Critical ischemia of the lower extremities: modern aspects of diagnosis and treatment

Critical limb ischemia (CLI) is a manifestation of peripheral artery disease (PDA) in patients with typical chronic ischemic resting pain or ischemic skin damage in the form of ulcers or gangrene, objectively confirmed by occlusive artery diseases. CLI has a high risk of painful (at and above the ankle) amputations, cardiovascular events and death. Ultrasound Doppler, ultrasound duplex scanning, non-invasive (MRA and CTA) angiography help determine the appropriateness and tactics for arterial revascularization. Reconstructive and reconstructive operations in the form of open and hybrid operations are the most successful when applying good quality autovena with a diameter of 3.0-3.5 mm. Balloon angioplasty and stenting form the basis of endovascular methods, drug-coated stents and drug-coated balloons provide a low frequency of repeated revascularizations. In patients with distal lesions of the arteries, if it is impossible to conduct direct revascularization, indirect methods of revascularization are used. Drug treatment before vascular surgery, perioperative period and long-term after surgery is aimed at risk factors for atherosclerosis and thromboangiitis obliteration, promotes wound healing, reduces the frequency of cardiovascular events and death. The state of the gene and cell therapy for the treatment in subset of patients with CLI not eligible for revascularization is reported

1. Norgren L., Hiatt W.R., Dormandy J.A. et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). IntAngiol., 2007, № 26, рр. 81–157.

2. Adam D.J., Beard J.D., Cleveland T. et al. BASIL trial participants Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005, № 366(9501), рр. 1925–1934.

3. Pokrovskiy A.V., KazakovY.I., Lukin I.B. Critical ischemia of the lower extremities. Infraingvinal lesion. Tver, 2018, 225 p. (In Russ.)

4. Poredos P., Blinc A., Novo S., Antignani P.L. How to manage Patients with polyvascular atherosclerotic disease. Position paper of the international Union of Angiology. Int Angiol., 2021, № 40(1), pp. 29–41.

5. Nishijima A., Yamamoto N.,Yoshida R. et al. Coronary artery disease in patients with critisal limb ischemia undergoing major amputation or not. Plast RekonstrSurg Glob Open., 2017, № 5(6), pp. 1377.

6. Gavrilenko A.V., Skrylev S.I. Surgical treatment of patients with critical ischemia of the lower extremities with lesions of the arteries of the femoral-potential-tiber segment. Surgery, 2004, № 8, рр. 36–42. (In Russ.)

7. Dibirov M.D., Dibirov A.A., Gadzhimuradov R.U. et al. Distal reconstructions in critical ischemia of the lower extremities in patients of older age groups. Surgery,2009, № 1, рр. 49–52. (In Russ.)

8. Abushov N.S., Abdullayev A.G., Zakirjaev E.D. et al. Results of combined surgical treatment of patients with obliterating thromboangiitis and critical ischemia of the lower extremities. Surgery, 2016, № 9, рр. 45–50. ([In Russ.)

9. Koygan A.A., BatalinIV., VavilovV.N. et al. Comparative results of various methods of arterial reconstruction in the defeat of the femoral-podkomenno-tibia segment in patients with chronic critical ischemia of the lower extremities. Regional blood circulation and microcirculation, 2017, № 16 (3), рр. 41–48. (In Russ.)

10. Uccioli L., Meloni M., Izzo V. et al. Critical limb ischemia: current challenges and future prospects. Vasc Health Risc Manag., 2018, № 14, рр. 63–74.

11. Criqui M.H., Fronek A., Klauber M.R. et al. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population. Circulation, 1985, № 71(3), рр. 516–522.

12. Young M.J., Adams J.E., Anderson G.F. et al. Medial arterial calcification in the feet of diabetic patients and matched non-diabetic control subjects. Diabetologia, 1993, № 36(7), рр. 615–621.

13. Park S.C., Choi C.Y., Ha Y.I. et al. Utility of toe-brachial index for diagnosis of peripheral artery disease. Arch Plast Surg., 2012, № 39(3), рр. 227–231.

14. Hingorani A., Ascher E., Marks N. Preprocedural imaging: new options to reduce need for contrast angiography. SeminVasc Surg., 2007, № 20(1), рр. 15–28.

15. Wertman R., Altun E., Martin D.R. et al. Risk of nephrogenic systemic fibrosis: evaluation of gadolinium chelate contrast agents at four American Universities. Radiology, 2008, № 248(3), рр.799–806.

16. Gerhard-Herman M.D., Gornik H.L., Barrett C. et al. 2016; AHA/ ACC lower extremity PAD guideline: executive summary. Circulation, 2016, № 13, рр. 1–64.

