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Critical Limb Ischemia: Surgical Perspectives and Options
VASCULAR DISEASE MANAGEMENT 2010;7(11):E214–E218
Critical limb ischemia (CLI) is a common vascular pathology with profound medical and socioeconomic implications. Eight to ten million Americans are presently thought to suffer from peripheral arterial disease, with approximately 500–1,000 new cases of CLI per million per year.1 The natural history of this disease has been well documented in recent studies: at 1 year, 25% will be dead, 30% will have undergone amputation, with only 45% remaining alive with both limbs.1 Although prevention of CLI remains the ideal, once diagnosed, management of CLI consists first of medical management of underlying cardiovascular risk factors, e.g., dyslipidemia and hypertension. There is evidence to suggest the beneficial effect of statins, thienopyridines and aspirin and, in certain cases, beta-blockers.1–5 Although it is clear that these agents are widely underused,6 it is equally clear that the outcomes remain dismal despite their use. The only established avenue to truly improving CLI outcomes remains revascularization. The rapid evolution of endoluminal technology has added substantially to the traditional open surgical options available to effect revascularization. Increasingly, therefore, practitioners are faced with choices among endovascular, open surgical, and combined so-called hybrid procedures.
The purpose of this article is to survey open surgical bypasses and to examine their relative merits in CLI. Before we embark on this survey, however, there is a foundational issue that must be addressed: Which class of interventions produces superior outcomes (e.g., amputation-free survival, primary patency, overall survival), endovascular or surgical? To date, the Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial has been the only substantive randomized, controlled trial comparing the two.7 Briefly, the BASIL trial examined the primary endpoints of overall survival and amputation-free survival in a bypass-first versus angioplasty-first intervention in 452 patients with severe leg ischemia, defined as rest pain or tissue loss with an arterial etiology greater than 2 weeks in duration, from 1999 to 2004. The essence of the results is succinctly stated by the authors themselves:
The BASIL trial suggests that those severe leg ischemia (SLI) patients who are likely to live at least 2 years are probably better served by a surgical bypass-first strategy, preferably with vein. Those SLI patients who are unlikely to live 2 years, and possibly those in whom vein is not available for bypass, are probably better served by a balloon angioplasty-first strategy because they are unlikely to survive to reap the longer-term benefits of surgery, they may be more likely to suffer surgical morbidity and mortality, and because angioplasty is significantly less expensive than surgery in the short-term.
Although hailed as an achievement in the field, the BASIL trial has also been widely criticized for a number of shortcomings. First, the authors examined patients with severe leg ischemia in contrast to CLI, which is often more clearly defined in the literature. Moreover, they did not provide any objective information regarding degree of limb ischemia such as ankle brachial index, toe or ankle pressure and transcutaneous oximetry. As such, the authors failed to distinguish different outcomes in the spectrum of patients that exists within the category of severe limb ischemia. For instance, although the authors did demonstrate that there was no difference in the number of patients with ankle pressures above and below 50 mmHg between the two arms, each group was individually inadequately powered.8 It is likely that patients with relatively higher ankle pressure may behave differently clinically in terms of overall survival and amputation-free survival, two of the primary endpoints, but the BASIL trial does not allow us to draw any easily translatable conclusions. Second, patients in the trial reportedly had no obvious best first intervention. The definition of patients who satisfied this criterion varied from center to center and among physicians. Additionally, the majority of patients evaluated at the enrolling institutions were not felt to be candidates for enrollment and the reasons for this remain unclear. The lack of preestablished clinical or anatomical criteria further compromises the ability to reach conclusions. On balance, the BASIL trial appears to suffer from several limitations whose significance remains uncertain. It is evident that the answer to the question of superiority of endovascular or surgical bypass has been perhaps suggested, but not definitively demonstrated, and there still remains controversy.
