Chronic Limb-threatening Ischemia Patients Research Articles

Impact of the Affordable Care Act on Revascularization Versus Amputation in Patients Presenting With Chronic Limb-Threatening Ischemia in Maryland.

The Affordable Care Act (ACA) aimed to expand Medicaid, enhance health care quality and efficiency, and address health disparities. These goals have potentially influenced medical care, notably revascularization rates in patients presenting with chronic limb-threatening ischemia (CLTI). This study examines the effect of the ACA on revascularization vs amputation rates in patients presenting with CTLI in Maryland. This was a retrospective analysis of the Maryland State Inpatient Database comparing the rate of revascularization to rate of major amputation in patients presenting with CLTI over 2 periods: pre-ACA (2007-2009) and post-ACA (2018-2020). In this study, we included patients presenting with CLTI and underwent a major amputation or revascularization during that same admission. Using regression analysis, we estimated the odds of revascularization vs amputation pre- and post-ACA implementation, adjusting for pertinent variables. During the study period, 12,131 CLTI patients were treated. Post-ACA, revascularization rate increased from 43.9% to 77.4% among patients presenting with CLTI. This was associated with a concomitant decrease in the proportion of CLTI patients undergoing major amputation from 56.1% to 22.6%. In the multivariate analysis, there was a 4-fold odds of revascularization among patients with CLTI compared to amputation (OR = 4.73, 95% CI 4.34-5.16) post-ACA. This pattern was seen across all insurance groups. The post-ACA period in Maryland was associated with an increased revascularization rate for patients presenting with CLTI with overall benefits across all insurance types.

Exploring the Other Side of the River: Early and Midterm Outcomes of Endovascular Pedal Arch Revascularization in Patients with Chronic Limb-Threatening Ischemia.

This study investigated the effect of patency of the pedal arch (PA) on wound healing rate and time, amputation-free survival (AFS), limb salvage, and limb-based patency (LBP) in chronic limb-threatening ischemia (CLTI) patients undergoing endovascular revascularization of infrainguinal arterial lesions. This prospective study included all CLTI patients presenting with wound, ischemia, and foot infection (WIfI) stages 2 to 4 (WIfI ischemia grades 2-3) who underwent endovascular revascularization of infrainguinal arterial disease between April 2019 and April 2021. Pedal angioplasty was attempted in all patients with significant steno-occlusive pedal artery disease. Patients were stratified according to Kawarada PA types. Successful PA revascularization (PAR) was counted when at least 1 pedal vessel is patent. Wound healing rate and time and Kaplan-Meier estimate of AFS and LBP at 2 years were evaluated and compared among the patient groups. A total of 120 patients were categorized according to PA type into type 1 (n = 34; 28.3%), type 2 (n = 64; 53.3%), and type 3 (n = 22; 18.3%). Pedal angioplasty was attempted in 97 patients and was technically successful in 75 patients (77.3%). Successful PAR (with or without pedal angioplasty) was achieved in 98 patients (81.7%). During the follow-up, successful PAR resulted in a better wound healing rate (86.7% vs 59.1%; P = 0.007), major amputation rates (5.1% vs 40.9%; P ≤ 0.001), and AFS (92.9% vs 72.7%; P = 0.018) compared with unsuccessful PAR. There were no significant differences between the 2 groups in wound healing time (3.76 ± 1.99 months vs 3.64 ± 1.94 months; P = 0.798, respectively) or LBP (80.6% vs 72.7%; P = 0.594, respectively). Global Limb Anatomic Staging System (GLASS) stage (odds ratio [OR] = 6.84; 95% CI, 1.30-36.03; P = 0.023) and unsuccessful PAR (OR = 21.64; 95% CI, 4.01-116.69; P ≤ 0.001) were independently associated with failure of wound healing, whereas site of wound lesion (OR = 5.52; 95% CI, 1.15-26.48; P = 0.033), GLASS stage (OR = 24.93; 95% CI, 2.84-218.69; P = 0.004), and unsuccessful PAR (OR = 22.44; 95% CI, 3.53-142.67; P = 0.001) were significant predictors of major amputation. Successful PAR is important for improving clinical outcomes of endovascular revascularization of CLTI patients such as wound healing, amputation-free survival, and limb salvage. Predictors of limb salvage were site of foot lesion, GLASS stage, and successful PAR, whereas GLASS stage and successful PAR were independently associated with improved wound healing. Pedal arch patency positively influences clinical outcomes in patients with chronic limb-threatening ischemia who have ischemic wounds undergoing endovascular revascularization. This study demonstrated that successful pedal arch revascularization (PAR) significantly improved wound healing, amputation-free survival, and limb salvage rates when compared to patients who did not achieve successful PAR. Additionally, the study identified the predictors of limb salvage as the site of foot lesions, GLASS staging, and successful PAR, while both GLASS staging and successful PAR were found to be independently associated with improved wound healing.