17. Willigendael E.M., Teijink J.A., Bartelink M.L. et al. Smoking and the patency of lower extremity bypass grafts: a meta-analysis. J Vasc Surg., 2005, № 42(1), рр. 67–74.

18. Armstrong E.J., Wu J., Singh G.D. et al. Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease. J Vasc Surg., 2014, № 60(6), рр. 1565–1571.

19. Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 highrisk individuals: a randomised placebo-controlled trial. Lancet, 2002, № 360(9326), рр. 7–22.

20. Rubins H.B., Robins S.J., Collins D. et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans affairs high-density lipoprotein cholesterol intervention trial study group. N Engl J Med., 1999, № 341(6), рр. 410–418.

21. ESH/ESC 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens., 2003, № 21(6), рр.1011–1053.

22. Bendick P.J., Glover J.L., Kuebler T.W. et al. Progression of atherosclerosis in diabetics. Surgery, 1983, № 93 (6), рр. 834–838.

23. Mozes G, Keresztury G, Kadar A, et al. Atherosclerosis in amputated legs of patients with and without diabetes mellitus. Int Angiol. 1998,17 (1), рр. 282–286.

24. Giurato L., Vainieri E., Meloni M. et al. Limb salvage in patients with diabetes is not a temporary solution but a life-changing procedure. Diabetes Care, 2015, № 38(10), рр.156–157.

25. Owen R.J., Hiremath S., Myers A. et al. Canadian association of radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012. Can Assoc Radiol J., 2014, № 65(2), рр. 96–105.

26. Aiello A., Anichini R., Brocco E. et al. Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE) NutrMetabCardiovasc Dis., 2014, № 24(4), рр. 355–369.

27. Bauer S.M., Cayne N.S., Veith F.J. New developments in the preoperative evalution and perioperative management of coronary artery disease in patients undergoing vascular surgery. JVasc Surg., 2010, № 51 (1), рр. 242–251.

28. Shalhoub J., Davies A.H., Franklin I.J. Cilostazol may improve outcome in critical limb ischemia. IntAngiol., 2009, № 28 (5), рр. 363–366.

29. Patel M.R., Conte M.S., Cutlip D.E. et al. Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from Peripheral Academic Research Consortium (PARC). J Am Coll Cardiol., 2015, № 65, рр. 931–941.

30. Romiti M., Albers M., Brochado-Neto F.C. et al. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg., 2008, № 47(5), рр. 975–981.

31. Zeller T., Micari A., Scheinert D. et al. IN. PACT DEEP Trial investigators. The IN.PACT DEEP clinical drug-coated ballon trial: 5-year outcomes. JACC Cardiovasc Interv., 2020, № 13, рр .431–443.

32. Larid J.R. Endovascular treatment of common femoral artery disease. J Am CollCardiol., 2011, № 58 (8), рр. 799–800.

33. Sticker H., Spinedi L., Limoni C. et al. Stent-assisted angioplasty (SAA) at the level of the common femoral artery bifurcation: Long-term outcomes. Cardiovasc. Interrvent.Radiol., 2020, № 43 (4), рр. 541–546.

34. Krankenberg H., Schlüter M., Steinkamp H.J. et al. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation, 2007, № 116, рр. 285–292.

35. Schillinger M., Sabeti S., Loewe C. et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery.NEngl J Med., 2006, № 354, рр.1879–1888.

36. George J.C., Rosen E.S., Nachtigall J. et al. SUPERA interwoven nitinol stent outcomes in above-knee Interventions (SAKE) study. J Vasc Interv Radiol., 2014, № 25, рр. 954–961.

37. Dake M.D., Ansel G.M., Jaff M.R. et al. Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: twelve-month Zilver PTX randomized study results. Circ Cardiovasc Interv., 2011, № 4, рр. 495–504.

38. Venermo M., Biancari F., Arvela E. et al. The role of chronic kidney disease as a predictor of outcome after revascularisation of the ulcerated diabetic foot. Diabetologia, 2011, № 54(12), рр. 2971–2977.

39. Chiu K.W., Davies R.S., Nightingale P.G. et al. Review of direct anatomical open surgical management of atherosclerotic aorto-iliac occlusive disease. Eur J Vasc Endovasc Surg., 2010, № 39 (4), рр. 460–471.

40. Singh N., Sidawy A.N., DeZee K.J. et al. Factors associated with early failure of infrainguinal lower extremity arterial bypass. J Vasc., 2008, № 47, рр. 556–561.

