symptomatic and/or requiring antiarrhythmic therapy, were no different between the groups (OR 1.78, 95% CI 0.85-3.76, p=0.13).Conclusions: Currently available data comparing milrinone to dobutamine in patients requiring inotropic support is limited. Dobutamine may be associated with a shorter LOS in the ICU, with a worrisome signal of increased risk of allcause mortality. Randomized data are needed to guide inotrope selection in patients with LCOS and/or CS. [ABSTRACT FROM AUTHOR]