Lower Extremity Critical Limb Ischemia Research Articles

Outcome and Distal Access Patency in Subintimal Arterial Flossing with Antegrade-Retrograde Intervention for Chronic Total Occlusions in Lower Extremity Critical Limb Ischemia

PurposeTo report the outcome and distal access patency of the Subintimal Arterial Flossing with Antegrade-Retrograde Intervention (SAFARI) technique for chronic total occlusion (CTO) in critical limb ischemia (CLI). Materials and MethodsFrom January 2009 to June 2015, 220 SAFARI procedures were performed for 200 limbs in 191 patients (108 males [56.5%]; median age, 70 years old; range, 36 to 97 years old) with CLI (9.4% were Fontaine classification 3; and 90.6% were Fontaine classification 4). Distal access was obtained from the distal superficial femoral artery (n = 6), popliteal artery (n = 49), anterior tibial artery (n = 56), dorsalis pedis (n = 51), peroneal artery (n = 12), posterior tibial artery (n = 45), and lateral plantar artery (n = 1). Distal access hemostasis was obtained with internal balloon tamponade in 71.4% (n = 157). Outcome measurements were technical success, freedom from major amputation and complications. Preprocedural angiograms of clinically driven repeat interventions were reviewed in 73 cases for distal access patency. ResultsTechnical success was achieved in 80.5% (n = 177). Reasons for technical failure include inability to obtain distal access (n = 3), cross the occlusion retrogradely (n = 16), re-enter the true lumen (n = 9), and achieve antegrade blood flow after the procedure (n = 15). Freedom from major amputation for technically successful procedures was 84.7%, 82.9%, and 81.9% at 6, 12, and 24 months, respectively. There were 3 cases of distal access bleeding with 1case that required coil embolization. The distal access remained patent in 80.8% of observable cases with repeated endovascular intervention. ConclusionsDistal retrograde arterial access (SAFARI) technique is safe and effective in the treatment of CTOs in the context of CLI, after failure of antegrade revascularization.

Outcomes of severe limb ischemia with tissue loss and impact of revascularization in haemodialysis patients with wound, ischemia, and foot infection (WIfI) stage 3 or 4.

Background: With growing prevalence, end-stage renal disease (ESRD) as well as critical limb ischemia (CLI) are both conditions associated with high morbidity and mortality rates. Patients and methods: A retrospective single-centre study provided data of a German interdisciplinary vascular centre. Seventy-seven consecutive haemodialysis (HD) inpatients (median age, 73.6 years) with 91 threatened limbs with Wound, Ischemia, and foot Infection (WIfI) clinical stage 3 or 4 were evaluated for in-hospital treatment of peripheral arterial disease, limb salvage rates, major amputation (MA)-free and overall survival. Results: The 1-year MA-free limb salvage rate was 82%. On multivariate analysis, a higher WIfI clinical stage (hazard ratio [HR], 7.54; p = 0.008) indicated a higher risk of MA, while at least one-vessel run-off to the foot after revascularization of any kind was associated with a lower risk of MA (HR, 0.17; p = 0.001). In the composite endpoint analysis, the 1-year MA-free overall survival rate was 65%. Patients with limbs in WIfI clinical stage 4 versus stage 3 carried a more than two-fold increased hazard of death or MA (HR, 2.63; p = 0.028), while revascularization was associated with reduced risk (HR, 0.40; p = 0.021). One-year overall survival (78%) was not associated with WIfI stage or revascularization but was worse in patients with previous symptomatic coronary artery disease (HR, 3.25; p = 0.039). During long-term follow-up over 12 years, MA-free survival probability was significantly lower in the WIfI stage 4 versus WIfI stage 3 group (HR, 1.58; p = 0.048) without significant differences in overall survival (HR, 1.10; p = 0.696). Conclusions: Lower-extremity CLI with tissue loss in HD patients is associated with high morbidity and mortality rates. WIfI clinical stage was predictive of 1-year MA-free survival, while revascularization significantly reduced MA risk but did not influence overall survival.

