Lesions In Critical Limb Ischemia Research Articles

Overview of the Virtual 2021 FDA's Circulatory System Devices Advisory Panel on Lutonix 014 Drug-Coated Percutaneous Transluminal Angioplasty Catheter for Below-the-Knee Lesions in Critical Limb Ischemia

Peripheral artery disease, along with subsequent critical limb ischemia (CLI), is highly prevalent, increases with age, and carries high morbidity and mortality. Specific devices for treatment of below-the-knee (BTK) lesions are limited. On February 17, 2021, the United States Food and Drug Administration convened a virtual meeting of the Circulatory System Devices Panel of the Medical Devices Advisory Committee to consider a premarket approval application for the Lutonix 014 Drug-Coated Balloon Percutaneous Transluminal Angioplasty Catheter (Becton, Dickinson and Company, Franklin Lakes, New Jersey) for the treatment of obstructive de novo or non-stented restenotic lesions in BTK vessels (popliteal, tibial, and peroneal arteries) in patients with CLI. We summarize the presentations and the panel deliberations, including voting outcome and recommendations for risk versus benefit.

Isolated femoral artery revascularisation with or without iliac inflow improvement - a less invasive surgical option in critical limb ischemia.

Background: Isolated femoral artery revascularisation (iFAR) represents a well-established surgical method in the treatment of peripheral arterial disease (PAD) involving common femoral artery disease. Data for iFAR in multilevel PAD are inconsistent, particularly in patients with critical limb ischemia (CLI). The aim of the study was to evaluate the outcome of iFAR in CLI regarding major amputation and reintervention and to identify associated risk factors for this outcome. Patients and methods: The data used have been derived from the German Registry of Firstline Treatment in Critical Limb Ischemia (CRITISCH). A total of 1200 patients were enrolled in 27 vascular centres. This sub-analysis included patients, which were treated with iFAR with/without concomitant iliac intervention. For detection of risk factors for the combined endpoint of major amputation and/or reintervention, selection of variables for multiple regression was conducted using stepwise forward/backward selection by Akaike's information criterion. Results: 95 patients were included (mean age: 72years±10.82; 64.2% male). Of those, 32 (33.7%) participants reached the combined endpoint. Risk factor analysis revealed continued tobacco use (odds ratio [OR] 2.316, confidence interval [CI] 0.832-6.674), TASC D-lesion (OR: 2.293, CI: 0.869-6.261) and previous vascular intervention in the trial leg (OR: 2.720, CI: 1.037-7.381) to be associated with reaching the combined endpoint. Conclusions: iFAR provides a reasonable, surgical option to treat CLI. Lesion length (TASC D) seems to have a negative impact on outcome. Further research is required to better define the future role of iFAR for combined femoro-popliteal lesions in CLI - best in terms of a randomised controlled trial.

Validation of randomized controlled trial-derived models for the prediction of postintervention outcomes in chronic limb-threatening ischemia

BackgroundChronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease and has a large impact on quality of life, morbidity, and mortality. Interventions are aimed at improving tissue perfusion and averting amputation and secondary cardiovascular complications with an optimal risk-benefit ratio. Several prediction models regarding postprocedural outcomes in CLTI patients have been developed on the basis of randomized controlled trials to improve clinical decision-making. We aimed to determine model performance in predicting clinical outcomes in selected CLTI cohorts. MethodsThis study validated the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL), Finland National Vascular registry (FINNVASC), and Prevention of Infrainguinal Vein Graft Failure (PREVENT III) models in data sets from a peripheral artery disease registry study (Athero-Express) and two randomized controlled trials of CLTI in The Netherlands, Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) and Percutaneous Transluminal Angioplasty and Drug-eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI). Receiver operating characteristic (ROC) curve analysis was used to calculate their predictive capacity. The primary outcome was amputation-free survival (AFS); secondary outcomes were all-cause mortality and amputation at 12 months after intervention. ResultsThe BASIL and PREVENT III models showed predictive values regarding postintervention mortality in the JUVENTAS cohort with an area under the ROC curve (AUC) of 81% and 70%, respectively. Prediction of AFS was poor to fair (AUC, 0.60-0.71) for all models in each population, with the highest predictive value of 71% for the BASIL model in the JUVENTAS population. The FINNVASC model showed the highest predictive value regarding amputation risk in the PADI population with AUC of 78% at 12 months. ConclusionsIn general, all models performed poor to fair in predicting mortality and amputation. Because the BASIL model performed best in predicting AFS, we propose use of the BASIL model to aid in the clinical decision-making process in CLTI. However, improvements in performance have to be made for any of these models to be of real additional value in clinical practice.

