Clinical and experimental evidence demonstrating the effects of tumor necrosis factor-alpha (TNF-α) in patients with heart failure continues to accumulate. It is well established that high concentrations of TNF-α appear in the circulation of patients with heart failure and that these levels have a directly proportional correlation with the patient's functional class. TNF-α levels also show a linear relation with prognosis. These circulating levels are responsible for the decreased expression of myocardial TNF-α receptors observed in heart failure. As a result of extrapolation of findings from experimental animals, we assume that TNF-α is deleterious to myocardial function in humans because it induces a negative inotropic state in patients who have not undergone heart transplant. Supporting this assumption is the fact that the resolution or improvement of pressure overload (obstructive hypertrophic myocardiopathy, by ethanol ablation) and volume overload (terminal dilated myocardiopathy, by ventricular assistance) states is accompanied by a decrease in myocardial TNF-α expression. The use of specific antagonists of circulating TNF-α in patients with symptomatic heart failure has been demonstrated to be safe and possibly effective. At present, multicenter studies are under way to assess the efficacy of this antagonism in a larger number of patients. If the results of these studies are favorable, we will have new therapeutic elements for managing patients with advanced hear failure. The transplanted heart behaves differently from the native heart. From the early stages of HTx, myocardial TNF-α expression is greatly increased (much more than in patients with heart failure) and not associated with contractile dysfunction, in contrast with what occurs in the native heart. However, we know that the transplanted heart soon develops ventricular hypertrophy, fibrosis, diastolic dysfunction, and late graft failure, even in the presence of normal epicardial coronary arteries. Clinical evidence suggests that TNF-α may be involved in these processes.
- Heart failure
- Heart transplant
- Tumor necrosis factor-alpha
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine