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Postprandial hyperlipaemia impairs endothelial function, possibly via oxidative-stress-mediated mechanisms. The aim of this study was to evaluate the acute effects of an oral triglyceride load (OTGL) on peripheral endothelial function in heart failure patients with reduced ejection fraction (HFrEF) compared to healthy controls.Prospective cross-sectional.We enrolled 47 patients with HFrEF and 20 healthy controls. Peripheral endothelial function was assessed with EndoPAT2000 technology using a reactive hyperaemia index (RHI) and pulse wave amplitude (PWA) at baseline (after 8-h overnight fasting) as well as 1, 2, 3 and 4-h post-OTGL consumption (250-ml cream drink). Pulse wave amplitude index (PWAI) was calculated as a ratio of PWA at each time point to the baseline PWA.RHI at baseline was lower in HFrEF patients compared to controls (1.7 ± 0.3 and 2.3 ± 0.6, respectively; P = 0.001). The OTGL accounted for a physiologic increase in PWA in healthy controls (p = 0.01), but this change was not observed in HFrEF patients. After 4 h, vasodilator response was significantly increased in healthy controls but not patients with HFrEF (2.3 ± 1.3 vs. 1.3 ± 0.8 respectively, P 0.05).The main finding of this study was the impaired postprandial dynamic changes in peripheral endothelial function in patients with HFrEF compared to healthy controls. A high-fat load that caused acute hypertriglyceridaemia significantly increased resting blood flow and peak flow at reactive hyperaemia in healthy subjects. By contrast, patients with HFrEF exhibited impaired dynamic changes in peripheral endothelial function after oral triglyceride load.

Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Increased levels of inflammatory markers play a role in the imbalance between muscle protein synthesis and degradation. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modulators (SARMs) have demonstrated similar results like testosterone at improving lean body mass (LBM) with less side effects on androgen-dependent tissue.This review outlines the ongoing clinical development in the field of SARMs and their effectiveness in improving body composition and physical function. The included articles were collected at pubmed.gov and analyzed integrally.There is an unmet clinical need for safe and effective anabolic compounds such as SARMs. Despite the effect on LBM shown by SARMs in phase II clinical trials, results on improved physical function and muscle strength are still lacking and long-term outcomes have to be assessed in these patients. Moreover, there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.

Endpoints of large-scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and - with less certainty - testosterone in highly selected patients. Erythropoiesis-stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co-morbidities such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state-of-the-art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co-morbidities may be important for these patient-related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

Cachexia is a multifactorial disease characterized by a pathologic shift of metabolism towards a more catabolic state. It frequently occurs in patients with chronic diseases such as chronic heart failure and is especially common in the elderly. In patients at risk, cardiac cachexia is found in about 10% of heart failure patients. The negative impact of cardiac cachexia on mortality, morbidity, and quality of life demonstrates the urgent need to find new effective therapies against cardiac cachexia. Furthermore, exercise training and nutritional support can help patients with cardiac cachexia. Despite ongoing efforts to find new therapies for cachexia treatment, also new preventive strategies are needed.

Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physic...

The last several years have seen increasing interest in understanding cachexia, muscle wasting, and physical frailty across the broad spectrum of patients with cardiovascular illnesses. This interest originally started in the field of heart failure, but has recently been extended to other areas such as atrial fibrillation, coronary artery disease, peripheral artery disease as well as to patients after cardiac surgery or transcatheter aortic valve implantation. Tissue wasting and frailty are prevalent among many of the affected patients. The ageing process itself and concomitant cardiovascular illness decrease lean mass while fat mass is relatively preserved, making elderly patients particularly prone to develop wasting syndromes and frailty. The aim of this review is to provide an overview of the available knowledge of body wasting and physical frailty in patients with cardiovascular illness, particularly focussing on patients with heart failure in whom most of the available data have been gathered. In addition, mechanisms of wasting and possible therapeutic targets are discussed.