Diabetes Is Associated With Decreased Limb Survival in Patients With Critical Limb Ischemia: Pooled Data From Two Randomized Controlled Trials.

Although never assessed prospectively, diabetes mellitus (DM) is assumed to negatively affect the outcomes of critical limb ischemia (CLI). DM was highly prevalent in two recently conducted randomized controlled trials in CLI patients, the PADI (Percutaneous Transluminal Balloon Angioplasty [PTA] and Drug Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia) and JUVENTAS (Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-Arterial Supplementation) trials. To determine the implications of DM in a population of patients with infrapopliteal CLI, clinical outcomes were compared in patients with and without DM. Individual data from patients with CLI (Rutherford category ≥4) were pooled. Patients were considered to have DM when this diagnosis was reported in the hospital electronic medical records. Rates of major amputation (above ankle level) and major events (major amputation or death) were compared between CLI patients with and without DM. Hazard ratios (HRs) were calculated. Of a total of 281 patients, DM was present in 49.1%. The major amputation rate at 5 years of follow-up was higher in patients with DM than in patients without DM (34.1% vs. 20.4%, P = 0.015). The major event and death rate did not differ. The unadjusted HR of DM for the major amputation risk was 1.87 (95% CI 1.12-3.12). Model factors with significant HRs in the multivariate analysis were baseline Rutherford category (HR 1.95; 95% CI 1.24-3.06) and ankle-brachial index (ABI) >1.4 (HR 2.78; 95% CI 1.37-5.64). CLI patients with DM are at a significantly higher risk of major amputation than CLI patients without DM. This increased risk is associated with a higher prevalence of baseline ABI >1.4 and more severe ischemia at initial presentation in patients with DM.

Transpopliteal stenting of femoral occlusions in patients with critical limb ischemia using a 4-French system.

In many patients with critical limb ischemia (CLI), transfemoral endovascular recanalization is the preferred treatment. Transpopliteal treatment may be used in patients with inaccessible groins. This retrospective study regards transpopliteal stenting of superficial femoral artery (SFA) occlusions using a 4F system. Eleven patients (4 male and 7 female [mean age 77years]) underwent 12 attempts of transpopliteal recanalization of long SFA occlusions (Trans-Atlantic InterSociety Consensus B through D). All patients had CLI (Rutherford 4 to 6) and were nonoperable due to poor general condition. Indications for transpopliteal access were proximal/flush SFA occlusions (n=5), failure of antegrade recanalization (n=4), infected femoral-femoral crossover bypass (n=2), and occlusion of both the native SFA and the femoral-popliteal bypass (n=1). The popliteal artery was punctured under ultrasound guidance. Occlusions were recanalized subintimally, and 4F compatible stents were implanted. Technical success rate (<30% residual stenosis) was achieved in 83% of cases. In two patients, stent dislocation occurred while the sheath was removed. One arteriovenous fistula was successfully treated with additional stenting. During 6-month follow-up, there were no major amputations, and three patients died from nonrelated causes. Fifty percent of patients alive after 6months improved to Rutherford score ≤3. The duplex restenosis (>50%) rate at 6months was 50%. Transpopliteal primary stenting of complex SFA lesions in CLI for a temporary bypass is now technically feasible using a 4F system. Technical results are promising. Clinical results after 6months are acceptable when taking into consideration that this approach may be the last option for limb salvage.

