Critical Limb Ischemia Patients Research Articles

Low admission blood pressure as a marker of poor 1-year survival in patients with revascularized critical limb ischemia.

To contrast the association between blood pressure (BP) level and antihypertensive medications at hospital admission with 1-year mortality in patients undergoing revascularization for critical limb ischemia (CLI). From November 2013 to May 2019, 315 consecutive patients were retrospectively included. A median of seven (IQR 3-13) separate readings were recorded for each patient before revascularization procedure and the average represented patient's mean BP. BP-lowering medications, clinical and biological parameters were recorded at baseline. The main outcome was total 1-year mortality. The cohort included 172 men (55%) and 143 women (45%), with a mean age of 77.9 ± 11.9 years. Treated hypertension was present in 245 (78%) patients; 288 (91%) patients had BP-lowering drug prescriptions (2.1 ± 1.3 medications at baseline). Mean SBP, DBP, mean BP (MBP) and pulse pressure (PP) were 132 ± 18, 70 ± 8, 90 ± 10 and 62 ± 16mmHg. During 1-year follow-up, 80 (25.4%) patients died. In single-pressure multivariate analysis, SBP (hazard ratio 0.97; 95% CI 0.96-0.99; P = 0.005), MBP (hazard ratio 0.96; 95% CI 0.92-0.99; P = 0.01), PP (hazard ratio 0.97; 95% CI 0.95-0.99; P = 0.009), but not DBP, were inversely correlated with 1-year mortality, independently of age, coronary heart disease, left ventricular ejection fraction, brain natriuretic peptide, serum albumin, institutionalized status and antihypertensive drugs. Association between SBP, MBP and PP with 1-year mortality had a quite linear reverse pattern. Among patients undergoing revascularization for CLI, there is an inverse correlation between admission SBP, MBP and PP with 1-year mortality. BP may represent a modifiable therapeutic target to prevent poor outcome in CLI patients.

Contemporary Revascularization Strategies and Outcomes Among Patients With Diabetes With Critical Limb Ischemia: Insights From the National Inpatient Sample.

The purpose of this study was to evaluate temporal trends in the frequency of revascularization and associated outcomes in patients with diabetes mellitus and critical limb ischemia (CLI). Little is known about outcomes following revascularization for CLI in patients with diabetes mellitus. Temporal trends in hospitalization for CLI among patients with diabetes were determined using the 2002-2015 National Inpatient Sample database. Propensity score matching was used to compare patients who underwent revascularization with those who did not and, separately, to compare those who underwent endovascular versus surgical revascularization. The main study outcome was in-hospital mortality. The analysis included 1,222,324 hospitalizations. The number of hospitalizations for CLI among patients with diabetes increased over time (ptrend< 0.001). There was an increase in the use of lower extremity revascularization, paralleled by a decline in in-hospital mortality during the study period. In the matched cohort, patients who were revascularized had lower in-hospital mortality (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.63 to 0.72) and major amputation (OR: 0.25; 95%CI: 0.24 to 0.27) compared with those who were treated medically. Compared with endovascular revascularization, those who underwent surgical revascularization had higher rates of in-hospital mortality (OR: 1.18; 95%CI: 1.04 to 1.35) but lower rates of major amputation (OR: 0.75; 95%CI: 0.70 to 0.81). Major bleeding, blood transfusion, post-operative infection, respiratory complications, discharges to nursing facility, and longer length of hospital stay were also more common among those who underwent surgery. In this national analysis of patients with DM and CLI, we demonstrated an increase in hospitalization for CLI among patients with diabetes in the United States. Although in-hospital mortality decreased over time regardless of the treatment strategy used, this outcome occurred less frequently among those who underwent revascularization than not. Compared with surgical revascularization, endovascular revascularization was associated with lower in-hospital mortality but higher rates of major amputation.

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia.

