Extracorporeal Shock Wave Therapy for Ischemic Cardiovascular Disorders

Abstract

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.

Effect of low-energy shockwave therapy on angiogenic factors in the penile tissue of diabetic rats

“…[19] It has been proved that L-ESWT treatment of human myocardial tissue undergoing ischemia upregulates the expression of VEGF and induces neovascularization devoid of any adverse effects. [19] A similar restorative effect of L-EWST on the VEGF expression levels was observed in our diabetic rats without any statistical significance.…”

Extracorporeal Low-Energy Shock-Wave Therapy Exerts Anti-Inflammatory Effects in a Rat Model of Acute Myocardial Infarction

“…Based on our previous studies, 7-11, 18 we performed low-energy SW therapy (0.1 mJ/mm 2 , approximately 10% of the energy used for the lithotripsy treatment, 200 shots, 1 Hz, to the whole heart) using a specially designed SW generator equipped with an echocardiographic probe (Storz Medical AG, Kreuzlingen, Switzerland) under inhalation anesthesia with 2% isoflurane. The SW group was subjected to SW therapy 3 times in the first week (1, 3 and 5 days after AMI), whereas the control group underwent the same procedures 3 times including anesthesia but without SW treatment.…”

“…First, in the present study, we chose the condition of SW therapy (eg, energy levels, number of shots) based on our previous studies 7-11, 18 and did not test other therapeutic conditions. It is reported to affect the inflammatory state and LV remodeling after AMI.…”

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

“…We have previously demonstrated that low-energy extracorporeal cardiac shock wave therapy improves myocardial ischemia in a porcine model of chronic myocardial ischemia and patients with severe angina pectoris through enhanced myocardial angiogenesis. [4][5][6][7] Recently, we have further demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy also induces angiogenesis and ameliorates myocardial ischemia in a porcine model of chronic myocardial ischemia. 8 LIPUS is also used for the treatment of patients with several diseases in orthopedics, dentistry, and brain stimulation.…”