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Arteriogenesis (collateral artery growth) is nature s rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. Important hallmarks of arteriogenesis are enhanced levels of shear stress across recruited collateral pathways. Experimentally, a therapeutic increase in shear stress may be achieved by artificial stenosis, ligation or arterio-venous shunting distal the site of occlusion/stenosis. But, how can we induce collateral growth in humans? External counterpulsation is an elegant method to enhance non-invasively the shear stress in the arterial system. It is a promising therapy for symptomatic patients who have coronary artery disease. However, the mechanism of action of ECP remains unclear. In this prospective, controlled, proof-of-concept study the effect of external counterpulsation on coronary collateral artery growth was investigated via invasive pressure measurements. After a 7 week treatment a significant increase of the collateral flow index and the fractional flow reserve were detected.