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Managing the Effects of Cardiac Cachexia

Carlson, Heather ANP-BC, ACHPN; Dahlin, Constance M. MSN, ANP-BC, ACHPN, FPCN, FAAN

Journal of Hospice & Palliative Nursing: February 2014 - Volume 16 - Issue 1 - p 15–20
doi: 10.1097/NJH.0000000000000039
Symptom Management Series
Free
CE

Although cachexia is common in cancer, it is poorly understood in noncancer diagnoses. This article reviews cancer cachexia in cardiac disease. The definition, pathophysiology, and assessment specific to cardiac disease are delineated. Diagnostic workup is discussed. Finally, pharmacological and nonpharmacological interventions are offered.

Heather Carlson, ANP-BC, ACHPN, is a palliative nurse practitioner at Palliative Care Service, North Shore Medical Center, Salem, Massachusetts.

Constance Dahlin, MSN, ANP-BC, ACHPN, FPCN, FAAN, is a palliative nurse practitioner at Palliative Care Service, North Shore Medical Center, Salem, Massachusetts, and director of Professional Practice at Hospice and Palliative Nurses Association, Pittsburgh, Pennsylvania.

Address correspondence to Constance M. Dahlin, MSN, ANP-BC, ACHPN, FPCN, FAAN, Hospice and Palliative Nurses Association, One Penn Center West, Suite 425, Pittsburgh, PA 15276-0100 (cdahlin3@gmail.com).

The authors have no conflicts of interest to disclose.

Cardiac cachexia is a symptom sequela of advanced heart failure that was identified thousands of years ago. Around 400 BC, Hippocrates first described cardiac cachexia in Greek citizens suffering from a condition in which “the flesh is consumed and becomes water, …the shoulders, clavicles, chest, and thighs melt away… the illness is fatal.”1 Although science has advanced since Hippocrates’ observations, the occurrence of cardiac cachexia still remains poorly understood.

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CASE STUDY

Mr S. is a 76-year-old man with class III New York Heart Association congestive heart failure (CHF) who was recently hospitalized for a CHF flare with resting dyspnea occurring and worsening with minimal activity. During an outpatient visit with his advanced practice registered nurse (APRN), he explained that overall he felt weak and tired. Mrs S. commented that Mr S. was too skinny. Mr S. noticed that his clothes felt a bit too loose. He had little interest in food or eating. He knew that he should eat, but his taste changes resulted in lack of desire. When his wife was able to coax him to eat, he felt full after only a few bites. During eating, Mr S. experienced worsened shortness of breath resulting in longer mealtimes.

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DEFINITION OF SYMPTOM

Cardiac cachexia is defined as a complex metabolic disorder involving progressive weight loss accompanied by muscle wasting, fatigue, and weakness. The associated weight loss involves both the loss of lean muscle mass as well as fat and bone. Skeletal muscle wasting and loss of body weight precede loss of cardiac mass and are late signs in heart failure.2,3 Once cachexia occurs, it is impossible to reverse the muscle wasting by increasing caloric intake alone.4,5 Primary cachexia refers to “unintentional weight loss of more than 5% premorbid weight in a 6-month period with concurrent body mass index of less than 20 kg/m2 in patients younger than 65 years or less than 22 kg/m2 in patients older than 65 years with albumin level of less than 3.5 g/L, decreased total protein levels, anemia, elevated triglycerides, elevated glucose, and elevated lactic acid.”5-7 Secondary cachexia is a result of unintentional weight loss subsequent to altered anabolic states from noncancer conditions (eg, infections, chronic renal failure, and chronic heart failure).5 This phenomenon occurs in both chronic right-sided heart failure and in severe advanced stages of heart failure. It has also been suggested that cachexia can develop progressively through phases of precachexia to refractory cachexia.6,8,9 Common symptoms include anorexia, nausea, constipation, early satiety, alteration in taste, dyspnea while eating, depression, weakness, and generalized deconditioning.7,8 These symptoms promote further weight loss, and cachexia is typically irreversible with just diet and nutrition modifications.6

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IMPORTANCE

With the aging population resulting in a higher percentage of chronic illness, the prevalence of heart failure is proportionally increasing. Early diagnosis of cardiac cachexia, followed by comprehensive, multidisciplinary management, will improve quality of life. Treatment promotes restoration of body balance, maintains function, preserves safety, and increases survival.

