The quest for a successful cell-based therapeutic approach for heart failure.
Ontology highlight
ABSTRACT:
SUBMITTER: Landin AM
PROVIDER: S-EPMC6515521 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
The quest for a successful cell-based therapeutic approach for heart failure.
Landin Ana Marie AM Hare Joshua M JM
European heart journal 20170301 9
Similar Datasets
Project description:Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.
| S-EPMC4090309 | biostudies-literature
Project description:Heart failure has reached epidemic proportions with the advances in cardiovascular therapies for ischemic heart diseases and the progressive aging of the world population. Efficient pharmacological therapies are available for treating heart failure, but unfortunately, even with optimized therapy, prognosis is often poor. Their last therapeutic option is, therefore, a heart transplantation with limited organ supply and complications related to immunosuppression. In this setting, cell therapies have emerged as an alternative. Many clinical trials have now been performed using different cell types and injection routes. In this perspective, we will analyze the results of such trials and discuss future perspectives for cell therapies as an efficacious treatment of heart failure.
| S-EPMC8072383 | biostudies-literature
Project description:BackgroundReduction of 30-day all-cause readmissions for heart failure (HF) has become an important quality-of-care metric for health care systems. Many hospitals have implemented quality improvement programs designed to reduce 30-day all-cause readmissions for HF. Electronic medical record (EMR)-based measures have been employed to aid in these efforts, but their use has been largely adjunctive to, rather than integrated with, the overall effort.ObjectivesWe hypothesized that a comprehensive EMR-based approach utilizing an HF dashboard in addition to an established HF readmission reduction program would further reduce 30-day all-cause index hospital readmission rates for HF.MethodsAfter establishing a quality improvement program to reduce 30-day HF readmission rates, we instituted EMR-based measures designed to improve cohort identification, intervention tracking, and readmission analysis, the latter 2 supported by an electronic HF dashboard. Our primary outcome measure was the 30-day index hospital readmission rate for HF, with secondary measures including the accuracy of identification of patients with HF and the percentage of patients receiving interventions designed to reduce all-cause readmissions for HF.ResultsThe HF dashboard facilitated improved penetration of our interventions and reduced readmission rates by allowing the clinical team to easily identify cohorts with high readmission rates and/or low intervention rates. We significantly reduced 30-day index hospital all-cause HF readmission rates from 18.2% at baseline to 14% after implementation of our quality improvement program ( P = .045). Implementation of our EMR-based approach further significantly reduced 30-day index hospital readmission rates for HF to 10.1% ( P for trend = .0001). Daily time to screen patients decreased from 1 hour to 15 minutes, accuracy of cohort identification improved from 83% to 94.6% ( P = .0001), and the percentage of patients receiving our interventions, such as patient education, also improved significantly from 22% to 100% over time ( P < .0001).ConclusionsIn an institution with a quality improvement program already in place to reduce 30-day readmission rates for HF, an EMR-based approach further significantly reduced 30-day index hospital readmission rates.
| S-EPMC7651943 | biostudies-literature
Project description:We present a patient with acute heart failure and new onset atrial fibrillation secondary to giant cell myocarditis with lone atrial involvement. The diagnosis was managed with cardiac magnetic resonance and confirmed by interventionally guided biopsy. In the future, diagnosis could be managed noninvasively for this rare entity as the gold standard. (Level of Difficulty: Advanced.).
| S-EPMC8743871 | biostudies-literature
Project description:Despite some success of pharmacotherapies targeting primarily neurohormonal dysregulation, heart failure is a growing global pandemic with increasing burden. Treatments that improve the disease by reversing heart failure at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators of gene expression, acting through complex biological networks, and playing thereby essential roles in disease progression. Adverse structural remodelling of the left ventricle due to myocardial infarction (MI) is a common pathological feature leading to heart failure. We previously demonstrated increased cardiomyocyte expression of the miR-212/132 family during pathological cardiac conditions. Transgenic mice overexpressing the miR-212/132 cluster (miR-212/132-TG) develop pathological cardiac remodelling and die prematurely from progressive HF. Using both knockout and antisense strategies, we have shown miR-132 to be both necessary and sufficient to drive the pathological growth of cardiomyocytes in a murine model of left ventricular pressure overload. Based on the findings, we proposed that miR-132 may serve as a therapeutic target in heart failure therapy. Here we provide novel mechanistic insight and translational evidence for the therapeutic efficacy in small and large animal models (n=135) of heart failure. We demonstrate strong PK/PD relationship, dose-dependent efficacy and high clinical potential of a novel optimized synthetic locked nucleic acid phosphorothioate backbone antisense oligonucleotide inhibitor of miR-132 (antimiR-132) as a next-generation heart failure therapeutic.