Microvascular blood flow disturbances predict poor outcome of revascularization in CLTI patients

Abstract Background We have recently established hypoxic microvascular remodelling as a critical pathomechanistic factor that limits oxygen diffusion to muscle in chronic limb threatening ischaemia (CLTI). Using animal models of experimental hind limb ischaemia we have also displayed the biological relevance of post-ischaemic microvascular remodelling in skeletal muscle. Our results indicate that differential microvascular changes associate to muscle damage and repair. The natural microvascular dynamics that inherently promote muscle recovery are defected in CLTI patients. Particularly, a progressive arterialization of capillaries in CLTI muscle differentiates the dynamics of the microvasculature from initially assisting muscle regeneration to aggravating ischaemic damage. Methods To establish the clinical relevance of the post-ischaemic microvascular changes in CLTI, we now have studied the effect of microvascular remodelling on the outcome of CLTI patients undergoing surgical or endovascular revascularization. Contrast enhanced ultrasound was used preoperatively to determine the microvascular status of CLTI patients (n=36) scheduled for immediate revascularization. Outcome events such as: hospitalization; reoperation; leg amputation; or death, were postoperatively followed from medical records up to 6 months after revascularization. Patients were grouped according to muscle capillary transit time (Tct) being either similar (n=18) or shorter (n=18) to that in the contralateral legs of the patients, and treatment outcomes were compared between groups. Results The results display consistent increases in postoperative event rates in all measured outcomes in the ShortTct group as compared to controls (at 1 month 8 vs. 2 events (rate ratio 4.00 (95%CI: 0.85-18.84, p=0.080)); at 3 months 13 vs. 4 events (rate ratio 3.25 (95%CI: 1.06-9.97, p=0.039)); at 6 months 17 vs. 9 events (rate ratio 1.89 (95%CI: 0.84-4.24, p=0.123))). For example, 5 vs. 0; 7 vs. 1; and 7 vs. 4 reoperations were detected in the ShortTct group as compared to controls at 1, 3 and 6 months, respectively. By 6 months after initial revascularization also 2 deaths were recorded in the ShortTct group as compared to no deaths in the controls. Conclusions Despite still small samples size in this study, these results suggest that microvascular blood flow disturbances, such as short preoperative muscle capillary transit time, can predict poor outcome of CLTI patients after revascularization. Importantly, the results also identify patients with microvascular blood flow disturbances a subgroup of CLTI patients that should likely receive more specialized care to improve outcomes. The results also call for immediate actions from the scientific community to improve clinical detection of microvascular alterations and to develop strategies to normalize microvascular function in CLTI patients.

Polymer Everolimus-Eluting Stent as Bailout Stenting for Below-the-Knee Artery Repair in Patients with Critical Limb-Threatening Ischemia: A Real-World National Registry.

Percutaneous old balloon angioplasty is still the preferred treatment for the treatment of below-the-knee (BTK) arteries in chronic limb-threatening ischemia (CLTI). In the case of a suboptimal angioplasty result, a bailout stenting is required. So far, few data are available to assess the outcomes of bailout stenting after BTK angioplasty. This study aims to investigate the 1-year efficacy and safety after implantation of a polymer everolimus-eluting stent (PEES) as bailout stenting for BTK repair in patients with CLTI in a real-world setting. This was a national multicenter prospective observational study. Patients with CLTI (Rutherford 4 to 6) BTK lesions (including P3) and requiring a bailout PEES due to dissection, thrombosis, or residual stenosis ≥30% after angioplasty were included. The freedom of a major adverse limb event at 12 months of the target limb was the primary endpoint. XIENCE assessed 106 limbs (CLTI, 96.2%; chronic total occlusion, 2.8%) in 106 patients (mean age 77.1 years; males, 71.7%; diabetes mellitus, 66.9%; chronic kidney failure, 36.8%) with CLTI undergoing PEES stenting as a bailout for BTK lesions. Bailout stenting was required after 75.5% and 26.4% of residual stenosis and dissection, respectively. The mean diameter and length of the PEES were 3 mm and 3.4 ± 0.5 cm, respectively. At 1 year, the freedom of a major adverse limb event was 79.6% (95% CI, 71.5%-88.7%), the major amputation rate was 6.2% (95% CI, 1.3%-11%), and the target revascularization rate was 14.9% (95% CI, 6.5%-22.5%). In CLTI patients with BTK lesions, PEES stenting showed safety and efficacy as bailout stenting for BTK arterial lesions. This confirms the need for PEES stenting in a real-world practice. The XIENCE study introduces the PEES as an effective bailout stenting option for patients with CLTI undergoing BTK revascularization, particularly for lesions under 4 cm. The study focuses on real-world cases where POBA alone is insufficient, demonstrating that PEES significantly improves outcomes by enhancing limb salvage and reducing the need for major amputations. For clinicians, this innovation offers a precise, size-adaptable solution, especially in cases where bailout stenting is required for short, focal lesions, improving both clinical and procedural results.

