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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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Abstract

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.

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References

  1. Roth GA, Forouzanfar MH, Moran AE, Barber R, Nguyen G, Feigin VL, Naghavi M, Mensah GA, Murray CJ (2015) Demographic and epidemiologic drivers of cardiovascular mortality. N Engl J Med 372:1333–1341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 75:886–891

    PubMed  Google Scholar 

  3. Henry TD, Satran D, Hodges JS, Johnson RK, Poulose AK, Campbell AR, Garberich RF, Bart BA, Olson RE, Boisjolie CR, Harvey KL, Amdt TL, Traverse JH (2013) Long-term survival in patients with refractory angina. Eur Heart J 34:2683–2688

    Article  PubMed  Google Scholar 

  4. Jespersen L, Abildstrom SZ, Hvelplund A, Prescott E (2013) Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol 102:571–581

    Article  PubMed  Google Scholar 

  5. Attanasio S, Schaer G (2011) Therapeutic angiogenesis for the management of refractory angina: current concepts. Cardiovasc Ther 29:e1–e11

    Article  PubMed  Google 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 110:3055–3061

    Article  PubMed  Google Scholar 

  7. Fukumoto Y, Ito A, Uwatoku T, Matoba T, Kishi T, Tanaka H, Takeshita A, Sunagawa K, Shimokawa H (2006) Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coron Artery Dis 17:63–70

    Article  PubMed  Google 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 74:589–591

    Article  PubMed  Google Scholar 

  9. Miller TD, Askew JW, Herrmann J (2014) Assessing clinical impact of myocardial perfusion studies: ischemia or other prognostic indicators? Curr Cardiol Rep 16:465

    Article  PubMed  Google Scholar 

  10. Khattab AA, Brodersen B, Schuermann-Kuchenbrandt D, Beurich H, Tölg R, Geist V, Schafer T, Richardt G (2007) Extracorporeal cardiac shock wave therapy: first experience in the everyday practice for treatment of chronic refractory angina pectoris. Int J Cardiol 121:84–85

    Article  PubMed  Google Scholar 

  11. Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, Fukumoto Y, Yasuda S, Shimokawa H (2010) Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coron Artery Dis 21:304–301

    Article  Google Scholar 

  12. Gotte G, Amelio E, Russo S, Marlinghaus E, Musci G, Suzuki H (2002) Short-time non-enzymatic nitric oxide synthesis from l-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Lett 520:153–155

    Article  CAS  PubMed  Google Scholar 

  13. Mariotto S, Cavalieri E, Amelio E, Ciampa AR, de Prati AC, Marlinghaus E, Russo S, Suzuki H (2005) Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide 12:89–96

    Article  CAS  PubMed  Google Scholar 

  14. Mariotto S, de Prati AC, Cavalieri E, Amelio E, Marlinghaus E, Suzuki H (2009) Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action. Curr Med Chem 16:2366–2372

    Article  CAS  PubMed  Google Scholar 

  15. Alunni G, Barbero U, Vario A, D’amico S, Pianelli M, Zema D, Bongiovanni F, Gaita F (2017) The beneficial effect of extracorporeal shockwave myocardial revascularization: 2 years of follow-up. Cardiovasc Revasc Med 18:572–576

    Article  PubMed  Google 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 20:330–338

    CAS  PubMed  Google Scholar 

  17. Aicher A, Heeschen C, Sasaki K, Urbich C, Zeiher AM, Dimmeler S (2006) Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation 114:2823–230

    Article  Google Scholar 

  18. Fu M, Sun CK, Lin YC, Wang CJ, Wu CJ, Ko SF, Chua S, Sheu JJ, Chiang CH, Shao PL, Leu S, Yip HK (2011) Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment. PLoS One 6:e24342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Apfel RE (1982) Acoustic cavitation: a possible consequence of biochemical uses of ultrasound. Br J Cancer Suppl 5:140–146

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Fisher AB, Chien S, Barakat AI, Nerem RM (2001) Endothelial cellular response to altered shear stress. Am J Physiol Lung Cell Mol Physiol 281:L529–L533

    Article  CAS  PubMed  Google Scholar 

  21. Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH (2007) Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling. J Am Coll Cardiol 49:2379–2393

    Article  CAS  PubMed  Google Scholar 

  22. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10:53–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li YS, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech 38:1949–1971

