Results of peripheral bypass surgery in patients with critical limb ischemia (CRITISCH registry)

The methodology of the CRITISCH study has been described elsewhere [3, 4]. A diagnosis of CLI symptoms of more than 2 weeks standing was the criterion for inclusion in the CRITISCH registry and CLI was defined as peripheral arterial occlusive disease and an ankle/brachial index of ≤ 0.4 and/or residual pain (Rutherford class 4 or Fontaine stage III) and/or trophic disorders or necrosis/gangrene in the lower extremities (Rutherford classes 5/6 or Fontaine stage IV). Study endpoints were as follows:

Primary efficacy:

Secondary endpoints:

Between January 2013 and September 2014 a total of 1200 CLI patients were prospectively included in the registry and 284 underwent peripheral bypass surgery. Of these 284 patients 75 underwent above-knee bypasses (group 1), 80 below-knee bypasses (group 2) and 129 crural/pedal bypasses (group 3). A total of 159 vein bypasses were performed compared with 125 synthetic bypasses. Autologous vein bypasses in groups 1, 2 and 3 were carried out in 36 %, 57.5 % and 66.7 %, respectively. The total patient population comprised 192 males and 92 females. Tables 1 and 2 provide patient age and gender, comorbidities and baseline findings for the three groups.

Table 1 also provides the modified PREVENT III (PIII) CLI risk score, designed to predict long-term outcome of infrainguinal vascular reconstruction in CLI patients [5, 6]. Points were assigned to each patient as follows: dialysis 4 points, tissue loss 3 points, age ≥75 years 2 points and coronary artery disease 1 point. The total number of points yields a score on the basis of which patients were stratified into risk categories as low risk (score ≤3), medium risk (score 4–7) and high risk (score ≥8).

The Vascular Study Group of New England database includes 2110 bypasses for CLI for the period 2003–2009 [7]. The mean patient age was 69.9 years, 5 years older than the mean age of the 797 claudication patients studied simultaneously. Some 24.7 % of CLI patients received a prosthetic graft. While hospital mortality was low (2.1 %) reoperations were required in 15 % of cases and wound infections were observed in 5.6 % of patients. During the 1‑year follow-up period 13.6 % of the patients died and the major amputation rate was 12.2 %. The primary graft patency rate was 66.4 % and the secondary patency rate was 77.4 %. Thus, the results for CLI were significantly less favorable compared with the intermittent claudication (IC) patients also investigated in the study. In the IC group 1‑year mortality was only 3.7 %, the major amputation rate 1.6 %, primary graft patency 78.9 % and secondary patency 89 % at 1 year. These results underline the impact of the baseline situation on the results of peripheral bypass surgery. As patients with CLI and IC have widely differing prognoses, the two groups need to be considered separately; this also applies to perioperative results. For CLI patients in the US nationwide inpatient sample (NIS), Sachs et al. [8] reported a hospital mortality of 2.6 % and a major amputation rate of 3.9 % following open bypass surgery, which is consistent with the results obtained in this study (hospital mortality in the total patient population for all bypasses 2.8 % and major amputation rate 3.5 %). Furthermore, the analysis conducted by Sachs et al. [8] showed the amputation rate to crucially depend on the stage of CLI. Patients with rest pain or ulcers exhibited a perioperative amputation rate following bypass surgery of only 1.0 % and 0.7 %, respectively, whereas a rate of 9.1 % was observed in patients with gangrene. We distinguished CLI according to the Rutherford categories. Patients with Rutherford grade 4 exhibited significantly fewer postoperative complications (complication rate 16.7 %) compared with Rutherford grade 6 patients (45.8 %) and only 69.4 % of bypasses were open on discharge in Rutherford grade 6 patients compared with 88.9 % in Rutherford grade 4 patients (Table 4), which was also a statistically significant difference. Similarly, run-off status had a significant effect on the immediate postoperative outcome: if no vessel was open, a graft patency rate of 64.5 % was seen at patient discharge, compared with 85.5 % in the case of run-off from at least one vessel. Similarly, an analysis of results performed by Hiramori et al. [9] of endovascular treatment for femoropopliteal lesions indicated that having any run-off at all is the key to a better outcome: the quality of the run-off is important, not the number of open vessels; however, it must be said that at 1‑year follow-up, amputation-free survival in the present study did not differ according to whether run-off was present at baseline or not (Table 7).