Mid-term results of popliteal-pedal inframalleolar vein bypasses in CLTI patients after previous failed tibial endovascular recanalization

Inframalleolar bypass still preserves its role in the modern endovascular era. Aim of this study was to evaluate the mid-term outcomes of "short" inframalleolar vein bypasses in patients with chronic limb-threatening ischemia (CLTI) after previous failed tibial endovascular recanalization. Between January 2015 and December 2021 107 CLTI patients in 3 Italian Departments of Vascular Surgery underwent "short" inframalleolar vein bypass after failed tibial endovascular recanalization. Early (30-day) and 3-year outcomes were evaluated in terms of survival, primary patency, primary assisted patency, secondary patency, and amputation-free survival. Univariate analysis of the perioperative factors affecting outcomes were performed by means of log-rank test. Associations of procedure variables were sought based on a multivariate Cox regression analysis. Distal anastomosis (inframalleolar) was mostly performed on dorsal pedis (64, 59.8%). At 30 days bypass occlusion was recorded in 5 cases (4.6%). Mean follow-up period was 20.5 ± 17.9 months. Estimated 3-year overall survival was 66.7%. Three-year estimates of primary patency, primary assisted patency, secondary patency, and amputation-free survival were 68.5%, 70.1%, 70.2%, and 76.7%, respectively. Multivariate analysis showed a negative association of insulin treatment with primary patency (HR 4.3, p = .04), primary assisted patency (HR 5.1, p = .02), and secondary patency (HR 5.1, p = .02). Negative association of long-term corticosteroid use was also found with primary patency (HR 7.8, p = .005), primary assisted patency (HR 8.7, p = .003), secondary patency (HR 8.7, p = .003), and amputation-free survival (HR 3.9, p = .05). "Short" vein bypasses to the foot arteries in CLTI patients yielded good mid-term overall patency, and limb salvage rates after a failed tibial endovascular recanalization. Insulin dependent diabetes mellitus, and long-term corticosteroid use seemed to affect the outcomes.

Female Patients Have Fewer Limb Amputations Compared to Male Patients in the BEST-CLI Trial

Female patients are less likely to be diagnosed with and treated for peripheral artery disease. When treated, there are also reported sex disparities in short- and long-term outcomes. We designed this study to compare outcomes after open and endovascular revascularization in the Best Endovascular versus best Surgical Therapy in patients with Critical Limb Ischemia (BEST-CLI) trial between females and males, and to examine outcomes of each revascularization type in an all-female cohort. In a secondary analysis of cohorts 1 and 2 of the BEST-CLI Trial, patients with chronic limb threatening ischemia (CLTI) undergoing open surgical bypass (with or without adequate conduit) and endovascular therapy were stratified by sex. In addition, in a female-only cohort, we evaluated differences in outcomes between treatment arm (combined all bypasses from cohorts 1 and 2 and compared to all endovascular treatment in cohorts 1 and 2). Outcomes included major amputation, reintervention, major adverse limb event (MALE, a composite of major amputation and reintervention), all-cause death, and composite outcome of MALE or all-cause death. Univariable and adjusted Cox regressions were used to assess outcome between males and females. Similar methods were used to assess differences in outcomes between treatment arm in females. Among 1830 patients, females were significantly underrepresented, comprising only 28% (n=519) of the BEST-CLI cohort. Overall, the characteristics of females enrolled in the trial had some differences compared to males: females were more likely to have rest pain alone (72% vs 60%, p <.0001) and when presenting with an ischemic wound, were less likely to have a wound infection (38% vs 47%, p = .01). Females were less likely to have an adequate single segment greater saphenous vein (SSGSV) available (82% vs 89%, p = .01). Controlled for baseline clinical factors, at one year, females had significantly lower rates of major limb amputation compared to males (HR .70, p = .023), which drove better amputation- and MALE- free survival rates. All-cause death at one year was not statistically different between sexes (11.8% vs 11.2%, p=.286). In the all-female cohort, results paralleled the overall trial; open surgical bypass (with any conduit) had significantly better outcomes compared to endovascular therapy. Specifically, among females undergoing endovascular therapy, the rate of major reintervention was particularly high compared to females undergoing open surgical bypass (24.8% vs. 10.5%, p < .001). Despite being underrepresented in BEST-CLI, the primary results of the trial, namely, improved MALE-free survival with open surgical bypass with SSGSV, were mirrored in the all female subset. Female patients enrolled in BEST-CLI had better amputation-free survival at one year compared to male patients. These findings suggest that in treating female CLTI patients considered appropriate for both open and endovascular revascularization, surgical bypass with optimal conduit is the preferred treatment option and can potentially ameliorate poor limb preservation outcomes associated with sex.