    Article  PubMed  Google Scholar 

  24. Traub O, Berk BC (1998) Laminar shear stress mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 18:677–685

    Article  CAS  PubMed  Google Scholar 

  25. Hatanaka K, Ito K, Shindo T, Kagaya Y, Ogata T, Eguchi K, Kurosawa R, Shimokawa H (2016) Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction. Am J Physiol Cell Physiol 311:C378–C385

    Article  PubMed  Google Scholar 

  26. Ha CH, Kim S, Chung J, An SH, Kwon K (2013) Extracorporeal shock wave stimulates expression of the angiogenic gene via mechanosensory complex in endothelial cells: mimetic effect of fluid shear stress in endothelial cells. Int J Cardiol 168:4168–4177

    Article  PubMed  Google Scholar 

  27. Briones E, Lacalle JR, Marin I (2009) Transmyocardial laser revascularization versus medical therapy for refractory angina. Cochrane Database Syst Rev 1:CD003712

    Google 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 356:1705–1710

    Article  Google Scholar 

  29. Salem M, Rotevatn S, Nordrehaug JE (2006) Long-term results following percutaneous myocardial laser therapy. Coron Artery Dis 17:385–390

    Article  PubMed  Google Scholar 

  30. Taylor RS, De Vries J, Bucher E, Dejongste MJ (2009) Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 9:13

    Article  PubMed  PubMed Central  Google 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 76:1486–1493

    Article  PubMed  Google Scholar 

  32. Saggini R, Figus A, Troccola A, Cocco V, Saggini A, Scuderi N (2008) Extracorporeal shock wave therapy for management of chronic ulcers in the lower extremities. Ultrasound Med Biol 34:1261–1271

    Article  CAS  PubMed  Google Scholar 

  33. Moretti B, Notarnicola A, Maggio G, Moretti L, Pascone M, Tafuri S, Patella V (2009) The management of neuropathic ulcer of the foot in diabetes by shock wave therapy. BMC Musculoskelet Disord 10:54

    Article  PubMed  PubMed Central  Google Scholar 

  34. Saito S, Ishii T, Kamogawa Y, Watanabe R, Shirai T, Fujita Y, Shirota Y, Fujii H, Ito K, Shimokawa H, Yamaguchi T, Kawaguchi Y, Harigae H (2016) Extracorporeal shock wave therapy for digital ulcers of systemic sclerosis: a phase 2 pilot study. Tohoku J Exp Med 238:39–47

    Article  CAS  PubMed  Google Scholar 

  35. Serizawa F, Ito K, Matsubara M, Sato A, Shimokawa H, Satomi S (2011) Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphedema. Eur J Vasc Endovasc Surg 42:254–260

    Article  CAS  PubMed  Google Scholar 

  36. Ogden JA, Alvarez RG, Levitt R, Marlow M (2001) Shock wave therapy (Orthotripsy) in musculoskeletal disorders. Clin Orthop Relat Res 387:22–40

    Article  Google Scholar 

  37. Birnbaum K, Wirtz DC, Siebert CH, Heller KD (2002) Use of extracorporeal shock-wave therapy (ESWT) in the treatment of non-unions. A review of the literature. Arch Orthop Trauma Surg 122:324–330

    Article  CAS  PubMed  Google Scholar 

  38. Wang CJ (2012) Extracorporeal shockwave therapy in musculoskeletal disorders. J Orthop Surg Res 7:11

    Article  PubMed  PubMed Central  Google Scholar 

  39. Al-Abbad H, Simon JV (2013) The effectiveness of extracorporeal shock wave therapy on chronic Achilles tendinopathy: a systematic review. Foot Ankle Int 34:33–41

    Article  PubMed  Google 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 121:1514–1525

    Article  PubMed  Google 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 25:745–755

    Article  PubMed  Google Scholar 

  42. Angulo JC, Arance I, de Las Heras MM, Meilan E, Esquinas C, Andres EM (2017) Efficacy of low-intensity shock wave therapy for erectile dysfunction: a systematic review and meta-analysis. Actas Urol Esp 41:479–490

    Article  CAS  PubMed  Google 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 391:31–40

