Although glycolysis increases in heart failure, the subsequent oxidation of glycolytically derived pyruvate (glucose oxidation) is impaired.6 This results in an uncoupling of glycolysis from glucose oxidation, increasing proton production, and decreasing cardiac efficiency.6 Two potential therapeutic approaches to overcome this problem are to increase mitochondrial pyruvate uptake or to stimulate PDH (the rate-limiting enzyme for glucose oxidation) (Figure 4). The gene discussed is PDP1; the disease is heart failure.