論文ID: CJ-23-0348
Background: Acute limb ischemia (ALI) is a limb- and life-threatening condition and urgent treatment including revascularization should be offered to patients unless the limb is irreversibly ischemic. The aim of this study was to investigate 1-year clinical outcomes and prognostic factors following revascularization in patients with ALI.
Methods and Results: A retrospective, multicenter, nonrandomized study examined 185 consecutive patients with ALI treated by surgical revascularization (SR), endovascular revascularization (ER), or hybrid revascularization (HR) in 6 Japanese medical centers from January 2015 to August 2021. The 1-year amputation-free survival (AFS) rate was estimated to be 69.2% (95% confidence interval [CI], 62.8–76.2%). There were no significant differences among SR, ER, and HR regarding both technical success and perioperative complications. Multivariate analysis revealed that Rutherford category IIb and III ischemia (hazard ratio [HR]: 1.86; 95% CI: 1.06–3.25), supra- to infrapopliteal lesion (HR: 2.06; 95% CI: 1.08–3.95), and technical failure (HR: 2.58; 95% CI: 1.49–4.46) were independent risk factors for 1-year AFS.
Conclusions: Rutherford category IIb and III ischemia, supra- to infrapopliteal lesions, and technical failures were identified as independent risk factors for 1-year AFS. Furthermore, patients with multiple risk factors had a lower AFS rate.
Acute limb ischemia (ALI), which requires timely recognition and urgent revascularization, is a limb- and life-threatening condition.1,2 Although surgical thrombo-embolectomy is still the first-line therapy for patients with ALI caused by embolic occlusion, endovascular therapy such as intra-arterial thrombolysis, thrombus aspiration, or mechanical thrombectomy has increased to about 30% of cases.3 Some studies report that intra-arterial thrombolysis, which has an inherent risk of bleeding complication, showed comparable outcomes for ALI compared with open surgery.4,5 In real-world clinical practice, however, revascularization strategies such as surgical revascularization (SR), endovascular revascularization (ER), or hybrid revascularization (HR) are selected based on the etiology of ALI, anatomic factors, amount of thrombus, patient’s comorbidities, and therapy-related risks. Furthermore, availability of devices such as mechanical thrombectomy devices differ by country. Despite considerable progress in the application of revascularization strategies, amputation-free survival (AFS) at 1 year following revascularization procedures has been reported as 50–70%;6–8 in particular, severe ischemia such as Rutherford category IIb and III has inferior outcomes compared with Rutherford category I and IIa.9,10
The RESCUE ALI (REtroSpective multiCenter study of endovascUlar or surgical intErvention for Acute Limb Ischemia) study enrolled patients with ALI following SR, ER, or HR to evaluate 1-year clinical outcomes and prognostic factors. Furthermore, this study investigated how prognostic factor clusters affected outcomes. Although there are some limitations regarding available devices and pharmacologic agents for the treatment of ALI in this study, this is collaborative research between vascular surgeons and interventional cardiologists in a “real-world” contemporary clinical setting.
The RESCUE ALI study is a retrospective, multicenter, nonrandomized study to investigate 1-year clinical outcomes and prognostic factors following revascularization in patients with ALI at 6 Japanese medical hospitals from January 2015 to August 2021. In this period, 185 consecutive patients with ALI were treated by SR, ER, or HR (Figure 1). As guideline recommended,11 these hospitals employed specialists in vascular or endovascular procedures and had a full range of facilities to manage patients with ALI. Of the 6 hospitals, 5 had both a vascular surgical center and a cardiovascular center, and 1 hospital had only a cardiovascular center. Patients with chronic symptomatic peripheral artery disease, upper limb acute ischemia, and blue toe syndrome were excluded from this study. All procedures were performed by vascular surgeons or interventional cardiologists. Clinical data collected from each hospital was entered into a database for analysis. The study protocol was developed in accordance with the Declaration of Helsinki and was approved by the ethical committee of each hospital. Informed consent to undergo the interventions listed was given by all patients or, if not possible, from their families. The authors have no conflicts of interest to disclose concerning this study.
