Decompensated heart failure and cachexia: Is it time to legalize anabolics?

Abstract

Heart failure is the leading cause of hospitalization in the western world with an annual cost estimated at $30 billions in the USA. Hospitalized patients with the syndrome are at 35– 50% short-term risk for death or rehospitalization [1] .C urrent medical and ICD therapy reduced the incidence of sudden cardiac death. However, these improvements in patient management will increase the percentage of patients progressing to advanced heart failure, a condition characterized by severe symptoms and lengthy hospitalizations. In these patients, it is very difficult to start life saving therapies, like ACEinhibitorsandbeta-blockersbecauseoftheinstabilityand theseverehemodynamicabnormalities.Manyofthesepatients are cachectic and inotrope dependent. Clinical management is more difficult in the presence of cardiac cachexia. Cachexia is present in 12–16% of outpatients with chronic heart failure [2] but the incidence increases in patients with end stage heart failure [3]. Although it is a syndrome associated with significant morbidity and mortality, there is currently no causal therapy for cachexia [2,4–7]. Over the past few years, cardiac cachexia has been brought into focus by a number of studies, fuelling an interest in defining optimal patient management strategies. Cachexia is characterized by muscle wasting and loss of fat and bone mass [8]. The pathophysiological mechanisms which lead to tissue wasting have not been clarified. However, it has been suggested that apoptosis and fibrosis [9,10], catabolic/anabolic imbalance, cytokines and other proinflammatory mediators, the ubiquitin system [11], natriuretic peptides [12], catecholamines [13], renin–angiotensin system [14], insulin resistance and abnormalities in the GH anabolic pathway, are all implicated in the pathogenesis of tissue wasting and cachexia [15]. Recently, Bocchi et al. [16], investigated the effects of high doses of recombinant human growth hormone (GH) in 6 patients with cardiac cachexia and decompensated advanced CHF (5 dobutamine-dependent). Inotropic therapy is associated with increased mortality and should be used only in selected patients with acute heart failure or in the so called inotrope-dependent patients ( 5 out of 6 in this study). Inotropic therapy has been used as a bridge to oral lifesaving therapies but not always with success. In the study of Bocchi et al. [16] ,G H improved impressively functional class and hemodynamics. Moreover, allowed discontinuation of inotropes infusion, permitted the