Amputation-free Survival Rates Research Articles

Rationale and Design of Therapeutic Angiogenesis by Cell Transplantation Using Adipose-Derived Regenerative Cells in Patients With Critical Limb Ischemia - TACT-ADRC Multicenter Trial.

Background: Despite the growing knowledge regarding optimal treatments for critical limb ischemia (CLI), there are still a considerable number of patients who have to undergo major limb amputation. Intramuscular injection of autologous adipose-derived regenerative cells (ADRCs) in these patients has shown therapeutic potential in improving tissue ischemia, in both preclinical and initial pilot studies. Here, we present a clinical protocol for ADRCs use in a multicenter trial.Methods and Results: The TACT-ADRC multicenter trial is a prospective, interventional, single-arm, open-labeled study at 8 hospitals in Japan, investigating the safety and feasibility of intramuscular injections of ADRCs and testing the hypothesis that this treatment promotes neovascularization and improves major amputation-free survival rates in patients with CLI who have no other treatment option. 40 patients with CLI will be enrolled and followed up from November 2015 to November 2020. Freshly isolated autologous ADRCs will be injected into the target ischemic limbs. Survival rate, adverse events, major limb amputation, ulcer size, 6-min walking distance, numerical rating scale, ankle–brachial pressure index, skin perfusion pressure and digital subtraction angiography will be evaluated at baseline and during 6 months’ follow-up.Conclusions: This trial will demonstrate whether implantation of autologous ADRCs is a safe and effective method for therapeutic angiogenesis, resulting in an improvement in major amputation-free survival rates in patients with CLI.

P1280IMPACT OF HAEMODIALYSIS IN PATIENTS UNDERGOING BYPASS SURGERY FOR PERIPHERAL ARTERY DISEASE WITH CRITICAL LIMB ISCHEMIA - 10-YEAR FOLLOW-UP STUDY -

Abstract Background and Aims Although lower extremities bypass surgery has been commonly performed as the standard option to treat peripheral artery disease with critical limb ischemia (CLI) even in patients on haemodialysis (HD) as well as general population, higher amputation and/or mortality rates still remains major clinical problems after bypass surgery in this population. In this 10-year follow-up study, we investigated the impact of HD on outcomes after surgical revascularization in patients with CLI. Method A total of 464 patients undergoing successfully elective bypass surgery were enrolled. We compared 304 HD patients with 335 limbs and 160 non-HD (NHD) patients with 183 limbs during 10 years follow-up period. Primary outcome was amputation-free survival (AFS) rate defined as freedom rate from composited endpoint with major amputation (limb amputation above ankle level) or all-cause mortality. To minimize the differences of clinical characteristics between the two groups, propensity score-matching with all baseline variables was performed. Results Prevalence of diabetes (55.6% vs. 33.8%), ulcer/gangrene (99.1% vs. 63.5%) and infra-popliteal artery disease (58.9% vs. 32.5%) were significantly higher in HD group compared to NHD group (p<0.0001 in all). Pre-procedural C-reactive protein (CRP) levels was also higher in HD group [14.0 (4.0-51.5) mg/l vs. 7.0 (2.0-34.0) mg/l, p=0.0015]. Inversely, age was younger in HD group than in NHD group (67±9 years vs. 72±8 years, p<0.0001). The 30-day mortality rate was comparable (3.3% in HD group vs. 1.3% in NHD group, p=0.16). During follow-up period (median of 48 months), 53 amputation (17.4%) and 102 death (33.6%) in HD group, and 17 amputation (10.6%) and 23 death (14.4%) in NHD group occurred, respectively. The 10-year AFS rate was significantly lower in HD group compared to NHD group [41.3% vs. 71.3%, hazard ratio (HR) 2.33, 95% confidence interval (CI) 1.64-3.41, p<0.0001). Similarly, limb salvage rate and survival rate was also lower in HD group than in NHD group (72.1% vs. 87.5%, HR 1.90, 95%CI 1.12-3.39, p=0.016, and 51.8% vs. 80.4%, HR 2.78, 95%CI 1.80-4.48, p<0.0001, respectively). In the propensity score-matched cohort, having no significant differences of all baseline characteristics between HD and NHD group (n=125 in each), the 10-year AFS rate and survival rate was still lower in HD group compared to NHD group (53.1% vs. 72.8%, HR 2.11, 95% CI 1.34-3.39, p=0.0012 and 58.6% vs. 84.9%, HR 3.72, 95% CI 2.09-7.06, p<0.0001, respectively). However, the limb salvage rate was statistically comparable between the two group (81.9% vs. 84.2%, HR 1.13, 95%CI 0.55-2.38, p=0.74). In addition, pre-procedural CRP levels could predict major amputation in HD patients (HR 1.06, 95%CI 1.01-1.10, p=0.024) but not NHD patients (HR 1.09, 95%CI 0.93-1.25, p=0.27). Conclusion The long-term AFS rate and survival rate were markedly lower in HD patients compared to NHD patients. However, the limb salvage rate was even between HD and NHD after adjustment for clinical characteristics. These results suggest that detection at the early stage of PAD may potentially improve the poor outcome. Pre-procedural inflammation status may also specifically affects the poor outcome in HD group.

