Breakthroughs in endovascular therapy for below-the-knee artery disease: from evolution of strategies to technological innovations_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

高喜翔 ,  郭連瑞

GAO Xixiang, GUO Lianrui Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P. R. China;

Corresponding?author：

郭連瑞, Email: lianruiguo@sina.com

Keywords：

below-the-knee artery disease; chronic limb-threatening ischemia; endovascular treatment

DOI：

10.7507/1007-9424.202511105

Video：

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Below-the-knee (BTK) artery disease is a major pathological basis for chronic limb-threatening ischemia (CLTI). In recent years, endovascular therapy has progressively emerged as a significant approach for the treatment of BTK arterial disease, with notable advancements achieved in treatment strategies, vascular preparation devices, and related techniques. The treatment strategy has evolved from “the Global Vascular Guidelines (GVG)” and “the International Working Group on the Diabetic Foot (IWGDF), the European Society for Vascular Surgery (ESVS), and the Society for Vascular Surgery (SVS) guidelines on peripheral artery disease in people with diabetes and a foot ulcer” to the “Woundosome” concept. This framework emphasizes “wound perfusion improvement” as the ultimate goal. In terms of vessel preparation devices, paclitaxel-coated balloons have demonstrated advantages in patency and limb salvage for complex lesions, while sirolimus-coated balloons show potential for a superior safety profile. Bioresorbable scaffolds offer a novel “support-then-absorb” solution. Technically, vascular preparation devices (e.g., shockwave balloon) effectively manage severe calcification, and deep venous arterialization provides a last resort for limb salvage in “no-option” patients. Future developments in this field will rely on generating higher-level clinical evidence and constructing personalized treatment pathways tailored to patient characteristics and available medical resources, aiming to continuously improve limb salvage rate and quality of life for CLTI patients.