Aorto-iliac Disease
Surgical treatment of aorto-iliac disease exists along a spectrum of mortality and patency rates. The gold standard surgical treatment of distal aortic and common iliac disease remains aorto-bifemoral bypass. Zukauskas et al reported on aorto-iliofemoral interventions in patients with CLI and multilevel disease who additionally required infra-inguinal revascularization.9 Aorto-bifemoral bypass carried a perioperative mortality of 3.8%, with primary patency rates at 1 and 5 years of 94.7% and 90.9%, respectively. This accords well with the results of a composite series of 4,302 aorto-bifemoral bypasses performed for both CLI and other reasons (e.g., claudication): perioperative and 1-year mortality rates of 3.1% and 3–7%, with primary patency at 1 and 5 years of 92–98% and 82–92%, respectively.10 Although aorto-iliac disease is often diffuse and bilateral, bona fide unilateral iliac disease exists. Some authors have nevertheless argued that the aorto-bifemoral bypass should be the preferred surgical intervention given that 6–12% of patients will progress to clinically significant contralateral disease within 5 years of the initial iliac intervention.9 Opponents argue that these rates of contralateral disease do not justify the excess physiologic stress and associated mortality risk given the option of, for instance, ilio-femoral bypass. Ilio-femoral bypass avoids aortic cross-clamping, is technically more straightforward and requires shorter operating time.9,11 Besides aorto-bifemoral bypass, Zukauskas’ series includes 288 patients with CLI treated with ilio-femoral bypass as the primary in-flow procedure.9 Again, the 30-day mortality (1.3%) and 1-year primary patency rates (94.1%) are comparable to McDaniel’s meta-analysis of 466 ilio-femoral bypass operations in a mixed claudication-CLI population with analogous figures of 0% mortality and 76–100% primary patency.10 Zukauskas’ 5-year primary patency rate of 88.5%9 is at the outer limit of Chiu’s range of 48–88% calculated from a meta-analysis of 723 procedures in a mixed population.12 Carsten et al, who have produced a more contemporary series in a majority-CLI population, also report a lower 5-year primary patency of 53.9%.11 Some authors have nevertheless cited these numbers to argue for the utility of ilio-femoral bypass over aorto-bifemoral bypass in unilateral disease given its favorable patency rates and diminished mortality.11,13
Extra-anatomic bypass defines an alternative spectrum of interventions for CLI and consists most commonly of femoro-femoral crossover bypass and axillo-femoral bypass, individually or together (“axillo-bifemoral bypass”). Traditional dogma holds that the principal advantage of extra-anatomic bypass is its lower operative stress and consequent utility in otherwise prohibitively high-risk patients, but also that this advantage comes at the price of reduced long-term patency. These assertions have been challenged recently. The relevant literature is exceptionally clouded given the varying reporting standards and the dramatically differing patient populations studied. Femoro-femoral bypass was initially touted as a lower-risk alternative for patients who did not qualify for anatomic reconstruction either because of comorbidities or a hostile abdomen. The indications have subsequently been liberalized by some groups with conflicting results. Regrettably, there are no randomized, prospective trials directly comparing femoro-femoral and aorto-bifemoral or ilio-femoral bypass procedures. Mingoli et al, however, retrospectively compared patients undergoing femoro-femoral bypass to a group undergoing aorto-bifemoral bypass with a similar comorbidity profile and to a random group of aorto-bifemoral bypass patients.13 Compared to the latter, femoro-femoral bypass patients had significantly higher age, fractions of cardiac and renal co-morbidities, hypertension and tobacco use, reflecting a more traditional application of extra-anatomic bypass to higher-risk patients. There was also an increased proportion of Rutherford’s peripheral arterial disease classes IV–VI. Hospital-stay mortality was 6%. Five-year primary patency and survival were 71% and 46%, respectively.
