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Cardiac cachexia is characterized by unintentional catabolic weight loss, decreased appetite, and inflammation and is common in patients with stage D (advanced) heart failure with reduced ejection fraction (HFrEF). Cardiac cachexia and related muscle-wasting syndromes are markers of, and a consequence of, the heart failure (HF) syndrome. Although many potential modalities for identifying cardiac cachexia exist, the optimal definition, diagnostic tools, and treatment options for cardiac cachexia remain unclear. Furthermore, it remains unclear whether attempts to reverse muscle wasting prior to advanced HF surgeries, such as left ventricular assist devices and heart transplantation, can improve outcomes. It is important that HF clinicians and dietitians are aware of the pathophysiology and mechanisms of muscle-wasting syndromes in patients with HF, to aid in the recognition and risk stratification of advanced HFrEF. Although the opportunities and rationale for attempting to address cardiac cachexia prior to advanced HF surgeries are uncertain, recent publications suggest that control of the neurohumoral syndrome of advanced HF may be important to permit the recovery of skeletal muscle mass., Competing Interests: Funding Support and Author Disclosures Dr Cogswell is a speaker for Abbott Laboratories. Dr Hackman has received speaker and consulting fees from Abbott; and has served on the speaking/advisory board for Medtronic. Dr Breathett has received research grant funding from the National Heart, Lung, and Blood Institute (grants K01HL142848, R01HL159216, R01HL16074), Health Resources and Services Administration of the U.S. Department of Health and Human Services, and Indiana University Clinical and Translational Sciences Institute. Dr Vest has received research grant funding from the National Heart, Lung, and Blood Institute (grant R01HL167113) and the National Center for Advancing Translational Sciences (grant RC2TR004377). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light-dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light-dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA β oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF., (© 2024. The Author(s).)

Cardiac cachexia is a deadly consequence of advanced heart failure that is characterised by the dysregulation of adipose tissue homeostasis. Once cachexia occurs with heart failure, it prevents the normal treatment of heart failure and increases the risk of death. Targeting adipose tissue is an important approach to treating cardiac cachexia, but the pathogenic mechanisms are still unknown, and there are no effective therapies available. Transcriptomics, metabolomics, and lipidomics were used to examine the underlying mechanisms of cardiac cachexia. Transcriptomics investigation of cardiac cachexia adipose tissue revealed that genes involved in fibrosis and monocyte/macrophage migration were increased and strongly interacted. The ECM-receptor interaction pathway was primarily enriched, as shown by KEGG enrichment analysis. In addition, gene set enrichment analysis revealed that monocyte chemotaxis/macrophage migration and fibrosis gene sets were upregulated in cardiac cachexia. Metabolomics enrichment analysis demonstrated that the sphingolipid signalling pathway is important for adipose tissue remodelling in cardiac cachexia. Lipidomics analysis showed that the adipose tissue of rats with cardiac cachexia had higher levels of sphingolipids, including Cer and S1P. Moreover, combined multiomics analysis suggested that the sphingolipid metabolic pathway was associated with inflammatory-fibrotic changes in adipose tissue. Finally, the key indicators were validated by experiments. In conclusion, this study described a mechanism by which the sphingolipid signalling pathway was involved in adipose tissue remodelling by inducing inflammation and fat fibrosis in cardiac cachexia., (© 2023. The Author(s).)

Objective: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD)., Animals: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10)., Methods: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatography-tandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10., Results: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences., Clinical Relevance: Some significant metabolite differences were identified between dogs with and without cardiac cachexia.

Background: Cardiac cachexia (CC) is associated with increased morbidity and mortality in persons with heart failure (HF). Compared to the biological underpinning of CC, little is known about the psychological factors. Thus, the overarching objective of this study was to determine whether depression predicts the onset of cachexia at 6 months in patients with chronic HF., Methods: 114 participants with a mean age of 56.7 ± 13.0 years, LVEF of 33.13 ± 12.30% and NYHA class III (48.0%) were assessed for depression using the PHQ-9. Body weight was measured at baseline and at 6 months. Patients who had ≥6% non-edematous unintentional weight loss were classified as cachectic. Univariate and logistic multivariate regression were used to examine the relationship between CC and depression, controlling for clinical and demographic variables., Results: Cachectic patients (11.4%) had significantly higher baseline BMI levels (31.35 ± 5.70 vs. 28.31 ± 4.73; p = .038), lower LVEF (mean = 24.50 ± 9.48 vs. 34.22 ± 12.18, p = .009), and depression scores (mean = 7.17 ± 6.44 vs. 4.27 ± 3.98, p = .049) when compared to their non-cachectic counterparts. In multivariate regression analysis, depression scores ( β = 1.193, p = .035) and LVEF ( β = .835, p = . 031) predicted cachexia after controlling for age, gender, body mass index, VO 2 max, and New York Heart Association class and accounted for 49% of the variance in Cardiac cachexia. When depression was dichotomized, depression and LVEF predicted 52.6% of the variance in CC., Conclusion: Depression predicts CC in patients with HF. Additional studies are needed to expand the knowledge of the role of the psychological determinants of this devastating syndrome.