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INCIDENCE

Cachexia, common in patients with advanced cancer and end-stage HIV/AIDS, affects patients with other progressive life-limiting illnesses such chronic obstructive pulmonary disease, CHF, end-stage heart disease, and chronic kidney disease.3 It is estimated that more than 80% of patients with advanced, noncancer illnesses experience cachexia. With higher frequency in the elderly, it will become more prevalent as increased numbers of patients develop heart failure.5 In 2008, 5.7 million Americans older than 65 years were hospitalized with heart failure.10 Statistics indicate that approximately 10% to 15% of patients with advanced CHF develop severe progressive weight loss, and two-thirds of patients with CHF develop muscle wasting.10 Studies have shown that approximately 10% of patients with either class III or IV New York Heart Association heart failure develop cachexia annually.7 Patients who develop cardiac cachexia have a 50% mortality rate in 18 months from time of their diagnosis.10 Because it becomes more pronounced in end-stage disease, cachexia has been found to be an important predictor of reduced survival in heart failure patients.6,7

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PATHOPHYSIOLOGY

Cardiac cachexia is not well understood. It is hypothesized that multiple pathways, including immunological, metabolic, and neurohormonal processes, are intricately involved in the activation of the complex mechanisms that result in cardiac cachexia. The precise etiology of the immune response activation within CHF has not been identified. Congestive heart failure alters gastrointestinal (GI) permeability, resulting in bowel wall edema, reducing intestinal absorption. Bacteria and endotoxins are allowed to subsequently stimulate inflammatory cytokine activation. These changes in the GI tract also result in systemic inflammation.7,10 It is theorized that hypoxia and the failing heart muscle are responsible for the release of inflammatory cytokines, specifically tumor necrosis factor α. Tumor necrosis factor α results in apoptosis or cellular death. This produces profound anorexia and exercise intolerance with simultaneous reduction in peripheral blood flow.7,10

The metabolic process corresponds to a higher metabolic rate, further necessitating increased caloric requirements in the presence of preexisting anorexia and fatigue. This response can occur in either the catabolic state with the release of the hormones leptin and growth hormone or the anabolic state with the release of ghrelin by cardiac myocytes and cells in the stomach lining, which increases the response to tumor necrosis factor α. The imbalance of anabolic and catabolic states leads to negative balance of energy within the body.10 Specific to cachexia caused by cardiac impairment, there is an increased muscle protein breakdown that differentiates it from cachexia caused by chronic obstructive pulmonary disease or cancer, which tends to reduce muscle protein synthesis.3,10 The inflammatory response resulting from heart failure leads to muscle breakdown resulting in fatigue, which significantly impacts a patient’s quality of life. This cycle of cardiac cachexia is demonstrated in Figure 1.

FIGURE 1

FIGURE 1

Tumor necrosis factor α decreases albumin production in the liver. Decreased protein synthesis produces an acceleration of lean tissue mass loss.10 Elderly patients with cardiac cachexia can develop fat malabsorption and GI protein loss.11 Again, a higher resting metabolic state in patients with advanced CHF requires the consumption of more calories just to accommodate respiratory effort. Patients with CHF have been found to have micronutrient deficiencies of folate and vitamins C, E, and B12.10 Inflammatory cytokines result in free radical production. However, antioxidants and repletion of vitamins C and E have been found to have the ability to suppress or decompose the elevated production of free radicals.11

