Ischemic heart disease is the leading cause of death and a major cause of hospital admissions, with the number of affected patients increasing worldwide. The current management of
ischemic heart disease has three major therapeutic options: medication,
percutaneous coronary intervention (PCI), and
coronary artery bypass grafting (CABG). However, the prognosis for patients with severe
ischemic heart disease without indications for PCI or CABG still remains poor due to the lack of effective treatments. It is therefore crucial to develop alternative therapeutic strategies for severe
ischemic heart disease. Extracorporeal
shock wave (SW)
therapy was introduced clinically more than 20 years ago to fragment
kidney stones, which has markedly improved the treatment of
urolithiasis. We found that a low-energy SW (about 10% of the energy density used for
urolithiasis) effectively increases the expression of
vascular endothelial growth factor (
VEGF) in cultured endothelial cells. Based on this in vitro study, we initiated in vivo studies and have demonstrated that extracorporeal cardiac SW
therapy with a low-energy SW up-regulates 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 promising results in animal studies, we performed a series of clinical studies in patients with severe
coronary artery disease without indication for PCI or CABG, including, firstly, an open trial followed by a placebo-controlled, double-blind study. In both studies, our extracorporeal cardiac SW
therapy improved symptoms, exercise capacity, and myocardial perfusion in patients with severe
coronary artery disease. Importantly, no procedural complications or adverse effects were noted. The SW
therapy was also effective in ameliorating
left ventricular remodeling after acute
myocardial infarction (MI) in pigs and in enhancing angiogenesis in hind-limb
ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute MI and in those with
peripheral artery disease. Thus, our extracorporeal cardiac SW
therapy appears to be an effective, safe, and non-invasive angiogenic approach in cardiovascular medicine and its indication could be extended to a variety of ischemic diseases in the near future. In this article, we briefly summarize our work in animals and humans, and discuss the advantages and perspectives of our extracorporeal SW
therapy.