Significance: Two of the leading causes of death worldwide are cancer and cardiovascular diseases. Most cancer patients suffer from a metabolic wasting syndrome known as cancer-induced cardiac cachexia, resulting in death in up to 30% of cancer patients. Main symptoms of this disease are severe cardiac muscle wasting, cardiac remodeling, and cardiac dysfunction. Metabolic alterations, increased inflammation, and imbalance of protein homeostasis contribute to the progression of this multifactorial syndrome, ultimately resulting in heart failure and death. Cancer-induced cardiac cachexia is associated with decreased quality of life, increased fatiguability, and decreased tolerance to therapeutic interventions., Recent Advances: While molecular mechanisms of this disease are not fully understood, researchers have identified different stages of progression of this disease, as well as potential biomarkers to detect and monitor the development. Preclinical and clinical studies have shown positive results when implementing certain pharmacological and non-pharmacological therapy interventions., Critical Issues: There are still no clear diagnostic criteria for cancer-mediated cardiac cachexia and the condition remains untreated, leaving cancer patients with irreversible effects of this syndrome. While traditional cardiovascular therapy interventions, such as beta-blockers, have shown some positive results in preclinical and clinical research studies, recent preclinical studies have shown more successful results with certain non-traditional treatment options that have not been further evaluated yet. There is still no clinical standard of care or approved FDA drug to aid in the prevention or treatment of cancer-induced cardiac cachexia. This review aims to revisit the still not fully understood pathophysiological mechanisms of cancer-induced cardiac cachexia and explore recent studies using novel treatment strategies., Future Directions: While research has progressed, further investigations might provide novel diagnostic techniques, potential biomarkers to monitor the progression of the disease, as well as viable pharmacological and non-pharmacological treatment options to increase quality of life and reduce cancer-induced cardiac cachexia-related mortality., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Astragalus polysaccharide (APS) is a key active ingredient isolated from Astragalus membranaceus that has been reported to be a potential treatment for obesity and diabetes by regulating lipid metabolism and adipogenesis, alleviating inflammation, and improving insulin resistance. However, whether APS regulates lipid metabolism in the context of cachexia remains unclear. Therefore, this study analysed the effects of APS on lipid metabolism and adipose expenditure in a heart failure (HF)-induced cardiac cachexia rat model.  METHODS: A salt-sensitive hypertension-induced cardiac cachexia rat model was used in the present study. Cardiac function was detected by echocardiography. The histological features and fat droplets in fat tissue and liver were observed by H&E staining and Oil O Red staining. Immunohistochemical staining, Western blotting and RT‒qPCR were used to detect markers of lipolysis and adipose browning in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Additionally, sympathetic nerve activity and inflammation in adipose tissue were detected., Results: Rats with HF exhibited decreased cardiac function and reduced adipose accumulation as well as adipocyte atrophy. In contrast, administration of APS not only improved cardiac function and increased adipose weight but also prevented adipose atrophy and FFA efflux in HF-induced cachexia. Moreover, APS inhibited HF-induced lipolysis and browning of white adipocytes since the expression levels of lipid droplet enzymes, including HSL and perilipin, and beige adipocyte markers, including UCP-1, Cd137 and Zic-1, were suppressed after administration of APS. In BAT, treatment with APS inhibited PKA-p38 MAPK signalling, and these effects were accompanied by decreased thermogenesis reflected by decreased expression of UCP-1, PPAR-γ and PGC-1α and reduced FFA β-oxidation in mitochondria reflected by decreased Cd36, Fatp-1 and Cpt1. Moreover, sympathetic nerve activity and interleukin-6 levels were abnormally elevated in HF rats, and astragalus polysaccharide could inhibit their activity., Conclusion: APS prevented lipolysis and adipose browning in WAT and decreased BAT thermogenesis. These effects may be related to suppressed sympathetic activity and inflammation. This study provides a potential approach to treat HF-induced cardiac cachexia., (© 2023. The Author(s).)

