Patients suffering from severe heart failure often experience weight loss and muscle weakness, also known as """"""""cardiac cachexia"""""""". This syndrome is characterized by loss of body weight, decreased functional status, and increased mortality. Although many factors are likely to be involved in the pathogenesis of wasting, weight loss must ultimately be the consequence of a negative energy imbalance. We will test the hypothesis that high levels of daily energy expenditure and sympathetic nervous system hyperactivity contribute to """"""""wasting"""""""" in heart failure patients. Thereafter, we will examine the clinical efficacy of chronic beta- blockade to attenuate the effects of high levels of energy expenditure and sympathetic activation on loss of fat-free mass and fat mass.
The first aim i s to determine whether total daily energy expenditure and sympathetic nervous system activity is higher in heart failure patients compared to age-matched healthy controls.
The second aim i s to determine whether treatment with chronic beta- adrenergic blockade added to standard therapy will reduce the high levels of daily energy expenditure and sympathetic nervous system activation compared to a placebo cohort. We will examine the impact of toprol therapy in a 6-month double-blind, placebo controlled randomized trial, specifically measuring and analyzing changes in: 1) total daily energy expenditure and its components, 2) sympathetic nervous system activity and 3) body composition in heart failure patients. Daily energy expenditure and its components (resting metabolic rate and physical activity) will be quantified from doubly labeled water and indirect calorimetry; sympathetic nervous system activity will be assessed from norepinephrine kinetics using infusions of 3H norepinephrine, and fat-free mass and fat mass from dual energy x- ray absorptiometry. This clinical trial will lay the groundwork for future nutritional and pharmacological strategies designed to restore energy balance, prevent cardiac cachexia and improve nutritional status in patients with heart failure.
