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Metabolic Modulation in Chronic Heart Failure Patients: Cardiac and Whole Body Effects

 

Mads Halbirk

Summary

The role of the metabolic abnormalities in chronic heart failure patients is unsettled. Animal studies and preliminary human studies have shown beneficial effects of altering substrate supply and metabolism, and metabolic modulation has been considered a promising new treatment strategy. In separate studies in congestive heart failure (CHF) patients, we studied metabolic and cardiac effects of1. 48-hour GLP-1 infusion2. 28-days acipimox treatmentas additional therapies to standard therapy.We studied non-diabetic CHF with ischemic heart disease. All studies were designed as randomized double-blind placebo-controlled cross-over studies. Efficacy measures were LVEF, diastolic function, tissue-Doppler regional myocardial function, exercise testing, non-invasive CO, and brain natriuretic peptide. Blood pressure, heart rate, and metabolic parameters were recorded. Sub-studies of whole body metabolism and skeletal muscle were performed at the completion of an intervention period, and patients were examined using hyperinsulinemic clamp, indirect calorimetry, forearm, and tracer methods.In both studies we achieved the intended metabolic modulation. Neither treatment had any effects on LVEF, Cardiac index, or exercise capacity. Tissue-Doppler indices and BNP remained unchanged. In both studies the degrees of myocardial scarring were extensive. During GLP-1 infusions hypoglycemic events were common (nine events in eight patients).In conclusion, we did not detect effects on the selected efficacy measures of cardiac function by the achieved metabolic modulation. Further studies are needed to characterize specific metabolic treatment strategies and to identify those patients in whom such treatments may be beneficial.