Cardiac cachexia is a muscle wasting process that often develops in those with chronic heart failure resulting in weight loss, low levels of physical activity, reduced quality of life, and is associated with a poor prognosis. The pathology of cardiac cachexia is complex with new evidence emerging that implicates several body systems. This review describes the pathophysiology associated with cardiac cachexia and addresses: 1) hormonal changes- neurohormonal abnormalities and metabolic hormone imbalance; 2) mechanisms of muscle wasting in cardiac cachexia, and the integral mechanisms between changed hormones due to cardiac cachexia and muscle wasting processes, and 3) associated abnormalities of gastrointestinal system that contribute to cardiac cachexia. These pleiotropic mechanisms demonstrate the intricate interplay between the affected systems and account for why cardiac cachexia is difficult to manage clinically. This review summarises current pathophysiology of cardiac cachexia and highlights symptoms of cardiac cachexia, implications for clinical practice and research gaps., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y. In contrast to many other health problems, fat accumulation in the heart is protective in this condition. Fat in the heart can be divided into epicardial, myocardial and cardiac steatosis. In this review, we describe and discuss these topics, pointing out the interconnection between heart failure and cardiac cachexia and the protective role of cardiac obesity. We also set the basis for possible screening methods that may allow for a timely diagnosis of cardiac cachexia, since there is still no cure for this condition. Several therapeutic procedures are discussed including exercise, nutritional proposals, myostatin antibodies, ghrelin, anabolic steroids, anti-inflammatory substances, beta-adrenergic agonists, medroxyprogesterone acetate, megestrol acetate, cannabinoids, statins, thalidomide, proteasome inhibitors and pentoxifylline. However, to this date, there is no cure for cachexia.

Introduction: Despitecardiac cachexia being a prevalent health problem among heart failure (HF) patients, it has been given little attention by nursing researchers. Therefore, this study aims to conduct a systematic review that investigates cardiac cachexia among patients with HF., Methodology: A systematic review will be performed according to the PRISMA guidelines to assess the findings of twelve selected studies which meet the inclusion criteria of the systematic review research. The selected articles were published between 2000 and 2020 across three databases: PubMed, CINAHL, and MEDLINE., Results: In comparison to cancer cachexia, cardiac cachexia has been insufficiently studied and is poorly understood. No definitive diagnostic method for cardiac cachexia has been identified in the literature. Age, smoking, and hypertension have been reported to be risk factors for cardiac cachexia. Cardiac cachexia has been significantly associated with lethal structural changes in the heart and has been measured using anthropometric measures and laboratory biomarkers. A combination of pharmacological and nonpharmacological treatments has been effectively implemented to manage cardiac cachexia., Conclusion: A focused multidisciplinary approachthat takes culture into consideration is required to set a variety of assessment and interventional strategies for the early detection and proper management of cardiac cachexia., (© 2021 Wiley Periodicals LLC.)

Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its course., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Heart failure (HF) is one of the most important global public health problems, as there is an increase in its prevalence and an estimated 23 million of the world's population live with this problem. HF is defined by the presence of structural and functional abnormalities of the cardiac muscle leading to an impairment of ventricular filling and ejection. Multiple comorbidities have been associated with an increased risk of developing cardiovascular diseases. Hypertension has been recognized as one of the most important factors, however, obesity, metabolic syndrome, as well as diabetes also play an important role in the onset of the disease. It is common to find in decompensated heart failure hospitalized patients an impaired nutritional status characterized mainly by the presence of nutritional deficiencies and sarcopenia, which can sometimes progress to cachexia. Therefore, an adequate evaluation through the correct use of nutritional risk tools should be the cornerstone to the prevention of risks. Multiple anthropometric and biochemical parameters are available to establish the nutritional status of hospitalized patients, however, alterations in blood volume presented in patients with HF may alter the result of such assessment. The effectiveness of dietary modifications in the prevention and treatment of different cardiovascular diseases enhanced by appropriate adherence to eating patterns such as the DASH and Mediterranean diet have been inversely associated with the incidence of HF., (Copyright: © 2021 Permanyer.)

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment., Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment., Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = -0.94; P = 0.036)., Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and 'healthy' EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Heart failure (HF) is a common complication of various cardiac diseases, and its incidence constantly increases. This is caused mainly by aging of populations and improvement in the treatment of coronary artery disease. As HF patients age, they tend to develop comorbidities, creating new problems for health-care professionals. Sarcopenia, defined as the loss of muscle mass and function, and cachexia, defined as weight loss due to an underlying illness, are muscle wasting disorders of particular relevance in the heart failure population, but they go mostly unrecognized. The coexistence of chronic HF and metabolic disorders facilitates the development of cachexia. Cachexia, in turn, significantly worsens a patient's prognosis and quality of life. The mechanisms underlying cachexia have not been explained yet and require further research. Understanding its background is crucial in the development of treatment strategies to prevent and treat tissue wasting. There are currently no specific European guidelines or recommended therapy for cachexia treatment in HF ("cardiac cachexia")., Competing Interests: The authors have declared no conflict of interest., (© 2020 Krysztofiak et al.)

Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in elderly patients with chronic diseases. The prevalence of sarcopenia in chronic heart failure (HF) patients amounts to up to 20% and may progress into cardiac cachexia. Muscle wasting is a strong predictor of frailty and reduced survival in HF patients. Despite many different techniques and clinical tests, there is still no broadly available gold standard for the diagnosis of sarcopenia. Resistance exercise and nutritional supplementation represent the currently most used strategies against wasting disorders. Ongoing research is investigating skeletal muscle mitochondrial dysfunction as a new possible target for pharmacological compounds. Novel agents such as synthetic ghrelin and selective androgen receptor modulators (SARMs) seem promising in counteracting muscle abnormalities but their effectiveness in HF patients has not been assessed yet. In the last decades, many advances have been accomplished but sarcopenia remains an underdiagnosed pathology and more efforts are needed to find an efficacious therapeutic plan. The purpose of this review is to illustrate the current knowledge in terms of pathogenesis, diagnosis, and treatment of sarcopenia in order to provide a better understanding of wasting disorders occurring in chronic heart failure.

Background: Heart Failure (HF) patients developed changes in body composition as overhydration, muscle-skeletal wear and cardiac cachexia (CC). The possible factors involved in the development of CC in Right Heart Failure (RHF) patients are venous congestion, nutrient malabsorption. However, in HF, the overhydration obscure the loss of fat-free mass and difficult the body composition assessment. Bioelectrical impedance vectorial analysis (BIVA) is a method validated and used for hydration status and body composition assessment in HF. The aim of this study was to investigate the body compositions changes assessment by BIVA in the subjects with and without RHF and evaluate the risk factors for devolvement CC in HF subjects., Material and Methods: Prospective cohort study. Subjects with confirmed diagnoses of HF, >18 years old without CC according to BIVA criteria were included. Subjects with congenital heart disease, cancer, HIV, and end-stage renal disease were excluded. Body composition was an assessment by BIVA. 288 HF patients were evaluated. RHF subjects had an impedance vector reduction (9.26 dR/H and -1.92 dXc/H, T2=14.9, D = 0.45, p<0.001), while subjects without RHF no-showed statistically significant changes (7.57 dR/H and 0.72 dXc/H, T2=3, D = 0.17, p = 0.200). The risks factors to development CC were age, RHF, phase angle < 5°, total body water were risks factors while handgrip strength was a protector factor., Conclusions: RHF has greater disturbances in body composition and is a risk factor to development CC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small-molecule inhibitor of MuRF1 in treating CHF-induced diaphragm myopathy and loss of contractile function., Methods: Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham-operated animals (sham) served as controls. One week post-left anterior descending coronary artery ligation animals were randomized into two groups-one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946-a recently described MuRF1-interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed., Results: Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P < 0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up-regulation of the MuRF1 and MuRF2 was attenuated after infarct., Conclusions: Our murine CHF model presented with diaphragm fibre atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Compound ID#704946 rescued from this partially, possibly by targeting MuRF1/MuRF2. However, at this stage of our study, we refrain to claim specific mechanism(s) and targets of compound ID#704946, because the nature of changes after 12 weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices., Objective: The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF)., Methods: We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality., Results: During a mean ± SD follow-up period of 2.5 ± 1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P < 0.0001]. CHE showed the best area under the curve value (0.745) for the prediction of all-cause mortality compared with the other objective nutritional indices. Net reclassification improvement afforded by adding CHE to the fully adjusted multivariable model was statistically significant for all-cause mortality (0.330; 95% CI: 0.112, 0.549, P = 0.0030)., Conclusion: CHE is a simple, strong prognostic marker for the prediction of all-cause mortality in patients with ADHF., (© American Society for Nutrition 2019.)