Study flow chart for patients with acute limb ischemia (ALI) who underwent revascularization at 6 Japanese medical hospitals from January 2015 to August 2021. The 185 consecutive patients with ALI were treated by surgical revascularization (SR), endovascular revascularization (ER), or hybrid revascularization (HR) during this period. The 24 patients who initially visited vascular surgical centers were referred to cardiovascular centers for ER, and the 26 patients who initially visited cardiovascular centers were referred to vascular surgical centers for SR or HR. Finally, of the 185 patients, SR, HR, and ER were performed in 79, 40, and 66 patients, respectively.
The selection of the initial revascularization or subsequent adjunctive treatment was at the operator’s discretion. Patients who initially visited vascular surgical centers but were at high risk for surgery due to prohibitive comorbidities or anatomic factors were referred to cardiovascular centers for ER. Patients who initially visited cardiovascular centers, but were not indicated for ER because of the amount of thrombus, such as occlusions of the aorta, were referred to vascular surgical centers for SR or HR. These decisions were based on the fact that many complicated endovascular procedures can currently be performed by interventional cardiologists in Japan. Catheter-directed thrombolysis (CDT) using urokinase with a maximum 240,000 units/day (health insurance covers up to 240,000 units/day in Japan) was performed as adjunctive therapy following HR or ER at the operator’s discretion. Tissue plasminogen activator (t-PA), which is not covered by Japanese health insurance, and pharmacomechanical thrombolysis (PMT), which is not available in Japan, were not used in this study.
Data DefinitionsALI was defined as sudden onset or acute deterioration of clinical symptoms of lower limb ischemia within the preceding 14 days.1 Severity of ischemia was assessed according to the Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) clinical categories of ALI (Rutherford category),9 with Rutherford category IIb and III ischemia classified as severe ALI. Smoking was defined as any history of smoking in the past or the present. Chronic renal failure was defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2, excluding hemodialysis. Valvular heart disease was defined as a history of cardiac valve surgery (replacement or repair) or transcatheter valve implantation. Congestive heart failure was defined as a history of hospitalization for heart failure. Atrial fibrillation included paroxysmal, persistent, or permanent atrial fibrillation. Lower extremity artery disease (LEAD) included intermittent claudication and chronic limb-threatening ischemia. Acute kidney injury was defined as an increase in the serum creatinine levels by ≥25% or ≥0.5 mg/dL within 48 h after the procedure.
OutcomesThe primary endpoint for analysis was the 1-year AFS; that is, freedom from the composite of major amputation and all-cause death. The secondary endpoints included overall survival, technical success, and perioperative complications. For HR, ER, or SR that was performed under angiographic guidance, technical success was achieved when in-line blood flow was restored to the pedal artery or the ankle without delay on final angiography. In SR without perioperative angiography, the intervention was considered technically successful when a palpable pulse or biphasic doppler signals were detected over ≥1 of the pedal vessels at the completion of the procedure.
Statistical AnalysisData are presented as the mean±standard deviation for continuous variables and as the frequency (percentage) for categorical variables, unless otherwise mentioned. A P value <0.05 was considered statistically significant, and 95% confidence intervals (CIs) are reported where appropriate. Differences of baseline characteristics among groups were tested using the one-way analysis of variance for continuous variables and the chi-squared test for discrete variables. The rate of AFS was estimated using the Kaplan-Meier method. The association of baseline characteristics with failure of AFS was investigated using a Cox proportional hazards regression model. The variables with statistical significance in the univariate model were entered in the subsequent multivariate model. All statistical analyses were performed with R, version 4.1.1 (R Development Core Team, Vienna, Austria).
