Dare to dream? Cell-based therapies for heart failure after DREAM-HF: Review and roadmap for future clinical study
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SUBMITTER: Johnston P
PROVIDER: S-EPMC10978179 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC6688717 | 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:Chronic heart failure is one of the most debilitating chronic conditions affecting millions of people and adding a significant financial burden to health care systems worldwide. Despite the significant therapeutic advances achieved over the last decade, morbidity and mortality remain high. Multiple catheter-based interventional therapies targeting different physiological and anatomical targets are already under different stages of clinical investigation. The present paper provides a technical overview of the most relevant catheter-based interventional therapies under clinical investigation.
| S-EPMC8897161 | biostudies-literature
Project description:BackgroundAdvanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life.ObjectivesThe authors investigated whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes.MethodsThe authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well-being (measured via the FACIT-Spiritual Well-Being scale [FACIT-Sp]), hospitalizations, and mortality.ResultsPatients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = -1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality.ConclusionsAn interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure [PAL-HF]; NCT01589601).
| S-EPMC5664956 | biostudies-literature
Project description:BackgroundDespite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF.Methods and resultsWe assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values < .0001). There was no evidence of a difference in outcomes between early and late WHF (all P values for comparison ≥ .2).ConclusionsWorsening HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments.
| S-EPMC4581586 | biostudies-literature
Project description:Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.
| S-EPMC4194170 | biostudies-literature
Project description:It is generally assumed that all estrogen receptor positive (ER+) breast cancers proliferate in response to estrogen and therefore examples of estrogen-induced regression of ER+ cancers are paradoxical. This review reexamines the estrogen regression paradox for the Luminal A subtype of ER+ breast cancers. The proliferative response to estrogen is shown to depend on the level of ER. Mechanistically, a window of opportunity study of pre-operative estradiol suggested that with higher levels of ER, estradiol could activate the DREAM-MMB (Dimerization partner, Retinoblastoma-like proteins, E2F4, and MuvB – MYB-MuvB) pathway to decrease proliferation. The response of breast epithelium and the incidence of breast cancers during hormonal variations that occur during the menstrual cycle and at the menopausal transition respectively suggest that a single hormone, either estrogen, progesterone or androgen could activate the DREAM pathway leading to reversible cell cycle arrest. Conversely, the presence of two hormones, could switch the DREAM-MMB complex to a pro-proliferative pathway. Using publicly available data, we examine the gene expression changes after aromatase inhibitors and ICI 182,780 to provide support for the hypothesis. This review suggests that it might be possible to integrate all current hormonal therapies for Luminal A tumors within a single theoretical schema.
2024-07-03 | GSE268001 | GEO
Project description:BackgroundWorsening renal function is common among patients hospitalized for acute decompensated heart failure (ADHF). When this occurs, subsequent management decisions often pit the desire for effective decongestion against concerns about further worsening renal function. There are no evidence-based treatments or guidelines to assist in these difficult management decisions. Ultrafiltration is a potentially attractive alternative to loop diuretics for the management of fluid overload in patients with ADHF and worsening renal function.Methods and resultsThe National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network designed a clinical trial to determine if ultrafiltration results in improved renal function and relief of congestion compared with stepped pharmacologic care when assessed 96 hours after randomization in patients with ADHF and cardiorenal syndrome. Enrollment began in June 2008. This paper describes the rationale and design of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF).ConclusionsTreating the signs and symptoms of congestion in ADHF is often complicated by worsening renal function. CARRESS-HF compares treatment strategies (ultrafiltration vs stepped pharmacologic care) for the management of worsening renal function in patients with ADHF. The results of the CARRESS-HF trial are expected to provide information and evidence as to the most appropriate approaches for treating this challenging patient population.
| S-EPMC3503538 | 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:We aimed to study whether jugular venous distension (JVD) and peripheral edema were associated with worse outcomes in patients with acute heart failure in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial. Of 7,141 patients in Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure, 7,135 had complete data on baseline JVD and peripheral edema status. Patients were grouped according to baseline examination findings: (1) no JVD or peripheral edema; (2) JVD only; (3) peripheral edema only; (4) JVD and peripheral edema. We used unadjusted and adjusted logistic or Cox regression analyses to assess associations between groups and the outcomes of index length of stay (LOS), in-hospital mortality, 30- and 180-day all-cause mortality. Patients with peripheral edema (Groups 3 and 4) had higher body mass index, NT-proBNP and BNP values, and more co-morbid disease, and reduced left ventricular ejection fraction compared with patients in Groups 1-2. The median (25th-75th) LOS for Groups 1-4 was 6 (4-9), 5 (4-8), 7 (4-11), and 6 days (4-10), respectively. For the 30-day and 180-day outcomes, adjusted analyses found no significant difference in risk for patients presenting with JVD only or peripheral edema only as compared with patients without evidence of JVD or peripheral edema (p >0.05 for all). The presence of both JVD and peripheral edema was associated with an adjusted 24% increase in risk for all-cause mortality at 30 days, but no risk difference at 180 days. In conclusion, in patients with heart failure presenting to the hospital with dyspnea, the presence of peripheral edema is associated with a longer hospital LOS, but no difference in short- and long-term clinical outcomes when compared with patients wihout peripheral edema. The combination of peripheral edema and JVD identifies the highest risk cohort for poor clinical outcomes.
| S-EPMC6924269 | biostudies-literature