It is important to pose the question in this context as to whether previous ipsilateral vascular interventions had a negative impact on results. This was not the case as far as the immediate postoperative result was concerned: the graft patency rate in the present patient population on discharge was 80.6 % (previous vascular intervention) and 85.5 % (no previous vascular intervention); however, better amputation-free survival was seen at 1 year in those patients who had not undergone previous vascular interventions (77 % vs. 68 %). This result shows a trend towards being consistent with observations in the Vascular Study Group of New England registry for 2003–2009 in this respect [10]. In that particular study, no immediate postoperative differences following infrainguinal bypasses were seen between patients with and without previous vascular interventions; however, the major amputation rate at 1 year among patients with previous endovascular interventions was significantly higher at 31 % compared with patients without previous ipsilateral revascularization (20 %). This observation has not been confirmed by others. Santo et al. [11] described the long-term outcome of 314 peripheral autologous vein bypasses (60 % infrapopliteal) in CLI patients. The 30-day mortality rate was 3.5 % and 5‑year outcomes were primary patency rate 45 %, secondary patency rate 64 %, limb salvage 89 % and amputation-free survival 49 %. No significant differences in outcome were seen according to whether patients had undergone previous endovascular interventions or not. It should be emphasized, however, that the 37 patients in the BASIL trial who received a bypass after initially failed angioplasty had a significantly worse amputation-free survival (p = 0.006) and somewhat worse overall survival (not significant) compared with the 184 bypass surgery-first patients [12].

This study determined the PREVENT III (PIII) CLI risk score, a stratification model designed to estimate amputation-free survival in CLI and infrainguinal bypass surgery patients. As Table 4 shows, the PIII CLI risk score correlates only partially with the postoperative complication rate and although patients in the lowest score group had fewer complications compared with the others, this difference was not significant. There were also no differences in graft patency rates in the three risk groups on discharge; however, the lower the PIII CLI risk score, the better the amputation-free survival at 1‑year follow-up (Table 7). Mc Phee et al. [13] analyzed 30-day unplanned readmission following peripheral bypass surgery in 1543 patients, 84.5 % of whom had CLI. Readmission, among other factors, was significantly related to the level of the distal anastomosis (e.g. popliteal, crural or pedal) and the lower the anastomosis, the more frequent readmissions were. In turn, the readmission rate correlated long-term with the amputation rate. These results provide evidence that the outcome of peripheral bypass surgery depends on the level of peripheral anastomosis. This was also demonstrated by Suckow et al. [2]. Patients receiving a vein bypass to the popliteal artery below the knee showed a primary graft patency rate of 78 % (prosthetic graft 74 %). Outcomes of bypasses targeting crural/pedal vessels were significantly less favorable (vein graft patency rate 62 % and prosthetic graft 66 %). What was striking in this study was that there were no significant differences between vein and prosthetic grafts in terms of primary patency at 1 year; however, the major amputation rate when the popliteal artery was the target and a prosthetic graft was used was worse (15 %) compared with when a vein graft was used (8 %); however, in the case of more distal crural/pedal anastomosis, there were no differences in major amputation rates between vein and prosthetic grafts (major amputation rate at 1 year for prosthetic grafts 19 % and for vein graft, 14 %). In our own patient population, freedom from amputation and hence also amputation-free survival (Fig. 2) at 12 months, was significantly higher if the graft target was above the knee compared with below-knee targets; however, this statement is only valid if, as shown in Fig. 2, no distinction is made between the type of graft material. Indeed, no difference was seen between the vein graft groups, whereas amputation-free survival at 1 year among patients receiving prosthetic grafts to suprapopliteal targets was 92 % and to infrapopliteal and crural targets 54 % and 56 %, respectively (Table 6).