AIMS Changes in heart failure (HF) patients' body composition may be associated with reduced exercise capacity. The aim of the present study was to determine the overlap in wasting syndromes in HF (cachexia and sarcopenia) and to compare their functional impact. METHODS AND RESULTS We prospectively enrolled 207 ambulatory male patients with clinically stable chronic HF. All patients underwent a standardized protocol examining functional capacity, body composition, and quality of life (QoL). Cachexia was present in 39 (18.8%) of 207 patients, 14 of whom also fulfilled the characteristics of sarcopenia (sarcopenia + cachexia group, 6.7%), whereas 25 did not (cachectic HF group, 12.1%). Sarcopenia without cachexia was present in 30 patients (sarcopenic HF group, 14.4%). A total of 44 patients (21.3%) presented with sarcopenia; however, 138 patients showed no signs of wasting (no wasting group, 66%). Patients with sarcopenia had lower strength and exercise capacity than both the no wasting and the cachectic HF group. Handgrip strength, quadriceps strength, peak oxygen uptake (VO2 ), distance in the 6-minute walk test (6MWT), and QoL results were lowest in the sarcopenia + cachexia group vs. the no wasting group (P

The prevalence of iron deficiency (ID) in outpatients with heart failure with preserved ejection fraction (HFpEF) and its relation to exercise capacity and quality of life (QoL) is unknown. 190 symptomatic outpatients with HFpEF (LVEF 58 ± 7%; age 71 ± 9 years; NYHA 2.4 ± 0.5; BMI 31 ± 6 kg/m2) were enrolled as part of SICA-HF in Germany, England and Slovenia. ID was defined as ferritin

Sarcopenia is a common feature, and affects 20-47% of patients with heart failure (HF). Sarcopenia is also an independent predictor of impaired functional capacity, even after adjusting for clinical relevant variables, which is associated with adverse outcome in patients with HF. Areas covered: Several different pathophysiological pathways are involved in sarcopenic processes including altered nutrient intake and absorption, hormonal factor, inflammatory processes, oxidative stress, cellular proteolysis, and unhealthy lifestyle. Nutritional therapy, physical activity and/or exercise training have been associated with improved muscle mass or physical performance in HF. Few studies reported beneficial effects for muscle mass and physical performance, in those who received angiotensin-converting enzyme (ACE) inhibitors, or/and beta-blocker. In addition, testosterone, selective androgen receptor modulators, ghrelin agonist and myostatin inhibitors are currently under study as possible future therapeutic options. Expert commentary: Regular and adequate level of physical activity and/or exercise training, and sufficient nutritional intake or special nutritional supplementation may represent the best strategy for prevention or delay of sarcopenia and worsening physical performance in patients with HF. Maximal tolerated dosages of standard therapies for HF such as ACE-inhibitors or beta-blockers are first-line strategy, however it is difficult to recommend other pharmacological agents as part of routine treatment of sarcopenia.

There is an increasing awareness of the prevalence of iron deficiency in patients with heart failure (HF), and its contributory role in the morbidity and mortality of HF. Iron is a trace element necessary for cells due to its capacity to transport oxygen and electrons. The prevalence of iron deficiency increases with the severity of HF. For a long time the influence of iron deficiency was underestimated, especially in terms of worsening of cardiovascular diseases and developing anaemia. In recent years, studies with intravenous iron agents in patients with iron deficiency and HF showed new insights into the improvement of iron therapy. Additionally, experimental studies supporting the understanding of iron metabolism and the resulting pathophysiological pathways of iron have been carried out. The aim of this mini review is to highlight why iron deficiency is recognised as an important comorbidity in HF.

Background Chronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, muscle loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic and tissue inflammation and further contribute to low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) may improve mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models. Methods We investigated the impact of AG continuous subcutaneous administration (AG) by osmotic minipump (50 nmol/kg/day for 28 days) compared with placebo (P) on skeletal muscle mitochondrial enzyme activities, mitochondrial biogenesis regulators transcriptional expression and insulin signalling in a rodent post-myocardial infarction CHF model. Results No statistically significant differences (NS) were observed among the three group in cumulative food intake. Compared with sham-operated, P had low mitochondrial enzyme activities, mitochondrial biogenesis regulators transcripts, and insulin signalling activation at AKT level (P