As illustrated in the study flow chart (Figure 1), the 24 patients who initially visited vascular surgical centers were referred to cardiovascular centers for ER, and the 26 patients who initially visited cardiovascular centers were referred to vascular surgical centers for SR or HR. Finally, of the 185 patients, SR, HR, and ER were performed for 79 (42.7%), 40 (21.6%), and 66 (35.7%) patients, respectively. Baseline characteristics of the study population are summarized in Table 1. The ER group had a higher prevalence of patients older than 70 years and with severe ALI defined as Rutherford category IIb and III ischemia. The SR group had a higher prevalence of aortoiliac artery occlusions and a lower prevalence of infrapopliteal artery occlusions compared with the ER group. When patients were divided into 3 groups according to the location of the occlusion, supra- to infrapopliteal occlusions (54.6%) comprised the majority in the ischemic limbs. There were no significant differences regarding the prevalence of supra- to infrapopliteal occluded lesions among the groups (54.4% of the SR group vs. 52.5% of the HR group vs. 56.1% of the ER group, P=0.72). Revascularization procedures are shown in Table 2. In the SR group, 49 patients (62%) were treated by angiography-guided Fogarty catheter thrombectomy. The HR group included 38 combined Fogarty catheter thrombectomies and endovascular therapy (EVT: 95%). In the ER group, combined balloon angioplasty and aspiration was performed in 30 patients (45.5%), and combined balloon angioplasty, aspiration, and stenting in 20 patients (30.3%). Table 3 lists the perioperative outcomes. Although there were no significant differences among the groups regarding technical success and perioperative complications, operation times were significantly longer in the HR group.
| Overall population (n=185) |
Surgical revascularization (n=79) |
Hybrid revascularization (n=40) |
Endovascular revascularization (n=66) |
P value | |
|---|---|---|---|---|---|
| Male sex | 107 (58%) | 44 (56%) | 27 (68%) | 36 (55%) | 0.42 |
| Age (years) | 76±14 | 73±16 | 75±14 | 79±11 | 0.007 |
| ≥70 | 136 (74%) | 50 (63%) | 29 (73%) | 57 (86%) | 0.007 |
| Smoking | 88 (48%) | 42 (53%) | 16 (40%) | 30 (45%) | 0.65 |
| Diabetes mellitus | 69 (37%) | 24 (30%) | 15 (38%) | 30 (45%) | 0.17 |
| Chronic renal failurea | 14 (8%) | 4 (5%) | 5 (13%) | 5 (8%) | 0.35 |
| Hemodialysis | 18 (10%) | 4 (5%) | 4 (10%) | 10 (15%) | 0.07 |
| Valvular heart disease | 6 (3%) | 3 (4%) | 0 (0%) | 3 (5%) | 0.17 |
| Congestive heart failure | 31 (17%) | 13 (16%) | 6 (15%) | 12 (18%) | 0.67 |
| Atrial fibrillation | 64 (35%) | 29 (37%) | 11 (28%) | 24 (36%) | 0.32 |
| History of LEAD | 62 (34%) | 28 (35%) | 11(28%) | 23 (35%) | 0.43 |
| History of ALI | 25 (14%) | 8 (10%) | 8 (20%) | 9 (14%) | 0.14 |
| Current malignancy | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | |
| Oral medication | |||||
| Aspirin | 48 (26%) | 19 (24%) | 7 (18%) | 22 (33%) | 0.07 |