Combined Antegrade–Retrograde Intervention to Improve Chronic Total Occlusion Recanalization in High-risk Critical Limb Ischemia

When conventional antegrade attempts (antegrade approach) to cross chronic total occlusion (CTO) lesions in critical limb ischemia (CLI) fail, and if surgical revascularization is not possible, limb outcomes may be expected to be poor. In this high-risk cohort, we sought to examine whether combined antegrade-retrograde intervention with the simultaneous use of a distal retrograde access (combined approach) improves recanalization success. From September 2011 to 2012, infrainguinal endovascular interventions were first attempted using antegrade approach in 27 consecutive patients (28 limbs) with CLI and infrainguinal CTO. All patients were poor surgical candidates. In the 11 limbs where antegrade approach failed, the combined approach was attempted. The primary end point was successful CTO lesion crossing. The secondary end points were technical success with ≤30% diameter residual stenosis of the target lesion, major amputation (transtibial or above), wound healing, target lesion revascularization (TLR), and access site complications that include hematoma requiring exploration or transfusion, arteriovenous fistula, or pseudoaneurysm. Of the 11 limbs that underwent combined approach, the primary end point was achieved in 9 limbs (82%). More notably, among the 28 limbs overall, CTO lesion crossing improved from 61% (95% confidence interval [CI]: 0.41-0.78) using antegrade approach alone to 93% (95% CI: 0.75-0.99) when supplemented by the combined approach. Similarly, the secondary end point of technical success improved from 50% (95% CI: 0.31-0.69) to 79% (95% CI: 0.59-0.91), respectively. Major amputation, wound healing (inclusive of postamputation status), and TLR rates were 9%, 100%, and 18%, respectively, during a median follow-up of approximately 4 months. No major procedural complications occurred with the combined approach. Among CLI patients who are poor surgical candidates, the combined approach is a viable, safe, and effective strategy to improve overall success with endovascular therapies.

Intraoperative Thrombolysis and Laser Atherectomy: Effective Treatment for TASC C and D Lesions in Critical Limb Ischemia

Objective: We postulate that catheter directed intraoperative thrombolysis in conjunction with laser atherectomy is a safe and effective treatment of TASC C and D critical limb ischemia. Methods: We retrospectively analyzed 411 patients who underwent 670 percutaneous, lower extremity interventions from September 2004 to October 2009. Indications for intervention were limb salvage (98.7%) and claudication (1.3%). TASC C lesions were present in 40.9% of patients and TASC D lesions in 59.1%. Gender was 51.0% male and 49.0% female. Average age was 69.5 ± 12.0 years, range: 30 to 97 years. Risk factors included hypertension (87.8%), diabetes (70.2%), coronary artery disease (56.4%), tobacco abuse (54.8%), hyperlipidemia (49.4%), COPD (36.6%), congestive heart failure (26.3%), renal insufficiency (23.7%), history of myocardial infarction (21.3%), history of TIA or CVA (20.0%), atrial fibrillation (16.6%), dialysis (16.0%), morbid obesity (14.9%), arrhythmia (7.3%), and pacemaker (6.1%). All procedures involved catheter directed arterial infusion of 2 to 10mg of tissue plasminogen activator into the lesion and laser atherectomy: 647 extremities required balloon angioplasty, and 326 extremities required stenting. Technical success required completion of the intended procedure. Clinical success required no deaths, strokes, myocardial infarctions, bleeding requiring transfusion, thromboemboli, infection, respiratory complications, or reinterventions within 30 days. Follow-up was at 24 hours, 30 days, 6 months, and then q 6 months. Kaplan Meier analysis was used for patency, limb salvage, and survival rates. Results: Technical success rate was 96.6%. Clinical success was 83.0%. Within 30 days post op, 6.2% required repeat intervention; 4.2% required amputation; 3.3% experienced post-operative complications; including bleeding requiring transfusion (1.1%), thromboemboli (1.0%), infection (0.7%), respiratory complications (0.4%), and myocardial infarction (0.1%); and 3.3% died. Patency, limb salvage, and survival rates are listed in Table 1. Conclusions: The combination of thrombolysis and laser atherectomy is safe and effective in treating TASC C and D lesions in this high-risk group of patients with critical limb ischemia.