Therapeutic Angiogenesis for Patients with Chronic Limb Threatening Ischemia: Promising or Hoax?

Chronic Limb Threatening Ischemia (CLTI) is a critical end-stage disease that leads to high amputation rates. Over the past few decades, therapeutic angiogenesis has attracted a lot of attention as a means to reduce the necessity for amputations. Especially gene- and cell therapy are regarded to as possible treatment modalities to restore the hampered blood flow. So far, early phase clinical trials often fail to prove significant clinical improvement in mortality, amputation rate and ulcer healing, but still conclude that therapeutic angiogenesis might be promising as therapy. The subsequent phase III clinical trials based on these indecisive early trials fail consistently to demonstrate clinical benefits leaving the promising early results unvalidated. In this review we will illustrate that designing good trials for CLTI patients is challenging, not in the last place since patients are often not eligible due to strict inclusion criteria. Moreover, in this review we advocate that clinical trials should be conducted with a low risk of bias and that it is of utmost importance to publish results, regardless of the outcome. It is definitely very concerning that many studies of a lower quality (due to small groups size or high chance for bias) reporting positive outcomes are published while good quality trials (often with larger group sizes) are stopped prematurely due to lack of effects and remain unpublished. This keeps the 'promising but not yet proven' image of these therapeutic neovascularization studies needless alive, with still new groups starting similar trials.

Prehabilitation for delirium prevention in elderly patients with chronic limb threatening ischemia

Elderly patients with Chronic Limb Threatening Ischemia (CLTI) undergoing revascularization are prone to delirium and prolonged hospitalization. Preoperative prehabilitation may prevent delirium and reduce the length of stay. This study investigates the effect of multimodal prehabilitation on delirium incidence in elderly CLTI patients undergoing revascularization. A comparative observational cohort study conducted in a large teaching hospital (intervention cohort n=101, retrospective control cohort n=207) and a university hospital (prospective control cohort n=48) from 2020 to 2023. Patients aged ≥ 65 years undergoing revascularization were included, with acute treatment or severe cognitive impairment as exclusion criteria. The three-week prehabilitation program included screening of general health and presence of delirium risk factors by a vascular nurse practitioner, screening and provision of personalized, home-based exercises by a physiotherapist, provision of nutritional advice by a dietician, and if indicated comprehensive geriatric assessment by a geriatrician, assessment of self-reliance and home situation by a prearranged homecare nurse, guidance and support for smoking cessation by a quit smoking coach, and anaemia treatment. Primary outcome was 30-day delirium incidence, analysed using regression models adjusting for potential confounders (age, physical impairment, history of delirium, preoperative anaemia and revascularization type). Secondary outcomes were length of stay, postoperative complications, 30-day mortality, and patient experiences. Median age (IQR) was 76 years (71-82). Delirium incidence was lower in the prehabilitation cohort (n=2/101, 2%) compared to controls (n=23/255, 9%; OR=0.21, 95%CI 0.05-0.89, p=.04). Adjusted analysis showed a non-significant delirium reduction (OR=0.28, 95%CI 0.06-1.3, p=.097). The prehabilitation cohort had a significantly shorter length of stay (2 [1-5] vs 4 [2-9] days; p=<.001), and fewer minor complications (14% vs 26%, p=.01). No differences were present in major complications and 30-day mortality. Patients reported high compliance and satisfaction (median score 8/10, IQR 7-9). Prehabilitation among elderly CLTI patients is safe and has the potential to yield multiple beneficial effects on general outcomes following revascularization, while also achieving high levels of patient satisfaction. Further validation and considering implementation in surgical settings is recommended.

Can wound blush be used as an indicator for termination of endovascular procedures in chronic limb-threatening ischemia patients?