Finally, subsequent neurohormonal abnormalities from impaired cardiac function lead to the development of cardiac cachexia. Given the complex systems involved, cachexia can occur shortly after the presentation of initial heart failure symptoms present or 3 to 6 months thereafter. The body releases angiotensin II, which signals water and sodium retention in the kidneys as well increase as aldosterone secretion. These hormones release norepinephrine, which decreases energy stores, impairing the autonomic reflex response.10 Another result of cardiac cachexia is impaired thyroid function, which affects cardiac contractility. This is caused by lower nutritional and caloric intake and low levels of testosterone in males. Of note, in a study about heart failure, low levels of testosterone were found in approximately 30% of men older than 65 years.10

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UNDERSTANDING THE EFFECTS OF THE CACHEXIA CYCLE

Assessment

Assessment begins with a thorough history of patient’s nutritional intake, weight loss, and symptoms (Table 1). There are several useful tools for measuring subjective reports of appetite loss and accompanying symptoms of cachexia. The Edmonton Symptom Assessment Scale–Revised is a 10-question Likert scale where patients indicate the severity of the symptoms they are experiencing, which includes pain, fatigue, drowsiness, nausea, appetite, dyspnea, anxiety, overall well-being, and any other symptoms they may be experiencing.12,13 Another tool is the Simplified Nutritional Assessment Questionnaire, which predicts weight loss.14 This questionnaire focuses on appetite, the taste, and daily food consumption. A low score of less than or equal to 14 indicates the potential for 5% weight loss in the next 6 months.14Table 1 is a simple assessment survey that reviews pertinent areas.

TABLE 1

TABLE 1

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Diagnostics

In addition to the subjective information, the nurse should obtain daily or weekly weights and encourage the patient to keep a daily food journal. Midarm circumference can be used to measure body fat and muscle mass in healthy individuals and can be used for longitudinal follow-up for patients with advanced illness while simultaneously serving as a prognostic indicator (Table 1).

There are some laboratory markers helpful in diagnosing cachexia, including prealbumin, cholesterol, and C-reactive protein. Prealbumin is the best marker of cardiac cachexia as it indicates protein-calorie malnutrition. C-reactive protein becomes elevated as a result of inflammation and is generally a nonspecific indicator but can be helpful to confirm a presumptive diagnosis of cachexia. Normal prealbumin levels are 16 to 35 mg/dL; a diagnosis of cardiac cachexia can be made when levels are less than 16, or if albumin is less than 3.2 g/L. Cholesterol may be lower in cardiac cachexia, and a total cholesterol level of less than 172 is associated with poor prognosis in cachectic patients.10 Body mass index is not an indicator of adequate body fat and muscle composition and should not be used in diagnosing cardiac cachexia.10

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CASE STUDY CONTINUED

Mr S. appeared to have some of the hallmark symptoms of cardiac cachexia. His weight was 144 lb, which was 15 lb less than his goal dry weight. His general appearance was frail, his arms were thin with notable muscle wasting, and his face appeared a bit sunken with bilateral temporal wasting. Blood values were significant. They revealed that his albumin had decreased from 3.4 to 2.9 g/L, indicating protein malnutrition, and his total protein had dropped from 7 to 5 g/L. In addition, his serum hemoglobin is low at 10 g/dL, and hematocrit fell to 30.4, indicating slight anemia. His cholesterol level was also a bit low at 180 mg/dL. His Karnofsky Performance Status Scale score was 50. The APRN asked him to complete the brief Simple Appetite Survey assessment, describing his appetite, feelings of fullness, the taste of food, and the amount he was typically able to eat. His score was 8, which indicated that he was at significant risk of losing more weight in the next few months.

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Diagnosing Cachexia

Cardiac cachexia results in loss of muscle, with or without loss of fat and bone. Hallmark symptoms of anorexia cachexia syndrome include loss of appetite, nausea, early satiety, anemia, weakness, fatigue, and food aversion.15 Assessment of depression is essential as cachexia may be a symptom of depression and poor functional status. Dyspnea should be assessed so that accommodations for oxygen during mealtimes can be made as necessary.

