Ischemic heart disease is the leading cause of death and the number of refractory severe patients is increasing. Therefore, it is crucial to develop new therapeutic strategies for severe
ischemic heart disease. We found that a low-energy
shock wave (SW) (about 10% of energy density that used for
urolithiasis) effectively increases the expression of
vascular endothelial growth factor (
VEGF) in cultured endothelial cells. Based on this in vitro study, we have started in vivo studies and have demonstrated that extracorporeal cardiac
shock wave therapy with a low-energy SW upregulates the expression of
VEGF, induces neovascularization, and improves
myocardial ischemia in a porcine model of chronic
myocardial ischemia without any adverse effects in vivo. On the basis of the promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic
therapy with low-energy SW for
ischemic heart disease. Our extracorporeal cardiac SW
therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe
coronary artery disease without indication of
percutaneous coronary intervention or coronary bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW
therapy was also effective to ameliorate LV remodeling after acute
myocardial infarction in pigs and to enhance angiogenesis in hindlimb
ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute
myocardial infarction and those with
peripheral artery disease. Thus, our extracorporeal cardiac SW
therapy is an effective, safe, and non-invasive angiogenic strategy in cardiovascular medicine and its indication is now rapidly expanding.