Predicting the outcomes of endovascular revascularization of chronic limb-threatening ischemia (CLTI) patients with foot wounds can be challenging. Angiographic wound blush (WB) assessment has been found to be a helpful tool to assess wound perfusion. The aim of this study is to evaluate WB during endovascular revascularization of CLTI patients and its effects on treatment outcomes. This prospective study included all CLTI patients with foot wounds who underwent successful endovascular revascularization of infrainguinal arterial disease between 2019 and 2021. Patients were grouped according to the WB status into positive WB (group A) and negative WB (group B). Both groups were compared for demographics, comorbidities, clinical picture, and 12-month limb-based patency (LBP) and amputation-free survival (AFS) rates. The study included 69 patients of Rutherford classes 5 (46.4%) and 6 (53.6%), with the main arterial lesion located at the femoropopliteal (58%) or infrapopliteal (42%) segments. Completion angiography showed positive WB in 38 (55.1%) patients and negative WB in 31 (44.9%) patients. Both groups were comparable regarding patient presentation, site of the main arterial lesion, and distribution of foot lesions in relation to the feeding artery. The overall 12-month LBP and AFS rates were 21.7% and 39.1%, respectively, with significantly better rates in group A than in group B (LBP, 31.6% vs 9.7%, p = 0.001 and AFS, 54.1% vs 22.2%, p = 0.006, respectively). Successful angiosome-based direct flow to the foot was achieved in 38 patients (55.1%), resulting in significantly better 12-month AFS rates than those with indirect revascularization (54.8% vs 26.3%, p = 0.036, respectively), despite the comparable 12-LBP rates between the direct and indirect revascularization groups (29% vs 15.8%, p = 0.133, respectively). Multivariate logistic regression analysis identified smoking as a significant predictor of a major amputation, whereas positive WB and successful direct revascularization were significant predictors of limb salvage. WB can serve as a predictor for AFS and LBP during endovascular revascularization of CLTI patients with foot wounds. A positive WB may guide the decision to conclude an endovascular procedure, potentially avoiding unnecessary complicated maneuvers to recanalize more vessels. Conversely, a negative WB may suggest the need for further revascularization attempts to augment wound perfusion and healing.

Allogenic Vertebral Body Adherent Mesenchymal Stromal Cells Promote Muscle Recovery in Diabetic Mouse Model of Limb Ischemia

Chronic limb threatening ischemia (CLTI) carries a significant risk for amputation especially in diabetic patients with poor options for revascularization. Phase I trials have demonstrated efficacy of allogeneic mesenchymal stromal cells (MSC) in treating diabetic CLTI. Vertebral bone adherent mesenchymal stromal cells (vBA-MSC) are derived from vertebral bodies of deceased organ donors which offer the distinct advantage of providing a 1,000x greater yield compared to that of living donor bone aspiration. This study describes the effects of intramuscular injection of allogenic vBA-MSC in promoting limb perfusion and muscle recovery in a diabetic CLTI mouse model. A CLTI mouse model was created through unilateral ligation of the femoral artery in male polygenic diabetic TALLYHO mice. Treated mice were injected with vBA-MSC into the gracilis muscle of the ischemic limb 7 days post ligation. Gastrocnemius or tibialis muscle was assessed post-mortem for fibrosis by collagen staining, capillary density via immunohistochemistry, and mRNA by quantitative real time PCR. Laser Doppler perfusion imaging and plantar flexion muscle testing were performed to quantify changes in limb perfusion and muscle function. Compared to vehicle control, treated mice demonstrated indicators of muscle recovery including decreased fibrosis, increased perfusion, muscle torque, and angiogenesis. PCR analysis of muscle obtained 7- and 30-days post vBA-MSC injection showed an upregulation in expression of MyoD1 (p = 0.03) and MyH3 (p = 0.008) mRNA representing muscle regeneration, VEGF-A (p = 0.002 ; p = 0.004) signifying angiogenesis as well as IL-10 (p < 0.001), T regulatory cell marker Foxp3 (p = 0.04), and M2-biased macrophage marker Mrc1 (CD206) (p = 0.02). These findings indicate human allogeneic vBA-MSC ameliorate ischemic muscle damage and rescue muscle function. These results in a murine model will enable further studies to develop potential therapies for diabetic CLTI patients.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers are Associated with Improved Amputation Free Survival in Chronic Limb-Threatening Ischemia

