Cachexia is a serious clinical consequence of almost all chronic diseases when reaching advanced stages. Its prevalence ranges from 5–15% in end‐stage chronic heart failure to 50–80% in advanced ...malignant cancer. Cachexia is also frequently occurring in patients with chronic kidney disease, chronic obstructive pulmonary disease (COPD) or neurological diseases, and rheumatoid arthritis. Mortality rates of patients with cachexia range from 15–25% per year in severe COPD through 20–40% per year in patients with chronic heart failure or chronic kidney disease to 20–80% in cancer cachexia. In the industrialized world (North America, Europe, and Japan) where epidemiological data are to some degree available, the overall prevalence of cachexia (due to any disease and not necessarily associated with hospital admission) is growing with the growth of the chronic illness prevalence, and it currently affects around 0.5–1.0% of the population, i.e. around 6–12 million people. From this, one can estimate that 1.5–2 million deaths are occurring in patients with cachexia per year. It is also a very significant health problem in other parts of the globe, but epidemiological data are scarce. The multifactorial nature of cachexia is now much better understood, and particularly, the role of inflammatory mediators and the imbalance of anabolism and catabolism are considered important therapeutic targets. Several approaches to develop cachexia and muscle wasting treatments have failed to be successful in phase III clinical trials, but new approaches are in development. Given the high prevalence and very high mortality associated with cachexia, advances are urgently needed for patients worldwide.
The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become ...available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re‐interpretation of information already considered in the 2016 ESC/HFA guidelines.
Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium–glucose co‐transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter‐defibrillators in non‐ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta‐analyses have given us the chance to provide refined recommendations in selected other areas.
Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.
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.
Patients with COVID‐19 disease are prone to develop significant weight loss and clinical cachexia. Three reports with altogether 589 patients that reported on weight loss and cachexia in COVID‐19 ...were identified. Disease severity of patients and the timing of the assessment during the disease course in these patients were variable—65 patients (11%) were intensive care treated at the time of assessment, and 183 (31%) were cared for in sub‐intensive or intermediate care structures. The frequency of weight loss ≥5% (that defines cachexia) was 37% (range 29–52%). Correlates of weight loss occurrence were reported to be raised C‐reactive protein levels, impaired renal function status, and longer duration of COVID‐19 disease. Underweight status by WHO criteria (BMI < 18.5 kg/m2) was only observed in 4% of patients analysing data from seven studies with 6661 patients. Cachexia assessment in COVID‐19 needs assessment of weight loss. COVID‐19 associated cachexia is understood to affect muscle and fat tissue as is also seen in many other chronic illness‐associated forms of cachexia. There are many factors that can contribute to body wasting in COVID‐19, and they include loss of appetite and taste, fever and inflammation, immobilization, as well as general malnutrition, catabolic–anabolic imbalance, endocrine dysfunction, and organ‐specific complications of COVID‐19 disease such as cardiac and renal dysfunction. Treatment of COVID‐19 patients should include a focus on nutritional support and rehabilitative exercise whenever possible. Specific anti‐cachectic therapies for COVID‐19 do not exist, but constitute a high medical need to prevent long‐term disability due to acute COVID‐19 disease.
Graphical Abstract
Graphical Abstract
The registry data presented by Mahmood et al.9 demonstrate that CAR T-cell recipients experience severe cardiac events (SCEs) at significant rates. In these ...patients, cardiovascular risk factors and cardiovascular disease atrial fibrillation and heart failure including a decline in left ventricular ejection fraction (LVEF) were significantly more frequent. CAR T-cell infusion exerts direct and indirect effects on the cardiovascular system (via cytokines, activated monocytes/macrophages, and/or directly from T cells). SCEs presented as heart failure, cardiogenic shock, and myocardial infarction, together with increased biomarkers. SCEs in turn were associated with overall and non-relapse mortality.
Background
Cachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for ...the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called ‘orphan diseases’. The cut‐off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population).
Methods
For this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top‐10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non‐hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status.
Results
We estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer).
Conclusions
The absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.
Abstract Cachexia in the context of heart failure (HF) has been termed cardiac cachexia, and represents a progressive involuntary weight loss. Cachexia is mainly the result of an imbalance in the ...homeostasis of muscle protein synthesis and degradation due to a lower activity of protein synthesis pathways and an over-activation of protein degradation. In addition, muscle wasting leads to of impaired functional capacity, even after adjusting for clinical relevant variables in patients with HF. However, there is no sufficient therapeutic strategy in muscle wasting in HF patients and very few studies in animal models. Exercise training represents a promising intervention that can prevent or even reverse the process of muscle wasting, and worsening the muscle function and performance in HF with muscle wasting and cachexia. The pathological mechanisms and effective therapeutic approach of cardiac cachexia remain uncertain, because of the difficulty to establish animal cardiac cachexia models, thus novel animal models are warranted. Furthermore, the use of improved animal models will lead to a better understanding of the pathways that modulate muscle wasting and therapeutics of muscle wasting of cardiac cachexia.
Background
Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute ...decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information.
Methods
Two hundred sixty‐eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co‐morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual‐energy X‐ray absorptiometry was present in 47 patients (17.5%).
Results
During a mean follow‐up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N‐terminal pro‐B‐type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01–3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction.
Conclusions
Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co‐morbidity.
We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti‐cancer therapies. This includes an ...increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways.
We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti‐cancer therapies.
The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients.
We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio‐oncology.
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