1.	Li J, Varcoe R, Manzi M, et al. Below-the-knee endovascular revascularization: a position statement. JACC Cardiovasc Interv, 2024, 17(5): 589-607.
2.	Benfor B, Sinha K, Lumsden AB, et al. Scoping review of atherectomy and intravascular lithotripsy with or without balloon angioplasty in below-the-knee lesions. J Vasc Surg Cases Innov Tech, 2023, 9(2): 101185. doi: 10.1016/j.jvscit.2023.101185.
3.	Cui HJ, Wu YF. Bioresorbable scaffolds for below-the-knee arterial disease: a literature review of new developments. Rev Cardiovasc Med, 2024, 25(4): 133. doi: 10.31083/j.rcm2504133.
4.	Chandra V, Lansky AJ, Sayfo S, et al. Thirty-day outcomes from the Disrupt PAD BTK Ⅱ study of the Shockwave Intravascular Lithotripsy System for treatment of calcified below-the-knee peripheral arterial disease. J Vasc Surg, 2025, 81(3): 710-719.
5.	Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg, 2019, 58(1S): S1-S109. e33. doi: 10.1016/j.ejvs.2019.05.006.
6.	Fitridge R, Chuter V, Mills J, et al. The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer. Diabetes Metab Res Rev, 2024, 40(3): e3686. doi: 10.1002/dmrr.3686.
7.	Patrone L, Pasqui E, Conte MS, et al. The “Woundosome” concept and its impact on procedural outcomes in patients with chronic limb-threatening ischemia. J Endovasc Ther, 2025, 32(6): 1765-1776.
8.	Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol, 2012, 60(22): 2290-2295.
9.	Zilinyi RS, Alsaloum M, Snyder DJ, et al. Surgical and endovascular therapies for below-the-knee peripheral arterial disease: a contemporary review. J Soc Cardiovasc Angiogr Interv, 2024, 3(3Part A): 101268. doi: 10.1016/j.jscai.2023.101268.
10.	Tirziu D, Saleh A, Huang H, et al. Safety and efficacy of endovascular treatment modalities for below-the-knee arterial disease: a systematic review and network meta-analysis. J Endovasc Ther, 2025: 15266028251344809. doi: 10.1177/15266028251344809.
11.	Zeller T, Baumgartner I, Scheinert D, et al. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN. PACT DEEP randomized trial. J Am Coll Cardiol, 2014, 64(15): 1568-1576.
12.	Zeller T, Micari A, Scheinert D, et al. The IN. PACT DEEP clinical drug-coated balloon trial: 5-year outcomes. JACC Cardiovasc Interv, 2020, 13(4): 431-443.
13.	Liistro F, Porto I, Angioli P, et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation, 2013, 128(6): 615-621.
14.	Morgan R. Commentary on drug-eluting balloon for below the knee angioplasty: five-year outcome of the DEBATE-BTK randomized clinical trial. Cardiovasc Intervent Radiol, 2022, 45(7): 1053-1054.
15.	Liistro F, Angioli P, Ventoruzzo G, et al. Randomized controlled trial of acotec drug-eluting balloon versus plain balloon for below-the-knee angioplasty. JACC Cardiovasc Interv, 2020, 13(19): 2277-2286.
16.	Jia X, Zhuang B, Wang F, et al. Drug-coated balloon angioplasty compared with uncoated balloons in the treatment of infrapopliteal artery lesions (AcoArt Ⅱ-BTK). J Endovasc Ther, 2021, 28(2): 215-221.
17.	Guo J, Ye M, Zhang W, et al. Drug-coated balloon angioplasty of infrapopliteal lesions in chronic limb-threatening ischemia: six-month outcomes of PRIME-WIFI. J Endovasc Ther, 2025, 32(5): 1489-1498.
18.	Linn YL, Choke ETC, Yap CJQ, et al. Utility of sirolimus coated balloons in the peripheral vasculature—a review of the current literature. CVIR Endovasc, 2022, 5(1): 29.
19.	Lemos PA, Farooq V, Takimura CK, et al. Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter. EuroIntervention, 2013, 9(1): 148-156.
20.	Tataru DA, Lazar FL, Onea HL, et al. Benefits and challenges of drug-coated balloons in peripheral artery disease: from molecular mechanisms to clinical practice. Int J Mol Sci, 2024, 25(16): 8749. doi: 10.3390/ijms25168749.
21.	Chan DYS, Wong JCL, Tang TY. Sirolimus coated balloons in peripheral arterial disease, what’s next?. Cardiovasc Diagn Ther, 2025, 15(1): 15-19.
22.	Choke E, Tang TY, Peh E, et al. MagicTouch PTA sirolimus coated balloon for femoropopliteal and below the knee disease: results from XTOSI pilot study up to 12 months. J Endovasc Ther, 2022, 29(5): 780-789.
23.	Choke ETC, Peh EYL, Tang TY, et al. MagicTouch PTA sirolimus-coated balloon for femoropopliteal and below-the-knee disease: 3-year outcomes of the XTOSI trial. Ann Vasc Surg, 2024, 106: 8-15.
24.	Tang TY, Yap C, Chan SL, et al. The utility of sirolimus eluting balloons in the setting of chronic limb threatening ischaemia in asian patients from Singapore—12 months results of the PRISTINE registry. Cardiovasc Intervent Radiol, 2024, 47(7): 863-874.
25.	Tang TY, Yap CJQ, Soon SXY, et al. 12-months results from the PRESTIGE study using sirolimus drug-eluting balloons in the treatment of complex BTK tibial atherosclerotic lesions in CLTI patients. Cardiovasc Revasc Med, 2022, 43: 143-146.
26.	Varcoe RL, Parikh SA, DeRubertis BG, et al. Evaluation of an infrapopliteal drug-eluting resorbable scaffold: design methodology for the LIFE-BTK randomized controlled trial. J Soc Cardiovasc Angiogr Interv, 2023, 2(4): 100964. doi: 10.1016/j.jscai.2023.100964.
27.	Varcoe RL, DeRubertis BG, Kolluri R, et al. Drug-eluting resorbable scaffold versus angioplasty for infrapopliteal artery disease. N Engl J Med, 2024, 390(1): 9-19.
28.	DeRubertis BG, Varcoe RL, Krishnan P, et al. Drug-eluting resorbable scaffold versus balloon angioplasty for below-the-knee peripheral artery disease: 2-year results from the LIFE-BTK trial. Circulation, 2025, 152(15): 1076-1086.
29.	Nugteren MJ, Welling RHA, Bakker OJ, et al. Vessel preparation in infrapopliteal arterial disease: a systematic review and meta-analysis. J Endovasc Ther, 2024, 31(2): 191-202.
30.	Shammas NW, Yates T, Sastry A, et al. Twelve-month outcomes of the prospective, multicenter, single-arm study of the 355-nm laser for treatment of below-the-knee arteries: final results of the Auryon BTK. J Endovasc Ther, 2025: 15266028251352772. doi: 10.1177/15266028251352772.
31.	Adams G, Soukas PA, Mehrle A, et al. Intravascular lithotripsy for treatment of calcified infrapopliteal lesions: results from the disrupt PAD Ⅲ observational study. J Endovasc Ther, 2022, 29(1): 76-83.
32.	Shishehbor MH, Powell RJ, Montero-Baker MF, et al. Transcatheter arterialization of deep veins in chronic limb-threatening ischemia. N Engl J Med, 2023, 388(13): 1171-1180.