P1256THE ASSOCIATION PROTEIN-ENERGY WASTING AND INFLAMMATION STATUS WITH MORTALITY AFTER LOWER EXTREMITIES REVASCULARIZATION IN PATIENTS ON HAEMODIALYSIS

Abstract Background and Aims Although lower extremity revascularization has been commonly performed in chronic haemodialysis (HD) patients with peripheral artery disease (PAD), poorer prognosis still remains major problems in such population. Recently, protein-energy wasting (PEW) or malnutrition have been considered to be strongly associated with chronic inflammation and advanced atherosclerosis in HD patients. We investigated the association of geriatric nutritional risk index (GNRI) as a surrogate marker of the PEW, C-reactive protein (CRP) and these joint role with prediction of amputation and/or mortality after lower extremity revascularization in chronic HD patients. Method We enrolled a total of 862 HD patients (age 67±10 years, diabetes 62.9%, critical limb ischemia 53.5%) who successfully underwent lower extremity revascularization (552 with endovascular therapy and 310 with bypass surgery). Patients were divided into tertiles according to GNRI levels; tertile 1 (T1): <80.0, T2: 80.0-96.6and T3: >96.6, and CRP levels; T1: <2.0mg/l, T2: 2.0-12.6mg/l and T3: >12.6mg/l, respectively. They were followed up for up to 8 years. Results During follow-up period (median: 43 months), 63 (7.3%) patients needed major amputation and 202 (23.4%) patients died. Kaplan-Meier analysis shows that amputation-free survival rates for 8 years were 47.5%, 51.6% and 66.5% in T1, T2 and T3 of GNRI, and were 65.8%, 58.7% and 33.2% in T1, T2 and T3 of CRP, respectively (p<0.0001 in both). After adjustment for age, previous coronary artery disease and critical limb ischemia as covariates with p<0.05 by univariate analysis, declined GNRI [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.57-3.07, p<0.0001 for T1 vs. T3] and elevated CRP (HR 1.78, 95%CI 1.24-2.59, p=0.0016 for T3 vs. T1) were identified as independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk of amputation and/or mortality was 3.77-fold higher (95%CI 1.97-7.69, p<0.0001) in theT1 of GNRI with T3 of CRP than in the T3 of GNRI with T1 of CRP. Similar results were obtained for amputation and mortality, respectively (Figure). Conclusion Among HD patients undergoing lower extremity revascularization, those with pre-procedural declined GNRI and elevated CRP frequently experienced amputation and/or mortality, furthermore, combination of both variables could stratify the risk of amputation and/or mortality.

Popliteal Artery Angioplasty for Chronic Total Occlusions with versus without the Distal Landing Zone

The purpose of this study was to evaluate the outcome of percutaneous transluminal angioplasty in patients with critical limb ischemia due to popliteal artery (PA) chronic total occlusions depending on the presence of a patent portion of the PA distal to the occlusive lesion-the distal landing zone (DLZ). We retrospectively analyzed 80 patients with critical limb ischemia (all Rutherford class 5-6), who underwent percutaneous transluminal angioplasty with or without stenting for PA chronic total occlusions with no inflow disease. Baseline demographic and clinical variables, periprocedural outcome, 12-month overall survival, limb salvage, primary patency, freedom from target lesion revascularization (TLR), amputation-free survival, and freedom from major adverse limb events in DLZ versus no-DLZ lesions were assessed. Of all patients (43 men; mean age 70.2y), 40 (50%) had DLZ in the PA, whereas another 40 (50%) did not (no-DLZ). Diabetes was significantly more common among DLZ patients and was found to be a risk factor for DLZ compared with no-DLZ lesions (HR 2.58; 95% CI 1.03-6.46; P=0.04). Other demographic and clinical variables were similar between the groups. The stenting rate was 45.0% versus 42.5% in DLZ versus no-DLZ (P=1.0). At 12months, there was no significant difference in primary patency (64.7% vs. 51.6%; P=0.156), overall survival (73.4% vs. 84.0%; P=0.283), amputation-free survival (60.0% vs. 68.8%; P=0.432), and limb salvage rate (93.6% vs. 82.2%; P=0.126) between DLZ and no-DLZ groups, respectively. However, freedom from TLR (92.1% vs. 67.7%; P=0.03) and major adverse limb events (80.1% vs. 41.8%; P=0.003) was significantly higher in DLZ compared with no-DLZ lesions (92.1% vs. 67.7%; P=0.03). Diabetes was found to be a significant risk factor for DLZ compared to no-DLZ lesions. Technical success and stenting rates were similar in DLZ versus no-DLZ patients. At 12months, there was no significant difference in limb salvage, primary patency, and overall survival between the study groups. The DLZ lesions were associated with a significantly higher freedom from TLR than no-DLZ lesions.

Intra-arterial thrombolysis in acute popliteal artery occlusion is a safe and effective technique reducing the rate of open surgery.