Vein grafts with infrapopliteal and crural targets therefore showed better outcomes than prosthetic grafts (Fig. 1). This is consistent with observations made in the retrospective analysis performed by Uhl et al. [14], who saw a primary patency rate of 68.2 % in the vein group and only 34.1 % in the heparin-bonded PTFE graft group at 3 years. The limb salvage rate was 81.8 % in the vein group vs. 56.5 % in the heparin-bonded PTFE graft group and patient survival was 62.8 % vs. 46.7 %, respectively. Neville et al. [15] also performed a retrospective comparison of heparin-bonded PTFE grafts (n = 62) and vein grafts (n = 50). Tibial artery bypasses were performed with heparin-PTFE grafts anastomosed using an autologous vein patch. The indication for surgery was CLI in the vast majority of cases (91.9 % in the PTFE group and 90 % in the vein group). At 86 %, the 1‑year primary vein graft patency rate was superior to that of PTFE grafts (75.4 %); however, there were no significant differences between the two groups in terms of amputation rates.

Some of the differences reported in the literature in results obtained from the comparison of vein vs. prosthetic grafts may be based on the fact that one study compared PTFE grafts and one study heparin-bonded PTFE grafts with vein grafts. Dorigo et al. [16] retrospectively evaluated results from an Italian multicenter registry and compared data on 180 below-knee bypasses using heparin-bonded PTFE prosthetic grafts in diabetic CLI patients with 133 autologous vein grafts for the same indication. They reported 30-day bypass patency rates for the 2 groups of 92.2 % and 93.2 %, respectively. Estimated patient survival rates at 48 months were 76.6 % (heparin-PTFE) vs. 72.7 % (vein). The primary graft patency rate was significantly better in the vein group (63.5 %) compared with the heparin-bonded PTFE-graft group (46.3 %). Differences in secondary graft patency (69.6 % vs. 57.5 %), limb salvage (82.4 % vs. 75.4 %), and amputation-free survival (64.4 % vs. 59.9 %) between vein and heparin-bonded PTFE grafts were not significant. Gessaroli et al. [17] undertook a comparison of vein vs. heparin-bonded grafts in a total of 74 femorocrural bypasses. This study found no differences in primary patency rates between the two graft materials (84 % for both groups) and the same applied to limb salvage rates (heparin-PTFE 87 % and vein 84 %) and 1‑year patient survival (87 % for both groups). Finally, Avgerinos et al. [18] reported on the retrospective analysis of a collective comprising a total of 407 infrainguinal bypasses including 116 popliteal (29 %), 226 tibial (56 %) and 65 pedal (16 %). Of these bypasses 96 % were in CLI patients whereby GSV grafts were performed in 63 % (n = 255), alternative autologous vein grafts (upper extremity veins and composite vein segments) in 26 % (106) and prosthetic grafts in 11 % (n = 47), of which 41 were heparin-bonded PTFE grafts. They reported a primary patency rate at 2 years of 47 % for the GSV bypasses, 24 % for the alternative veins and 43 % for the prosthetic bypasses. Secondary patency at 2 years was calculated at 75 %, 57 % and 46 %, respectively, for the three groups. In this particular investigation, using GSV was significantly superior in terms of secondary patency compared with the other materials used; however, there was no significant difference between the alternative vein grafts and prosthetic grafts. The 2‑year limb salvage rates were 86 %, 78 % and 72 %, respectively. These differences were not statistically significant. The key message of this investigation was that in the absence of the GSV as bypass material, complex reconstruction with alternative autologous vein grafts confers no advantages over heparin-bonded PTFE prosthetic grafts in below-knee bypasses. It should be noted that no distinction was made in our study between PTFE grafts with and without heparin bonding.

The present study had a number of limitations: study design was a retrospective analysis of prospectively recorded data, the study was not randomized and the number of patients in each group was small. In this respect it is not possible to exclude a type II statistical error in the analysis of the different endpoints between groups as well as in the subgroup analysis. The statistically significant differences should be considered with caution. Clinical evaluations of patients as well as angiographic and duplex ultrasound results were analyzed by the attending physician and the data entered in the registry. There was no core laboratory or adverse event committee. This registry reflects the results of the 27 participating centers; however, these are not necessarily representative of the situation in all vascular centers in Germany. Furthermore, it should be noted from a critical perspective that the results of revascularization also depend on anticoagulation and antiplatelet therapy. The present study was not able to analyze concomitant medication over time.