There is some variation in formulating a cardiac cachexia diagnosis. One approach is to make the diagnosis once patients experience nonedematous weight loss of more than 7.5% of their entire body weight over a 6-month period.10 Another approach is to make the diagnosis after involuntary loss of total body weight greater than 10%.11 This weight loss must occur while in a euvolemic state and in the absence of other cachectic states such as cancer or AIDS/HIV.

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CARDIAC CACHEXIA MANAGEMENT

Treatment

Traditional management of fatigue and cachexia in palliative patients has focused on energy conservation. Evidence has demonstrated that diminished physical activity actually promotes fatigue and contributes to muscle deconditioning.4 The current primary focus of treatment for patients with cardiac cachexia is to maximize caloric and protein intake while participating in daily, strength-building exercises, while balancing the patient’s symptoms and quality of life (see Figure 2 and Table 2).

FIGURE 2

FIGURE 2

TABLE 2

TABLE 2

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Dietary

The minimum caloric recommendations for patients with cachexia can be as high as 2800 kcal/d with 1.5 to 2.0 g of protein a day. Dietary supplements of thiamine, folate, vitamins C and D, and fish oil are recommended to decrease inflammatory process and improve micronutrients.10 Patients should be encouraged to eat smaller, more frequent meals to avoid fatigue. A consult to a cardiac nutritionist offers information to the patient and family regarding high-calorie foods necessary for weight gain. Moreover, he/she can assist in meal planning and serving sizes while incorporating patient food preferences.

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Pharmacological

There are limited pharmacological treatments available for cardiac cachexia. Rather than reversing cachexia itself, these medications are aimed at stimulating appetite.

Megestrol acetate (Megace) has been shown to improve fatigue and increase appetite in patients at dose of 160 mg/d. Symptomatic improvement in appetite is expected in less than a week after starting the medication. Weight gain occurs in 25% of patients and may take up to several weeks after starting treatment with megestrol acetate. Dose recommendation for weight gain is 480 to 800 mg/d; titrate dose slowly to avoid dose-related adverse effects. Adverse effects of megestrol acetate include edema, hyperglycemia, adrenal suppression, elevated liver enzymes, and higher risk of deep venous thrombus.16,17 It should be noted that megestrol acetate is contraindicated in patients with certain cancers such as GI cancers, due to potential for embolism.17

Alternatively, a trial of corticosteroids may stimulate appetite as well as decrease nausea. The effects, however, are usually limited to a few weeks, and adverse effects from corticosteroids increase over time.17 Prednisolone (prednisone) 20 to 40 mg/d or dexamethasone (Decadron) 4 to 6 mg/d is recommended, but only for short periods. However, there are considerations for its use in this cardiac population. First, many patients with CHF may have comorbid conditions. Steroid use in patients with diabetes mellitus should to be tightly monitored because glucose levels can rise. Because CHF affects the kidneys, these patients need to have their renal status monitored for any potential alternations. Finally, caution is essential for geriatric patients because steroids may cause delirium, particularly in patients with renal impairment.

Dronabinol (Marinol) is a synthetic cannabinoid that has been approved by the Food and Drug Administration for treatment of anorexia in patients with HIV/AIDS as well as an antiemetic for chemotherapy-induced nausea/vomiting. Some studies have shown its efficacy for improving appetite in cancer patients. However, the effects on cachexia appear to be limited, and its use does not result in any weight gain.18 Doses can start low, usually at 2.5 mg twice a day, to account for any other comorbidities the patient may have. Most patients will have a response with this dose; however, the daily range can go from 2.5 to 20 mg daily. Again, consideration should be given to the patient population as some patients may experience worsening nausea and delirium.18 Safety for geriatric patients is imperative because they may experience delirium or confusion. Common adverse effects include euphoric sensation, dizziness, confusion, and somnolence and typically resolved within the first 3 days of medication initiation.17