Acute popliteal artery occlusion is a frequent clinical entity with a risk of major amputation. Several attitudes are possible and treatment is not standardized. The purpose of this study is to demonstrate safety and effectiveness of intra-arterial thrombolysis in acute popliteal artery occlusion. This is a retrospective analysis of a prospective database of patients treated by intra-arterial thrombolysis for acute lower-limb ischemia due to popliteal artery occlusion between 2001 and 2014.The primary endpoint was technical and clinical success. Etiologies and etiologic treatment, amputation-free survival, in-hospital mortality and bleeding complications rates were secondary endpoints. Seventy-one patients, with a mean 6-day-old ischemic time before thrombolysis, were analyzed. Technical and clinical success was 90% and 87% respectively. Etiology was embolic in 33 patients (cardiac N.=14, aortic=6, unknown=13) and thrombotic in 38 (atheromatous N.=19, entrapment N.= 4, popliteal aneurysm N.=11, Buerger N.=2, thrombophilia N.=1, hyperhomocysteinemia N.=1). Survival and amputation-free survival at 30 days were 97% and 94% respectively. There were no major bleeding complications. Intra-arterial thrombolysis of acute popliteal artery occlusion is an effective technique which reduces the rate of open surgery. The risk of bleeding complications is very low.

Long-Term Clinical Outcomes of Autologous Bone Marrow Mononuclear Cell Implantation in Patients With Severe Thromboangiitis Obliterans.

Patients with severe Buerger disease, also known as thromboangiitis obliterans (TAO), are at risk of major limb amputation. It has been shown that autologous bone marrow mononuclear cell (BM-MNC) implantation improves the condition of critical limb ischemia in TAO patients. This study was conducted to further clarify the long-term (>10 years) results of autologous BM-MNC implantation in patients with TAO.Methods and Results:An observational study was conducted of the long-term results of BM-MNC implantation in 47 lower limbs of 27 patients with TAO. The mean (±SD) follow-up period was 12.0±8.6 years. There was no major amputation event up to 10 years of follow-up in patients treated with BM-MNC implantation. The overall amputation-free survival rates were significantly higher in patients who underwent BM-MNC implantation than in internal controls and historical controls. There was no significant difference in amputation-free survival rates between the historical and internal controls. There was also no significant difference in overall survival between patients who underwent BM-MNC implantation and the historical controls. BM-MNC transplantation successfully prevented major limb amputation over a period of >10 years in patients with severe TAO who had no other therapeutic options.

P.108 Cannabinoid receptor 1 epigenetic regulation and effect of probiotic treatment in anorexia nervosa

Acute lower extremity ischemia (ALI) is a serious condition with substantial morbidity and mortality. ALI refers to recent onset of lower extremity pain; long-standing lower extremity ischemia is dealt with elsewhere in this book. If ALI is severe and prolonged, the patient may develop progressive paresthesia, motor dysfunction, and eventually tissue infarction in the lower extremity. The rapidity plus severity of the onset of symptoms depend on the location, extent, and degree of collateral pathways around the obstruction. The estimated incidence of ALI is approximately 1.4–2.6 cases per 10,000 patients per year. ALI accounts for approximately 20% of inpatient peripheral vascular cases and amputation rates of 10%–30%. After the presenting event, the 1-year mortality rates of ALI are approximately 15%–20% along with low amputation-free survival rates of approximately 50%–65%. The two principal causes of ALI are (1) embolic, in which an artery may become occluded when an embolus becomes dislodged from a proximal source, and (2) thrombotic, in which occlusion of a native artery occurs in the setting of severe atherosclerotic disease.

Long-Term Outcomes after Infrainguinal Revascularization in Patients with Critical Limb Ischemia on End-Stage Renal Disease Patients (ESRD) and Comparison Results with Non-ESRD Population

Infrainguinal revascularization in end-stage renal disease patients is controversial, despite of patency and limb salvage rates observed in several studies. This study provides more favourable overall survival and amputation free-survival rates than the contemporary study of the same characteristics. The revascularization of patients with ESRD is frequently conditioned by poor survival. With the data we provide, approximately half of the patients were alived and their limb was salvaged at 3 years, and this is encouraging. Thus, we can be more aggressive in daily practice and offer revascularization in ESRD patients. Objective: This study analyzed long-term outcomes and evaluate the benefits and limits of infrainguinal revascularization (IR) both surgical and endovascular revascularization with critical limb ischemia (CLI) in patients with and without ESRD. Material and Methods: A total of 1188 patients were prospectively collected and analyzed retrospectively. We included 108 (9.1%) patients with ESRD and of them 70 (64.8%) receiving hemodialysis. Results: The 30-day mortality rate was higher in ESRD group (5.6 vs. 1.8, p=0,009). The second patency was similar in both groups at 1 and 3 years (87.6% and 85.3% vs. 82.9% and 81.6%). ESRD patients had a lower overall survival and amputation free-survival (AFS) (at 1 year 79.6% vs. 91.8% and at 3 years 57.9% vs. 79.1%, p<0.001) and (at 1 year 68.2% vs. 78.8% and at 3 years 45.7% vs. 64.6%, p<0,001) than non- ESRD patients. The limb salvage rates achieved excellent outcomes during follow-up at 1 and 3 years. (83.5% and 83.2% vs. 66.0% and 77.6% (p=0.194). Cox regression analysis showed that hemodialysis was an independent predictor of all-cause mortality and AFS (HR=2.38, 95% CI 1.54- 3.68, p<0,001). Octogenarian patients and coronary disease was independent predictor of all-cause mortality (HR=3.05, 95% CI 2.3-4.01, p<0.001) and (HR=1.49, 95% CI 1.14-1.95, p=0.03). Conclusions: The long-term patency and limb salvage rates in patients who underwent IR with CLI and ESRD was comparable with non- ESRD patients. Despite, the overall survival and amputation free-survival rates was poorer in ESRD patients, we advocated for aggressive revascularization attitude in ESRD patients but we must individualize treatment decision and should be offered revascularization for patients with acceptable life expectancy.

