Empagliflozin and the Prevention of Heart Failure: Will Reverse Translation Lead to New Paradigms for the Treatment of Heart Failure?∗.
Ontology highlight
ABSTRACT:
SUBMITTER: Mann DL
PROVIDER: S-EPMC6034482 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Clinical depression is a serious mental disorder characterized by low mood, anhedonia, loss of interest in daily activities, and other symptoms, and is associated with severe consequences including suicide and increased risk of cardiovascular events. Depression affects nearly 15% of the population. The standard of care for the last 50 years has focused on monoamine neurotransmitters, including such treatments as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, these treatments have significant limitations: they can take weeks before showing mood-altering effects, and only one to two out of ten patients shows clinical effects beyond those associated with placebo. A major paradigm shift in research into the treatment of depression is underway, based on promising results with the glutamatergic NMDA receptor antagonist ketamine. Further research has demonstrated the significance of glutamatergic pathways in depression and the association of this system with the stress pathway and magnesium homeostasis. Treatment with NMDA receptor antagonists and magnesium have shown the ability to sprout new synaptic connections and reverse stress-induced neural changes, opening up promising new territory for the development of drugs to meet the unmet need in patients with clinical depression.
| S-EPMC3936783 | biostudies-literature
Project description:Structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (JPC-2997, JPC-3186, and JPC-3210) were conducted for preclinical development for malaria treatment and/or prevention. Of these compounds, JPC-3210 [4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, lower in vitro cytotoxicity in mammalian cell lines, longer plasma elimination half-life, and greater in vivo efficacy against murine malaria.
| S-EPMC4862471 | biostudies-literature
Project description:Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists.
| S-EPMC4637457 | biostudies-other
Project description:Reliable estimates of heart failure are lacking in India because of the absence of a surveillance programme to track incidence, prevalence, outcomes and key causes of heart failure. Nevertheless, we propose that the incidence and prevalence rates of heart failure are rising due to population, epidemiological and health transitions. Based on disease-specific estimates of prevalence and incidence rates of heart failure, we conservatively estimate the prevalence of heart failure in India due to coronary heart disease, hypertension, obesity, diabetes and rheumatic heart disease to range from 1.3 to 4.6 million, with an annual incidence of 491 600-1.8 million. The double burden of rising cardiovascular risk factors and persistent 'pre-transition' diseases such as rheumatic heart disease, limited healthcare infrastructure and social disparities contribute to these estimates. Staging of heart failure, introduced in 2005, provides a framework to target preventive strategies in patients at risk for heart failure (stage A), with structural disease alone (B), with heart failure symptoms (C) and with end-stage disease (D). Policy-level interventions, such as regulations to limit salt and tobacco consumption, are effective for primordial prevention and would have a wider impact on prevention of heart failure. Clinical preventive interventions and clinical quality improvement interventions, such as treatment of hypertension, atherosclerotic disease, diabetes and acute decompensated heart failure are effective for primary, secondary and even tertiary prevention.
| S-EPMC3913650 | biostudies-other
Project description:Despite the many medications already available, patients with heart failure often have disease exacerbations, reduced quality of life, and increased mortality, highlighting the need for new treatment approaches. We explore drugs currently in development.
| S-EPMC5720489 | biostudies-other
Project description:The management of heart failure has changed significantly over the last 30 years, leading to improvements in the quality of life and outcomes, at least for patients with a substantially reduced left ventricular ejection fraction (HFrEF). This has been made possible by the identification of various pathways leading to the development and progression of heart failure, which have been successfully targeted with effective therapies. Meanwhile, many other potential targets of treatment have been identified, and the list is constantly expanding. In this review, we summarise planned and ongoing trials exploring the potential benefit, or harm, of old and new pharmacological interventions that might offer further improvements in treatment for those with HFrEF and extend success to the treatment of patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and other heart failure phenotypes.