1. Li J, Varcoe R, Manzi M, et al. Below-the-knee endovascular revascularization: a position statement. JACC Cardiovasc Interv, 2024, 17(5): 589-607.
2. Benfor B, Sinha K, Lumsden AB, et al. Scoping review of atherectomy and intravascular lithotripsy with or without balloon angioplasty in below-the-knee lesions. J Vasc Surg Cases Innov Tech, 2023, 9(2): 101185. doi: 10.1016/j.jvscit.2023.101185.
3. Cui HJ, Wu YF. Bioresorbable scaffolds for below-the-knee arterial disease: a literature review of new developments. Rev Cardiovasc Med, 2024, 25(4): 133. doi: 10.31083/j.rcm2504133.
4. Chandra V, Lansky AJ, Sayfo S, et al. Thirty-day outcomes from the Disrupt PAD BTK Ⅱ study of the Shockwave Intravascular Lithotripsy System for treatment of calcified below-the-knee peripheral arterial disease. J Vasc Surg, 2025, 81(3): 710-719.
5. Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg, 2019, 58(1S): S1-S109. e33. doi: 10.1016/j.ejvs.2019.05.006.
6. Fitridge R, Chuter V, Mills J, et al. The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer. Diabetes Metab Res Rev, 2024, 40(3): e3686. doi: 10.1002/dmrr.3686.
7. Patrone L, Pasqui E, Conte MS, et al. The “Woundosome” concept and its impact on procedural outcomes in patients with chronic limb-threatening ischemia. J Endovasc Ther, 2025, 32(6): 1765-1776.
8. Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol, 2012, 60(22): 2290-2295.
9. Zilinyi RS, Alsaloum M, Snyder DJ, et al. Surgical and endovascular therapies for below-the-knee peripheral arterial disease: a contemporary review. J Soc Cardiovasc Angiogr Interv, 2024, 3(3Part A): 101268. doi: 10.1016/j.jscai.2023.101268.
10. Tirziu D, Saleh A, Huang H, et al. Safety and efficacy of endovascular treatment modalities for below-the-knee arterial disease: a systematic review and network meta-analysis. J Endovasc Ther, 2025: 15266028251344809. doi: 10.1177/15266028251344809.
11. Zeller T, Baumgartner I, Scheinert D, et al. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN. PACT DEEP randomized trial. J Am Coll Cardiol, 2014, 64(15): 1568-1576.
12. Zeller T, Micari A, Scheinert D, et al. The IN. PACT DEEP clinical drug-coated balloon trial: 5-year outcomes. JACC Cardiovasc Interv, 2020, 13(4): 431-443.
13. Liistro F, Porto I, Angioli P, et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation, 2013, 128(6): 615-621.
14. Morgan R. Commentary on drug-eluting balloon for below the knee angioplasty: five-year outcome of the DEBATE-BTK randomized clinical trial. Cardiovasc Intervent Radiol, 2022, 45(7): 1053-1054.
15. Liistro F, Angioli P, Ventoruzzo G, et al. Randomized controlled trial of acotec drug-eluting balloon versus plain balloon for below-the-knee angioplasty. JACC Cardiovasc Interv, 2020, 13(19): 2277-2286.
16. Jia X, Zhuang B, Wang F, et al. Drug-coated balloon angioplasty compared with uncoated balloons in the treatment of infrapopliteal artery lesions (AcoArt Ⅱ-BTK). J Endovasc Ther, 2021, 28(2): 215-221.
17. Guo J, Ye M, Zhang W, et al. Drug-coated balloon angioplasty of infrapopliteal lesions in chronic limb-threatening ischemia: six-month outcomes of PRIME-WIFI. J Endovasc Ther, 2025, 32(5): 1489-1498.
18. Linn YL, Choke ETC, Yap CJQ, et al. Utility of sirolimus coated balloons in the peripheral vasculature—a review of the current literature. CVIR Endovasc, 2022, 5(1): 29.