| P2Y12 inhibitor | 42 (23%) | 14 (18%) | 9 (23%) | 19 (29%) | 0.11 |
| Cilostazol | 20 (11%) | 11 (14%) | 4 (10%) | 5 (8%) | 0.22 |
| Anticoagulant | 40 (22%) | 25 (32%) | 9 (23%) | 6 (9%) | <0.001 |
| Statin | 36 (19%) | 18 (23%) | 3 (8%) | 15 (23%) | 0.04 |
| Time from onset (h) | 38±69 | 41±78 | 49±82 | 27±45 | 0.12 |
| Time from onset ≥24 h | 79 (43%) | 31 (39%) | 18 (45%) | 30 (45%) | 0.45 |
| Non-severe ALI (Rutherford category I and IIa) | 136 (74%) | 63 (80%) | 33 (83%) | 40 (61%) | 0.02 |
| Rutherford category I | 67 (36%) | 39 (49%) | 20 (50%) | 8 (12%) | |
| Rutherford category IIa | 69 (37%) | 24 (30%) | 13 (33%) | 32 (48%) | |
| Severe ALI (Rutherford category IIb and III) | 49 (26%) | 16 (20%) | 7 (18%) | 26 (39%) | 0.02 |
| Rutherford category IIb | 43 (23%) | 15 (19%) | 6 (15%) | 22 (33%) | |
| Rutherford category III | 6 (3%) | 1 (1%) | 1 (3%) | 4 (6%) | |
| De novo lesion | 149 (81%) | 63 (80%) | 32 (80%) | 54 (82%) | 0.81 |
| Occlusion site | |||||
| Aorta | 8 (4%) | 6 (8%) | 2 (5%) | 0 (0%) | 0.02 |
| Iliac artery | 48 (26%) | 30 (38%) | 14 (35%) | 4 (6%) | <0.001 |
| CFA | 54 (29%) | 31 (39%) | 13 (33%) | 10 (15%) | 0.001 |
| SFA | 127 (69%) | 53 (67%) | 31 (78%) | 43 (65%) | 0.18 |
| Pop | 125 (68%) | 49 (62%) | 25 (63%) | 51 (77%) | 0.04 |
| IP | 109 (59%) | 35 (44%) | 21 (53%) | 53 (80%) | <0.001 |
| Area of occluded lesion | |||||
| Suprapopliteal limited lesion | 47 (25%) | 24 (30%) | 14 (35%) | 9 (14%) | 0.02 |
| Popliteal to infrapopliteal limited lesion | 37 (20%) | 12 (15%) | 5 (13%) | 20 (30%) | 0.03 |
| Supra- to infrapopliteal lesion | 101 (55%) | 43 (54%) | 21 (53%) | 37 (56%) | 0.72 |
| No runoff of the below the knee artery before procedure |
108 (58%) | 36 (46%) | 26 (65%) | 46 (70%) | 0.003 |
| Aortic plaque | 22 (12%) | 16 (20%) | 0 (0%) | 6 (9%) | 0.002 |
| Left ventricular thrombosis | 3 (2%) | 0 (0%) | 2 (5%) | 1 (2%) | 0.21 |
| TEVAR/EVAR thrombosis | 4 (2%) | 4 (5%) | 0 (0%) | 0 (0%) | 0.06 |
| In situ thrombosis | 29 (16%) | 6 (8%) | 7 (18%) | 16 (24%) | 0.02 |
| Failed stent | 6 (3%) | 1 (1%) | 1 (3%) | 4 (6%) | 0.40 |
| Failed bypass | 19 (10%) | 11 (14%) | 4 (10%) | 4 (6%) | 0.12 |
| Popliteal aneurysm | 2 (1%) | 1 (1%) | 0 (0%) | 1 (2%) | 0.43 |
| Peak CPK (IU/L) | 4,368±11,888 | 4,847±15,156 | 4,601±11,798 | 3,621±5,930 | 0.54 |
| Median peak CPK, IU/L (IQR) | 746 (142–3,357) | 395 (142–2,439) | 654 (133–2,915) | 1,139 (267–4,102) | 0.13 |
| Peak CPK ≥746 IU/L | 92 (50%) | 36 (46%) | 20 (50%) | 36 (54%) | 0.36 |
Continuous values are shown as mean±standard deviation; categorical data are given as number (percentage). aDefined as estimated glomerular filtration rate <30 mL/min/1.73 m2, excluding hemodialysis. ALI, acute limb ischemia; CFA, common femoral artery; CPK, creatine phosphokinase; EVAR, endovascular aneurysm repair; IP, infrapopliteal artery; LEAD, lower extremity artery disease; Pop, popliteal artery; SFA, superficial femoral artery; TEVAR, thoracic endovascular aortic repair.