An Unusual Suspect: Esophageal Mucosal Dissection: A Rare Complication of Nasogastric Intubation

Introduction: Nasogastric intubation (NGT) is a frequently performed inpatient procedure for various indications. It is usually considered a safe procedure with only few reported serious complications. We report a case of patient who developed hematemesis after nasogastric intubation and was found to have esophageal mucosal dissection. A 59-year-old female was admitted to vascular surgery for bilateral lower extremity critical limb ischemia. Patient underwent bilateral above knee amputation and femoro-femoral bypass. Postoperative course was complicated by sepsis and respiratory failure needing mechanical ventilation and acute renal failure requiring hemodialysis in ICU. Patient was also fully anticoagulated with heparin infusion. On day 10 of ICU admission, a nasogastric tube was placed for enteral nutrition. Immediately after nasogastric intubation, patient was noted to have hematemesis and subsequently 2g/dl drop in hemoglobin from baseline. Patient was managed with nil per os, intravenous PPI, fluids and blood transfusions. Heparin infusion was stopped. Emergent EGD was performed, which revealed clots at upper esophagus sphincter (UES) and a linear submucosal track extending from UES to the gastroesophageal junction (GEJ), blood clots and esophagitis in the lower esophagus and normal stomach and duodenum. Patient did not have any bleeding or drop in hemoglobin for next 72 hours. EGD was repeated after 4 days, which showed healing of previously noted esophageal submucosal tract without active bleeding. Over the next week, patient’s condition continued to deteriorate due to ongoing sepsis despite broad spectrum antibiotics and supportive care. Patient’s code status was changed to comfort care as per patient’s wishes. In conclusion, nasogastric intubation can lead to serious complications such as esophageal mucosal dissection. Conservative management is recommended for this rare complication and spontaneous healing is expected outcome. This case highlights the importance of practicing caution while placing nasogastric tube especially in critically ill patients.Figure 1: Esophageal mucosal dissection due to nasogastric intubation.

Effect of Systemic Urokinase Infusion After Lower Limb Percutaneous Transluminal Angioplasty on Limb Salvage Rate in Patients with Late-stage Critical Limb Ischemia

To evaluate the effect of systemically administered urokinase (UK) after percutaneous transluminal angioplasty with or without stent (PTA±stent) on the reduction in the rate and level of amputation in patients with critical limb ischemia (CLI) with tissue loss. This was an observational, nonrandomized, retrospective study of 183 Taiwanese patients with Rutherford stage 5 or 6, and Fontaine stage 4 lower extremity CLI. Patients received either PTA±stent or PTA±stent+UK infusion (250,000IU, daily for 5 days). PTA of the iliac, femoral, anterior tibial artery, posterior tibial artery, and peroneal arteries was included. Amputation was classified as minor, with direct wound healing, and minor amputation or surgical debridement of toes and major, with below- (BKA) and above-knee amputation (AKA). In groups of patients with comparable baseline characteristics, 85 and 90 patients received PTA±stent and PTA±stent+UK, respectively. There were 24 major limb amputations performed. A significant majority (20/24 (83.3%) were performed in patients who did not receive adjuvant urokinase, compared with 4/24 (16.7%) of patients who did receive urokinase (p= 0.000287). There was a significant increase in the limb salvage rate for infrapopliteal lesions in patients treated with PTA+UK (12/72 with UK; 60/72 without UK; p≤.0001). Intracranial hemorrhage (n=1) and bleeding at the inguinal puncture site (n=2) were reported in the PTA±stent+UK group. Eight deaths (one in the PTA±stent+UK group; seven in the PTA±stent) occurred during the study. Systemic administration of UK with the PTA±stent procedure may reduce the requirement for major amputation in patients with CLI with tissue loss (Rutherford 5 or 6). The difference is more pronounced in patients undergoing infrapopliteal interventions. However, these findings need to be confirmed in a randomized prospective study.

Long-Term Results for Primary Bypass Versus Primary Angioplasty/Stent for Lower Extremity Critical Limb Ischemia

Long-Term Results for Primary Bypass Versus Primary Angioplasty/Stent for Lower Extremity Critical Limb Ischemia

Cellular Therapy With Ixmyelocel-T to Treat Critical Limb Ischemia: The Randomized, Double-blind, Placebo-controlled RESTORE-CLI Trial

Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adverse events. Efficacy assessments included time to first occurrence of treatment failure (TTF; major amputation of injected leg; all-cause mortality; doubling of total wound surface area from baseline; de novo gangrene) and amputation-free survival (AFS; major amputation of injected leg; all-cause mortality). A total of 77 patients underwent bone marrow or sham aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24 patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically meaningful 32% reduction in event rate that was not statistically significant (P = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank test). Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option.

Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia

Cell therapy is a novel experimental treatment modality for patients with critical limb ischemia (CLI) of the lower extremities and no other established treatment options. This study was conducted to assess the safety and clinical efficacy of intramuscular injection of autologous tissue repair cells (TRCs). A prospective, randomized double-blinded, placebo controlled, multicenter study (RESTORE-CLI) was conducted at 18 centers in the United States in patients with CLI and no option for revascularization. Enrollment of 86 patients began in April 2007 and ended in February 2010. For the prospectively planned interim analysis, conducted in February 2010, 33 patients had the opportunity to complete the trial (12 months of follow-up), and 46 patients had completed at least 6 months of follow-up. The interim analysis included analysis of both patient populations. An independent physician performed the bone marrow or sham control aspiration. The aspirate was processed in a closed, automated cell manufacturing system for approximately 12 days to generate the TRC population of stem and progenitor cells. An average of 136 ± 41 × 10(6) total viable cells or electrolyte (control) solution were injected into 20 sites in the ischemic lower extremity. The primary end point was safety as evaluated by adverse events, and serious adverse events as assessed at multiple follow-up time points. Clinical efficacy end points included major amputation-free survival and time to first occurrence of treatment failure (defined as any of the following: major amputation, death, de novo gangrene, or doubling of wound size), as well as major amputation rate and measures of wound healing. There was no difference in adverse or serious adverse events between the two groups. Statistical analysis revealed a significant increase in time to treatment failure (log-rank test, P = .0053) and amputation-free survival in patients receiving TRC treatment, (log-rank test, P = .038). Major amputation occurred in 19% of TRC-treated patients compared to 43% of controls (P = .14, Fisher exact test). There was evidence of improved wound healing in the TRC-treated patients when compared with controls at 12 months. Intramuscular injection of autologous bone marrow-derived TRCs is safe and decreases the occurrence of clinical events associated with disease progression when compared to placebo in patients with lower extremity CLI and no revascularization options.

Sticky Platelet Syndrome: An Unusual Presentation of Arterial Ischemia

A 48-year-old woman presented with bilateral lower extremity critical limb ischemia. In addition to this, her work-up revealed multiple other thromboembolic insults including cerebral and visceral emboli. Initial laboratory findings were significant for an indeterminate platelet count, secondary to platelet clumping. After appropriate emergent surgical treatment including bilateral lower extremity embolectomy, the patient was empirically anticoagulated with a direct thrombin inhibitor. Further embolic work-up discovered bilateral renal and splenic infarctions as well as a large mobile mitral vegetation. Finally, an upper extremity duplex revealed left axillary, left subclavian, and right internal jugular acute deep vein thromboses. Mitral valve replacement was performed to remove the septic source. A series of hypercoagulability studies was done, and results were positive for lupus anticoagulants. Months after her recovery, the patient was tested and found to be positive for sticky platelet syndrome.

Occurrence of Digital Photoplethysmography Waveforms in Patients with Lower-Extremity Critical-Limb Ischemia

Purpose Digital photoplethysmography (PPG) has been proposed as an alternative to Doppler technology for measuring ankle pressures and ankle-brachial indices (ABIs). However, in patients with critical-limb ischemia (CLI), digital waveforms may not be detectable, which would negate digital pressure measurement and ABI calculation. In this study we evaluated the presence of digital PPG waveforms in patients with lower-extremity CLI (ABI &lt; 0.40). Methods From January through December 2007, vascular laboratory patients who had a lower-extremity physiological study, including an ankle waveform, PPG waveform analysis of their great toe, and an ABI of =0.40, were prospectively entered into a database. ABIs and waveforms were obtained in the standard fashion. Patients with incomplete waveform data and CLI follow-up examinations were excluded from the analysis. Subjects were separated into 2 groups: those with digital PPG waveforms (group 1) and those with flatline digital waveforms (group 2). Each group was evaluated for audible posterior tibial (PT) and dorsalis pedis (DP) Doppler signals. Results A total of 160 extremities (140 patients) with CLI were identified during the study period; 45 patients and 53 extremities were excluded. There were 41% (44/107) group 1 and 59% (63/107) group 2 extremities. In group 2 extremities, 67% (42/63) had flatline ankle waveforms, 40% (25/63) had absent PT and DP Doppler signals, and 60% (38/63) had one or more audible PT or DP signals. Conclusions Less than one half of the extremities with CLI had digital PPG waveforms. However, 60% of those limbs with flatline digital waveforms had one or more audible pedal Doppler signal, requiring a more detailed noninvasive evaluation with a Doppler ABI endpoint. Automated digital PPG devices may be inadequate for ABI evaluation of patients with CLI.