Despite these preoperative differences, there was no difference in perioperative mortality, limb salvage or primary graft patency relative to both of the comparison groups. Only long-term survival was lower in the femoro-femoral group relative to the random group of aorto-bifemoral bypass patients. Furthermore, within the femoro-femoral group, there was no difference in patency based on whether CLI or claudication was the indication for surgery. Thuijls et al report a contemporary series of 95 femoro-femoral bypasses with 51.8% of cases for either rest pain or tissue loss with similar outcomes: 30-day and 1-year mortality rates of 7.6% and 13%, respectively.14 Overall primary patency at 1 year was 88.2%. The five-year primary patency appears to be substantially lower at 57.3%. Importantly, this analysis also found that the indication for surgery, claudication or CLI did not impact primary patency. Examination of other series also indicates comparable mortality between femoro-femoral bypass and anatomic reconstruction, but with wide-ranging patency rates.15,16 An array of variables including bypass material (e.g., ring-reinforced polytetrafluoroethylene versus Dacron), bypass conduit diameter, patency of the recipient limb superficial femoral artery, and status of the donor iliac system have been studied with varying results.13,14,17–19 Despite the controversy regarding the impact of some of these factors, it is at the very least evident that femoro-femoral bypass provides a beneficial alternative for unilateral disease in those patients felt to be too ill for direct aortic reconstruction. Increasingly, interventional therapy offers options for these patients, even in the setting of severe occlusive disease. Surgical therapy provides a valuable method of revascularization that has proven benefit in severe aorto-iliac disease and can be utilized in those patients for whom endovascular options are either high risk (e.g., proximal, juxtarenal aortic occlusion) or who are severely prone to failure (e.g., bilateral extensive iliac and common femoral occlusive disease).
Infra-inguinal Disease
Research on infra-inguinal bypass outcomes is both extensive and nuanced. Indeed, primary patency rates are so intimately related to the technical details of bypass — conduit material, diameter, graft length and so forth — that interpretation of generic outcomes without references to these details must be done with caution (Table 1). The most recent and detailed information on infra-inguinal bypass using venous conduits is derived from the Project of Ex-vivo vein graft Engineering via Transfection III (PREVENT III),20 a randomized placebo-controlled double-blinded multicenter trial of edifoligide as a means of preventing vein-graft failure. Although the agent under investigation did not appear to have any significant impact on primary patency or limb salvage, it provided high-quality prospective data on lower-extremity bypasses with vein graft. There were several significant findings. First, the trial supported the previously accepted hierarchy of conduit material with respect to 1-year primary patency: single-segment greater saphenous vein (64.4% 1-year patency) is superior to arm vein or small saphenous vein (51.5%), which in turn is preferable to spliced vein (42.4%). Although not tested in PREVENT III, prosthetic grafts have been previously shown to be substantially inferior to vein graft.21 Second, within the group of patients with greater saphenous vein (GSV) conduit, diameter was a significant determinant of patency. Bypasses with GSV diameters 3.5 mm, which had 1-year primary patency of 68.4%. Third, length of bypass was inversely related to primary patency at 1 year: 60 cm (53.7%). Orientation of conduit, reversed versus excised non-reversed, had no effect on primary patency. Graft origin had a trivial impact on primary patency, with popliteal origin providing the best performance and a hazard ratio for patency loss of 0.67 (0.47–0.95) relative to those with common femoral artery origin. Location of distal insertion — popliteal, tibial, pedal — was insignificant.
A separate issue that has undergone evaluation in several contemporary studies is the potential advantage of endoscopic versus open GSV harvest. Besides the theoretical advantages generic to all minimally invasive approaches (diminished wound complications and postoperative pain, improved cosmesis), it has been postulated that endoscopic harvest may reduce vein trauma and thereby improve long-term patency. The existing evidence is both conflicting and incomplete. Rousou et al prospectively compared endothelial function and microscopic appearance in open and endoscopic GSV harvests.22 Specimens obtained endoscopically demonstrated both diminished endothelial function and more histologic damage via immunofluoroscence techniques. Others, using alternative tests of endothelial integrity, have arrived at the opposite conclusion.23,24 Gazoni et al retrospectively examined the results of 88 femoral to below-the-knee GSV bypasses and found no statistical difference in primary patency, with a mean follow-up time of 21 months.25 There was, however, a trend towards superior patency in the endoscopic group (92.8% vs. 80.9% at 21 months). Pullatt et al performed a retrospective analysis of 324 lower-extremity bypasses using GSV harvested via single-incision, endoscopy or a non-endoscopic minimally invasive technique (two or more “minimal incisions with long intervening skin bridges”).26 Demographic criteria were identical among the groups with the exception that a greater proportion of patients in the endoscopic group were women and more likely to use tobacco. The distribution of techniques among the type of bypass was also unequal. Single incision was used more frequently in tibial and pedal bypasses, while endoscopic and non-endoscopic minimally invasive techniques were more frequently used in femoral below-knee popliteal and femoral above-knee popliteal bypasses, respectively. Overall, single-incision harvest had the highest 5-year primary patency rate. There were no differences in patency between endoscopic and non-endoscopic minimally invasive cases. Comparison between the single-incision group and a composite group of endoscopic and non-endoscopic minimally invasive patients found no difference in primary patency in femoro-popliteal bypasses and superiority of single-incision harvest in tibial and pedal cases.
