Double-Blind and Placebo-Controlled Study of the Effectiveness and Safety of Extracorporeal Cardiac Shock Wave Therapy for Severe Angina Pectoris

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp he number of patients with severe angina pectoris without indications for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is rapidly increasing worldwide and their prognosis still remains poor. 1,2 Thus, it is crucial to develop new therapeutic strategies for these patients. We have previously demonstrated that extracorporeal cardiac shock wave (SW) therapy with low-energy SW (≈10% of the energy density used for urolithiasis) ameliorates myocardial ischemia and dysfunction in a porcine model of chronic myocardial ischemia in vivo. 3, 4 We subsequently demonstrated in an open trial that our SW therapy effectively improved chest pain symptoms and exercise tolerance without any adverse effects in 9 patients with severe angina pectoris. 3,5 In the present study, to further confirm the effectiveness and safety of our SW therapy, we performed a double-blind placebo-controlled trial in patients with severe angina pectoris. MethodsWe enrolled 8 consecutive patients with severe angina pectoris who already had undergone CABG or PCI, but who no longer had further indications for these therapies even though they still suffered from stable effort angina under intensive medication (M/F, 5/3; age, 70±3 years) (Table).The patients were treated with one series of placebo and the SW therapy in a double-blind and cross-over manner with an interval of 3 months. One series of therapy comprised 3 sessions per week. Throughout the study, the patient and the doctor in charge were not informed of the type of therapy. We performed the SW therapy (200 shoots/spot at 0.09 mJ/mm 2 for 40-60 spots per session; Modulith SLC, Storz Medical, Kreuzlingen, Switzerland) as described previously. 3,5 As placebo, the patients underwent the procedure of SW therapy but without irradiation. The patients were followed-up for 3 months after completion of the therapy. We evaluated symptoms using the Canadian Cardiovascular Society (CCS) class score, the patient's requirement for nitroglycerin, 5 exercise tolerance in a 6-min walk, and a cardiopulmonary exercise test, and cardiac function assessed by MRI (Achieva 1.5 T, Philips, Eindhoven, Netherlands). The left ventricular ejection fraction (LVEF) was measured using contiguous short-axis slices obtained by cine MRI; end-diastolic and end-systolic endocardial traces were used to determine end-diastolic and end-systolic left ventricular (LV) volumes, respectively. We also evaluated the number of circulating progenitor cells in peripheral blood by FACS analysis 2 days before the 1 st session and 1 h after the 3 rd session in 7 of the 8 patients Background: Low-energy shock wave (SW) therapy has improved myocardial ischemia in both a porcine model and in patients with severe angina pectoris.

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

“…We have developed a non-invasive angiogenic therapy with extracorporeal low-energy shock waves (SW), and have demonstrated its efficacy and safety in a porcine model of chronic myocardial ischemia 7 and patients with angina pectoris. 8, 9 Furthermore, we have demonstrated that SW therapy ameliorates LV remodeling after AMI in pigs in vivo. 10, 11 However, it remains to be examined whether SW therapy also exerts anti-inflammatory effects on AMI in addition to its angiogenic effects.…”

Shock wave treatment enhances endothelial proliferation via autocrine vascular endothelial growth factor

“…ESWT is an effective, safe, and non-invasive therapeutic strategy for severe coronary artery disease (Fukumoto et al, 2006;Khattab et al, 2007;Kikuchi et al, 2010;Vasyuk et al, 2010). In this study, we demonstrated that SW treatment up-regulates the expression of VEGF in HUVECs, leading to an increase in VEGF protein secretion.…”

“…Extracorporeal shock wave therapy (ESWT) has been recently introduced as a novel noninvasive option for the treatment of patients with severe coronary artery disease, such as angina pectoris, ischemic heart failure, and systolic dysfunction (Fukumoto et al, 2006;Khattab et al, 2007;Kikuchi et al, 2010;Vasyuk et al, 2010). ESWT has been shown to promote coronary angiogenesis in the ischemic myocardium and improve myocardial function in vivo in a porcine model of chronic myocardial ischemia (Nishida et al, 2004).…”

Extracorporeal Shock Wave Therapy for Digital Ulcers of Systemic Sclerosis: A Phase 2 Pilot Study

“…Myocardial blood flow and cardiac function were improved and enhanced VEGF production was observed in vitro and in vivo. The efficacy and safety of ESWT for patients with angina pectoris has also been reported (Fukumoto et al 2006;Kikuchi et al 2010). Moreover, Hayashi et al (2012) reported that endothelial nitric oxide synthase played a critical role in ESWT-induced accelerated wound healing in diabetic mice by promoting VEGF expression and neovascularization.…”