| S-EPMC6985084 | biostudies-literature
Project description:Aim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined. The primary study objective was to determine on a genome-wide basis whether intraoperative and intraportal treatment of the allograft with tacrolimus reduces inflammatory signature in the liver. The secondary objective was the causally test, whether suppression of genes belongong to the ontologies of inflammation and immune response by tacrolimus will lead to a better initial function of the liver. randomized double-blind, placebo-controlled trial
2012-04-12 | E-GEOD-25338 | biostudies-arrayexpress
Project description:Biventricular pacing has revolutionised the treatment of heart failure in patients with sinus rhythm and left bundle branch block; however, left ventricular-lead placement is not always technically possible. Furthermore, biventricular pacing does not fully normalise ventricular activation and, therefore, the ventricular resynchronisation is imperfect. Right ventricular pacing for bradycardia may cause or worsen heart failure in some patients by causing dyssynchronous ventricular activation. His bundle pacing activates the ventricles via the native His-Purkinje system, resulting in true physiological pacing, and, therefore, is a promising alternate site for pacing in bradycardia and traditional CRT indications in cases where it can overcome left bundle branch block. Furthermore, it may open up new indications for pacing therapy in heart failure, such as targeting patients with PR prolongation, but a narrow QRS duration. In this article we explore the physiology, technology and potential roles of His bundle pacing in the prevention and treatment of heart failure.
| S-EPMC6020230 | biostudies-literature
Project description:IntroductionCardiac implantable electronic devices (CIEDs) have opened new doors, improving the quality, and increasing the duration of life by providing support of heart rate, atrioventricular and interventricular synchrony, thereby preventing sudden cardiac death. Nevertheless, these devices can pose some risks to the patients, including pacemaker-mediated cardiomyopathy and endocarditis.Case presentationWe elucidate the case of a patient who had severe Tricuspid Regurgitation as a result of single chamber Implantable Cardioverter Defibrillator (ICD) placement which led to right heart failure (RHF). His chief complaints were generalized fatigability and difficulty climbing steps at home. He also had orthopnea but denies paroxysmal nocturnal dyspnea. Despite using home diuretic regimen (Torsemide 40 gm daily), his continued to increase. He did not respond well to intravenous diuretics that time so decision was made to start Aquapheresis to which he responded very well.DiscussionTV dysfunction associated with CIED leads can be investigated and diagnosed using different techniques. These pillars of diagnostic tests include two-dimensional (2D), 3D, and Doppler echocardiography. Presence of holosystolic hepatic vein flow reversal is key in diagnosing severe TR, whereas normal antegrade systolic flow excludes the possibility of moderate and severe TR.ConclusionCIED leads causing tricuspid valve impairment has become increasingly recognized over the recent times; however, the evidence underlying this trend has been derived primarily from retrospective analyses. In order to circumvent these issues, leadless pacemakers and subcutaneous ICD devices should be considered.
| S-EPMC8203726 | biostudies-literature
Project description:BackgroundIn dilated cardiomyopathies (DCMs) changes in expression of protein-coding genes are associated with reverse remodeling, and these changes can be regulated by microRNAs (miRs). We tested the general hypothesis that dynamic changes in myocardial miR expression are predictive of β-blocker-associated reverse remodeling.MethodsForty-three idiopathic DCM patients (mean left ventricular ejection fraction 0.24 ± 0.09) were treated with β-blockers. Serial ventriculography and endomyocardial biopsies were performed at baseline, and after 3 and 12 months of treatment. Changes in RT-PCR (candidate miRs) or array-measured miRs were compared based on the presence (R) or absence (NR) of a reverse-remodeling response, and a miR-mRNA-function pathway analysis (PA) was performed.ResultsAt 3 months, 2 candidate miRs were selectively changed in Rs, decreases in miR-208a-3p and miR-591. PA revealed changes in miR-mRNA interactions predictive of decreased apoptosis and myocardial cell death. At 12 months, 5 miRs exhibited selective changes in Rs (decreases in miR-208a-3p, -208b-3p, 21-5p, and 199a-5p; increase in miR-1-3p). PA predicted decreases in apoptosis, cardiac myocyte cell death, hypertrophy, and heart failure, with increases in contractile and overall cardiac functions.ConclusionsIn DCMs, myocardial miRs predict the time-dependent reverse-remodeling response to β-blocker treatment, and likely regulate the expression of remodeling-associated miRs.Trial registrationClinicalTrials.gov NCT01798992.FundingNIH 2R01 HL48013, 1R01 HL71118 (Bristow, PI); sponsored research agreements from Glaxo-SmithKline and AstraZeneca (Bristow, PI); NIH P20 HL101435 (Lowes, Port multi-PD/PI); sponsored research agreement from Miragen Therapeutics (Port, PI).
| S-EPMC5256135 | biostudies-literature