Though clearly a limited retrospective study, the findings are certainly suspicious and warrant further investigation. It is very likely that surgeon experience, technical proficiency with the varied approaches, along with the extent of vein to be harvested will impact outcomes considerably. For those patients with CLI, lesions that are less amenable to interventional therapy, who have acceptable autogenous saphenous vein, along with a life expectancy > 2 years, autogenous saphenous vein bypass offers the best chance to rapidly and durably revascularize the limb. Increasingly, those patients with CLI are older, with inadequate vein, and in these patients the choice must be made between composite vein grafting, alternative interventional therapies and prosthetic grafting. There is a paucity of data regarding the best way to proceed with these patients, however in most instances, an initial attempt at percutaneous therapy, if feasible, seems the most reasonable initial maneuver. For this reason, in most settings we will attempt to obtain venous mapping prior to proceeding with angiography to help determine whether an interventional treatment should be attempted at the same time.
Conclusion
CLI has bleak outcomes and limb revascularization is the mainstay of therapy for most patients. There are quickly multiplying options for intervention, even within the category of surgical bypass. Distal aortic and bilateral iliac disease is best treated via aorto-bifemoral bypass. Ilio-femoral bypass is an alternative for unilateral iliac disease. High-risk patients should undergo extra-anatomic bypass. The application of this class of procedures to the low- to moderate-risk patient is of unknown merit. Infra-inguinal bypass is best performed with GSV with a diameter > 3.5 mm. Orientation of the vein and insertion point have little impact on patency, while conduit length and origin have marginal effect. The utility and long-term results of endoscopic harvesting remain to be seen.
References
1. Norgren L, Hiatt W, Dormandy J, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45:S5–S67.
2. Varu VN, Hogg ME, Kibbe MR. Critical limb ischemia. J Vasc Surg 2010;51:230–241.
3. Schanzer A, Hevelone N, Owens C, et al. Statins are independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia. J Vasc Surg 2008;47:774–781.e1.
4. Conte MS, Bandyk DF, Clowes AW, et al. Risk factors, medical therapies and perioperative events in limb salvage surgery: Observations from the PREVENT III multicenter trial. J Vasc Surg 2005;42:456–464.
5. Diehm N, Silvestro A, Baumgartner I, et al. Chronic critical limb ischemia: European experiences. J Cardiovasc Surg (Torino) 2009;50:647–653.
6. Conte M, Bandyk D, Clowes A, et al. Results of PREVENT III: A multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery. J Vasc Surg 2006;43:742–751.
7. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): Multicentre, randomised controlled trial. Lancet 2005;366:1925–1934.
8. Conte MS. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia. J Vasc Surg 2010;51:69S–75S.
9. Zukauskas G, Ulevicius H, Janusauskas E. An optimal inflow procedure for multi-segmental occlusive arterial disease: Ilio-femoral versus aorto-bifemoral bypass. Cardiovasc Surg 1998;6:250–255.
10. McDaniel M, Macdonald P, Haver R, Littenberg B. Published results of surgery for aortoiliac occlusive disease. Ann Vasc Surg 1997;11:425–441.
11. Carsten CG 3rd, Kalbaugh CA, Langan EM 3rd, et al. Contemporary outcomes of iliofemoral bypass grafting for unilateral aortoiliac occlusive disease: A 10-year experience. Am Surg 2008;74:555-9; discussion 9–60.
12. Chiu KWH, Davies RSM, Nightingale PG, et al. Review of direct anatomical open surgical management of atherosclerotic aorto-iliac occlusive disease. Eur J Vasc Endovasc Surg 2010;39:460–471.
13. Mingoli A, Sapienza P, Feldhaus RJ, et al. Comparison of femorofemoral and aortofemoral bypass for aortoiliac occlusive disease. J Cardiovasc Surg (Torino) 2001;42:381–387.