BackgroundIn the Heart Outcomes Prevention Evaluation (HOPE) study, investigators found that ramipril was associated with improved survival as well as decreased MI and stroke rates in patients with peripheral arterial disease. Nonetheless, their effect on chronic limb-threatening ischemia (CLTI)-specific outcomes is unclear. We aim to assess the effect of ACEIs/ARBs on amputation-free survival in CLTI patients undergoing peripheral vascular intervention (PVI) in a Medicare-linked database. MethodsPatients undergoing PVI in the VQI-VISION database were included. Primary outcome included amputation-free survival. Kaplan Meier survival and multivariable Cox regression analyses were used to assess one-year outcomes. ResultsA total of 34,284 patients were included, and 46.3% of whom were discharged on ACEIs/ARBs. Patients discharged on ACEIs/ARBs were more likely to be smokers, diabetics, and hypertensive. They were also more likely to present with rest pain. The overall one-year survival for patients on ACEIs/ARBs vs those who are not was (79.1% vs 69.4%, P<0.001). Freedom from amputation was 87.8% for patients on ACEIs/ARBs vs 84.2% for those who were not (P<0.001). Amputation-free survival was 70.5% vs 59.5% for ACEIs/ARBs vs no ACEIs/ARBs (P<0.001). After adjusting for potential confounders, ACEIs/ARBs use was associated with lower one-year mortality (HR: 0.77, 95%CI (0.7-0.8), P<0.001), amputation (HR: 0.89, 95%CI (0.8-0.9), P<0.001), and amputation or death (HR: 0.79, 95%CI (0.76-0.8), P<0.001). ConclusionsACEIs/ARBs were independently associated with lower amputation, improved survival, and amputation-free survival at one year in CLTI patients undergoing PVI. The fact that more than half the patients were not discharged on these medications presents an area for potential quality improvement.

Impact of Peripheral Angioplasty on Wound Oxygenation and Healing in Patients with Chronic Limb-Threatening Ischemia Measured by Near-Infrared Spectroscopy.

Managing chronic limb-threatening ischemia (CLTI) is challenging due to difficulties in assessing tissue oxygen saturation in ulcers. Near-infrared spectroscopy (NIRS) is a non-invasive method for measuring tissue oxygen saturation (StO2). This study evaluated the effects of endovascular treatment (EVT) on StO2 and wound healing in CLTI patients, comparing NIRS to standard ankle-brachial index (ABI) measurements. Using the Duesseldorf PTA Registry, 43 CLTI patients were analyzed: 27 underwent EVT, and 16 received conservative treatment. ABI assessed macrocirculation, while NIRS measured wound, wound area, and mean foot StO2 at baseline, post-EVT, and four-month follow-up. Wound severity was classified by wound area and wound, ischemia, and foot infection (WIfI) score. Wound StO2 increased significantly (median (interquartile range (IQR)), 38 (49.3) to 60 (34.5)%, p = 0.004), as did wound area StO2 (median (IQR), 70.9 (21.6) to 72.8 (18.3)%, p < 0.001), with no significant changes in the control group by four-month follow-up. Wound area decreased significantly after EVT (mean ± SD, 343.1 ± 267.8 to 178.1 ± 268.5 mm2, p = 0.01) but not in the control group. Changes in wound StO2, wound area StO2, and WIfI score correlated with wound area reduction, unlike ABI. This small exploratory study shows that NIRS-measured StO2 improvements after EVT correlate with reduced wound area and WIfI scores, highlighting NIRS as a potential enhancement for CLTI wound management in addition to ABI.

Treatment of chronic limb-threatening ischemia (CLTI) based on BEST-CLI and BASIL-2

The rate of vascular recanalizations in CLTI is increasing worldwide. Safety and efficacy of surgical versus endovascular treatment in CLTI patients was investigated in 2 prospective randomized trials with contrasting results. The BEST-CLI trial randomized 1830 patients with CLTI, the Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL-2) trial included 345 patients with CLTI. Best-CLI evaluated outcome events as the primary endpoint, which includes major reinterventions in addition to major amputations and death. Only half of the CLTI patients received a crural intervention or surgery. There were no differences in major amputations or death. After a median follow-up (FU) of 2,7 years, the surgery group showed significantly better results compared to the endovascular group, due to fewer re-interventions. BASIL-2 used amputation-free survival as the primary outcome and only included patients with lower leg lesions. After a median FU of 40 months, endovascular therapy was found to be superior. The extremely high mortality rate was remarkable in both studies. The BEST-CLI study represents CLTI patients only to a limited degree, whereas the BASIL-2 study presents the treatment of CLTI patients with below-the-knee-lesions quite well. Both studies confirm that patients with CLTI should be treated in specialized centers that offer both crural surgery and endovascular therapy. Cardiovascular risk factor management must play a more important role in reducing the high mortality associated with CLTI.

Discrepancy in opioid prescription patterns for Black or African American patients following lower extremity bypass surgery for chronic limb-threatening ischemia