Background: Weight loss is a strong prognostic factor in chronic heart failure (CHF); however, little is known about its effects in patients with mild CHF. Therefore, we investigated the effects of weight loss in patients with mild CHF., Methods and Results: We analyzed a total of 242 outpatients with mild CHF from the J-MELODIC study cohort. Weight loss was defined as ≥5% weight loss in 1 year. Twenty-seven patients (11.2%) lost ≥5% weight in 1 year. Weight loss was associated with higher rates of underweight and worsening renal function in 1 year compared with the absence of ≥5% weight loss. The predictors of weight loss included edema, B-type natriuretic peptide, and diabetes mellitus at baseline. Although weight loss was significantly associated with subsequent cardiovascular death or hospitalization for HF (log-rank P = .002) and subsequent death from any cause (log-rank P = .002), underweight was not associated with these outcomes (log-rank P = .356 and P = .168, respectively). Even after adjusting for covariates, weight loss was a significant and independent risk factor for subsequent cardiovascular death or hospitalization for HF (hazard ratio 3.22, 95% confidence interval 1.10-8.41; P = .034)., Conclusions: In patients with mild CHF, ≥5% weight loss was a significant predictor for subsequent cardiovascular death or hospitalization for HF., (Copyright © 2018. Published by Elsevier Inc.)

Patients suffering from chronic heart failure (CHF) show an increased prevalence (~20% in elderly CHF patients) of loss of muscle mass and muscle function (i.e. sarcopenia) compared with healthy elderly people. Sarcopenia, which can also occur in obese patients, is considered a strong predictor of frailty, disability, and mortality in older persons and is present in 5-13% of elderly persons aged 60-70 years and up to 50% of all octogenarians. In a CHF study, sarcopenia was associated with lower strength, reduced peak oxygen consumption (peak VO 2 , 1173 ± 433 vs. 1622 ± 456 mL/min), and lower exercise time (7.7 ± 3.8 vs. 10.22 ± 3.0 min, both P < 0.001). Unfortunately, there are only very limited therapy options. Currently, the main intervention remains resistance exercise. Specialized nutritional support may aid the effects of resistance training. Testosterone has significant positive effects on muscle mass and function, and low endogenous testosterone has been described as an independent risk factor in CHF in a study with 618 men (hazard ratio 0.929, P = 0.042). However, the use of testosterone is controversial because of possible side effects. Selective androgen receptor modulators have been developed to overcome these side effects but are not yet available on the market. Further investigational drugs include growth hormone, insulin-like growth factor 1, and several compounds that target the myostatin pathway. The continuing development of new treatment strategies and compounds for sarcopenia, muscle wasting regardless of CHF, and cardiac cachexia makes this a stimulating research area., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF-1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined., Methods: We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double-blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure., Results: Patients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14-48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12-66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment., Conclusions: Carvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Obesity is known to be associated with the development of heart failure (HF). However, the relationship between the body mass index (BMI) and acute HF (AHF) remains to be elucidated. Eight hundred and eight AHF patients were enrolled in this study. The patients were assigned to four groups according to their BMI values: severely thin (n = 11, BMI <16), normal/underweight (n = 579, 16 ≤ BMI <25), overweight (n = 178, 25 ≤ BMI <30) and obese (n = 40, BMI ≥30). The patients in the severely thin group were more likely to be female, have systolic blood pressure (SBP) <100 mmHg and have valvular disease than normal/underweight patients. The patients in the overweight group were significantly younger than those in the normal/underweight, and those in the overweight group were more likely to have SBP ≥140 mmHg and hypertensive heart disease and less likely to have valvular disease than the patients in the normal/underweight group. The prognosis, including all-cause death, was significantly poorer among patients who were severely thin than those who were normal/underweight, overweight and significantly better among those who were overweight than those who were normal/underweight, severely thin and obese patients. A multivariate Cox regression model identified that severely thin [HR: 3.372, 95% confidence interval (CI) 1.362-8.351] and overweight (HR: 0.615, 95% CI 0.391-0.966) were independent predictors of 910-day mortality as the reference of normal/underweight. Overweight patients tended to have SBP ≥140 mmHg and be relatively young, while severely thin patients tended to have SBP <100 mmHg and be female. These factors were associated with a better prognosis of overweight patients and adverse outcomes in severely thin patients. These factors may contribute to the "obesity paradox" in severely decompensated AHF patients.