41. Schanzer A., Hevelone N., Owe.ns C.D. et al. Technical factors affecting autogenous vein graft failure: observations from a large multicenter trial. J Vasc Surg., 2007, № 46, рр. 1180–1190.

42. Izumi Y., Magishi K, Shimuzi N. The results of in situ saphenous bypass for infrainguinal arterial reconstruction: comparision between two types of valvulotomes. Int J Angiol., 2010, № 19 (4), рр. 126–128.

43. Twine C.P., McLain A.D. Graft type for femoro-popliteal bypass surgery. Cochrane database of syst rev., 2010, CD001487. https://doi. org/10.1002/14651858

44. Lumsden A.B., Morrissey N.J. Randomized controlled trial comparing the safety and efficacy between the FUSION BIOLINE heparin-coated vascular graft and the standard expanded polytetrafluoroethylene graft for femoropoplitealbypass. JVasc Surg., 2015, № 61(3), рр. 703–712.

45. Daenens K., Schepers S., Fourneau I. et al. Heparin-bonded ePTFE grafts compared with vein grafts in femoropopliteal and femorocrural bypasses: 1- and 2-year results. J Vasc Surg., 2009, № 49, рр. 1210–1216.

46. Chang C.K., Scali S.T., Feezor R.J. et al. Defining utility and predicting outcome of cadaveric lower extremity bypass grafts in patients with critical limb ischemia. J. Vasc Surg., 2014, № 60, рр. 1554–1564.

47. Dargon P.T., Landry G.J. Buerger’s disease. Ann Vasc.Surg. 2012,26(6), рр.871-880.

48. Hida N, Onta T. Current status of patients with Buerger disease in Japan. Ann Vasc Dis., 2013, № 6(3), рр. 617–623.

49. Karanth V.K.L, Karanth T.K, Sun Z., Karanth L. Lumbar sympathectomy techniques for critical lower limb ischaemia due to non reconstructable peripheral arterial disease (protocol). Cohrane database of systematic rewiews, 2015, № 2, CD 011519.

50. Abushov N.S., Aliyev Z.M., Zeynalova G.M. Experience of complex surgical treatment of patients with critical ischemia of the lower extremities with obliterating thromboangiitis. Cardiology and cardiovascular surgery, 2012, № 4, рр. 55–57. [In Russ.]

51. Piriou V., Feugier P., Granger S. et al. Ischaemia of the lower limbs: anaesthesia and intensive care. Ann Fr Anesth Reani., 2004, № 23 (12), рр. 1160–1174.

52. Rogers A, Walker A., Schug S. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia. Results from an overview of randomized trails. BMJ, 2002, № 321 (167), рр. 1493–1497.

53. Standi T., Gottschalk A. Epidural anesthesia step by step to success. Anestesiol Intensiv med Notfall med Schmerziher, 2007, № 42(2), рр. 90–99.

54. Powell R.J., Simons M., Mendelsohn F.O. et al. Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation, 2008, № 118(1), рр. 58–65.

55. Ko S.H., Bandyk D.F. Therapeutic angiogenesis for critical limb ischemia. Semin Vasc Surg., 2014, № 27(1), рр. 23–31.

56. Liu Y., Xu Y., Fang F. et al. Therapeutic efficacy of stem cell-based therapy in peripheral arterial disease: a meta-analysis. PLoS One., 2015, № 10(4), e0125032.

57. Wang Z.X., Li D., Cao J.X. et al. Efficacy of autologous bone marrow mononuclear cell therapy in patients with peripheral arterial disease. J Atheroscler Thromb., 2014, № 21(11), рр. 1183–1196.

58. Saito Y., Sasaki K., Katsuda Y. et al. Effect of autologous bonemarrow cell transplantation on ischemic ulcer in patients with Buerger`s disease. Circ J., 2007, № 71, рр. 118–-1192.

59. Tateishi-Yuyama E., Matsubara H., Murohara T. et al. Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone-morrow cells: a pilot study and a randomised controlled trial. Lancet, 2002,и№ 360 (9331), рр. 427–435.

60. PeetersWeem S.M., Teraa M., de Borst G.J. et al. Bone marrow derived cell therapy in critical limb ischemia: a meta-analysis of randomized placebo controlled trials. Eur J Vasc Endovasc Surg., 2015, № 50(6), рр. 775– 783.

61. Catrina S.B., Okamoto K., Pereira T. et al. Hyperglycemia regulates hypoxia-inducible factor 1-alpha protein stability and function. Diabetes, 2004, № 53(12), рр. 3226–3232.