Body wasting is a serious complication that affects a large proportion of patients with heart failure. Muscle wasting, also known as sarcopenia, is the loss of muscle mass and strength, whereas cachexia describes loss of weight. After reaching guideline-recommended doses of heart failure therapies, the most promising approach to treating body wasting seems to be combined therapy that includes exercise, nutritional counselling, and drug treatment. Nutritional considerations include avoiding excessive salt and fluid intake, and replenishment of deficiencies in trace elements. Administration of omega-3 polyunsaturated fatty acids is beneficial in selected patients. High-calorific nutritional supplements can also be useful. The prescription of aerobic exercise training that provokes mild or moderate breathlessness has good scientific support. Drugs with potential benefit in the treatment of body wasting that have been tested in clinical studies in patients with heart failure include testosterone, ghrelin, recombinant human growth hormone, essential amino acids, and β2-adrenergic receptor agonists. In this Review, we summarize the pathophysiological mechanisms of muscle wasting and cachexia in heart failure, and highlight the potential treatment strategies. We aim to provide clinicians with the relevant information on body wasting to understand and treat these conditions in patients with heart failure.

Aims Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. Methods and results From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls. During a mean follow-up of 27 months, 82 patients (57%) died from any cause. The mean resting heart rate of healthy subjects was 70 ± 13 b.p.m., and that of cancer patients was 79 ± 14 b.p.m. (P< 0.0001). As a sensitivity analysis, we excluded control subjects taking a beta-blocker, but resting heart rate remained increased in cancer patients vs. controls (P < 0.0001). Resting heart rate ≥75 b.p.m. [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.16–2.94; P = 0.01] significantly predicted survival in univariable analyses and remained an independent predictor of survival in a multivariate model (HR 1.67, 95% CI 1.01–2.78; P = 0.04). Furthermore, the heart rate stayed significant in a second model that included age and sex as well. Conclusion The present study is the first to show that resting heart rate independently of haemoglobin and tumour stage predicts survival in patients with advanced colorectal, pancreatic, and non-small cell lung cancer, and may therefore represent a therapeutic target.

Frailty is a functional term that describes a decline in physiological functions that leads to dependency, vulnerability to stressors, high risk for adverse health outcomes, increased risk of falls, and increased morbidity and mortality. The central role of inflammation and the cross-talk between frailty and sarcopenia have led to a condition termed physical frailty, in which muscle atrophy is viewed as the biological substratum of physical frailty. Different paradigms of ageing, including "inflamm-ageing", "oxi-inflamm-ageing", and "inflamm-inactivity" reveal inflammation as a common driver of age-related frailty. The key role of inflammation in frailty conditions have led to numerous studies screening for potential inflammatory biomarkers of frailty. This review summarizes the present knowledge of inflammatory biomarkers that are considered promising tools to evaluate frailty. Inflammatory biomarkers for different pathophysiological pathways have been identified, and can be divided into markers of inflammation, oxidative stress, muscle protein turnover and physical inactivity. Described candidate inflammatory biomarkers could support diagnosis, prognosis, and therapeutic decisions in frail elderly. Furthermore, exercise training and nutritional counselling could be implemented in the standard care of the elderly in order to prevent, delay, or ameliorate frailty and to reduce the levels of blood inflammatory biomarkers. Such tools and decision-making outcomes would improve selection and treatment of the elderly and contribute to the ultimate goal - healthy ageing.