Background: Cachexia is a common complication in patients with advanced heart failure (HF) associated with inflammatory response activation. Atrial fibrillation (AF) is the most frequent arrhythmia (26%), probably both exacerbate the cardiac cachexia (CC)., Objectives: Evaluate the association of cardiac cachexia and atrial fibrillation in heart failure patients., Material and Methods: In a case control study, CC was diagnosed by electrical bioimpedance with vectorial analysis (BIVA). Subjects with congenital heart disease, cancer, HIV, drug use and other causes than HF were excluded., Results: Of the 359 subjects analyzed (men: 52.9%) median age 65years (55-74). Those with CC were older [72 (61-67)] vs. without [62 (52-70) years old, p<0.01]. During follow-up 47.8% of subjects developed CC and 17.27% AF, this was significantly more frequent in cachectic patients CC (23% vs 12.11%, OR: 2.17, 95% CI: 1.19-4.01, p=0.006). Subjects, with AF had lower left ventricular ejection fraction (25.49±12.96 vs. 32.01±15.02, p=0.08), lower posterior wall thickness (10.03±2.12 vs. 11.00±2.47, p=0.007), larger diameter of the left atrium (49.87±9.84 vs. 42.66±7.56, p<0.001), and a higher prevalence of CC (85.42% vs. 69.77%, p=0.028). The 50.58% of was in NYHA class I. In NYHA III, 22.95% were in AF vs. 12.10% with not AF (p=0.027)., Conclusion: The frequent coexistence of CC and AF as HF complications indicate greater severity of HF, regardless of its type of HF., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Heart failure (HF) is the main cause of mortality and morbidity in Western countries. Although evidence-based treatments have substantially improved outcomes, prognosis remains poor with high costs for health care systems. In patients with HF, poor dietary behaviors are associated with unsatisfactory quality of life and adverse outcome. The HF guidelines have not recommended a specific nutritional strategy. Despite the role of micronutrient deficiency, it has been extensively studied, and data about the efficacy of supplementation therapy in HF are not supported by large randomized trials and there is limited evidence regarding the outcomes. The aim of the present review is to analyze the state-of-the-art of nutritional deficiencies in HF, focusing on the physiological role and the prognostic impact of micronutrient supplementation.

The mortality associated with end-stage heart failure (HF) is high despite the development of new and increasingly effective drugs and non-pharmacological therapies. Repetitive hospitalizations predict fatal outcomes and each hospitalization should prompt individual conversations with the patient, the family, and the caregivers. A multidisciplinary disease management program promotes the education of patients and their families and modifies their behavior, with a view to ultimately improve the prognosis and quality of life. From the early to the late stages of HF, a multidisciplinary disease management program should be implemented. In Western societies this multidisciplinary management has long been debated and endorsed, in contrast to Japan, where it has just begun. In 2012, the Japanese Nursing Association launched a certification in chronic HF nursing. A Japanese version of HF disease management should soon be developed in its own social environment., (Copyright © 2015. Published by Elsevier Ltd.)

Objectives: Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition in CC and that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place., Methods: Body composition with regard to FFM, FM, and body fat distribution was assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and individuals with prior myocardial infarction-both n = 19) who were followed for 12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial dysfunction were measured., Results: N-terminal proBNP (NT-proBNP), midregional proANP (MR-proANP), and total adiponectin were elevated in CHF (p<0.001) and correlated inversely to BMI and FM. An inverse correlation was observed between pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was unaltered in all groups even though FM increased by 1.35 kg (p<0.05) and FFM decreased by 0.5 kg (p<0.05) in CC patients. The latter correlated inversely to baseline NT-proBNP, MR-proANP, and MR-proADM (p<0.05). No correlation to changes in FM was found., Conclusions: FM was associated with plasma NPs and total adiponectin at baseline; whereas changes in FM and FFM did not correlate to changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but FM increased, despite stable body weight in CC., (© 2013.)

Cardiac cachexia (CC) affects a large proportion of patients with chronic heart failure, a major public health issue in western countries. The pathophysiology of CC is complex and multifactorial, resulting from several factors interacting in a complex system with metabolic, immune and neurohormonal consequences, triggered to protect the heart and the circulation from damage. Despite the adverse clinical effects, CC diagnosis is not straightforward and has not specifically been targeted, with therapeutic strategies only comprising interventions with appetite stimulants, and anti-inflammatory substances. Here we review the molecular pathways underlying CC-related muscle wasting aiming to provide clues for the definition of CC-specific biomarkers and for the development of drugs that prevent and/or counteract muscle impairment, which will certainly impact the management of cardiovascular disorders., (© 2013.)

Background: The goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON)., Methods: In this non-randomized, retrospective case-control study, 32 middle-aged patients (81% males) with advanced systolic HF (80%≥ NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient>15 mm Hg) were studied before and after initiation of SILD (dose 73 ± 25 mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3 months and the long-term outcome were compared between groups., Results: SILD significantly reduced pulmonary vascular resistance (-32% vs. baseline), transpulmonary gradient (-25%) and increased cardiac output (+15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by -4.8%, absolutely by 4.3 ± 6 kg). During follow-up (median 349 days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30 days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p=0.0048)., Conclusions: In patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Abstract Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light–dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light–dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA β oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.