14. Thuijls G, Vanlaake L, Lemson M, Kitslaar P. Usefulness and applicability of femorofemoral crossover bypass grafting. Ann Vasc Surg 2008;22:663–667.
15. Kim Y, Lee J, Kim H, Huh S. Factors affecting the long-term patency of crossover femorofemoral bypass graft. Eur J Vasc Endovasc Surg 2005;30:376–380.
16. Mii S, Eguchi D, Takenaka T, et al. Role of femorofemoral crossover bypass grafting for unilateral iliac atherosclerotic disease: A comparative evaluation with anatomic bypass. Surg Today 2005;35:453–458.
17. Aburahma A. Selecting patients for combined femorofemoral bypass grafting and iliac balloon angioplasty and stenting for bilateral iliac disease. J Vasc Surg 2001;33:93–99.
18. Johnson WC, Lee KK. Comparative evaluation of externally supported Dacron and polytetrafluoroethylene prosthetic bypasses for femorofemoral and axillofemoral arterial reconstructions. Veterans Affairs Cooperative Study #141. J Vasc Surg 1999;30:1077–1083.
19. Ricco J, Probst H. Long-term results of a multicenter randomized study on direct versus crossover bypass for unilateral iliac artery occlusive disease. J Vasc Surg 2008;47:45–54.e1.
20. Schanzer A, Hevelone N, Owens CD, et al. Technical factors affecting autogenous vein graft failure: Observations from a large multicenter trial. J Vasc Surg 2007;46:1180–1190.
21. Conte MS. Technical factors in lower-extremity vein bypass surgery: How can we improve outcomes? Sem Vasc Surg 2009;22:22–233.
22. Rousou L, Taylor K, Lu X, et al. Saphenous vein conduits harvested by endoscopic technique exhibit structural and functional damage. Ann Thorac Surg 2009;87:62–70.
23. Lancey RA, Cuenoud H, Nunnari JJ. Scanning electron microscopic analysis of endoscopic versus open vein harvesting techniques. J Cardiovasc Surg (Torino) 2001;42:297–301.
24. Meyer DM, Rogers TE, Jessen ME, et al. Histologic evidence of the safety of endoscopic saphenous vein graft preparation. Ann Thorac Surg 2000;70:487–491.
25. Gazoni L, Carty R, Skinner J, et al. Endoscopic versus open saphenous vein harvest for femoral to below the knee arterial bypass using saphenous vein graft. J Vasc Surg 2006;44:282–288.
26. Pullatt R, Brothers T, Robison J, Elliott B. Compromised bypass graft outcomes after minimal-incision vein harvest. J Vasc Surg 2006;44:289–295.
27. Ballard J, Millssr J. Surgical management of critical limb ischemia. Tech Vasc Interv Radiol 2005;8:169–174. 2
8. Curi MA, Skelly CL, Meyerson SL, et al. Conduit choice for above-knee femoropopliteal bypass grafting in patients with limb-threatening ischemia. Ann Vasc Surg 2002;16:95–101.
29. Takagi H, Goto S-N, Matsui M, et al. A contemporary meta-analysis of Dacron versus polytetrafluoroethylene grafts for femoropopliteal bypass grafting. J Vasc Surg 2010;52:232–236.
30. Arvela E, S’derstr’m M, Alb’ck A, et al. Arm vein conduit vs prosthetic graft in infrainguinal revascularization for critical leg ischemia. J Vasc Surg 2010;52:616–623.
31. Aulivola B, Pomposelli FB. Dorsalis pedis, tarsal and plantar artery bypass. J Cardiovasc Surg (Torino) 2004;45:203–212.
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Samir K. Shah, MD*, Khanjan H. Baxi, MD§, Daniel G. Clair, MD* From the *Vascular Surgery Department, The Cleveland Clinic, Cleveland, Ohio; and the §University of South Carolina School of Medicine, Columbia, South Carolina. The authors report no conflicts of interest regarding the content herein. Address for correspondence: Daniel G Clair, 9500 Euclid Avenue, Desk F30, Cleveland, Ohio 44195, E-mail: claird@ccf.org