19. Lemos PA, Farooq V, Takimura CK, et al. Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter. EuroIntervention, 2013, 9(1): 148-156.
20. Tataru DA, Lazar FL, Onea HL, et al. Benefits and challenges of drug-coated balloons in peripheral artery disease: from molecular mechanisms to clinical practice. Int J Mol Sci, 2024, 25(16): 8749. doi: 10.3390/ijms25168749.
21. Chan DYS, Wong JCL, Tang TY. Sirolimus coated balloons in peripheral arterial disease, what’s next?. Cardiovasc Diagn Ther, 2025, 15(1): 15-19.
22. Choke E, Tang TY, Peh E, et al. MagicTouch PTA sirolimus coated balloon for femoropopliteal and below the knee disease: results from XTOSI pilot study up to 12 months. J Endovasc Ther, 2022, 29(5): 780-789.
23. Choke ETC, Peh EYL, Tang TY, et al. MagicTouch PTA sirolimus-coated balloon for femoropopliteal and below-the-knee disease: 3-year outcomes of the XTOSI trial. Ann Vasc Surg, 2024, 106: 8-15.
24. Tang TY, Yap C, Chan SL, et al. The utility of sirolimus eluting balloons in the setting of chronic limb threatening ischaemia in asian patients from Singapore—12 months results of the PRISTINE registry. Cardiovasc Intervent Radiol, 2024, 47(7): 863-874.
25. Tang TY, Yap CJQ, Soon SXY, et al. 12-months results from the PRESTIGE study using sirolimus drug-eluting balloons in the treatment of complex BTK tibial atherosclerotic lesions in CLTI patients. Cardiovasc Revasc Med, 2022, 43: 143-146.
26. Varcoe RL, Parikh SA, DeRubertis BG, et al. Evaluation of an infrapopliteal drug-eluting resorbable scaffold: design methodology for the LIFE-BTK randomized controlled trial. J Soc Cardiovasc Angiogr Interv, 2023, 2(4): 100964. doi: 10.1016/j.jscai.2023.100964.
27. Varcoe RL, DeRubertis BG, Kolluri R, et al. Drug-eluting resorbable scaffold versus angioplasty for infrapopliteal artery disease. N Engl J Med, 2024, 390(1): 9-19.
28. DeRubertis BG, Varcoe RL, Krishnan P, et al. Drug-eluting resorbable scaffold versus balloon angioplasty for below-the-knee peripheral artery disease: 2-year results from the LIFE-BTK trial. Circulation, 2025, 152(15): 1076-1086.
29. Nugteren MJ, Welling RHA, Bakker OJ, et al. Vessel preparation in infrapopliteal arterial disease: a systematic review and meta-analysis. J Endovasc Ther, 2024, 31(2): 191-202.
30. Shammas NW, Yates T, Sastry A, et al. Twelve-month outcomes of the prospective, multicenter, single-arm study of the 355-nm laser for treatment of below-the-knee arteries: final results of the Auryon BTK. J Endovasc Ther, 2025: 15266028251352772. doi: 10.1177/15266028251352772.
31. Adams G, Soukas PA, Mehrle A, et al. Intravascular lithotripsy for treatment of calcified infrapopliteal lesions: results from the disrupt PAD Ⅲ observational study. J Endovasc Ther, 2022, 29(1): 76-83.
32. Shishehbor MH, Powell RJ, Montero-Baker MF, et al. Transcatheter arterialization of deep veins in chronic limb-threatening ischemia. N Engl J Med, 2023, 388(13): 1171-1180.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest ArticlesBreakthroughs in endovascular therapy for below-the-knee artery disease: from evolution of strategies to technological innovations

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