Background: Chronic heart failure (CHF) is a complex clinical syndrome associated with muscle wasting, which can progress to cardiac cachexia. Myostatin, a negative regulator of muscle growth, has been implicated in the pathophysiology of muscle wasting in CHF patients and suggested as a potential biomarker. The objective of this study was to investigate serum myostatin concentration in patients with CHF with preserved and reduced ejection fraction. Methods: The authors conducted a single-centre study comparing serum myostatin levels, functional and echocardiographic parameters, muscle mass, strength and function in patients with CHF to a control group without CHF. The study group was further divided into sub-groups with preserved and reduced or mildly reduced ejection fraction. Results: Results showed no significant differences in myostatin concentration between CHF patients and controls, and no correlation with sarcopenia or dynapenia. However, a higher myostatin concentration was found in patients with impaired systolic function (Me = 1675 pg/mL vs. Me—884.5 pg/mL; p = 0.007). A positive correlation between myostatin concentration and muscle mass (r = 0.27; p = 0.04), and functional parameters such as Norton (r = 0.35; p < 0.01), I-ADL (r = 0.28; p = 0.02) and Barthel scale (r = 0.27; p = 0.03) scores, was also observed. Conclusions: Myostatin appears to play a role in muscle wasting and its progression to cardiac cachexia in patients with impaired ejection fraction. Further research is needed to confirm these findings and explore myostatin's potential as a biomarker for muscle loss and a target for pharmacotherapeutic agents in this population of patients. [ABSTRACT FROM AUTHOR]

Mature mediastinal teratomas are infrequent, slow growing, and often asymptomatic. Traditionally, they present in the fourth decade or earlier and are found in the anterior mediastinum. These teratomas are often found incidentally on imaging, and surgical resection can be a challenge due to the size and location of the tumor; however, complete surgical excision is usually curative. Our case represents an infrequent benign giant (25 cm × 18 cm × 12 cm) mature intrathoracic mediastinal teratoma with uncommon clinical presentation of congestive heart failure and cardiac cachexia. The rare location of the tumor in the mid posterior mediastinum, very large teratoma, clinical presentation with right ventricular failure and cardiac cachexia, preoperative diagnostic dilemma, perioperative surgical challenge, and management marks this case unique. [ABSTRACT FROM AUTHOR]

Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Cachexia is a complex and multifactorial syndrome defined as severe weight loss and muscle wasting which frequently goes unrecognised in clinical practice [1]. It is a debilitating syndrome, resulting in patients experiencing decreased quality of life and an increased risk of premature death; with cancer cachexia alone resulting in 2 million deaths per annum [2]. Most work in this field has focused on cancer cachexia, with cardiac cachexia being relatively understudied – despite its potential prevalence and impact in patients who have advanced heart failure. We report here the protocol for an exploratory study which will: 1. focus on determining the prevalence and clinical implications of cardiac cachexia within advanced heart failure patients; and 2. explore the experience of cachexia from patients’ and caregivers’ perspectives. Methods A mixed methods cross-sectional study. Phase 1: A purposive sample of 362 patients with moderate to severe heart failure from two Trusts within the United Kingdom will be assessed for known characteristics of cachexia (loss of weight, loss of muscle, muscle mass/strength, anorexia, fatigue and selected biomarkers), through basic measurements (i.e. mid-upper arm circumference) and use of three validated questionnaires; focusing on fatigue, quality of life and appetite. Phase 2: Qualitative semi-structured interviews with patients (n = 12) that meet criteria for cachexia, and their caregivers (n = 12), will explore their experience of this syndrome and its impact on daily life. Interviews will be digitally recorded and transcribed verbatim, prior to qualitative thematic and content analysis. Phase 3: Workshops with key stakeholders (patients, caregivers, healthcare professionals and policy makers) will be used to discuss study findings and identify practice implications to be tested in further research. Discussion Data collected as part of this study will allow the prevalence of cardiac cachexia in a group of patients with moderate to severe heart failure to be determined. It will also provide a unique insight into the implications and personal experience of cardiac cachexia for both patients and carers. It is hoped that robust quantitative data and rich qualitative perspectives will promote crucial clinical discussions on implications for practice, including targeted interventions to improve patients’ quality of life where appropriate.