Primary patency and amputation free survival after endovascular management of infrarenal aorta total occlusions.

Endovascular therapy (EVT) has increasingly been used even after the development of new techniques and technologies. EVT has displayed durable early and mid-term outcomes for infrarenal aorta occlusions (IAO). Nonetheless, little is known regarding their long-term outcomes and predictors of restenosis. A total of 55 consecutive patients (age, 58.8±6.97 years; 67.2% male; 42% critical limb ischemia) from a single-center database, undergoing EVT for IAO disease between January 2011 and March 2019 were retrospectively analyzed. The outcome measures were primary patency rate and amputation free survival calculated by the Kaplan-Meier method. Independent predictors of restenosis were assessed by Cox proportional hazard regression model. In 49 patients (89.1%), technical success was achieved. In total, 190 stents (65 self-expandable stents, 60 balloon-expandable stents) were implanted. During the follow up of 34.5±28 months, 7 patients experienced loss of patency. Primary patency rates were 96%, 82%, and 75% at 1, 3, and 5 years, respectively, and amputation free survival rates were 100%, 90%, and 82% at 1, 3, and 5 years, respectively. In this study, five-year outcomes of primary patency and amputation free survival for EVT of infrarenal aorta total occlusive lesions were favorable. None of the demographic, lesion, and device factors were independently associated with loss of primary patency.

Kidney Transplantation Reduces the Risk of Critical Limb Ischemia and/or Amputation Among Patients With End-stage Renal Disease on Hemodialysis

Introduction: The objective of the study was to analyze the risk of critical limb ischemia and/or amputation among patients with end-stage renal disease (ESRD) entering a hemodialysis (HD) program and to evaluate the possible protective effect associated with kidney transplantation. Methods: Retrospective cohort including all ESDR patients that started on HD program at our institution between 2000 and 2010. Collected variables included baseline characteristics (pre-entry in hemodialysis), time on HD program, kidney transplantation and the development of critical limb ischemia and/or need for minor or major amputation. Patients with previous symptomatic peripheral arterial disease or amputation were excluded. Statistics: Cox regression model adjusted for all variables related to 1) critical limb ischemia and/or minor/major amputation and 2) renal transplantation. Results: The study group included 336 patients (mean age = 63 years, 221 (66 %) male). The mean follow up was 6, 7 years, with an average time on HD of 4,2 years, and 92 patients (27,4 %) underwent transplantation. Critical limb ischemia and/or amputation free survival rates were 88,6 % and 79,6 % at 5 and 10 years, respectively. The mean follow-up was 6.5 years, and 22 revascularization procedures for critical limb ischemia, 26 minor amputations and 18 major amputations were performed. Kidney transplantation was associated with a protective effect over the development of critical limb ischemia and/or amputation (HR: 0,065; p: < 0,001), after adjustment for diabetes mellitus (HR: 7,316; p< 0,001), a total cholesterol < 125mg/ml (HR: 2,538; p=0,003), time on HD (HR: 1,000; p: 0,003) and male gender (HR: 2,109; p: 0,040). Long-term survival rates of the cohort were 56,8 % and 32,7 % at 5 and 10 years respectively, but decreased to 47 % at 1 year and 18.2 % at 5 years once critical limb ischemia and/or amputation occurred. Conclusion: Patients on HD program show a notorious risk of critical limb ischemia and/or amputation over time. Once this complication occurs patient's survival is markedly reduced. Transplantation confers an independent protective effect over the development of critical limb ischemia and/or amputation. Disclosure: Nothing to disclose

The Endorevolution – Going Further in Endovascular Techniques Dedicated to Neuroischemic Diabetic Foot