| Surgical revascularization (n=79) |
Hybrid revascularization (n=40) |
Endovascular revascularization (n=66) |
|
|---|---|---|---|
| Surgery | |||
| Angiography-guided Fogarty catheter thrombectomy | 49 | 38 | 0 |
| Blind Fogarty catheter thrombectomy | 12 | 0 | 0 |
| Bypass surgery | 12 | 0 | 0 |
| Saphenous vein graft | 5 | 0 | 0 |
| Prosthetic conduit | 7 | 0 | 0 |
| Angiography-guided Fogarty catheter thrombectomy + endarterectomy |
2 | 0 | 0 |
| Angiography-guided Fogarty catheter thrombectomy + bypass surgery |
4 (All prosthetic conduit) |
2 (Saphenous vein graft x1, Prosthetic conduit x1) |
0 |
| EVT | |||
| POBA | 0 | 22 | 12 |
| POBA+aspiration | 0 | 3 | 30 |
| POBA+stenting | 0 | 1 | 4 |
| POBA+aspiration+stenting | 0 | 0 | 20 |
| Stenting | 0 | 13 | 0 |
| EVT+CDT | 0 | 0 | 8 |
| (missing data) | 1 | ||
| Hybrid | |||
| Fogarty catheter thrombectomy + EVT | 0 | 38 | 0 |
| Fogarty catheter thrombectomy + bypass surgery + EVT | 0 | 2 | 0 |
| Hybrid+CDT | 0 | 5 | 0 |
CDT, catheter-directed thrombolysis; EVT, endovascular therapy; POBA, plain old balloon angioplasty.
| Overall population (n=185) |
Surgical revascularization (n=79) |
Hybrid revascularization (n=40) |
Endovascular revascularization (n=66) |
P value | |
|---|---|---|---|---|---|
| Operation time (min) | 139±86 | 138±106 | 165±83 | 125±54 | 0.004 |
| (missing data) | 13 (7%) | 7 (7%) | 5 (7%) | 1 (1%) | 0.84 |
| Contrast dose (mL) | 67±71 | 23±40 | 109±69 | 108±70 | <0.001 |
| Technical success | 0.07 | ||||
| Success | 131 (71%) | 62 (78%) | 26 (65%) | 43 (65%) | |
| Failure | 54 (29%) | 17 (22%) | 14 (35%) | 23 (35%) | |
| Perioperative complications | 0.73 | ||||
| None | 164 (89%) | 70 (89%) | 36 (90%) | 58 (88%) | |
| MNMS | 12 (6%) | 6 (8%) | 3 (8%) | 3 (5%) | |
| Distal embolism | 4 (2%) | 2 (3%) | 0 (0%) | 2 (3%) | |
| Acute kidney injury | 2 (1%) | 1 (1%) | 0 (0%) | 1 (1%) | |
| Vascular perforation | 2 (1%) | 0 (0%) | 1 (2%) | 1 (1%) | |
| Hematoma | 1 (1%) | 0 (0%) | 0 (0%) | 1 (1%) |
Continuous values are shown as mean±standard deviation; categorical data are given as number (percentage). MNMS, myonephropathic metabolic syndrome.
During a mean follow-up of 11.8±7.1 months, a composite of major amputation and all-cause death occurred in 58 patients. The 1-year AFS rate was estimated to be 69.2% (95% CI, 62.8–76.2%) (Figure 2). As shown in Table 4, severe ALI (Rutherford category IIb and III), supra- to infrapopliteal lesion, and technical failure were independently associated with an increased risk of adverse outcome; the adjusted hazard ratios (HRs) were 1.86 (95% CI, 1.06–3.25; P=0.03), 2.06 (1.08–3.95; P=0.02), and 2.58 (1.49–4.46; P<0.001), respectively. Indeed, patients with multiple risk factors, as a group, had a lower AFS rate (Figure 3). No runoff of the below the knee artery before procedure and peak creatine phosphokinase (CPK) ≥746 IU/l were significantly associated with the outcome in the univariate model, but not in the multivariate model (Table 4). The overall survival rates at 6 months and 1 year were 76.8% (95% CI, 70.9–83.1%) and 74.6% (95% CI, 68.6–81.1%), respectively (Figure 4). The causes of death are shown in the Supplementary Table.
