A multicenter trial of extracorporeal cardiac shock wave therapy for refractory angina pectoris: report of the highly advanced medical treatment in Japan
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We have previously demonstrated that cardiac shock wave therapy (CSWT) effectively improves myocardial ischemia through coronary neovascularization both in a porcine model of chronic myocardial ischemia and in patients with refractory angina pectoris (AP). In this study, we further addressed the efficacy and safety of CSWT in a single-arm multicenter study approved as a highly advanced medical treatment by the Japanese Ministry of Health, Labour and Welfare. Fifty patients with refractory AP [mean age 70.9 ± 12.6 (SD) years, M/F 38/12] without the indications of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were enrolled in 4 institutes in Japan. Ischemic myocardial regions in the left ventricle (LV) were identified by drug-induced stress myocardial perfusion imaging (MPI). Shock waves (200 shots/spot at 0.09 mJ/mm2) were applied to 40–60 spots in the ischemic myocardium 3 times in the first week. The patients were followed up for 3 months thereafter. Forty-one patients underwent CSWT and completed the follow-up at 3 months. CSWT markedly improved weekly nitroglycerin use [from 3.5 (IQR 2 to 6) to 0 (IQR 0 to 1)] and the symptoms [Canadian Cardiovascular Society functional class score, from 2 (IQR 2 to 3) to 1 (IQR 1 to 2)] (both P < 0.001). CSWT also significantly improved 6-min walking distance (from 384 ± 91 to 435 ± 122 m, P < 0.05). There were no significant changes in LV ejection fraction evaluated by echocardiography and LV stroke volume evaluated by cardiac magnetic resonance imaging (from 56.3 ± 14.7 to 58.8 ± 12.8%, P = 0.10, and from 52.3 ± 17.4 to 55.6 ± 15.7 mL, P = 0.15, respectively). Percent myocardium ischemia assessed by drug-induced stress MPI tended to be improved only in the treated segments (from 16.0 ± 11.1 to 12.1 ± 16.2%, P = 0.06), although no change was noted in the whole LV. No procedural complications or adverse effects related to the CSWT were noted. These results of the multicenter trial further indicate that CSWT is a useful and safe non-invasive strategy for patients with refractory AP with no options of PCI or CABG.
KeywordsAngiogenesis Cardiac shock wave therapy Refractory angina pectoris Myocardial ischemia
We thank Dr. Ernest H. Marlinghaus (Storz Medical AG, Switzerland) for valuable comments on our study. We also appreciate Daisuke Ito, a radiology technologist, for preparing blinded images of MPI.
This study was supported by grants-in-aid for scientific research grant from the Japan agency for medical research and development (JP15lk0201011).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in this study.
- 2.Williams B, Menon M, Satran D, Hayward D, Hodges JS, Burke MN, Johnson RK, Pulose AK, Traverse JH, Henry TD (2010) Patients with coronary artery disease no amenable to traditional revascularization prevalence and 3-year mortality. Catheter Cardiovasc Interv 75:886–891Google Scholar
- 6.Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, Matsumoto Y, Kajihara N, Eto M, Matsuda T, Yasui H, Takeshita A, Sunagawa K (2004) Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation 110:3055–3061CrossRefGoogle Scholar
- 8.Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, Hao K, Fukumoto Y, Takahashi J, Takeda M, Nakayama M, Yasuda S, Kuriyama S, Tsuji I, Shimokawa H (2010) Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J 74:589–591CrossRefGoogle Scholar
- 16.Nirala S, Wang Y, Peng YZ, Yang P, Guo T (2016) Cardiac shock wave therapy shows better outcomes in the coronary artery disease patients in a long term. Eur Rev Med Pharmacol Sci 20:330–338Google Scholar
- 19.Apfel RE (1982) Acoustic cavitation: a possible consequence of biochemical uses of ultrasound. Br J Cancer Suppl 5:140–146Google Scholar
- 27.Briones E, Lacalle JR, Marin I (2009) Transmyocardial laser revascularization versus medical therapy for refractory angina. Cochrane Database Syst Rev 1:CD003712Google Scholar
- 28.Osterele SN, Sanborn TA, Ali N, Resar J, Ramee SR, Heuser R, Dean L, Knopf W, Schofield P, Schaer GL, Reeder G, Masden R, Yeung AC, Burkhoff D (2000) Percutaneous transmyocardial laser revascularization for severe angina: the PACIFIC randomized trial. Potential class improvement from intramyocardial channels. Lancet 356:1705–1710CrossRefGoogle Scholar
- 31.Serizawa F, Ito K, Kawamura K, Tsuchida K, Hamada Y, Zukeran T, Shimizu T, Akamatsu D, Hashimoto M, Goto H, Watanabe T, Sato A, Shimokawa H, Satomi S (2012) Extracorporeal shock wave therapy improves the walking ability of patients with peripheral artery disease and intermittent claudication. Circ J 76:1486–1493CrossRefGoogle Scholar
- 40.Yamaya S, Ozawa H, Kanno H, Kishimoto KN, Sekiguchi A, Tateda S, Yahata K, Ito K, Shimokawa H, Itoi E (2014) Low-energy extracorporeal shock wave therapy promotes VEGF expression and neuroprotection and improves locomotor recovery after spinal cord injury. J Neurosurg 121:1514–1525CrossRefGoogle Scholar
- 41.Yahata K, Kanno H, Ozawa H, Yamaya S, Tateda S, Ito K, Shimokawa H, Itoi E (2016) Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury. J Neurosurg Spine 25:745–755CrossRefGoogle Scholar
- 43.Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprienlian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP, ORBITA investigators (2018) Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet 391:31–40CrossRefGoogle Scholar