It is well known that angiotensin-converting enzyme inhibitors reduce morbidity and improve survival in patients with CHF. However, they may also have a role in the treatment of cardiac cachexia as well. Angiotensin-converting enzyme inhibitors have been found to reduce bacteria translocation, preserve GI function, and reduce protein breakdown, thus reducing loss of muscle mass.10 Enalapril, at a daily dose of 20 mg, has been shown to reduce development of weight loss in patients with CHF and may be used in patients with cardiac cachexia as their blood pressure tolerates. Studies have also shown that patients with cardiac cachexia who took a β-blocker for 6 months experienced greater weight gain, along with increased leptin levels, than did those with noncachectic CHF.10

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Interdisciplinary Care

Social Work

A social work consult may be beneficial to both the patient and family. Cachexia surrounds the issues of food and intake, and is fraught with food as the symbol for love and life. A discussion to separate the symptom from its meaning is essential to promoting peaceful mealtimes. Patients need support in telling family members that they are trying to eat and not rejecting family or their attempts to promote food intake. Families need support in not making food the sole indicator of social interaction, love, and life.

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Rehabilitative Services

A consult to rehabilitation services may be helpful, if the patient does not already have one as part of the CHF program. A physical therapist can distinguish between deconditioning and weakness and offer strategies to manage associated dyspnea. An occupational therapist can help with meal planning so that the patient is not so fatigued with preparation, and he/she does not eat. A respiratory therapist may help with dyspnea during meals and help promote more efficient and effective eating.

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Nursing

The role of nursing is pivotal in caring for a patient with cardiac cachexia. Nurses participate in all stages of care including assessment, treatment, education, and overall support. This complicated cluster of symptoms often reflects unmet needs of a patient with advanced cardiac disease. The nurse assesses the physical and psychosocial effects of weight loss and plays an important role in supporting the patient and their family. Assessment includes review of patient’s appetite, oral intake, amount of weight loss, level of fatigue, and evaluation of secondary symptoms including dyspnea, depression, and discomfort.16,18 Patient education should occur because patients may struggle to understand the correlation between weight loss and fatigue and how to best manage those symptoms.

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Evidence-Based Comprehensive Programs

Numerous multidisciplinary programs have been developed in the oncology and palliative care settings to maximize treatment of cachexia by improving patient’s symptoms, functional status, and food intake and decreasing level of fatigue, most notably the Cancer Nutrition and Rehabilitation Programme at McGill University in Canada and the Cancer Appetite and Rehabilitation Clinic in Pennsylvania.4 The aim of a multidisciplinary program is multifaceted. There are simultaneous strategies to manage cachexia. First there is treatment for elements of cachexia with administration of calories, nutrients, and protein. Second, there is the implementation of an exercise program designed for patients with end-stage cardiac to decrease loss and strength. Finally, systemic inflammation, which triggers anorexia, through medications and dietary supplements is reduced.

The Adelaide Hills Community Health Service (AHCHS) of South Australia developed a similar type of home-based program for their palliative care patients involving a 3-step program. The aim of the AHCHS program is to slow down the inflammatory response while providing a high-protein diet and tailored exercise focusing on building and preserving muscle mass.4 Initial assessments are conducted by members of the interdisciplinary team, which includes nursing, occupational therapy, and physical therapy, and an APRN monitors the patient’s progress, medications, and symptoms.