Heart failure (HF) is one of the most important global public health problems, as there is an increase in its prevalence and an estimated 23 million of the world's population live with this problem. HF is defined by the presence of structural and functional abnormalities of the cardiac muscle leading to an impairment of ventricular filling and ejection. Multiple comorbidities have been associated with an increased risk of developing cardiovascular diseases. Hypertension has been recognized as one of the most important factors, however, obesity, metabolic syndrome, as well as diabetes also play an important role in the onset of the disease. It is common to find in decompensated heart failure hospitalized patients an impaired nutritional status characterized mainly by the presence of nutritional deficiencies and sarcopenia, which can sometimes progress to cachexia. Therefore, an adequate evaluation through the correct use of nutritional risk tools should be the cornerstone to the prevention of risks. Multiple anthropometric and biochemical parameters are available to establish the nutritional status of hospitalized patients, however, alterations in blood volume presented in patients with HF may alter the result of such assessment. The effectiveness of dietary modifications in the prevention and treatment of different cardiovascular diseases enhanced by appropriate adherence to eating patterns such as the DASH and Mediterranean diet have been inversely associated with the incidence of HF. [ABSTRACT FROM AUTHOR]

Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y. In contrast to many other health problems, fat accumulation in the heart is protective in this condition. Fat in the heart can be divided into epicardial, myocardial and cardiac steatosis. In this review, we describe and discuss these topics, pointing out the interconnection between heart failure and cardiac cachexia and the protective role of cardiac obesity. We also set the basis for possible screening methods that may allow for a timely diagnosis of cardiac cachexia, since there is still no cure for this condition. Several therapeutic procedures are discussed including exercise, nutritional proposals, myostatin antibodies, ghrelin, anabolic steroids, anti-inflammatory substances, beta-adrenergic agonists, medroxyprogesterone acetate, megestrol acetate, cannabinoids, statins, thalidomide, proteasome inhibitors and pentoxifylline. However, to this date, there is no cure for cachexia.

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While angiotensin II (ang II) has been implicated in the pathogenesis of cardiac cachexia (CC), the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT) but not in TNF alpha type 1 receptor knockout (TNFR1KO) mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h) as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC), the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss.

Purpose of review Heart failure is a frequent problem in an ageing population, associated with high rates of morbidity and mortality. Today, it is important to not only treat heart failure itself but also the related comorbidities. Among them, cardiac cachexia is one of the major challenges. It is a complex multifactorial disease with a negative impact on quality of life and prognosis. Therefore, prevention, early recognition and treatment of cardiac cachexia is essential. Recent findings Cardiac cachexia frequently presents with skeletal as well as heart muscle depletion. Imaging-based diagnostic techniques can help to identify patients with cardiac cachexia and muscle wasting. Several blood biomarkers are available to detect metabolic changes in cardiac cachexia. Summary Several studies are currently ongoing to better comprehend the underlying pathophysiological mechanisms of cardiac cachexia and to find new treatments. It is essential to diagnose it as early as possible to initiate therapy. [ABSTRACT FROM AUTHOR]

Regardless current achievements of medicine, chronic heart failure (CHF) is still the leading cause of cardiovascular morbidity and mortality. A special cohort in CHF mortality are patients with progressive body mass loss. Recently the assessment of cachexia is restricted only with the tests revealing present atrophy, but not to predict it. Therefore, of the most significant investigation directions is search for reliable biomarkers of early diagnostics and efficacy assessment. The article focuses on the main biomarkers having potential prediction value and recommended for cardiac cachexia assessment.

Heart failure is often accompanied by severe malnutrition, which in combination with chronic inflammation, neurohormonal activation and reduced physical activity, is involved in the vicious cycle of heart failure, with progressive deterioration to cardiac cachexia. To date no specific treatment has been found for the cardiac cachexia syndrome. Although several alternative therapeutic trials have been investigated, the main treatment strategy for cardiac cachexia consists of nutritional intervention and exercise training. The main goal of nutritional intervention is maintenance of the body weight (without edema) within the normal range or slightly lower, and the avoidance of further tissue loss with long-term energy substrate restoration. No specific recommendations have been published for macro- and micronutrient ingredients. Patients should cover their daily caloric needs according to their activities, with individualized increases in the amount of proteins and sufficient vitamins and electrolytes. Particular attention should be paid to the needs of those patients with renal dysfunction or gut malabsorption and those on chronic diuretic treatment. Prolonged periods of fasting should be avoided. Enteral nutrition is the method of choice, if feasible, but parenteral supplementation may be indicated. Exercise training, and particularly aerobic training and or strength training, are strongly recommended for improving skeletal muscle abnormalities in heart failure with cachexia. Exercise training induces beneficial effects in protein synthesis, with anabolic, anti-inflammatory and anti-oxidative stress effects. Further study is needed to investigate the pathophysiological mechanisms of the cardiac cachexia syndrome and to develop specific preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]