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. 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.
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. 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. 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.
(Enlarge Image)
Figure 1.
Understanding the effects of the cachexia cycle. Based on the information in Springer et al.
Tumor necrosis factor α decreases albumin production in the liver. Decreased protein synthesis produces an acceleration of lean tissue mass loss. Elderly patients with cardiac cachexia can develop fat malabsorption and GI protein loss. 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. 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.
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. 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.