Kaplan-Meier estimates of amputation-free survival (AFS) in the overall population of 185 patients. The 1-year AFS rate was estimated to be 69.2%. SE, standard error.
| Unadjusted HR | Adjusted HR | |
|---|---|---|
| Male sex | 0.61 [0.36–1.01] (P=0.056) | N/I |
| Age ≥70 years | 1.18 [0.65–2.16] (P=0.59) | N/I |
| Smoking | 0.71 [0.42–1.20] (P=0.20) | N/I |
| Diabetes mellitus | 0.79 [0.46–1.37] (P=0.41) | N/I |
| Chronic renal failurea | 1.52 [0.65–3.54] (P=0.33) | N/I |
| Hemodialysis | 1.07 [0.43–2.72] (P=0.87) | N/I |
| Valvular disease | 0.51 [0.07–3.69] (P=0.50) | N/I |
| Chronic heart failure | 1.53 [0.82–2.83] (P=0.18) | N/I |
| Atrial fibrillation | 0.77 [0.44–1.35] (P=0.36) | N/I |
| History of LEAD | 0.73 [0.42–1.29] (P=0.28) | N/I |
| History of ALI | 0.96 [0.46–2.03] (P=0.92) | N/I |
| Aspirin use | 0.64 [0.33–1.24] (P=0.19) | N/I |
| P2Y12 inhibitor use | 0.75 [0.39–1.45] (P=0.40) | N/I |
| Cilostazol use | 0.72 [0.29–1.79] (P=0.48) | N/I |
| Anticoagulant use | 0.90 [0.48–1.70] (P=0.74) | N/I |
| Statin use | 1.02 [0.54–1.92] (P=0.96) | N/I |
| Time from onset ≥24 h | 0.61 [0.35–1.06] (P=0.079) | N/I |
| Severe ALI (Rutherford category IIb and III) | 2.38 [1.41–4.02] (P=0.001) | 1.86 [1.06–3.25] (P=0.03) |
| De novo lesion | 0.95 [0.51–1.80] (P=0.88) | N/I |
| Site of occlusion (vs. suprapopliteal limited lesion) | ||
| Popliteal to infrapopliteal limited lesion | 2.28 [0.83–6.28] (P=0.11) | N/I |
| Supra- to infrapopliteal lesion | 2.10 [1.19–3.70] (P=0.01) | 2.06 [1.08–3.95] (P=0.02) |
| No runoff of the below the knee artery before procedure | 2.05 [1.14–3.71] (P=0.02) | 1.05 [0.53–2.09] (P=0.86) |
| Aortic plaque | 0.59 [0.22–1.67] (P=0.32) | N/I |
| Left ventricular thrombosis | 1.15 [0.16–8.36] (P=0.89) | N/I |
| TEVAR/EVAR thrombosis | 2.54 [0.79–8.15] (P=0.11) | N/I |
| In situ thrombosis | 1.08 [0.53–2.21] (P=0.81) | N/I |
| Failed stent | 1.01 [0.25–4.14] (P=0.99) | N/I |
| Failed bypass | 0.43 [0.13–1.37] (P=0.15) | N/I |
| Popliteal aneurysm | 1.50 [0.21–10.8] (P=0.69) | N/I |
| Peak CPK ≥746 IU/L | 2.20 [1.28–3.78] (P=0.004) | 1.48 [0.83–2.64] (P=0.17) |
| Revascularization strategy (vs. surgical revascularization) | ||
| Hybrid revascularization | 1.10 [0.56–2.15] (P=0.78) | N/I |
| Endovascular revascularization | 0.98 [0.54–1.76] (P=0.94) | N/I |
| Technical failure | 3.35 [1.99–5.61] (P<0.001) | 2.58 [1.49–4.46] (P<0.001) |
Data are HRs [95% confidence intervals] (P values). aDefined as estimated glomerular filtration rate <30 mL/min/1.73 m2, excluding hemodialysis. HR, hazard ratio; N/I, not included. Other abbreviations as in Table 1.
