Advances in Therapy

, Volume 29, Issue 8, pp 698–707 | Cite as

Shockwave Therapy in Patients with Peripheral Artery Disease

  • Marco Matteo Ciccone
  • Angela NotarnicolaEmail author
  • Pietro Scicchitano
  • Marco Sassara
  • Santa Carbonara
  • Mariagrazia Maiorano
  • Biagio Moretti
Original Research



Previous studies support the fact that extracorporeal shockwave (SW) induces angiogenesis and improves symptoms in patients affected by limb ischemia. The aim of this study was to evaluate the effects of SW therapy in patients with peripheral artery disease (PAD).


Twenty-two patients were enrolled in this study and were randomly assigned into two groups: SW treatment (12 patients, 67 ± 9 years) and control (10 patients, 68 ± 12 years). The inclusion criteria were the following: age over 40 years, PAD diagnosis, optimal medical therapy, and ankle-brachial index less than 0.9. SW therapy was administered using the Minilith® SL1 litotriptor with an ultrasound guide able to detect the target area using a B-mode technique and a 7.5 MHz convex probe emitting 2,000 impulses with an energy flux density of 0.03 mJ/mm2.


The variation in the degree of stenosis before and after treatment was statistically significant between the groups (−9% ± −10% vs. 0% ± 0%; P = 0.001). In addition, a significantly higher number of treated patients than controls showed a reduction in the Fontaine stage (12 [63%] vs. 0 [0%]; P < 0.001). This result was confirmed by analyzing the difference in patients’ pain-free walking distance before and after SW therapy (76 ± 46 m vs. 0 ± 0 m for treated patients vs. controls; P < 0.001) and the difference in pain severity (measured on a pain scale; −1.4 ± 0.5 in the treated patients vs. −0.2 ± 0.4 in the controls; P < 0.001).


On the basis of these results the authors hypothesized a direct effect of SW on the ultrastructural composition of the vessel walls, inducing a reduction in artery stenosis. These data support the application of SW therapy as a new medical tool to improve the natural clinical course of PAD.