Six-month clinical outcomes after below-the-knee angioplasty for critical limb ischemia in patients on hemodialysis

To evaluate 6-month clinical outcomes after below-the-knee (BTK) angioplasty for critical limb ischemia (CLI) in patients on hemodialysis (HD). Subjects were 69 serial patients (81 limbs, 123 vessels) who underwent percutaneous transluminal angioplasty (PTA) for primary treatment of infrapopliteal lesions in CLI from June 2004 to December 2008. Subjects were classified into two groups for the comparative study of clinical outcomes: the patients on HD: the HD group (35 patients, 45 limbs, 71 vessels, 66±11years) and the patients not on HD: the non-HD group (34 patients, 36 limbs, 52 vessels, 69±9years). A non-randomized retrospective comparative study was conducted to obtain clinical outcomes at 6months. In clinical results at 6months, a higher percentage of tendency toward repeat PTA for the treated leg in the HD group (28.9 vs. 11.1%, p=0.059), but it was not statistically significant. There was no significant difference in the rate of major amputation (11.1 vs. 5.5%) between the two groups. However, the percentage of repeat PTA performed twice or more times (13.3 vs. 0%, p=0.031) and all-cause mortality (17.1 vs. 0%, p=0.012) in the HD group was significantly higher than in the non-HD group. The HD group had a significantly lower rate of freedom from all-cause mortality, major amputation, or repeat PTA in the 6-month follow-up compared to the non-HD group, with the HD group 51.4% and the non-HD group 85.3% (logrank test p=0.003). Although there are more HD patients requiring repeat revascularization compared to the general population, the 6-month outcomes of limb salvage after BTK angioplasty for CLI in HD patients were not significantly different from the general population.

Update on PADI trial: Percutaneous transluminal angioplasty and drug-eluting stents for infrapopliteal lesions in critical limb ischemia

The Percutaneous transluminal Angioplasty and Drug eluting stents for Infrapopliteal lesions in critical limb ischemia (PADI) trial is a prospective, multicenter, randomized, controlled, double-arm study investigating the safety and efficacy of primary paclitaxel-eluting stent implantation vs primary percutaneous transluminal angioplasty (PTA) in infrapopliteal lesions in critical limb ischemia (CLI). PTA with provisional "bailout" stent implantation is currently an accepted treatment for arterial obstructions in CLI, including those in below-the-knee arteries. A drawback compared to open bypass surgery is the relatively high restenosis rate. One proposed method to reduce restenosis is the use of drug-eluting stents (DES), as these have shown good results in the coronary bed. Primary DES implantation for focal obstructions in infrapopliteal arteries in CLI potentially reduces restenosis compared to PTA alone and may subsequently prolong effect of treatment, allowing for better wound healing, and preventing recurrence of symptoms. In this article, we report on rationale, design, and progress of the PADI trial, which investigates the safety and efficacy of a paclitaxel-eluting stent system compared to PTA with provisional bare metal stent implantation.

Long-term responses of porcine coronary arteries to overlapping thin-strut, bioabsorbable coated low-dose paclitaxel-eluting stent

Purpose: The purpose of our study was to evaluate the procedural success, 6-month patency, and clinical outcome of a new 4F sheath-compatible, selfexpanding nitinol stent after failed conventional angioplasty or atherectomy of infrapopliteal lesions in critical limb ischemia (CLI). Methods: Clinical records of 13 patients with CLI (Rutherford class 4–6), who underwent stent implantation following percutaneous transluminal angioplasty (PTA) and/or atherectomy were reviewed. Stent placement was carried out due flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical evaluation and color-flow and duplex Doppler ultrasonography were performed. Technical success, primary patency at 6 months, and clinical improvement as defined by Rutherford with clinical and hemodynamic measures and complications were evaluated. Results: A total of 19 arterial territories were intervened upon. 4F Sheathcompatible, self-expanding nitinol stent system (XPERT; Abbott Vascular) with a diameter of 3–5 mm and a length of 20–60 mm was used. A total of 29 stents were deployed. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 90%. The mean resting ankle-brachial index at baseline was 0.40±0.1 and significantly increased to 0.90±0.13 (Pb.001) at 24 h after intervention and 0.84±0.15 at 6-month follow-up (P b.001). The sustained clinical improvement rate was 78% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 85%. One patient (7.7%) developed major access site bleeding requiring transfusion. Conclusions: Nitinol self-expanding stents in infrapopliteal arteries can be deployed safely with good short-term patency rate and clinical benefit in the treatment of CLI.