Critical limb ischemia (CLI) constitutes the most severe form of peripheral arterial disease (PAD), it is characterized by progressive blockade of arterial vessels, commonly correlated to atherosclerosis. Currently, revascularization strategies (bypass grafting, angioplasty) remain the first option for CLI patients, although less than 45% of them are eligible for surgical intervention mainly due to associated comorbidities. Moreover, patients usually require amputation in the short-term. Angiogenic cell therapy has arisen as a promising alternative for these “no-option” patients, with many studies demonstrating the potential of stem cells to enhance revascularization by promoting vessel formation and blood flow recovery in ischemic tissues. Herein, we provide an overview of studies focused on the use of angiogenic cell therapies in CLI in the last years, from approaches testing different cell types in animal/pre-clinical models of CLI, to the clinical trials currently under evaluation. Furthermore, recent alternatives related to stem cell therapies such as the use of secretomes, exosomes, or even microRNA, will be also described.

Comparative performance analysis of interventional devices for the treatment of ischemic disease in below-the-knee lesions: a systematic review and meta-analysis

This meta-analysis aimed to evaluate the device performance of conventional balloon catheters (POBA), drug-coated balloons (DCB), bare-metal stents (BMS), and drug-eluting stents (DES) in below-the-knee (BTK) ischemic lesions with regard to lesion characteristics. Online searches of PubMed, Web of Science, and Cochrane databases (2010–2019) were conducted for each of the test devices. Primary patency rates (pp) and major amputation rates 1 year after the use of each device were analyzed using a random-effects meta-analysis model. Meta-regression analysis was conducted to test associations between the outcomes and lesion characteristics. The analysis included 18 studies reporting on 24 separate cohorts comprising 2,438 patients. DES demonstrated the best pp among the test devices (83.6%; 95% confidence interval = 78.4–88.8%, studies = 8; I2 = 66%, P = 0.005). A negative coefficient between lesion length and pp (P = 0.002) was obtained. The ratio of critical limb ischemia (CLI) patients impacted the amputation rates (P = 0.031), whereas no statistically significant difference was found between the devices. DES showed favorable pp in BTK lesions; however, as the lesion lengths using DES were short, pp in long lesions still needs to be evaluated. Shorter lesions gained better pp. A higher ratio of CLI patients resulted in increased amputation rates.

Critical limb ischemia patients clinically improving with medical treatment have lower neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios.

Inflammation is a component in the pathogenesis of critical limb ischemia. We aimed to assess how inflammation affects response to treatment in patients treated for critical limb ischemia using neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocytes ratios (PLR) as markers of inflammation. Patients in a single tertiary cardiovascular center with critical limb ischemia unsuitable for surgical or interventional revascularization were retrospectively identified. Data were collected on medical history for risk factors, previous surgical or endovascular revascularization, and outcome. A standard regimen of low molecular weight heparin, aspirin, statins, iloprost infusions, and a standard pain medication protocol were applied to each patient per hospital protocol. Patients with improvement in ischemic pain and healed ulcers made up the responders group and cases with no worsening pain or ulcer size or progression to minor or major amputations made up the non-responders group. Responders and Non-responders were compared for risk factors including pretreatment NLR and PLR. 268 included patients who were not candidates for surgical or endovascular revascularization were identified. Responders had significantly lower pretreatment NLR (4.48 vs 8.47, p < 0.001) and PLR (162.19 vs 225.43, p = 0.001) values. After controlling for associated risk factors NLR ≥ 4.63 (p < 0.001) and PLR ≥ 151.24 (p = 0.016) were independently associated with no response to treatment. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocytes ratio are markers of inflammation that are reduced in patients improving with medical treatment suggesting a decreased state of inflammation before treatment in responding patients.