Intermittent claudication Peripheral artery disease Shockwave therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adam DJ, Bradbury AW. TASC II document on the management of peripheral arterial disease. Eur J Vasc Endovasc Surg. 2007;33:1–2.PubMedCrossRefGoogle Scholar
  2. 2.
    Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(Suppl. 1):S1–S296.PubMedGoogle Scholar
  3. 3.
    Frick M, Weidinger F. Endothelial function: a surrogate endpoint in cardiovascular studies? Curr Pharm Des. 2007;13:1741–1750.PubMedCrossRefGoogle Scholar
  4. 4.
    Liao JK, Bettmann MA, Sandor T, Tucker JI, Coleman SM, Creager MA. Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 1991;68:1027–1034.PubMedCrossRefGoogle Scholar
  5. 5.
    Wong WT, Wong SL, Tian XY, Huang Y. Endothelial dysfunction: the common consequence in diabetes and hypertension. J Cardiovasc Pharmacol. 2010;55:300–307.PubMedCrossRefGoogle Scholar
  6. 6.
    Mariotto S, de Prati AC, Cavalieri E, Amelio E, Marlinghaus E, Suzuki H. Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action. Curr Med Chem. 2009;16:2366–2372.PubMedCrossRefGoogle Scholar
  7. 7.
    Lazzerini G, Del Turco S, Basta G, O’Loghlen A, Zampolli A, Caterina RD. Prominent role of NFkappaB in the induction of endothelial activation by endogenous nitric oxide inhibition. Nitric Oxide. 2009;2:184–191.CrossRefGoogle Scholar
  8. 8.
    Zhou MS, Schulman IH, Raij L. Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension: role of nuclear factor kappa B activation. J Hypertens. 2010;28:527–535.PubMedCrossRefGoogle Scholar
  9. 9.
    Fukumoto Y, Ito A, Uwatoku T, et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coron Artery Dis. 2006;17:63–70.PubMedCrossRefGoogle Scholar
  10. 10.
    Nishida T, Shimokawa H, Oi K, et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation. 2004;110:3055–3061.PubMedCrossRefGoogle Scholar
  11. 11.
    Gutersohn A, Caspari GH, Marlinghaus E, Haude M. Comparison of cardiac shock wave therapy and percutaneous myocardial laser revascularisation therapy in end stage CAD patients with refractory angina. Paper presented at: World Congress of Cardiology and ESC Conference; September 2, 2006; Barcelona, Spain.Google Scholar
  12. 12.
    Aicher A, Heeschen C, Sasaki K, Urbich C, Zeiher AM, Dimmeler S. 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. 2006;114:2823–2830.PubMedCrossRefGoogle Scholar
  13. 13.
    Corrado EM, Wang CJ, McClure S, et al. Guidelines ISMST_Newsletter 2009-03 No5 Available at: Accessed Jul 26 2012.
  14. 14.
    National Institutes of Health, National Heart, Lung and Blood Institute Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. NIH publication no. 02-5215 September 2002. Available at: Accessed Jul 26 2012.
  15. 15.
    Staikov IN, Arnold M, Mattle HP, et al. Comparison of the ECST, CC, and NASCET grading methods and ultrasound for assessing carotid stenosis. European Carotid Surgery Trial. North American Symptomatic Carotid Endarterectomy Trial. J Neurol. 2000;247:681–686.PubMedCrossRefGoogle Scholar
  16. 16.
    Ciccone M, Di Noia D, Di Michele L, et al. The incidence of asymptomatic extracoronary atherosclerosis in patients with coronary atherosclerosis. Int Angiol. 1993;12:25–28.PubMedGoogle Scholar
  17. 17.
    Srámek A, Bosch JG, Reiber JH, Van Oostayen JA, Rosendaal FR. Ultrasound assessment of atherosclerotic vessel wall changes: reproducibility of intima-media thickness measurements in carotid and femoral arteries. Invest Radiol. 2000;3:699–706.Google Scholar
  18. 18.
    Caruana MF, Bradbury AW, Adam DJ. The validity, reliability, reproducibility and extended utility of ankle to brachial pressure index in current vascular surgical practice. Eur J Vasc Endovasc Surg. 2005;29:443–451.PubMedCrossRefGoogle Scholar
  19. 19.
    Hooi JD, Stoffers HE, Kester AD, van RJ, Knottnerus JA. Peripheral arterial occlusive disease: prognostic value of signs, symptoms, and the ankle-brachial pressure index. Med Decis Making. 2002;22:99–107.PubMedGoogle Scholar
  20. 20.
    Belcaro G, Nicolaides AN, Marlinghaus EH, et al. Shock waves in vascular diseases: an in-vitro study. Angiology. 1998;49:777–788.PubMedCrossRefGoogle Scholar
  21. 21.
    Ciccone M, di Noia D, Liquori M, di Michele L, Novo S, Rizzon P. Determination of arterial diameters, length and mass of the plaque, and theoretical volume in the internal carotid artery by quantitative vascular echography. Angiology. 1993;44:314–320.PubMedCrossRefGoogle Scholar
  22. 22.
    Smilde TJ, Wollersheim H, Van Langen H, Stalenhoef AF. Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness. Clin Sci (Lond). 1997;93:317–324.Google Scholar
  23. 23.
    Koshiyama K, Kodama T, Yano T, Fujikawa S. Structural change in lipid bilayers and water penetration induced by shock waves: molecular dynamics simulations. Biophys J. 2006;91:2198–2205.PubMedCrossRefGoogle Scholar
  24. 24.
    Mariotto S, Cavalieri E, Amelio E, et al. Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide. 2005;12:89–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Ciampa AR, Carcereri de Prati A, Amelio E, et al. Nitric oxide mediates anti-inflammatory action of extracorporeal shock waves. FEBS Lett. 2005;579:6839–6845.PubMedCrossRefGoogle Scholar
  26. 26.
    Gotte G, Amelio E, Russo S, Marlinghaus E, Musci G, Suzuki H. Short time non-enzymatic nitric oxide synthesis from l-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Lett. 2002;520:153–155.PubMedCrossRefGoogle Scholar
  27. 27.
    Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non invasive angiogenic strategy. Tohoku J Exp Med. 2009;219:1–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Angehrn F, Kuhn C, Sonnabend O, Voss A. Extracorporeal shock waves as curative therapy for varicose veins? Clin Interv Aging. 2008;3:175–182.PubMedGoogle Scholar
  29. 29.
    Belcaro G, Cesarone MR, Dugall M, et al. Effects of shock waves on microcirculation, perfusion, and pain management in critical limb ischemia. Angiology. 2005;56:403–407.PubMedCrossRefGoogle Scholar
  30. 30.
    De Sanctis MT, Belcaro G, Nicolaides AN, et al. Effects of shock waves on the microcirculation in critical limb ischemia (CLI) (8-week study). Angiology. 2000;51:S69–S78.PubMedCrossRefGoogle Scholar
  31. 31.
    Belcaro G, Nicolaides AN, Cesarone MR, et al. Shock waves (SW) noninvasive extracorporeal thrombolysis treatment (NISWT). Angiology. 1999;50:707–713.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2012

Authors and Affiliations

  • Marco Matteo Ciccone
    • 2
  • Angela Notarnicola
    • 1
    Email author
  • Pietro Scicchitano
    • 2
  • Marco Sassara
    • 2
  • Santa Carbonara
    • 2
  • Mariagrazia Maiorano
    • 1
  • Biagio Moretti
    • 1
  1. 1.Department of Neuroscience and Organs of Sense, Orthopedics Section, Faculty of Medicine and SurgeryUniversity of Bari, General HospitalBariItaly
  2. 2.Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO)University of BariBariItaly

Personalised recommendations