Introduction: The prevalence of Diabetes Mellitus (DM) is increasing. Diabetic patients have a 15-25% lifetime risk of developing a foot ulcer and its annual incidence can reach 25-30% if arterial disease is present. Diabetic angiopathy is a unique vascular disease that has predilection for below-the-knee arteries. Endovascular techniques have been revolutionizing the revascularization of neuroischemic diabetic foot (NIDF) patients, showing consistently high limb salvage rates.In addition, the survival of NIDF patients reaches 50% at 5 years after revascularization and limb salvage, but decreases to 50% at 2 years after a major amputation. Methods: Retrospective institutional review of consecutive patients requiring endodistal revascularization (January 2010 - December 2018). The aim of the present study is to report our experience concerning NIDF patients who underwent tibial arteries revascularization. The primary outcomes were to evaluate the technical success, the limb salvage, the rate of major and minor amputation and the global survival of this population. Results: This study included 373 patients, which corresponded to 540 limbs. The mean age was 70,8 years-old; 66,2% were men, with a mean time of diagnosed diabetes of 15 years. The comorbidities presented were hypertension (81%), hypercholesterolemia (44%), chronic renal disease (31,9%; of those 42,8% in hemodialysis) and smoking (20,1%).Isolated rest pain was present in 4,6% of the patients and foot ulcer in 95,4%. The iliac sector was concomitantly treated in 0,9% of the procedures and the femoro-popliteal sector in 62,6%. Femoral antegrade approach, was obtained in 90,5% of the procedures. The retrograde distal approach was made when the anterograde revascularization failed to cross the occlusion (7,6% of procedures). Direct revascularization according to the respective angiosome was obtained in 59,1% of the cases. In the femoro-popliteal sector, PTA was performed in 49,7% of the procedures (2,4% with DEB) and recanalization and stenting in 47,9%. Tibial arteries stenting was performed in 2% of procedures, as a bail-out technique. The technical success (defined as crossing the occlusion and recanalization to a pedal vessel) was achieved in 85,5% of the procedures. The median follow-up (FU) time was 8 months (mo).During FU, 13,6% of patients was submitted to major amputation and 35,1% to minor amputation. The major amputation free-survival rate was 81,7% at 12 mo and the rate of complete healing at 12 mo was 66,9%. The 12 mo global survival was 81%. Direct angiossomic revascularization (p=0,03) and the number of tibial arteries recanalized (p=0,01) were associated with higher rates of limb salvage and healing. In the opposite side, there was association between the increasing of renal dysfunction and the absence of healing (p=0,04). The endovascular reintervention rate was 21,3% and the median time was 225 days after the first procedure. Conclusion: With the introduction of devices specifically designed for the treatment of below-the-knee vascular disease, recanalization of the tibial and pedal arteries has become technically feasible. The results of this study on endodistal revascularization, highlights the need to prioritize investigation and revascularization in NIDF to improve the outcome of foot ulcer, giving the possibility of salvaging a greater number of limbs. Disclosure: Nothing to disclose

Contemporary outcomes of infrapopliteal atherectomy with angioplasty versus balloon angioplasty alone for critical limb ischemia

ObjectiveLimited data exist comparing atherectomy (At) with balloon angioplasty for infrapopliteal peripheral arterial disease. The objective of this study was to compare the outcomes of infrapopliteal At with angioplasty vs angioplasty alone in patients with critical limb ischemia. MethodsThis is a retrospective, single-center, longitudinal study comparing patients undergoing either infrapopliteal At with angioplasty or angioplasty alone for critical limb ischemia, between January 2014 and October 2017. The primary outcome was primary patency rates. Secondary outcomes were reintervention rates, assisted primary patency, secondary patency, major adverse cardiac events, major adverse limb events, amputation-free survival, overall survival, and wound healing rates. Data were analyzed in multivariate generalized linear models with log rank tests to determine survival in Kaplan-Meier curves. ResultsThere were 342 infrapopliteal interventions, 183 percutaneous balloon angioplasty (PTA; 54%), and 159 atherectomies (At) with PTA (46%) performed on 290 patients, with a mean age of 67 ± 12 years; 61% of the patients were male. The PTA and At/PTA groups had similar demographics, tissue loss (79% vs 84%; P = .26), ischemic rest pain (21% vs 16%; P = .51), mean follow-up (19 ± 9 vs 20 ± 9 months; P = .32), mean number of vessels treated (1.7 ± 0.8 vs 1.9 ± 0.8; P = .08) and the mean lesion length treated (6.55 ± 5.00 cm vs 6.02 ± 4.00 cm; P = .08), respectively. Similar 3-month (96 ± 1% vs 94 ± 1%), 6-month (85 ± 2% vs 86 ± 3%), 12-month (68 ± 3% vs 69 ± 4%), and 18-month (57 ± 4% vs 62 ± 4%) primary patency rates were seen in the two groups (P = .87). At/PTA patients had significantly higher reintervention rates as compared with the PTA patients (28% vs 16%; P = .02). Similar assisted primary patency rates (67 ± 4% vs 69 ± 4%; P = .78) and secondary patency rates (61 ± 4% vs 66 ± 4%; P = .98) were seen in the PTA and At/PTA groups at 18 months. The 30-days major adverse cardiac event rates (3% vs 2%; P = .13) and 30-day major adverse limb event rates (5% vs 4%; P = .2) were similar in both groups. Wound healing rates (72 ± 3% vs 75 ± 2%; P = .12), 1-year amputation-free survival (68 ± 4.1% vs 70 ± 2%; P = .5), and 1-year overall survival (76 ± 4% vs 78 ± 4%; P = .39) rates did not differ in the PTA and At/PTA groups. THE At/PTA group had higher local complication rates (7 [4%] vs 1 [0.5%]; P = .03) ConclusionsAt with angioplasty provides similar patency rates compared with angioplasty alone for infrapopliteal peripheral arterial disease, but associated with higher reintervention and local complication rates. Further appropriately designed studies are required to determine the exact role of At in this subset of patients.