Patients with critical limb ischemia (CLI) not suitable for revascularization: the “dark side” of CLI

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease (PAD). Its prognosis is poor, with high rates of limb amputation and cardiovascular mortality. The international guidelines consider limb revascularization as the first line of the treatment strategy for CLI. However, despite the progress of revascularization techniques, many patients with CLI are still considered not suitable for these procedures and treated with conservative limb treatments. We have consulted the most important guidelines on PAD and CLI published over the past two decades focusing on the epidemiology, treatment, and outcomes of CLI patients not suitable for revascularization. Our review shows that only the TASC guidelines report 25% of CLI patients conservatively treated. Regarding the treatments, all the guidelines agree that the conservative treatment is based on the best medical management of cardiovascular risk factors associated with pain drugs and wound management. Other treatments such as prostanoids, spinal cord stimulation, vasodilators, or angiogenic therapies have shown uncertain positive outcomes in reducing limb amputation and mortality. In conclusion, this work outlines the scarce consideration that the guidelines have had about these patients over the past two decades. However, this review tries to draw the main novelties and possible future treatments for the better management of this group of patients still resident in the “dark side” of the CLI.

Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis

Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFβ, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFβ, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD.

Pathology of critical limb ischemia; comparison of plaque characteristics between anterior and posterior tibial arteries

Background and Aims: There are some studies analyzing plaques in peripheral arteries using intravascular imaging devices. However, few pathological studies have examined the characteristics of plaques in the peripheral arteries with critical limb ischemia (CLI). This study is aimed to evaluate plaque characteristics between anterior and posterior tibial arteries using amputated lower limb specimens in CLI patients.

PMD6 Marginal Cost of Lower-LIMB Amputation in Germany

Lower-limb amputation is an undesired outcome in patients with critical limb ischemia (CLI), majorly impacting quality of life of the patients. In Germany, total no. of ischemic lower-limb amputations remains high, more than 50,000/year, despite availability of guideline recommended therapies at early stages. We calculated the first-year marginal cost of amputation as an additional healthcare expenditure to CLI treatment, imposed only by the amputation, in an average CLI patient from German healthcare system perspective. Major cost-components per amputation and their sources were identified as a) outpatient visits (general practitioner and podiatrist) from the uniform valuation scale (EBM), b) hospital stay (in-patient and nursing) from German Diagnosis-Related Groups (aG-DRG), c) rehabilitation from the literature of German Pension Insurance (DRV), and d) medical aid by adjusting the yearly cost in an earlier study for inflation. The base-costs of EBM were multiplied by assuming 10 outpatient visits, the rehabilitation rate was multiplied by literature-suggested average 3 weeks of stay, and the flat-rates of aG-DRG were multiplied by 14.2 days of average length of stay as provided as in ‘flat-rates per case’ catalog by Institute for the Hospital Renumeration System (InEK). Average first year costs per amputation for outpatient visits, hospital stay, rehabilitation, and medical aid were 223.00 €, 7,021.87 €, 2,520.00 €, and 9,903.00 € respectively. Average marginal cost of amputation sums up to 19,668.00 € per amputation in the first year of amputation. In addition to poor health outcomes and low quality of life due to amputation, the marginal cost of lower-limb amputation, when applied to the total no. of amputations every year, imposes a significant economic burden to German healthcare system. Timely and patient-centric management of CLI may not only save limbs and lives but also reduce amputation-related health-care costs.

Characteristics and Outcome for Persons with Diabetic Foot Ulcer and No-Option Critical Limb Ischemia.

