570 Prevalence and prognosis of cardiac cachexia in acute heart failure patients

Aims Cachexia is characterized by a pathological shift of metabolism towards a catabolic state. The prevalence of cardiac cachexia in heart failure (HF) patients is around 10% and it recognizes a negative prognostic impact. In this study we would like to evaluate prevalence and prognosis of cardiac cachexia in acute heart failure (AHF) patients. Methods and results This is an observational retrospective study enrolling patients with diagnosis of acute heart failure (AHF) de novo or not, admitted to our department from January 2015 to September 2018 within 12 h from emergency department admission. Patients underwent to clinical examination, laboratory analysis and echocardiography. Cardiac cachexia was defined as unintentional weight loss, with or without skeletal muscle wasting, of at least 5% of baseline weight during the previous year. For the diagnosis, three of the following factors are also required: anorexia, fatigue, reduced muscle strength, reduced fat-free mass index, and abnormalities in blood biomarkers (haemoglobin ≤12 g/dl, serum albumin <3.2 g/dl, elevated IL-6, or increased C-reactive protein).1 Patients were followed for 1 year after hospital discharge for the composite outcome of HF re-hospitalization and cardiovascular death through 1 year. A total of 415 AHF patients were included in this analysis. 111 patients met the criteria for the diagnosis of cardiac cachexia. Median age was 78(70–83) years. Patients with cardiac cachexia showed higher age [79 (73–84) vs. 77 (68–82) years; P = 0.005], length of hospital stay [12 (8–15) vs. 9 (6–13) days; P = 0.004], and RDW [14.9 (13.9–16.3) vs. 15.3 (14.3–16.9); P = 0.02] with respect to patients without cachexia. Moreover, patients with cachexia demonstrated reduced eGFR [53 (38–68) vs. 48 (31–60) ml/min/m2; P = 0.03] and TAPSE [18 (15–20) vs. 15 (14–19) mm; P = 0.002] compared to patients without cachexia. No differences were found among groups in terms of NTproBNP. In-hospital mortality was higher in patients with cachexia compared to other patients (6.3% vs. 1.3%; P = 0.005). Univariate Cox regression analysis confirmed the poor prognosis of patients with cachexia at one month [HR: 2.53 (1.24–5.19); P = 0.01], six months [HR: 2.47 (1.61–3.77); P < 0.001] and 1 year [HR: 2.04 (1.40–2.98); P < 0.001]. Conclusions Patients with cardiac cachexia were characterized by renal dysfunction and right ventricle dysfunction. These alterations should act as worsening factors in terms of abdominal venous congestion and subsequent malabsorption. Finally, in our population, cardiac cachexia was related to poor short term and long term outcome as confirmed by recent studies.

Polymorphism of the ITGAM gene (rs7193943) and bioelectric impedance analysis as potential predictors of cachexia in chronic heart failure

Cardiac cachexia (CC) is an unfavorable metabolic syndrome leading to exacerbation of chronic heart failure (CHF) and a higher risk of death. The main factor contributing to the development of cachexia is the ongoing inflammatory process mediated by genes (e.g. Integrin Subunit Alpha M—ITGAM). The study aimed to assess the relationship between a single nucleotide polymorphism (SNP) -323G > A of the ITGAM and the occurrence of nutritional disorders in patients with CHF. 157 CHF patients underwent clinical and nutritional screening. Body composition was evaluated by bioelectrical impedance analysis (BIA). Patients with cachexia were characterized by significantly lower weight, body mass index (BMI), lower fat mass (FM), albumin, and hemoglobin. Lower values of BIA parameters: capacitance of membrane (Cm), phase angle (PA), and impedance ratio (Z200/Z5) were noted in women. Those patients demonstrated significantly higher values of creatinine, c-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and pulmonary artery systolic pressure (PASP). A significantly higher risk of cachexia was reported in patients: aged ≥ 74 years (OR 3.55), with renal failure (OR 3.75), New York Heart Association classification (NYHA) III-IV (OR 2.83), with moderate or severe malnutrition according to the score of subjective global assessment (SGA) (OR 19.01) and AA genotype of ITGAM gene (OR 2.03). Determination of the -323G > A SNP in the ITGAM may prove to be a useful marker (after confirmation in further studies and appropriate validation) in the assessment of the risk of nutritional disorders in patients with CHF.