Preoperative Nutritional Status is an Independent Predictor of the Long-Term Outcome in Patients Undergoing Open Bypass for Critical Limb Ischemia

The nutritional status before treatment has been reported to be significantly associated with the prognosis of patients with various diseases. The aim of this study was to examine whether or not this applies to patients undergoing open bypass for critical limb ischemia (CLI). The preoperative nutritional status of patients who underwent de novo infrainguinal bypass for CLI from January 2000 to December 2017 was retrospectively evaluated using the geriatric nutritional risk index (GNRI) and controlling nutritional status (CONUT) score. Patients were divided into 4 groups based on the GNRI or CONUT score; group I, normal nutrition; group II, mild malnutrition; group III, moderate malnutrition, and group IV, severe malnutrition. The amputation-free survival (AFS), overall survival (OS), and limb salvage (LS) rates up to 5 years were calculated by Kaplan-Meier method and a Cox proportional hazard regression analysis was performed to elucidate whether or not the nutritional indices were independently associated with these outcomes. A total of 373 patients were included. The median observation term was 969days. There were significant differences in the AFS and OS of the 4 groups divided based on the GNRI and CONUT score. The 2- and 5-year AFS rates of groups I, II, III, and IV, divided based on the GNRI, were 81% and 56%, 72% and 48%, 56% and 27%, and 56% and 12%, respectively (P<0.001), while those based on the CONUT score were 75% and 55%, 72% and 41%, 50% and 6%, and 30% and 30%, respectively (P<0.001). The GNRI (groups III+IV) was an independent predictor of AFS (Hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.27-2.69; P<0.001) and OS (HR, 2.26; 95% CI, 1.50-3.41; P<0.001), while the CONUT score (groups III+IV) was also an independent predictor of AFS (HR, 1.68; 95% CI, 1.13-2.49; P=0.011) and OS (HR, 1.64; 95% CI, 1.07-2.49; P=0.024). However, neither nutritional index was an independent predictor of LS. The preoperative nutritional status, as measured by the GNRI or CONUT score, was significantly associated with AFS and OS in patients undergoing infrainguinal bypass for CLI.

Comparison of Cryopreserved Arterial Allografts Versus Heparin-bonded Vascular Grafts in Infragenicular Bypass for Chronic Limb Threatening Ischemia

The purpose of this study was to compare cryopreserved arterial allograft (CAA) to heparin-bonded prosthesis (HBP) in infragenicular bypasses for patients with chronic limb-threatening ischemia (CLTI). This retrospective study took place in 2 university hospitals and included 41 consecutive patients treated for CLTI. In the absence of a suitable saphenous vein, an infragenicular bypass was performed using either CAA (24 cases) or HBP (17 cases). Kaplan-Meyer analysis compared primary and secondary patency and amputation-free survival rates. Binomial logistic regression analyzed risk factors for major amputation and thrombosis. The mean followup was 18.5months (±14.3) in the CAA group, 17.6 (±6.1) in the HBP group. In the CAA group, primary and secondary patency rates at 12months were 52% (±10.6) and 61% (±10.3), compared to 88% (±7.8) and 94% (±5.7) in the HBP group, respectively. The difference in patency rates was not statistically different (P=0.27 and P=0.28, respectively). The statistically significant factors of graft thrombosis were, a stage 4 from the WIfI classification (Wound Ischemia foot Infection) with a 6 times higher risk (P=0.04), and a distal anastomosis on a leg artery with a 9 times higher risk of thrombosis (P=0.03). Amputation-free survival rates at 18months were similar between the groups (CCA: 75% (±9) versus HBP: 94% (±6), P=0.11). Patients classified as WIfI stage 4 had 13 times higher odds to undergo major amputation than patients with WIfI stage 2 or 3 (95% CI, 1.16-160.93; P=0.04). The intervention was longer in the CCA group of 74min (278min±86) compared to the HBP group (203min±69). This difference was statistically significant (95% CI, 17.86-132.98), t(35)=2.671, P=0.01. CCA is not superior to HBP in infragenicular bypasses for CLTI, and may not be worth the extra cost and the longer operative duration.

P4710Impact of therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells implantation in critical limb ischemia with collagen disease

Abstract Background Many patients with collagen disease (CD), particularly systemic sclerosis (SSc) and collagen disease-associated vasculitis (CDV), develop critical limb ischemia (CLI) which leads to limb amputation. In SSc vasculopathy, intimal hyperplasia, abnormal vascular contraction, and intravascular micro thrombus due to autoimmune abnormalities are main causes of inadequate blood supply that lead to the development of CLI. Moreover, in CDV, presence of inflammation cells infiltrates and destruction of the vascular wall also lead to vascular stenosis or obstruction. However, conventional therapies including revascularization via surgical bypass showed poor outcomes in CLI patients with CD. Therefore, establishment of new methods to improve peripheral circulation for limb salvage are required. Purpose After discovering that circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow participate in postnatal neovascularization, autologous bone marrow-derived mononuclear cells (BM-MNCs) has been performed as a new treatment for many no-option CLI patients caused by arteriosclerosis obliterans, thromboangiitis obliterans or CD. In this study, we would like to assess the long-term clinical outcomes after autologous BM-MNCs implantation in CLI patients with SSc and CDV. Methods This study was a retrospective, multicenter, observational, and non-controlled study. We assessed no-option CLI patients with CD who were performed the autologous BM-MNCs implantation in 10 institutes. Overall survival (OS), major-amputation-free (MAF) and amputation-free survival (AFS) rates were primary endpoints of this study. In addition, we assessed improvements of ischemic pain as visual analogue scale (VAS) scores. Safety endpoints were defined as cardiovascular events and all-cause adverse events within 6 months after implantation. Results A total of 69 patients (39 with SSc–related diseases (SSc group) and 30 with CDV (CDV group)), were included in this study. The median follow-up duration was 36.5 months. The 10-year OS rate was 59.1% in the SSc group and 82.4% in the CDV group, respectively. The 10-year MAF rates were 97.4% and 82.6%, respectively. The 10-year AFS rates were 57.6% and 67.8%, respectively (Figure 1). The number of major or minor amputations in the SSc group trended to be less than that in the CDV group. In addition, significant improvement in VAS scores were observed in both groups (Figure 2). No patients died, no cardiovascular events, and no severe adverse events associated with BM-MNCs implantation were noted within 6 months after this therapy in both groups. Figure 1 Conclusions The BM-MNCs implantation may be feasible in no-option CLI patients with CD. Improvement of ischemic symptoms by BM-MNCs implantation was significant in both groups and, in the SSc group, limb salvage rate tended to be higher than the CDV group.