The study aimed to evaluate clinical and vascular characteristics, as well as outcomes, for diabetic persons with foot ulceration and no-option critical limb ischemia (CLI). The study group included a sample of patients admitted to our diabetic foot unit because of a new diabetic foot ulcer and CLI. All subjects were managed using a limb salvage protocol which includes lower-limb revascularization. According to whether or not the revascularization procedure was a success, patients were respectively divided into two groups: successfully treated CLI patients (ST-CLI) and no-option CLI patients (NO-CLI). Failed revascularization was considered in the case of technical recanalization failure of occluded vessels (inability to overcome the obstruction) and/or absence of arterial flow to the foot. Limb salvage, major amputation, and death after 1 year of follow-up were evaluated and compared between the two groups. Overall, 239 patients were included, 74.9% belonging to ST-CLI and 25.1% to NO-CLI. NO-CLI patients reported more cases of ischemic heart disease (80 vs. 62.1, p = 0.008), heart failure (63.3 vs. 32.4%, p < 0.0001), and end-stage renal disease (ESRD) (60 vs. 25.7%) than ST-CLI patients. In addition, more vessels were affected in the NO-CLI group (5.2 ± 1.6 vs. 4 ± 1.5, p < 0.0001), and there was more involvement of tibio-peroneal trunk (50 vs. 30.2%, p = 0.006), anterior tibial (93.3 vs. 82.7, p = 0.03), posterior tibial (93.3 vs. 73.7%, p = 0.0005), peroneal (70 vs. 48%, p = 0.002), and below-the-ankle arteries (73.3 vs. 39.1%, p < 0.0001) than ST-CLI. The 1 year outcomes for the whole population were 69.9% limb salvage, 10.9% major amputation, and 19.2% death. The outcomes for NO-CLI and ST-CLI were, respectively, as follows: limb salvage (13.8 vs. 73.4%, p < 0.0001), amputation (30 vs. 4.5%, p = 0.0001), and mortality (50 vs. 8.9%, p < 0.0001). NO-CLI patients showed a more severe pattern of peripheral arterial disease (PAD) with distal arterial lesions and worse outcomes than ST-CLI.

Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization

ObjectivesThe purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM). BackgroundRadiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated. MethodsPatients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization. ResultsSPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization. ConclusionsSPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359)

Abstract 14653: Genome-wide Association Study of Peripheral Artery Disease and Critical Limb Ischemia Identifies Novel Genetic Loci and Coagulation Pathways

Introduction: The pathogenesis of peripheral artery disease (PAD) and critical limb ischemia (CLI) are poorly understood. Hypothesis: We hypothesize that genetic factors related to abnormalities in coagulation or fibrinolysis, in addition to atherosclerosis, could play an important role in PAD patients and PAD with CLI patients. Methods: A genome-wide association study (GWAS) was performed testing for associations between single-nucleotide variants (SNVs) and PAD case-control (3,190 cases and 463,495 controls) and subgroup analysis of PAD with CLI case-control (142 cases and 3,048 controls) in the UK Biobank cohort. To further validate the results, we selected SNVs with the most significant Cochrane-Armitage trend p values without evidence of strong linkage disequilibrium (r2 &gt; 0.8) for PAD with CLI case-control in the BioMe Biobank. We tested for association using BOLT-LMM with adjustment for age, sex, BMI, and the first ten principal components to control for population structure. The SNV association tests' significance level was set at P &lt; 5x10–8 after Bonferroni correction. Results: 363 SNVs from 81 genetic loci reached the threshold for statistical significance based on a Bonferroni correction (p &lt;5x10–8). (Figure) We then performed a subgroup analysis between PAD patients and PAD with CLI patients in the UK Biobank. We identified 63 SNVs with 52 genetic loci independent for PAD with CLI in the UK Biobank. We further validated those 63 SNVs with 52 genetic loci in the BioMe Biobank. In the validation cohort, 2 genetic loci ( PLG and CDKN2B ) were independent for PAD with CLI. On pathway analyses, we identify several new loci that implicate thrombotic, inflammation, glycosaminoglycan synthesis, coagulation, and fibrinolytic pathways involved in PAD along with known atherosclerosis pathways (p &lt;0.05). Conclusions: We show that PLG gene related to coagulation pathways in PAD may play an important role in coagulation-related PAD pathogenesis.

Plantar thermography predicts freedom from major amputation after endovascular therapy in critical limb ischemic patients.