BackgroundDisparity in the allocation of medical services and resources based on race is present within the health care industry today, including the prescription of postoperative analgesics. The purpose of this study was to evaluate the presence of race-based disparity in the prescription of postdischarge opioids after lower extremity bypass (LEB) surgery for chronic limb-threatening ischemia (CLTI). MethodsRetrospective analysis was conducted on adult CLTI patients who underwent LEB from 2000 to 2023 in the TrinetX database. Patients were stratified into two groups based on race: White (group I) and black or African American (AA) (group II). Primary outcomes were defined as oral opioid prescriptions at 7 days and 30 days after discharge, and mortality at 1 year postoperatively. Secondary outcomes included length of stay and 30-day postoperative outcomes, including myocardial infarction, pulmonary embolism, cerebral vascular accident, deep vein thrombosis, acute kidney injury, major amputation, minor amputation, major adverse cardiac events, and major adverse limb events. Stratified analysis was conducted based on disease stage (rest pain vs lower extremity ulcer vs gangrene). Univariate analysis was performed via two-sample t test and χ2 test. Logistic regression was performed to estimate the association of Black or AA (vs White) race while controlling for pertinent preoperative potential confounders. ResultsThere were 3345 patients who met the inclusion criteria. Group I included 2661 White patients and group II included 684 Black or AA patients. Group II patients were more likely to be younger, female, present with gangrene, and have a history of hypertension, diabetes, chronic kidney disease, or diabetic neuropathy. At both 7 and 30 days after discharge, the Black or AA cohort had significantly lower rates of opioid prescriptions (33.2% vs 42.5% and 35.8% vs 47.2%, respectively) (all P < .05). Stratification by indication showed that opioid prescription disparity persisted despite black or AA patients presenting at worse stages of disease both at 7 and 30 days after discharge (7 days: rest pain 43.4% vs 33.7% [P = .013], ulcer 41.4% vs 31.7% [P = .027], gangrene, 42.7% vs 33.6% [P = .006] and 30 days: rest pain 47.8% vs 37.1% [P = .007], ulcer 45.4% vs 33.5% [P = .007], gangrene, 48.2% vs 36.1% [P < .001]). Adjusted analysis confirmed that Black or AA race was associated with lower rates of 7- (adjusted odds ratio, 0.607; P = .001) and 30-day (adjusted odds ratio, 0.56; P = .001) postdischarge opioid prescriptions. ConclusionsBlack or AA patients were less likely to receive postdischarge opioid prescriptions compared with their White counterparts at 7 and 30 days after LEB for CLTI.

Vcam1+ Fibro-adipogenic Progenitors Mark Fatty Infiltration in Chronic Limb Threatening Ischemia.

Skeletal muscle health and function is a critical determinant of clinical outcomes in patients with peripheral arterial disease (PAD). Herein, we identify fatty infiltration, the ectopic deposition of adipocytes in skeletal muscle, as a histological hallmark of end-stage PAD, also known as chronic limb threatening ischemia (CLTI). Leveraging single cell transcriptome mapping in mouse models of PAD, we identify a pro-adipogenic mesenchymal stromal cell population marked by expression of Vcam1 (termed Vcam1+ FAPs) that expands in the ischemic limb. Mechanistically, we identify Sfrp1 and Nr3c1 as regulators of Vcam1+ FAP adipogenic differentiation. Loss of Sfrp1 and Nr3c1 impair Vcam1+ FAP differentiation into adipocytes in vitro. Finally, we show that Vcam1+ FAPs are enriched in human CLTI patients. Collectively, our results identify a pro-adipogenic FAP subpopulation in CLTI patients and provide a potential therapeutic target for muscle regeneration in PAD.

Impact of Cilostazol Administration on Prevention of Aspiration Pneumonia in Patients With Chronic Limb-Threatening Ischemia.

Cilostazol has reported effectiveness for preventing aspiration pneumonia in patients with ischemic stroke, but whether it is similarly beneficial for patients with chronic limb-threatening ischemia (CLTI) is unclear. This retrospective single-center study enrolled 1,368 CLTI patients treated with endovascular therapy (EVT). In the multivariate analysis, predictors for aspiration pneumonia were age (hazard ratio [HR] 1.06 [95% confidence interval (CI) 1.03-1.10]), non-ambulatory status (HR 2.54 [95% CI 1.38-4.65]), the Geriatric Nutritional Risk Index (HR 0.97 [95% CI 0.95-0.99]), and cilostazol (HR 0.37 [95% CI 0.16-0.87]). Cilostazol administration reduced the risk of aspiration pneumonia in patients with CLTI undergoing EVT.