Endovascular-First Treatment Is Associated With Improved Amputation-Free Survival in Patients With Critical Limb Ischemia.

Critical limb ischemia remains a difficult disease to treat, with limited level one data. The BEST-CLI trial (Best Endovascular vs Best Open Surgical Therapy in Patients with Critical Limb Ischemia) is attempting to answer whether initial treatment with open surgical bypass or endovascular therapy improves outcomes, although it remains in enrollment. This study aims to compare amputation-free survival and reintervention rates in patients treated with initial open surgical bypass or endovascular intervention for ischemic ulcers of the lower extremities. Using California nonfederal hospital data linked to statewide death data, all patients with lower extremity ulcers and a diagnosis of peripheral artery disease who underwent a revascularization procedure from 2005 to 2013 were identified. Propensity scores were formulated from baseline patient characteristics. Inverse probability weighting was used with Kaplan-Meier analysis to determine amputation-free survival and time to reintervention for open versus endovascular treatment. Mixed-effects Cox proportional hazards modeling was used to adjust for patient ability to manage their disease and hospital revascularization volume. A total of 16 800 patients were identified. Open surgical bypass was the initial treatment in 5970 (36%) while 10 830 (64%) underwent endovascular interventions. Patients in the endovascular group were slightly younger compared with the open group (70 versus 71 years, ±12 years; P<0.001). Endovascular-first patients were more likely to have comorbid renal failure (36% versus 24%), coronary artery disease (34% versus 32%), congestive heart failure (19% versus 15%), and diabetes mellitus (65% versus 58%; all P values <0.05). After inverse propensity weighting as well as adjustment for patient ability to manage their disease and hospital revascularization experience, open surgery first was associated with a worse amputation-free survival (hazard ratio, 1.16; 95% CI, 1.13-1.20) with no difference in mortality (hazard ratio, 0.94; 95% CI, 0.89-1.11). Endovascular first was associated with higher rates of reintervention (hazard ratio, 1.19; 95% CI, 1.14-1.23). Patients with critical limb ischemia have multiple comorbidities, and initial surgical bypass is associated with poorer amputation-free survival compared with an endovascular-first approach, perhaps due to increased severity of wounds at the time of presentation.

Below-the-Ankle Angioplasty in Patients with Critical Limb Ischemia: A Systematic Review and Meta-Analysis.

To evaluate the safety and effectiveness of below-the-ankle (BTA) angioplasty and to assess whether additional BTA angioplasty after below-the-knee (BTK) angioplasty would improve clinical outcomes in patients with critical limb ischemia. Two authors independently performed the search, study selection, assessment of methodological quality, and data extraction for this systematic review and meta-analysis. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched. Articles were eligible if it was reported that BTA angioplasty was performed and if the articles were published in English and had the full text available. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) score. The primary outcome was 12-month limb salvage rate. Secondary outcomes were 12-month amputation-free survival, technical success, complications, survival, and freedom from reintervention. Ten articles met the inclusion criteria, reporting a total of 478 patients with BTA angioplasty performed in 524 legs. Three of the 10 included studies compared BTK angioplasty only to BTK angioplasty and additional BTA angioplasty. The pooled 12-month limb salvage rate was 92% (95% confidence interval [CI], 0.88-0.96). No statistically significant difference was found in limb salvage when additional BTA angioplasty was compared to BTK angioplasty only (odds ratio [OR], 1.23; 95% CI, 0.61-2.49). The pooled 12-month amputation-free survival was 78% (95% CI, 0.69-0.87). No statistically significant difference was found in amputation-free survival rate when additional BTA angioplasty was compared to BTK angioplasty only (OR, 1.58; 95% CI, 0.95-2.64). The methodological quality of the studies included was moderate, according to the MINORS score. This systematic review and meta-analysis showed that additional BTA angioplasty is a safe and feasible procedure, with a 92% pooled proportion of limb salvage at 12 months.

Combined percutaneous direct puncture of occluded artery - antegrade intervention for recanalization of below the knee arteries.

We aimed to assess the technical success of the combined percutaneous direct puncture of occluded artery - antegrade intervention technique, as well as the clinical effectiveness of treatment, on the basis of changes in the Rutherford classification. Between June 2015 and July 2018, 441 patients underwent endovascular recanalization due to lower limb peripheral arterial disease at our center. Of these, 18 patients (4%; 15 males, 3 females; mean age, 63.2 years) had failed antegrade recanalization and percutaneous retrograde access because of long segment occlusion, arterial rupture or dissection. Combined percutaneous direct puncture of occluded artery and antegrade approach was applied to these patients. Clinical follow-up examinations were performed at 1 month, 3 months, 6 months, and annually thereafter. The mean follow-up period was 22.8±10.9 months. The mean procedure time was 93.6±28.2 min. Technical success was achieved in 14 patients (78%). Complete restoration of arterial flow in the punctured vessel could not be achieved in 4 patients (22%). Minor complications occurred in 4 of 18 procedures (22%). Amputation-free survival and limb salvage rates (83.3% and 100%, respectively) were the same for 12 and 24 months. Technical success in lower limb peripheral arterial disease may be improved with the use of a combined percutaneous direct puncture of occluded artery - antegrade intervention, particularly for patients in whom other techniques are not a viable option.