Background Sarcopenia has been recently identified as a co-morbidity in patients with heart failure. Whether sarcopenia affects prognosis in non-cachectic HF patients is unknown. Purpose To assess the determinants of sarcopenia and its prognostic value in elderly males with HF. Methods A total of 73 non-diabetic, non-cachectic, male patients with HF and reduced left ventricular ejection fraction ≤40% (age: 68±7 years, left ventricular ejection fraction 29±8%) were enrolled. Sarcopenia was evaluated in accordance with revised definition of European working group on sarcopenia in older people 2 from 2018. Probable sarcopenia (or presarcopenia) was defined as low muscle strength, evaluated by lowest tertile of grip strength. A sarcopenia diagnosis was confirmed by the presence of low muscle quantity in addition to the low muscle strength, expressed as lowest tertile of appendicular skeletal muscle mass (ASM) adjusted by height square. Muscle mass was measured by dual energy X-ray absorptiometry. Patients were divided into 3 groups according to the diagnosis of the presarcopenia/sarcopenia/nonsarcopenia and were compared in respect to survival. Results 14 (19%) and 13 (18%) patients were diagnosed with presarcopenia and sarcopenia, respectively. They were older compared to nonsarcopenia patients (72±6 and 73±6 vs. 65±7, p Survival sarcopenia in heart failure Conclusions The rate of presarcopenia and sarcopenia was high in non-cachectic, elderly men with HF, and these patients have impaired survival compared to the patients with normal skeletal muscle status. Acknowledgement/Funding Grant of the Ministery of Science of Republic of Serbia 175033

Background Anaemia and iron deficiency (ID) are important factors for muscle function and exercise capacity in patients with chronic heart failure (HF). Their interaction in HF remains to be defined. Methods A total of 280 out-patients with stable chronic HF were enrolled with mean age of 67.0±10.7 years, 21%female, mean left ventricular ejection fraction (LVEF) was 38.9±13.4%, mean Body Mass Index (BMI) 29.3±5.5 kg/m2]. Anaemia was defined according to World Health Organization criteria [Haemoglobin (Hb) Results A total of 89 (32%) chronic HF patients had anaemia and 142 (51%) had iron deficiency at baseline. Patients with anaemia showed significant lower exercise capacity compared to patients without anaemia (peak VO2: 15.3±4.6 vs. 18.5±4.8 kg/min p0.05). Conclusion Both anaemia and ID are strongly associated with reduced exercise capacity in patients with HF. The effect of anaemia and iron deficiency together is stronger than that of anemia and ID alone. Reduced SPPB, 6MWT, and HGS are important risk factors for the development of anaemia or ID.

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.

Inadequate nutritional status has been linked to poor outcomes in patients with heart failure (HF). Skeletal muscle wasting affects about 20% of ambulatory patients with HF. The impact of nutritional intake and appetite on skeletal muscle wasting has not been investigated so far. We sought to investigate the impact of nutritional status on muscle wasting and mortality in ambulatory patients with HF. We studied 130 ambulatory patients with HF who were recruited as a part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) program. Muscle wasting was defined according to criteria of sarcopenia, i.e., appendicular skeletal muscle mass two standard deviations below the mean of a healthy reference group aged 18–40 years. Nutritional status was evaluated using the Mini-Nutritional Assessment—Short Form (MNA-SF). Functional capacity was assessed as peak oxygen consumption (peak VO2) by cardiopulmonary exercise testing, 6‑minute walk testing, and the Short Physical Performance Battery (SPPB). At baseline, 19 patients (15%) presented with muscle wasting. Patients with muscle wasting had significantly lower values of peak VO2, 6‑minute walk distance, SPPB, and MNA-SF score than patients without (all p < 0.05). In multivariate analysis, MNA-SF remained an independent predictor of muscle wasting after adjustment for age and New York Heart Association class (odds ratio [OR] 0.66; confidence interval [CI] 0.50–0.88; p < 0.01). A total of 16 (12%) patients died during a mean follow-up of 21 months. In Cox regression analysis, MNA-SF (OR 0.80, CI 0.64–0.99, p = 0.04), left ventricular ejection fraction (OR 0.93, CI 0.86–0.99, p = 0.05), and peak VO2 (OR 0.78, CI 0.65–0.94, p = 0.008) were predictors of death. MNA-SF is an independent predictor of muscle wasting and mortality in ambulatory patients with HF. Nutritional screening should be included as a fundamental part of the overall assessment of these patients.