Kaplan-Meier estimates of amputation-free survival (AFS) by the accumulation of risk factors in 185 patients. Risk factors are (1) severe ALI (Rutherford category IIb/III), (2) supra- to infrapopliteal lesion, and (3) technical failure. The 1-year AFS rate was 92.5%, 71.1%, 52.5%, and 25.0% in the patients without 0 factors, with 1 risk factor, with 2 risk factors, and with 3 risk factors, respectively. SE, standard error.
Kaplan-Meier estimates of overall survival in the 185 patients. The 6-month and 1-year survival rates were estimated to be 76.8% and 74.6%, respectively. SE, standard error.
The RESCUE ALI study documents the 1-year clinical outcomes and prognostic factors following revascularization for ALI in real-world practice. The 1-year AFS rate was estimated to be 69.2%, similar to previous reports.6–8 In this study we identified 3 independent risk factors for 1-year AFS: severe ALI (Rutherford category IIb and III), supra- to infrapopliteal lesion, and technical failure. Regardless of the revascularization strategy there were no significant differences regarding the 1-year AFS rate; however, the 1-year AFS rate was 92.5% in the patients without the risk factors, and 25.0% in those with the 3 risk factors. To the best of our knowledge, this is the first study to demonstrate the 1-year risk of AFS and 1-year AFS rates according to the accumulation of risk factors.
Similar to the present study, previous studies have reported that Rutherford category IIb or III ischemia is associated with an increased risk of major amputation and death at 1 year.7,10,12 It has also been reported that the clinical success and AFS following SR and ER were inferior in patients with Rutherford category IIb compared with Rutherford category IIa.13,14 The present study included Rutherford category IIb and III in 23.2% and 3.3% of patients, respectively. Although the ER group had a higher prevalence of both categories (39.4% vs. 20.3% in SR group vs. 17.5% in HR group, P=0.02), there were no significant differences compared with SR and HR regarding both technical success and perioperative complications. Therefore, it is thought that the results were not caused by any differences in the revascularization strategy. Previous studies have, in contrast, indicated that ER might be a valuable first-line approach when urgent reperfusion is needed even in patients with severe ischemia.7,15 As described in a recent guideline,11 patients with Rutherford category IIb ischemia have a condition in which the limb is immediately threatened but salvageable if promptly revascularized. Rutherford category III is considered irreversible limb ischemia, however, there is a small chance of limb salvage in patients with short duration of motor deficit. Although Rutherford category ≥IIb comprised the minority of ischemic limbs in the present study, it was independently associated with an increased risk of AFS as a result of its severity.
There have been no reports, thus far, regarding any association between the site of the occlusion and clinical outcomes following revascularization in patients with ALI. The present study demonstrated that supra- to infrapopliteal lesions, in 54.6% of the present patients, were an independent risk factor for 1-year AFS. A probable explanation for this finding is that lesions extending from the suprapopliteal artery to the infrapopliteal artery have a higher thrombus burden or a larger territory of lower limb ischemia when compared with lesions limited to the suprapopliteal or popliteal to infrapopliteal arteries. There were no significant differences regarding the prevalence of supra- to infrapopliteal occlusions and technical success according to the revascularization strategy in the present study. Lesions that extend from the suprapopliteal artery to the infrapopliteal artery may require a more complicated revascularization procedure and longer operation time irrespective of the revascularization strategy, which may lead to worsening limb ischemia and a greater risk of complications, especially in elderly and frail patients.