Safety and clinical benefits of nitinol self-expanding stents in infrapopliteal arteries in patients with critical limb ischemia

Purpose: The purpose of our study was to evaluate the procedural success, 6-month patency, and clinical outcome of a new 4F sheath-compatible, selfexpanding nitinol stent after failed conventional angioplasty or atherectomy of infrapopliteal lesions in critical limb ischemia (CLI). Methods: Clinical records of 13 patients with CLI (Rutherford class 4–6), who underwent stent implantation following percutaneous transluminal angioplasty (PTA) and/or atherectomy were reviewed. Stent placement was carried out due flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical evaluation and color-flow and duplex Doppler ultrasonography were performed. Technical success, primary patency at 6 months, and clinical improvement as defined by Rutherford with clinical and hemodynamic measures and complications were evaluated. Results: A total of 19 arterial territories were intervened upon. 4F Sheathcompatible, self-expanding nitinol stent system (XPERT; Abbott Vascular) with a diameter of 3–5 mm and a length of 20–60 mm was used. A total of 29 stents were deployed. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 90%. The mean resting ankle-brachial index at baseline was 0.40±0.1 and significantly increased to 0.90±0.13 (Pb.001) at 24 h after intervention and 0.84±0.15 at 6-month follow-up (P b.001). The sustained clinical improvement rate was 78% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 85%. One patient (7.7%) developed major access site bleeding requiring transfusion. Conclusions: Nitinol self-expanding stents in infrapopliteal arteries can be deployed safely with good short-term patency rate and clinical benefit in the treatment of CLI.

Novel thin-strut, bioabsorbable sol-gel coated, low-dose paclitaxel-eluting stent: evaluation in porcine coronary arteries

Purpose: The purpose of our study was to evaluate the procedural success, 6-month patency, and clinical outcome of a new 4F sheath-compatible, selfexpanding nitinol stent after failed conventional angioplasty or atherectomy of infrapopliteal lesions in critical limb ischemia (CLI). Methods: Clinical records of 13 patients with CLI (Rutherford class 4–6), who underwent stent implantation following percutaneous transluminal angioplasty (PTA) and/or atherectomy were reviewed. Stent placement was carried out due flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical evaluation and color-flow and duplex Doppler ultrasonography were performed. Technical success, primary patency at 6 months, and clinical improvement as defined by Rutherford with clinical and hemodynamic measures and complications were evaluated. Results: A total of 19 arterial territories were intervened upon. 4F Sheathcompatible, self-expanding nitinol stent system (XPERT; Abbott Vascular) with a diameter of 3–5 mm and a length of 20–60 mm was used. A total of 29 stents were deployed. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 90%. The mean resting ankle-brachial index at baseline was 0.40±0.1 and significantly increased to 0.90±0.13 (Pb.001) at 24 h after intervention and 0.84±0.15 at 6-month follow-up (P b.001). The sustained clinical improvement rate was 78% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 85%. One patient (7.7%) developed major access site bleeding requiring transfusion. Conclusions: Nitinol self-expanding stents in infrapopliteal arteries can be deployed safely with good short-term patency rate and clinical benefit in the treatment of CLI.

Two-Year Outcome after Xpert Stent Implantation for Treating Below the Knee Lesions in Critical Limb Ischemia

We investigated the efficacy of Xpert (Abbott Vascular, Abbott Park, IL) nitinol stents for the treatment of infrapopliteal lesions in patients with Critical Limb Ischemia (CLI). Between May 2005 and November 2007, 94 CLI patients (70 male, mean age 73.5 years) received 134 Xpert stents in 102 limbs. Seventy-nine patients (71.2%) were scored as Rutherford Category 4, 31 patients (27.9%) as Category 5 and 1 patient (0.9%) as Category 6. Primary endpoint of this study was defined as 2-year duplex derived primary patency. Secondary endpoints were 2-year limb salvage rate and the absence of reintervention after the index procedure. Kaplan Meier analysis reported 2-year primary patency and limb salvage rates of 54.4% and 90.8%, respectively. Stratification by lesion location did not reveal any significant differences in 2-year primary patency rates in proximal and distal below the knee lesions. Our results suggest that treatment with nitinol Xpert stents can be considered effective for treating CLI patients, with satisfying patency outcome.