Natriuretic peptides play an important role in the diagnosis and risk stratification of patients with acute and chronic heart failure. Multiple studies have shown that these peptides are liable to the influence of individual factors. For N-terminal-pro-B-type natriuretic peptide (NT-proBNP) some of these confounding factors have been evaluated over the years such as age, gender, New York Heart Association (NYHA) class and body mass index (BMI). The aim of this study was to establish confounding factors of mid-regional pro-atrial natriuretic peptide (MR-proANP) assessment.We studied 684 patients (94% male, age 61.2±11.2, left ventricular ejection fraction [LVEF]35%-45%, NYHA class (I/II/III/IV: 8.4/45.8/39.5/6.3%), ischaemic aetiology 71%, body mass index [BMI] 26.5±4.3kg/m(2), mean MR-proANP 296.0±281.0pmol/L, mean NT-proBNP 2792.0±5328.6pg/mL, mean creatinine level 110.2±38.0μmol/L and mean haemoglobin 13.9±1.5g/dL) with clinically stable chronic heart failure. MR-proANP levels increased with increasing NYHA class (p0.0001) and an increasing BMI category was associated with decreasing values of MR-proANP (p0.0001). We found MR-proANP to be independently associated with BMI, creatinine, ischaemic aetiology, LVEF and NYHA class. Meanwhile, NT-proBNP was independently associated with BMI, creatinine, haemoglobin, LVEF and NYHA class.MR-proANP is subject to the almost identical influencing factors like NT-proBNP. The effects of anaemia warrant further study.

Aims Circulating immune cells have a significant impact on progression and outcome of heart failure. Long non-coding RNAs (lncRNAs) comprise novel epigenetic regulators which control cardiovascular diseases and inflammatory disorders. We aimed to identify lncRNAs regulated in circulating immune cells of the blood of heart failure patients. Methods and results Next-generation sequencing revealed 110 potentially non-coding RNA transcripts differentially expressed in peripheral blood mononuclear cells of heart failure patients with reduced ejection fraction. The up-regulated lncRNA Heat2 was further functionally characterized. Heat2 expression was detected in whole blood, PBMNCs, eosinophil and basophil granulocytes. Heat2 regulates cell division, invasion, transmigration and immune cell adhesion on endothelial cells. Conclusion Heat2 is an immune cell enriched lncRNA that is elevated in the blood of heart failure patients and controls cellular functions.

Changes in heart failure (HF) patients' body composition may be associated with reduced exercise capacity. The aim of the present study was to determine the overlap in wasting syndromes in HF (cachexia and sarcopenia) and to compare their functional impact.We prospectively enrolled 207 ambulatory male patients with clinically stable chronic HF. All patients underwent a standardized protocol examining functional capacity, body composition, and quality of life (QoL). Cachexia was present in 39 (18.8%) of 207 patients, 14 of whom also fulfilled the characteristics of sarcopenia (sarcopenia + cachexia group, 6.7%), whereas 25 did not (cachectic HF group, 12.1%). Sarcopenia without cachexia was present in 30 patients (sarcopenic HF group, 14.4%). A total of 44 patients (21.3%) presented with sarcopenia; however, 138 patients showed no signs of wasting (no wasting group, 66%). Patients with sarcopenia had lower strength and exercise capacity than both the no wasting and the cachectic HF group. Handgrip strength, quadriceps strength, peak oxygen uptake (VOLosing muscle with or without weight loss appears to have a more pronounced role than weight loss alone with regard to functional capacity and QoL among male patients with chronic HF.ClinicalTrials.gov Identifier NCT01872299.

Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physical well-being and reduced quality of life. Cutoff values have been identified for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin, 100 μg/l, or ferritin, 100 to 300 μg/l, with transferrin saturation of 20%. Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products. Most clinical studies have been performed using ferric carboxymaltose with good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class. Data from meta-analyses also suggest beneficial effects for hospitalization rates for heart failure and reduction in cardiovascular mortality rates. A prospective trial to investigate effects on morbidity and mortality is currently ongoing. This paper highlights current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options.

Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies, and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartate-resistant acid phosphatase 5a, and novel substances like epigallocatechin-3-gallate. In summary, the progress to combat muscle wasting is in full swing, and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon support by improved and more helpful strategies.

BACKGROUND C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke. METHODS Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m(2)) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA. RESULTS CAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p

AIMS Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P