Gastrointestinal and Liver Issues in Heart Failure Sundaram, Varun; Fang, James C
Circulation (New York, N.Y.),
2016-April-26, 2016-Apr-26, 2016-04-26, 20160426, Volume:
133, Issue:
17
Journal Article
Peer reviewed
Open access
Heart failure affects ≈23 million people worldwide and continues to have a high mortality despite advancements in modern pharmacotherapy and device therapy. HF is a complex clinical syndrome that can ...result in the impairment of endocrine, hematologic, musculoskeletal, renal, respiratory, peripheral vascular, hepatic, and gastrointestinal systems. Although gastrointestinal involvement and hepatic involvement are common in HF and are associated with increased morbidity and mortality, their bidirectional association with HF progression remains poorly fathomed. The current understanding of multiple mechanisms, including proinflammatory cytokine milieu, hormonal imbalance, and anabolic/catabolic imbalance, has been used to explain the relationship between the gut and HF and has been the basis for many novel therapeutic strategies. However, the failure of these novel therapies such as anti–tumor necrosis factor-α has resulted in further complexity. In this review, we describe the involvement of the gastrointestinal and liver systems within the HF syndrome, their pathophysiological mechanisms, and their clinical consequences.
Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases. The ...median survival of this group of patients after diagnosis is ∼1 yr. Here we show that the levels of H3K27 di- and trimethylation (H3K27me2 and H3K27me3) are reduced globally in H3.3K27M patient samples due to the expression of the H3.3K27M mutant allele. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.
The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ...ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.
In 2015, empagliflozin, an inhibitor of sodium–glucose cotransporter 2 (SGLT2), lowered the composite cardiovascular end point in the EMPA-REG trial
1
involving patients with type 2 diabetes mellitus ...who were at increased cardiovascular risk. What was remarkable in that finding was that the benefit was driven by reductions in hospitalization for heart failure and cardiovascular mortality but not by a lower frequency of myocardial infarction or stroke. Moreover, empagliflozin appeared to slow deterioration in renal function, and the heart-failure benefits persisted in the presence of renal dysfunction. These early observations regarding heart failure were extended and confirmed in two subsequent trials . . .
Reverse left ventricular (LV) remodeling and recovery of LV function are associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction. A growing body of ...evidence suggests that even among patients who experience a complete normalization of LV ejection fraction, a significant proportion will develop recurrent LV dysfunction accompanied by recurrent heart failure events. This has led to intense interest in understanding how to manage patients with heart failure with recovered ejection fraction (HFrecEF). Because of the lack of a standard definition for HFrecEF, and the paucity of clinical data with respect to the natural history of HFrecEF patients, there are no current guidelines on how these patients should be followed up and managed. Accordingly, this JACC Scientific Expert Panel reviews the biology of reverse LV remodeling and the clinical course of patients with HFrecEF, as well as provides guidelines for defining, diagnosing, and managing patients with HFrecEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Traditionally, the only definitive therapy for patients who have advanced, medically refractory heart failure was replacement of the heart with another human heart. However, transplantation is an ...inadequate option in light of the large number of potential candidates, the lack of donors, and the coexisting conditions that make most potential candidates ineligible for transplantation. In this context, ventricular assist devices, or heart pumps, become an attractive option for patients who have advanced heart failure.
Rather than replacing the human heart completely, ventricular assist devices serve in a true “assistance” capacity by supplementing the cardiac output of the native but weakened . . .
Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play crucial roles in maintaining redox homeostasis in biological systems. This Minireview summarizes the most significant ...current challenges in the field of thiol‐reactive probes for biomedical research and diagnostics, emphasizing the needs and opportunities that have been under‐investigated by chemists in the selective probe and sensor field. Progress on multiple binding site probes to distinguish Cys, Hcy, and GSH is highlighted as a creative new direction in the field that can enable simultaneous, accurate ratiometric monitoring. New probe design strategies and researcher priorities can better help address current challenges, including the monitoring of disease states such as autism and chronic diseases involving oxidative stress that are characterized by divergent levels of GSH, Cys, and Hcy.
Probing biothiols: Cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play crucial roles in human health. There are very few molecular probes and abiotic sensors that can simultaneously discriminate among biothiols. Recent progress on probes featuring multiple binding sites to distinguish Cys, Hcy, and GSH is summarized, and a variety of unmet critical needs and opportunities for chemists in the thiol probe field are discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Background The number of centers with left ventricular assist device (LVAD) research programs focused on cardiac recovery is very small. Therefore, this phenomenon has been reported in ...real-world multi-center registries as a rare event. Objectives This study evaluated the incidence of cardiac recovery with an a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a recovery predictive model. Methods The study included LVAD recipients registered in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Cardiac recovery was evaluated in BTR and non-BTR patients. A weighted score was derived and externally validated in patients of the Utah Cardiac Recovery (UCAR) program. Results Of 15,138 INTERMACS patients, cardiac recovery occurred in 192 (1.3%). The incidence of recovery was 11.2% (n = 14) in BTR compared with 1.2% (n = 178) in non-BTR patients (p < 0.0001). Independent predictors of recovery included: age <50 years, non-ischemic cardiomyopathy, time from cardiac diagnosis <2 years, absence of ICD, creatinine ≤1.2 mg/dl, and LVEDD <6.5 cm (c-index: 0.85; p < 0.0001). A weighted score termed I-CARS, effectively stratified patients based on their probability of recovery. I-CARS was validated in the UCAR cohort (n = 190) with good performance (AUC: 0.94; 95% CI: 0.91 to 0.98). One-year survival after LVAD explantation, available in INTERMACS for 21 (11%) patients, was 86%. Conclusions The incidence of cardiac recovery is higher in patients implanted with an a priori BTR strategy. We developed a simple tool to help identify patients in whom recovery is feasible. In BTR patients with favorable characteristics, I-CARS suggests a 24% probability of successful LVAD explantation. Large-scale studies to better address post-explantation outcomes are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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