The Utility of Sirolimus Eluting Balloons in the Setting of Chronic Limb Threatening Ischaemia in Asian Patients from Singapore – 12 Months Results of the PRISTINE Registry

PurposeThe aim of PRISTINE was to evaluate the 6 and 12 months safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon for treatment of complex lower limb occlusive lesions (TASC II C & D) in patients with chronic limb threatening ischemia (CLTI) from Singapore.MethodsPRISTINE was a prospective, non-randomized, single arm, observational, multi-investigator, single-center clinical study. Complication-free survival at 30 days was the safety clinical endpoint. Immediate technical success (ability to cross and dilate the lesion and achieve residual angiographic stenosis < 30%), 6-month primary vessel patency, limb salvage, clinically driven target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest.ResultsSeventy five patients were included. There were 50 (68.0%) males; mean age, 69.0 ± 10.7 years. CLTI severity was based on the Rutherford Scale (R5 = 51; R6 = 17). Significant co-morbidities included diabetes mellitus (n = 68; 91.0%) and end-stage renal failure (n = 28; 37.0%). 112 atherosclerotic lesions were treated (TASC II D = 58 (52%); 76 (67%) de novo). There was 100% technical success. Mean lesion length treated was 22.4 ± 13.9 cm. Primary vessel patencies at 6 and 12 months were 64/86 (74%) and 43/74 (58%) and freedom from clinically driven TLR were 72/86 (84%) and 55/74 (74%) respectively. AFS was 61/73 (84.0%; five deaths and seven major lower extremity amputation) at 6-months. Mean Rutherford score improved from 5.1 ± 0.55 at baseline to 1.1 ± 2.05 (p < 0.05) at one year and there was a wound healing rate of 38/48 (79%) at the same timepoint.ConclusionsThe Selution SLR™ drug eluting balloon is safe and efficacious in treating highly complex infra-inguinal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients with a high incidence of diabetes and end-stage renal failure. It is associated with highly satisfactory acute technical and clinical success, 12-month target lesion patency and AFS.Level of EvidenceLevel 2b, Individual Cohort Study.Graphical

A Free Bypass Flap for Chronic Limb-threatening Ischemia.

Recently, significant inframalleolar disease seems to increase in chronic limb-threatening ischemia (CLTI) patients, making identifying sufficient outflow vessels in the foot challenging. In these difficult situations, free tissue transfer is a valuable tool to provide a low-resistance vascular bed to the affected part. However, there remains concern that free tissue transfer may impede adequate perfusion of the higher resistance diseased vascular bed. To improve perfusion of the affected area directly, the authors have developed a concept of a free bypass flap, adding bypass surgery to free tissue transfer. After anastomosis with the recipient vessels in a conventional manner for free tissue transfer, bypass surgery to the foot is performed by anastomosis of the branch of the flap pedicle with the diseased artery to the foot. A retrospective chart review of nine CLTI patients was performed to analyze the outcomes of free bypass flap transfer between 2018 and 2023. The flap success rate was 100% (n = 9). Postoperative angiography or echo confirmed the patency of all but one bypass vessel (n = 8). There were six fatalities, however, due to causes other than foot lesions, with an average observation period of 16 months. The limb salvage rate was 89% (n = 8). A free bypass flap enhances the overall blood circulation to the foot. Due to its high patency rate of bypass vessels, it is a valuable method for preserving the limbs of highly comorbid patients with CLTI.

Effect of diabetes on hypoxic microvascular remodeling and muscle damage in chronic limb threatening ischemia

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Finnish Academy/Research Council of Finland. The Finnish Foundation for Cardiovascular Research Background Hypoxia-induced arterialization of skeletal muscle capillaries has recently been identified as an important pathological feature that aggravates ischemic damage in chronic limb threatening ischemia (CLTI). Diabetes is also known to worsen the outcome of CLTI patients but its contribution to capillary arterialization and skeletal muscle pathology under ischemia is still largely unknown. Purpose To study how diabetes affects capillary arterialization and skeletal muscle pathology in CLTI. Methods Amputation muscle samples from CLTI patients (n=21 patients x3 samples) were histologically analyzed, grouped according to microvascular changes and RNA sequencing was performed. Differentially expressed genes, differentially regulated signaling pathways and histology between diabetics and non-diabetics were studied among corresponding microvascular groups. Also, spatial transcriptomics (n=2 patients) was applied to understand the mechanisms through which diabetes alters differential capillary responses on the tissue level. Results Diabetes differentially regulated gene expression of different angiogenic and arteriogenic factors including HIF1A, VEGFA, FLT1, NOTCH1, NOTCH3, NOS1 and ITGB3 in the CLTI muscles. This differential transcriptomic regulation translated as increased sprouting on the level of muscle capillaries, and also affected myofiber pathology. Muscle samples in diabetic patients often presented myofiber swelling and cell death that were uncommon in samples of non-diabetic patients. Conclusion Diabetic patients on the level of muscle transcriptional regulation show changes that can explain observed differential microvascular remodeling and worsened myofiber pathology. These results broaden our understanding of the causes for the exceptionally bad outcome of diabetics among CLTI patients.

Bypass Surgery as a Viable Option for Chronic Limb-threatening Ischemia Patients With Chronic Kidney Disease

Bypass Surgery as a Viable Option for Chronic Limb-threatening Ischemia Patients With Chronic Kidney Disease