As illustrated in the study flow chart, selection of the initial revascularization strategy was made by the vascular surgeons or interventional cardiologists. SR, HR, and ER were performed in 42.7%, 21.6%, and 35.7% of patients, respectively. When focusing on the etiology of ALI, embolic occlusions occurred in 62% (49/79) of the SR group, 32.5% (13/40) of the HR group, and 46.9% (31/66) of the ER group. Technical success, which was defined as restoration of in-line blood flow to the pedal artery or ankle without delay on final angiography or when a palpable pulse or biphasic doppler signals were detected over ≥1 of the pedal vessels at completion of the procedure, was achieved in 70.8% of patients in the present study. Although there was no significant difference regarding technical success and perioperative complications among the groups, the SR group tended to have a higher technical success rate compared with the ER group. A probable explanation for this is that in the SR group bypass surgery could be performed if intravascular recanalization was not achieved. Another possible explanation is that 82.1% (55/67) of patients treated by thrombectomy in the SR group underwent angiography-guided procedures. Previous studies report that completion angiography following thrombo-embolectomy is recommended because residual thrombi are common and their identification was associated with a reduced risk of re-intervention and limb loss.16,17
The TOPAS (Thrombolysis or Peripheral Arterial Surgery) trial, which randomized patients with ALI secondary to native arterial or bypass graft occlusion of <14 days’ duration, demonstrated that AFS rates at 1 year were similar (65% in the urokinase group vs. 70% in the surgery group, P=0.23), but significantly more bleeding occurred in those randomized to urokinase (13% in the urokinase group vs. 6% in the surgery group, P=0.005).5,18 In the present study, CDT was performed in 8 cases (12%) of the ER group and one of the reasons why primary CDT was not used is that the average age in the ER group was 79±11 years, which was older than the urokinase group (65±0.8 years) in the TOPAS trial. Another factor to consider is that health insurance in Japan only covers a maximum of 240,000 units of urokinase/day and does not cover the use of t-PA. Although urokinase was available during this study period, there is a possibility in near future that it will be unavailable in Japan due to suspension of sales and supply. Lack of urokinase in a revascularization procedure may negatively affect outcomes after the treatment of ALI.
In the present study, the ER group, when compared with the SR group, had a lower prevalence of suprapopliteal limited lesions and a higher prevalence of popliteal to infrapopliteal limited lesions. This trend may reflect the selection of revascularization strategy for ALI. A previous study in which SR, HR, and ER were performed in 43%, 19%, and 38%, respectively, of patients with ALI, reported that the rate of ER performed in the aortoiliac artery (12%) was significantly lower than the rate of ER in infra-inguinal artery (54%),19 and an earlier Japanese nationwide registry regarding EVT for ALI reported that a suprapopliteal lesion was an independent risk factor for in-hospital complications including in-hospital death within 30 days, urgent surgery, bleeding requiring transfusion, and distal embolism following EVT.20 One possible explanation for this is that patients with suprapopliteal lesions can have a higher thrombus burden or a larger territory of lower limb ischemia when compared with isolated infrapopliteal lesions.
No runoff of the below the knee artery before procedure was significantly associated with the outcome in the univariate model, but not in the multivariate model in the present study. This may suggest that no runoff of the below the knee artery before procedure was relevant to the severity of symptoms at the time, but that prognosis was associated with Rutherford category IIb or III ischemia and supra- to infrapopliteal lesions rather than the presence of distal artery disease.
CPK, which is one marker of skeletal muscle damage, may be useful when estimating the risk of major amputation or limb preservation in ALI. A previous study reported that the risk of amputation in patients with a normal CPK at presentation was 4.6% (95% CI, 0.0–9.7%) vs. 56.2% (95% CI, 39.1–73.4%) in those with an elevated CPK.21 In the present study, peak CPK ≥746 IU/L was significantly associated with the outcome in the univariate model, but not in the multivariate model.
Study LimitationsThis study was a nonrandomized, retrospective study based on a small number of cases. In addition, it included site and selection biases, such as the ER group having a higher prevalence of older patients, infrapopliteal artery occlusions, and severe ALI (Rutherford category IIb, and III). PMT, which is not available in Japan, and t-PA, which is not covered by Japanese health insurance, were not used in this study. Further limitations include the lack of independent angiographic core laboratory adjudication.
Rutherford category IIb and III ischemia, supra- to infrapopliteal lesions, and technical failure were identified as independent risk factors for 1-year AFS. Furthermore, patients with multiple risk factors had a lower AFS rate.
N.A. is a member of the Circulation Journal’s Editorial Board. The other authors declare no association with any individual, company, or organization having a vested interest in the subject matter/products mentioned in this article.
This study was approved by the ethical committee of Tokeidai Memorial Hospital (Reference no. 21-18).
The de-identified participant data will not be shared.
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-23-0348
