Chronic heart failure: an example of a systemic chronic inflammatory disease resulting in cachexia
Introduction
The syndrome of chronic heart failure comprises a central cardiac event, whose importance is diluted with time. Chronic heart failure is no longer a pure cardiac entity, but involves several, initially adaptive and later detrimental, neurohumoral compensatory mechanisms. Moreover, peripheral manifestations of the disease, such as endothelial dysfunction [1], skeletal muscle changes [2], [3], and disturbances in ventilatory control [4], are major determinants of the symptoms of chronic heart failure patients. Meticulous dissection of the various components of this disease has provided tremendous progress in terms of pathophysiology.
In an attempt to identify a common circulating factor to explain the severe weight loss and anorexia, characteristic of both terminally ill heart failure and cancer patients, Levine et al. [5] were the first to observe elevated levels of cachectin or tumor necrosis factor (TNF)-α in patients with severe chronic heart failure. Their landmark study led to a paradigm shift in heart failure research. Since then, numerous investigations have identified a new portfolio of biologically active molecules, termed cytokines, to play an important role in the development and progression of heart failure. Technical improvements in the detection and measurement of cytokines and their receptors, the development of genetically engineered molecules and knock-out animals, and the availability of huge collections of blood samples derived from patients enrolled in mega-trials, made it possible to rapidly gain insight in this domain.
Whereas the presence of immune activation in chronic heart failure is now widely accepted, as well as the prognostic relevance of chronic inflammation [6], [7], [8], the site and the source of cytokine production are still a matter of controversy. Although the inciting event is located in the heart, cross-talk between the myocardium on the one hand, and the immune system, peripheral tissues and organs on the other hand, will lead to the overproduction of proinflammatory cytokines and, inevitably, to their detrimental effects. This plausible explanation reinforces the overall view that heart failure is no longer a pure cardiac disease, but a multi-system disorder.
Section snippets
Neurohumoral adaptations
Irrespective of etiology, cardiac failure begins with an insult to pump function. Progression of the disease, however, is characterised and dominated by the involvement of peripheral organs, tissues and cells. These homeostatic mechanisms serve adaptation in acute conditions, but cause further deterioration of cardiac function over the long term. Hence, the stage for a vicious circle is set.
Some 50 years ago, management of heart failure patients aimed at symptom alleviation by the reduction of
Conclusion
The challenge in the management of patients with chronic heart failure lies in the integration of the multiple facets of the disease. Treatment with ACE-inhibitors, spironolactone and beta-blockade provide rectification of the neurohumoral maladaptative processes. Recent insights in the pathophysiology of this syndrome, however, have urged clinicians to enter novel therapeutic domains. These include modification of other neurohormonal pathways, such as endothelin antagonism and interference
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