2014 Distinguished Scientist - William R. Hiatt, MD, Master of the Society for Vascular Medicine (MSVM), FAHA
William R. Hiatt’s clinical research career has focused on peripheral artery disease (PAD) and understanding the mechanisms underlying the disease pathophysiology as a basis for developing new treatments. Peripheral artery disease is an atherosclerotic disorder that limits blood flow to exercising muscle, but the resultant functional limitations are not well explained by the hemodynamic disease severity. With funding from the NIH Academic Award in Vascular Disease, Dr. Hiatt and his colleague Dr. Eric Brass hypothesized that chronic alterations in skeletal muscle metabolism were a key component of the disease pathophysiology. A series of coordinated studies over the ensuing 15 years demonstrated marked alterations in PAD skeletal muscle metabolism including accumulation of metabolic intermediates of oxidative metabolism (muscle acylcarnitines) in proportion to the reduction in peak exercise performance, profound evidence of mitochondrial DNA injury, alterations in muscle oxidative enzyme expression and decrease in the activity of the electron transport chain. These findings provided evidence of an acquired skeletal muscle mitochondrial myopathy in PAD and served as a basis to develop novel therapeutic interventions. Subsequent studies tested the clinical benefits and mechanisms of response to supervised exercise training that served as a basis for current ACC-AHA guidelines in PAD. Numerous clinical trials have evaluated the role of drugs (L-carnitine derivatives, PDE-3 inhibitors, prostaglandins, 5-hydroxytryptimine antagonists, antiplatelet drugs, antibiotics, lipid drugs, nitric oxide modulating drugs), biologics (gene therapy and cell therapy) and devices (peripheral catheters) in treating all clinical stages of PAD. Dr. Hiatt has been supported in his research by CPC Clinical Research; a non-profit created by the University of Colorado as a stand-along but affiliated Academic Clinical Trials Organization. Since 2003 Dr. Hiatt’s clinical research has been informed by service on FDA advisory panels including the Cardiovascular and Renal Drugs Advisory Committee and currently the Endocrinologic and Metabolic Drugs advisory committee.