    Article  PubMed  Google Scholar 

  44. Yang P, Guo T, Wang W, Peng YZ, Wang Y, Zhou P, Luo ZL, Cai HY, Zhao L, Yang HW (2013) Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease. Heart Vessels 28:284–291

    Article  PubMed  Google Scholar 

  45. Schmid JP, Capoferri M, Wahl A, Eshtehardi P, Hess OM (2013) Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective placebo-controlled randomized trial. Cardiovasc Ther 31:e1–e6

    Article  CAS  PubMed  Google Scholar 

  46. Leibowitz D, Weiss AT, Rott D, Durst R, Lotan C (2013) The efficacy of cardiac shock wave therapy in the treatment of refractory angina: a pilot prospective, randomized, double-blind trial. Int J Cardiol 167:3033–3034

    Article  PubMed  Google Scholar 

  47. Alunni G, Marra S, Meynet I, D’amico M, Elisa P, Fanelli A, Molinaro S, Garrone P, Deberardinis A, Campana M, Lerman A (2015) The beneficial effect of extracorporeal shockwave myocardial revascularization in patients with refractory angina. Cardiovasc Revasc Med 16:6–11

    Article  PubMed  Google Scholar 

  48. Wang Y, Guo T, Cai HY, Ma TK, Tao SM, Sun S, Chen MQ, Gu Y, Pang JH, Xiao JM, Yang XY, Yang C (2010) Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease. Clin Cardiol 33:693–699

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kaller M, Faber L, Bogunovic N, Horstkotte D, Burchert W, Lindner O (2015) Cardiac shock wave therapy and myocardial perfusion in severe coronary artery disease. Clin Res Cardiol 104:843–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vasyuk YA, Hadzegova AB, Shkolnik EL, Kopeleva MV, Krikunova OV, Iouchtchouk EN, Aronova EM, Ivanova SV (2010) Initial clinical experience with extracorporeal shock wave therapy in treatment of ischemic heart failure. Congest Heart Fail 16:226–230

    Article  PubMed  Google Scholar 

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Acknowledgments

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.

Funding

This study was supported by grants-in-aid for scientific research grant from the Japan agency for medical research and development (JP15lk0201011).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yoku Kikuchi, Kenta Ito, Tomohiko Shindo, Kiyotaka Hao, Takashi Shiroto, Yasuharu Matsumoto, Jun Takahashi & Hiroaki Shimokawa

  2. Department of Cardiovascular Medicine, Ishikawa Prefectural Central Hospital, Kanazawa, Japan

    Takao Matsubara

  3. Department of Cardiovascular Medicine, Fujita Health University Hospital, Toyoake, Japan

    Akira Yamada & Yukio Ozaki

  4. Department of Cardiovascular Medicine, Chiba-Nishi General Hospital, Matsudo, Japan

    Michiaki Hiroe & Kazuo Misumi

  5. Department of Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Hideki Ota, Kentaro Takanami & Kei Takase

  6. Department of Radiology, Miyagi Cardiovascular and Respiratory Center, Kurihara, Japan

    Tomomichi Hiraide

  7. Division of Epidemiology, Department of Health Informatics and Public Health, Tohoku University School of Public Health, Graduate School of Medicine, Sendai, Japan

    Fumiya Tanji, Yasutake Tomata & Ichiro Tsuji

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  1. Yoku Kikuchi
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  2. Kenta Ito
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  3. Tomohiko Shindo
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  4. Kiyotaka Hao
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  5. Takashi Shiroto
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  6. Yasuharu Matsumoto
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  7. Jun Takahashi
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  8. Takao Matsubara
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  9. Akira Yamada
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  10. Yukio Ozaki
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  11. Michiaki Hiroe
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  12. Kazuo Misumi
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  13. Hideki Ota
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  18. Yasutake Tomata
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  19. Ichiro Tsuji
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  20. Hiroaki Shimokawa
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Correspondence to Hiroaki Shimokawa.

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The authors declare that they have no conflict of interest.

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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.

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Informed consent was obtained from all individual participants included in this study.

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Kikuchi, Y., Ito, K., Shindo, T. et al. A multicenter trial of extracorporeal cardiac shock wave therapy for refractory angina pectoris: report of the highly advanced medical treatment in Japan. Heart Vessels 34, 104–113 (2019). https://doi.org/10.1007/s00380-018-1215-4

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