Prognostic significance of epicardial adipose tissue in heart failure with preserved and reduced ejection fraction

Background Increased epicardial adipose tissue (EAT) thickness correlates with metabolic syndrome, insulin resistance, microvascular dysfunction and enhanced pericardial restraint. Purpose We measured echocardiographic EAT thickness in heart failure (HF) patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction to determine whether EAT could bear prognostic significance at clinical follow-up. Methods We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. A composite of cardiovascular death and HF-related hospitalization was chosen as endpoint during follow-up. Results Patients with HFpEF displayed higher EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p<0.0001). During a median follow-up of 20.9 months (IQR 15–25 months), we reported 34 cardiovascular deaths and 146 HF hospitalizations, with no significant differences between the two HF subsets. EAT predicted adverse events independently from body mass index and well-established markers of poor prognosis (e.g., NT-proBNP, peak oxygen consumption). The risk of adverse events increased with increasing EAT thickness in HFpEF and with EAT thinning in HFrEF. Kaplan-Meier analyses for the composite endpoint showed that in HFpEF, the survival probability was significantly lower in patients with thicker EAT than those with thinner EAT. In HFrEF, conversely, patients with thicker EAT had a higher survival probability than those with reduced EAT thickness (Figure 1). Conclusion EAT accumulation is more marked in HFpEF than HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcome, which may be due to increased mechanical restraint and secretion of pro-inflammatory and pro-atherogenic adipokines. In HFrEF, greater EAT thickness seems to have a protective role, while EAT thinning is associated with a worse prognosis, likely reflecting a catabolic state (i.e. cardiac cachexia). Larger studies will clarify whether EAT is a bystander or an active player in the different HF phenotypes. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Sarcopenia-derived exosomal micro-RNA 16-5p disturbs cardio-repair via a pro-apoptotic mechanism in myocardial infarction in mice

Sarcopenia is a pathophysiological malfunction induced by skeletal muscle atrophy. Several studies reported an association between sarcopenia-induced cardiac cachexia and poor prognosis in heart disease. However, due to lack of an established animal models, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood. Here, we developed a novel sarcopenia-induced cardiac repair disturbance mouse model induced by tail suspension (TS) after cardiac ischemia and reperfusion (I/R). Importantly, we identified a specific exosomal-microRNA marker, miR-16-5p, in the circulating exosomes of I/R-TS mice. Of note, sarcopenia after I/R disturbed cardiac repair and raised the level of circulating-exosomal-miR-16-5p secreting from both the atrophic limbs and heart of TS mice. Likewise, miR-16-5p mimic plasmid disturbed cardiac repair in I/R mice directly. Additionally, in neonatal rat ventricular myocytes (NRVMs) cultured in vitro under hypoxic conditions in the presence of a miR-16-5p mimic, we observed increased apoptosis through p53 and Caspase3 upregulation, and also clarified that autophagosomes were decreased in NRVMs via SESN1 transcript interference-mediated mTOR activation. In conclusion, we show the pro-apoptotic effect of sarcopenia-derived miR-16-5p, which may be behind the exacerbation of myocardial infarction. Therefore, miR-16-5p can be a novel therapeutic target in the context of cardiac repair disturbances in sarcopenia–cachexia.