2020-01-09 | PXD015337 | Pride
Project description:Heart failure (HF) constitutes a significant clinical problem and is associated with a sizeable burden for the healthcare system. Numerous novel techniques, including device interventions, are investigated to improve clinical outcome. A review of the most notable currently studied devices targeting pathophysiological processes in HF was performed. Interventions regarding autonomic nervous system imbalance, i.e., baroreflex activation therapy; vagus, splanchnic and cardiopulmonary nerves modulation; respiratory disturbances, i.e., phrenic nerve stimulation and synchronized diaphragmatic therapy; decongestion management, i.e., the Reprieve system, transcatheter renal venous decongestion system, Doraya, preCardia, WhiteSwell and Aquapass, are presented. Each segment is divided into subsections: potential pathophysiological target, existing evidence and weaknesses or unexplained issues. Novel therapeutic devices represent great potential in HF therapy management; however, further evidence is necessary to fully evaluate their utility.
| S-EPMC9331275 | biostudies-literature
Project description:Chronic heart failure is a major public-health problem with a high prevalence, complex treatment, and high mortality. A careful and comprehensive analysis is needed to provide optimal (and personalized) therapy to heart failure patients. The main 4 non-invasive imaging techniques (echocardiography, magnetic resonance imaging, multi-detector-computed tomography, and nuclear imaging) provide information on cardiovascular anatomy and function, which form the basis of the assessment of the pathophysiology underlying heart failure. The selection of imaging modalities depends on the information that is needed for the clinical management of the patients: (1) underlying etiology (ischemic vs non-ischemic); (2) in ischemic patients, need for revascularization should be evaluated (myocardial ischemia/viability?); (3) left ventricular function and shape assessment; (4) presence of significant secondary mitral regurgitation; (5) device therapy with cardiac resynchronization therapy and/or implantable cardiac defibrillator (risk of sudden cardiac death). This review is dedicated to assessment of myocardial viability, however "isolated assessment of myocardial viability" may be clinically not meaningful and should be considered among all those different variables. This complete information will enable personalized treatment of the patient with ischemic heart failure.
| S-EPMC4490177 | biostudies-literature
Project description:Aims:We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results:The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left ventricular end diastolic volume: -4%, P = 0.002), and increased LVEF (+14%, P < 0.0001) relative to baseline values. Gene profiling revealed that EV-treated hearts were enriched for tissue reparative pathways. Conclusion:Extracellular vesicles secreted by iPSC-Pg are effective in the treatment of CHF, possibly, in part, through their specific miRNA signature and the associated stimulation of distinct cardioprotective pathways. The processing and regulatory advantages of EV could make them effective substitutes for cell transplantation.
| S-EPMC6251654 | biostudies-literature
Project description:BACKGROUND:Several risk factors including Ischemic heart disease, uncontrolled hypertension, high output Heart Failure (HF) from shunting through vascular hemodialysis access, and anemia, contribute to development of HF in patients with End-Stage Renal Disease (ESRD). Guidelinedirected medical and device therapy for Heart Failure with Reduced Ejection Fraction (HFrEF) has not been extensively studied and may have limited safety and efficacy in patients with ESRD. RESULTS:Maintenance of interdialytic and intradialytic euvolemia is a key component of HF management in these patients but often difficult to achieve. Beta-blockers, especially carvedilol which is poorly dialyzed is associated with cardiovascular benefit in this population. Despite paucity of data, Angiotensin-converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs) when appropriately adjusted by dose and with close monitoring of serum potassium can also be administered to these patients who tolerate beta-blockers. Mineralocorticoid receptors in patients with HFrEF and ESRD have been shown to reduce mortality in a large randomized controlled trial without any significantly increased risk of hyperkalemia. Implantable Cardiac-defibrillators (ICDs) should be considered for primary prevention of sudden cardiac death in patients with HFrEF and ESRD who meet the implant indications. Furthermore in anemic iron-deficient patients, intravenous iron infusion may improve functional status. Finally, mechanical circulatory support with leftventricular assist devices may be related to increased mortality risk and the presence of ESRD poses a relative contraindication to further evaluation of these devices.
| S-EPMC5872264 | biostudies-literature
Project description:Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, 29P, was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50μg/kg 29P or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that 29P treatment significantly restored cardiac function and structure indicating the protective effect of 29P treatment in this model of heart failure. Importantly, 29P treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, 29P reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with 29P provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.
2024-03-12 | GSE247309 | GEO