Dietitians encourage patients to consume 1.4 to 2 g of eicosapentaenoic acid (EPA) to reduce systemic inflammation. Eicosapentaenoic acid can be found in oily fish including salmon and mackerel or in vitamin supplements. They also instruct patients to eat a high-protein diet with whey protein supplements and daily recommendations of 1.2 to 2.0 g of protein per kilogram of body weight to help in building muscle mass. Patients of AHCHS are trained by physical therapists in resistance exercises with light weights and repetitive movements to build muscle strength. These exercises can be done in sitting or lying position for those palliative patients who do not have the strength to perform them in a standing position. Patients of AHCHS who completed the program were found to have higher Karnofsky Performance Status Scale scores than the national Australian average. Subjective responses from palliative patients enrolled in the AHCHS program reported overall improvement in function with reduced fatigue, allowing them to maintain autonomy and a sense of control, although some patients did report increased pill burden because of the numerous supplements.4

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CASE STUDY CONCLUSION

After explaining the diagnosis of cardiac cachexia to Mr S. and his wife, the APRN discussed his prognosis, treatment options, and goals of care with both of them (Figure 2). Mr S. agreed to meet with a nutritionist to learn about higher-calorie and -protein food options that he can try. His wife was eager to learn about what types of food she can prepare for him to get him to gain a little weight and now understands to make small frequent meals throughout the day. The APRN prescribed him a trial of daily megestrol acetate 160 mg, along with fish oil supplements in hopes of stimulating his appetite and instructed him to keep a daily food journal and monitor his weight. Finally, the APRN arranged a home physical therapy evaluation to determine exercises that can be accommodated to his current functional status.

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SUMMARY

Cardiac cachexia is a common symptom experienced with advanced heart disease. The pathophysiology is complex and not well understood, and the impact it has on morbidity, mortality, and health care expenditure is underestimated.2 It impairs patient’s quality of life by decreasing their level of functioning and can lead to depression. The nurse’s assessment is crucial in determining the diagnosis and formulating treatment plan. Management of cardiac cachexia includes dietary, pharmacological, and nonpharmacological treatments and works best when done by a multidisciplinary team. Future advances in pharmacology will hopefully lead to targeted drug therapy specific to preventing muscle and fat loss in end-stage heart disease. Overall, more research is needed to improve long-term prognosis of cardiac cachexia.

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References

1. Katz AM, Katz PB. Disease of the heart in the works of Hippocrates. Br Med J. 1962; 24 (3): 257–264.
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3. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle. 2010; 1 (1): 1–5.
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12. Edmonton Zone Palliative Care Program. Assessment Tools. 2013. http://www.palliative.org/newpc/proffesionals/tools/tools.html. Accessed October 31, 2013.
13. Watanabe S, Nekolaichuk C, Beaumont C, Johnson L, Myers J, Strasser F. A multi-center comparison of two numerical versions of the Edmonton Symptom Assessment System in palliative care patients. J Pain Symptom Manage. 2011; 41: 456–468.
14. Rolland Y. Screening older people at risk of malnutrition or malnourished using the Simplified Nutritional Appetite Questionnaire (SNAQ): a comparison with the mini-nutritional assesment (MNA) tool. J Am Med Dir Assoc. 2012; 13 (1): 31–34.
15. Morley J. Calories and cachexia. Curr Opin Clin Nutr Metab Care. 2009; 12 (6): 607–610.
16. Bruera E, Yennurajalingam S. Palliative care: overview of fatigue, weakness and asthenia. Up to Date. 2013. Last updated November 8, 2012. http://www.uptodate.com/contents/palliative-care-overview-of-fatigue-weakness-and-asthenia. Accessed October 29, 2013.
17. Jatoi A. Anorexia and cachexia. Online Cancer Management: A Multidisciplinary Approach. 2013. http://www.cancernetwork.com/cancer-management/anorexia-cachexia/article/10165/1802855. Accesssed May 15, 2013.
18. Bruera E, Dev R. Palliative care: assessment and management of anorexia and cachexia. Up to Date. 2013. Last updated August 22, 2013 http://www.uptodate.com/contents/palliative-care-assessment-and-management-of-anorexia-and-cachexia. Accessed October 29, 2013.
Figure

Figure

Keywords:

cachexia; cardiac cachexia; heart failure

© 2014 by The Hospice and Palliative Nurses Association.