Prevalence and effect of cardiac cachexia in advanced heart failure patients living in northern ireland

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Northern Ireland Chest Heart and Stroke Background/Introduction: Cardiac cachexia (CC) is a multifactorial wasting syndrome, resulting in significant weight loss and reduction in muscle mass. This is reflected in a detrimental effect on the patients’ physical condition, quality of life and increases the patient’s risk of premature death. Nonetheless, cardiac cachexia remains frequently unrecognised in clinical practice and therefore understudied. Purpose To determine the prevalence and effect of cardiac cachexia in 200 patients with advanced heart failure (NYHA class III-IV) living in Northern Ireland. Methods A mixed methods cross sectional study of patients recruited from a regional heart failure centre. A total of 200 patients with NYHA class III-IV heart failure were consented, enrolled and detailed data collected from their records. Anthropometric measures were taken (i.e. measures of lean muscle mass and fat tissue) and each individual completed three validated questionnaires - EQ-5D-5L (quality of life), FACIT-Fatigue and FAACT (various wellbeing subscales). Results This population was predominately male (65.5%), with an average age of 74.4 years. Of the 200 NYHA class III-IV patients recruited, 30 were identified as cachectic (15%) Physically, cachectic patients were approximately 25 kg lighter than non-cachectic patients (p < 0.01) with an average BMI of 21.8 ± 4.4. The cachectic group showed significant reductions in mid-upper arm circumference (p < 0.01), skinfold thickness (p < 0.01) and upper arm fat area (p < 0.01), in comparison to the non-cachectic group. Measures of muscle mass were reduced, for example upper arm muscle circumference and area (p < 0.01), as well as grip strength (p < 0.01 for both right and left hands). Quality of life results from the EQ-5D-5L [see figure part b)] indicated an overall reduction for the cachectic group (p = 0.047). Of the EQ-5D-5L subscales, mobility and ‘usual activities’ were significantly reduced (p = 0.02 and p < 0.01 respectively), highlighting a significant change in the daily routine and ability of these patients. The FACIT-Fatigue questionnaire showed cachectic patients to be significantly more fatigued (p < 0.01) [see figure part a)], whilst the FAACT demonstrated reduced physical wellbeing (p = 0.02) and greater issues with diet and appetite (p < 0.01). Conclusions This is the first prevalence study of cardiac cachexia within Northern Ireland. The 15% prevalence rate shows that the syndrome is relatively common in the advanced heart failure population. Cardiac Cachexia has severe physical consequences, attributed to an individual’s weight loss in both fat and muscle tissue. Such changes may explain the subsequent decrease in mobility and the ability of these patients to conduct their ‘usual activities’. Increased fatigue, reduced physical wellbeing and issues with diet and appetite only intensify these dire physical effects. It is hoped that these results will highlight the impact of this syndrome and promote targeted interventions.

The phenomenon of weight loss in patients with chronic heart failure

A characteristic sign of chronic heart failure (CHF) is a high frequency of comorbid conditions, one of which is the phenomenon of weight loss. Cardiac cachexia is a systemic metabolic disorder characterized by an unintentional decrease in body weight due to loss of all body components, namely, skeletal muscle, adipose tissue and bone tissue, and identified as a marker of nutritional status, has prognostic value in patients with CHF, regardless of age, NYHA class, left ventricular ejection fraction, and peak oxygen consumption. The article discusses the prevalence, criteria, prognostic significance of cardiac cachexia, as well as immune, metabolic and neurohormonal pathogenetic mechanisms that lead to anabolic-catabolic imbalance and contribute to the progression of CHF. Given the methodological difficulties of proper assessment of unintentional body weight loss over a certain previous period of outpatient follow-up in patients with CHF, it becomes urgent to determine the objective («static») characteristics of the nutritional status of patients, which are associated with an unfavorable clinical prognosis. The article demonstrates the results of our own research to determine prognostic factors based on indicators of the nutritional status of patients the clinical significance of the loss of individual body components is highlighted, preventive and therapeutic approaches to influence body weight loss in patients with CHF are described – nutritional support, neurohormonal blockade, the effect on the intestinal microflora, correction of anemia and iron deficiency, the use of appetite stimulants, immunomodulatory agents, anabolic hormones and physical training.