Amputation-free Survival in Patients with Critical Limb Ischemia Treated with Paclitaxel-eluting Stents and Paclitaxel-coated Balloons

The aim of this study was to evaluate the performance of paclitaxel-eluting stents (PESs) and paclitaxel-coated balloons (PCBs) on amputation-free survival in patients with critical limb ischemia (CLI). A retrospective review of all patients with Rutherford stage 5 and 6 limb ischemia undergoing endovascular revascularization with paclitaxel-related technology, both PES and PCB, was carried out over a 4-year period. Clinical grading was determined by Rutherford classification and the Society for Vascular Surgery's Wound, Ischemia, and foot Infection (WIfI) scoring system. Clinical and angiographic follow-up was reviewed based on intention-to-treat analysis. The primary endpoint of this study was amputation-free survival at 12months. Secondary endpoints included wound healing, freedom from target lesion revascularization, and patency of target vessels at 12months. Follow-up occurred at 3, 6, and 12months postoperatively. Target lesion patency was defined as <50% stenosis, based on a duplex velocity ratio of less than or equal to 2. Postoperative ankle-brachial index (ABI) and duplex ultrasound were performed to verify successful treatment. Outcomes were evaluated using Kaplan-Meier and Cox proportional-hazards models. A total of 88 limbs were revascularized in 88 patients. Drug-eluting stent (DES) was used as the sole drug technology in 56 patients (60.7% men, median age 70.5years) and drug-coated balloon (DCB) was used as the sole drug technology in 32 patients (46.9% men, median age 66years). Baseline demographics were well matched except for a higher prevalence of occluded target lesions in the DES group (41.1% vs. 12.5%; P=0.004). Limbs were treated for Rutherford stage 5 CLI in 71.6% and stage 6 CLI in 28.4%. Univariate analysis identified no dependent factors affecting limb salvage, except for the use of DCBs. After 12months of follow-up, amputation-free survival was significantly higher in the DES group than in the DCB group (88.5% vs. 71.1%; P=0.0443). Wound healing rates after 1year were also higher in the DES group (83.9% vs. 59.4%; P=0.0198). Freedom from target lesion revascularization was no different between patients treated with DESs and patients treated with DCBs (90.6% vs. 85.7%; P=0.518). Primary patency at 12months in patients treated with DESs was significantly higher than in patients treated with PCBs (80.4% vs. 58.1%; P=0.0255). Overall, drug technology represents a viable option for patients with CLI; a cohort not represented in major randomized trials. In our experience, femoropopliteal lesions treated with DESs have higher primary patency rates than those treated with DCBs. This was found to support higher amputation-free survival rates in patients treated with paclitaxel DESs than those treated with paclitaxel DCB. The use of paclitaxel DESs for CLI was also associated with significantly improved wound healing compared with DCBs. Our data suggest improved outcomes with DESs compared with DCBs; however, these patients represent a nonrandomized, heterogenous group that were treated with the operator's best judgment.

Diabetic Limb Salvage With Endovascular Revascularisation and Free Tissue Transfer: Long-Term Follow up

Combining vascular bypass surgery with free flap coverage is one of the treatment methods for complex soft tissue defects in the ischaemic lower limb. Endovascular revascularisation has become the first line treatment for limb ischaemia in many centres. Surgeons now perform free tissue transfer after angioplasty. The early and long-term limb salvage rate in diabetic patients who had undergone infrapopliteal endovascular revascularisation and free flap reconstruction are assessed. This was retrospective study of all consecutive diabetic patients who had undergone endovascular revascularisation with free flap reconstruction for lower limb salvage between 2008 and 2014. They were followed up for at least 2 years or to death (mean follow up 39 ± 17 months). Cox regression analysis was used to analyse variables influencing outcome. There were 55 patients who had undergone 60 procedures. Five patients had undergone the procedure to the contralateral leg. All tissue lesions were Wagner–Meggit classification Grades 3 or 4. Thirty-six patients had TASC C lesions and 24 patients with TASC D lesions. Combined below knee triple vessel disease was seen in 30% of the cases, 28% involved both the anterior and posterior tibial artery, 7% and 2% involved the anterior tibial or the posterior tibial and the peroneal arteries. The free flap success rate was 95%. The peri-operative mortality was 1.7%. Twenty-one cases required surgical re-intervention. Mean length of hospital admission was 32 ± 9 days. One and five year amputation free survival rates were 94% and 68%, patient survival rates were 95% and 67%, limb salvage rates were 93% and 91% and respectively. The results show that excellent early and late limb salvage can be achieved with free tissue transfer based on endovascular revascularisation of infrapopliteal arteries. This can be a further treatment option in diabetic patients with complex soft tissue defects.