Cell-Based Therapies for Heart Failure.
Ontology highlight
ABSTRACT:
SUBMITTER: Campos de Carvalho AC
PROVIDER: S-EPMC8072383 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the absence of VIP, VIP knockout mice have dysregulation in key heart failure genes: 1) Force Generation and Propagation; 2) Energy Production and Regulation; 3) Ca(+2) Cycling; 4) Transcriptional Regulators. VIP administration leads to coronary dilation in human subjects. In heart failure patients, VIP levels are elevated as a plausible endogenous protective effect. With the development of elastin polymers to stabilize VIP and prevent its degradation, VIP may therefore have a chance to satisfy the unmet need as a potential treatment for acute heart failure.
| S-EPMC4603524 | biostudies-literature
Project description:Although substantial advances have been made in treating ischemic heart disease and subsequent heart failure, the overall morbidity and mortality from these conditions remain high. Stem cell-based therapy has emerged as a promising approach for prompting cardiac rejuvenation. Various cell types have been tested in the clinical arena, proving consistent safety results. As for efficiency outcomes, contradictory findings have been reported, partly due to inconsistency in study protocols but also due to poor survival, engraftment and differentiation of transplanted cells in the hostile milieu of the ischemic host tissue. Studies have varied in terms of route of delivery, type and dose of implanted stem cells, patient selection and randomization, and assessment of therapeutic effect. Founded on the main achievements and challenges within almost 20 years of research, a number of official documents have been published by leading experts in the field. Core recommendations have focused on developing and optimizing effective strategies to enrich cell retention and their regenerative potential. Issued consensus and position papers have stemmed from an unmet need to provide a harmonized framework for future research, resulting in improved therapeutic application of cell-based therapies for cardiac regeneration and repair.
| S-EPMC6716081 | biostudies-literature
Project description:This in-depth review of sex differences in advanced heart failure therapy summarizes the existing literature on implantable cardioverter defibrillators, biventricular pacemakers, mechanical circulatory support, and transplantation with a focus on utilization, efficacy/clinical effectiveness, adverse events, and controversies. One will learn about the controversies regarding efficacy/clinical effectiveness of implantable cardioverter defibrillators and understand why these devices should be implanted in women even if there are sex differences in appropriate shocks. Individuals will learn about the sex differences with biventricular pacemakers with respect to ventricular remodeling and reduction in heart failure hospitalizations/mortality, as well as, possible mechanisms. We will demonstrate sex differences in heart transplantation and waitlist survival. Despite similar survival for women and men with left ventricular assist devices, there are sex differences in adverse events. These devices do successfully bridge women and men to transplant, yet women are less likely than men to have a left ventricular assist at time of listing and time of transplantation. Finally, one will learn about the concerns regarding poor outcome for men who receive female donor hearts and discover this may not be due to sex, but rather size. More research is needed to better understand sex differences and further improve advanced heart failure therapy for both women and men.
| S-EPMC6383806 | biostudies-literature
Project description:Recovery of ventricular function occurs in a subset of patients with advanced heart failure treated with medical and/or mechanical therapy. Finding strategies that induce ventricular recovery through induction of repair, regeneration, or "rejuvenation" is a long-sought goal of research programs. Cell-based strategies, use of recombinant growth and survival factors, and gene delivery are under investigation. In this brief article we highlight a few of the biological approaches in development to treat heart failure.
| S-EPMC5214584 | biostudies-literature
Project description:Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Often the syndrome is characterized by congestion, and is associated with long hospital admissions and high risk of readmission and further healthcare expenditure. Despite a limited evidence-base, diuretics remain the first-line treatment for congestion. Loop diuretics are typically the first-line diuretic strategy with some evidence that initial treatment with continuous infusion or boluses of high-dose loop diuretic is superior to an initial lower dose strategy. In patients who have impaired responsiveness to diuretics, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. The use of intravenous low-dose dopamine is no longer supported in heart failure patients with preserved systolic blood pressure and its use to assist diuresis in patients with low systolic blood pressures requires further study. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence-base is not robust, and its place in clinical practice is yet to be established. Several novel pharmacological agents remain under investigation.
| S-EPMC4824339 | biostudies-literature
Project description:BackgroundCell-based therapy has long been considered a promising strategy for the treatment of heart failure (HF). However, its effectiveness in the clinical setting is now doubted. Because previous meta-analyses provided conflicting results, we sought to review all available data focusing on cell type and trial design.Methods and findingsThe electronic databases PubMed, Cochrane library, ClinicalTrials.gov, and EudraCT were searched for randomized controlled trials (RCTs) utilizing cell therapy for HF patients from January 1, 2000 to December 31, 2020. Forty-three RCTs with 2855 participants were identified. The quality of the reported study design was assessed by evaluating the risk-of-bias (ROB). Primary outcomes were defined as mortality rate and left ventricular ejection fraction (LVEF) change from baseline. Secondary outcomes included both heart function data and clinical symptoms/events. Between-study heterogeneity was assessed using the I2 index. Subgroup analysis was performed based on HF type, cell source, cell origin, cell type, cell processing, type of surgical intervention, cell delivery routes, cell dose, and follow-up duration. Only 10 of the 43 studies had a low ROB for all method- and outcome parameters. A higher ROB was associated with a greater increase in LVEF. Overall, there was no impact on mortality for up to 12 months follow-up, and a clinically irrelevant average LVEF increase by LVEF (2.4%, 95% CI = 0.75-4.05, p = 0.004). Freshly isolated, primary cells tended to produce better outcomes than cultured cell products, but there was no clear impact of the cell source tissue, bone marrow cell phenotype or cell chricdose (raw or normalized for CD34+ cells). A meaningful increase in LVEF was only observed when cell therapy was combined with myocardial revascularization.ConclusionsThe published results suggest a small increase in LVEF following cell therapy for heart failure, but publication bias and methodologic shortcomings need to be taken into account. Given that cardiac cell therapy has now been pursued for 20 years without real progress, further efforts should not be made.Study registry numberThis meta-analysis is registered at the international prospective register of systematic reviews, number CRD42019118872.
| S-EPMC8730409 | biostudies-literature
Project description:Patients have an ongoing unmet need for effective therapies that reverse the cellular and functional damage associated with heart damage and disease. The discovery that ~1%-2% of adult cardiomyocytes turn over per year provided the impetus for treatments that stimulate endogenous repair mechanisms that augment this rate. Preclinical and clinical studies provide evidence that cell-based therapy meets these therapeutic criteria. Recent and ongoing studies are focused on determining which cell type(s) works best for specific patient population(s) and the mechanism(s) by which these cells promote repair. Here we review clinical and preclinical stem cell studies and anticipate future directions of regenerative medicine for heart disease.
| S-EPMC7202446 | biostudies-literature
Project description:The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
| S-EPMC4204003 | biostudies-literature
Project description:Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.
| S-EPMC8164213 | biostudies-literature
Project description:Background Race influences medical decision making, but its impact on advanced heart failure therapy allocation is unknown. We sought to determine whether patient race influences allocation of advanced heart failure therapies. Methods and Results Members of a national heart failure organization were randomized to clinical vignettes that varied by patient race (black or white man) and were blinded to study objectives. Participants (N=422) completed Likert scale surveys rating factors for advanced therapy allocation and think-aloud interviews (n=44). Survey results were analyzed by least absolute shrinkage and selection operator and multivariable regression to identify factors influencing advanced therapy allocation, including interactions with vignette race and participant demographics. Interviews were analyzed using grounded theory. Surveys revealed no differences in overall racial ratings for advanced therapies. Least absolute shrinkage and selection operator regression selected no interactions between vignette race and clinical factors as important in allocation. However, interactions between participants aged ≥40 years and black vignette negatively influenced heart transplant allocation modestly (-0.58; 95% CI, -1.15 to -0.0002), with adherence and social history the most influential factors. Interviews revealed sequential decision making: forming overall impression, identifying urgency, evaluating prior care appropriateness, anticipating challenges, and evaluating trust while making recommendations. Race influenced each step: avoiding discussing race, believing photographs may contribute to racial bias, believing the black man was sicker compared with the white man, developing greater concern for trust and adherence with the black man, and ultimately offering the white man transplantation and the black man ventricular assist device implantation. Conclusions Black race modestly influenced decision making for heart transplant, particularly during conversations. Because advanced therapy selection meetings are conversations rather than surveys, allocation may be vulnerable to racial bias.
| S-EPMC6915287 | biostudies-literature