Although plantar thermography can evaluate the immediate perfusion result after an endovascular therapy (EVT) has been performed, a relevant wound outcome study is still lacking.This study was to investigate whether angiosome-based plantar thermography could predict wound healing and freedom from major amputation after EVT in patients with critical limb ischemia (CLI)[1].All 124 patients with CLI (Rutherford category 5 and 6) who underwent EVT from January 2017 to February 2019 were prospectively enrolled. All patients received thermography both before and after EVT. Both wound healing and freedom from major amputation at the 6-month follow-up period were recorded. There were 61 patients in the healing group and 63 patients in the non-healing group, whereas the major amputation total was 14 patients. The mean pre- and post-EVT temperature of the foot was significantly higher in the healing group than in the non-healing group (30.78 °C vs 29.42 °C, P = .015; and 32.34 °C vs 30.96 °C, P = .004, respectively). DIFF2 was significantly lower in the non-healing group (-1.38 vs -0.90, P = .009). DIFF1 and DIFF2 were significantly lower in the amputation group (-1.85 °C vs -1.11 °C, P = .026; and -1.82 °C vs -1.08 °C, P = .004). Multivariate analysis showed that DIFF2 stood out as an independent predictor for freedom from major amputation (hazard ratio 0.51, P = .045). Receiver operating characteristic curve analysis showed a DIFF2 cut-off value of -1.30 °C, which best predicts freedom from major amputation.Plantar thermography is associated with wound healing and helps predict freedom from major amputation in CLI patients undergoing EVT.

Impact of endovascular pedal arteries revascularization on wound healing in patients with critical limb ischemia

Background: Critical limb ischemia (CLI) is the final consequence of peripheral arterial disease (PAD). The management of this complex patient population often warrants a multidisciplinary approach with collaboration between endovascular interventionist, vascular surgeons, podiatrist, infectious disease, and wound care specialist. Objective of the study was to evaluate the impact of endovascular pedal arteries revascularization on wound healing in patients with critical limb ischemia.Methods: This was an interventional study conducted on 30 consecutive CLI patients underwent infra-genicular endovascular revascularization who attended to the outpatient department and emergency, Suez Canal university hospital complaining of symptoms of critical lower limb ischemia involving the foot (rest pain, ulcer and gangrene), during the period study from June 2017 till January 2019. Full detailed history, full examination, lab investigation, radiological imaging was done.Results: The pain intensity decreased from 7 to 4 post-procedural at 2nd day post-op, then to 3 at one week follow up and then it totally disappeared at one month follow up visit. The remaining patients who had incomplete PAA reported faster relieve of pain and more dramatic improve over time as it was totally relieved post procedural by time of discharge. The overall mean time required to achieve wound healing was 15±8 weeks.Conclusion: Successful pedal artery revascularization significantly improved wound healing in patients with CLI. Endovascular revascularization is effective to facilitate healing of wounds in CLI and can be performed without significant complications.

Percutaneous Deep Foot Vein Arterialization IVUS-Guided in No-Option Critical Limb Ischemia Diabetic Patients.

To report our clinical experience with IVUS-guided percutaneous deep vein arterialization (pDVA) to treat chronic critical limb ischemia (cCLI) patients with no-endovascular or surgical options approach due to creation of an arteriovenous fistula (AVF). In a 2 years period, 14 no-option cCLI patients were treated with percutaneous deep vein arterialization (pDVA) by creating an AVF with a IVUS-guided system between posterior tibial artery and its satellite deep vein. Technical success was defined as successful AVF creation and venous perfusion of the wound site. Patients' characteristics, procedure details, mortality and wound outcomes were assessed prospectively. Successful pDVA was successfully performed in all patients (mean age 82 years) without any procedural complications. Clinical improvement was achieved in all patients with resolution of rest pain, tissue formation of granulation tissue or both; only 3 major amputations were performed within the study period with a limb salvage rate of 78%. Median wound healing time was 4.8 months. pDVA is a safe and feasible revascularization technique alternative in no-option cCLI patients.

Peripheral Arterial Disease in Persons with Diabetic Foot Ulceration: a Current Comprehensive Overview.

In developed countries, the prevalence of persons with diabetes and peripheral arterial disease (PAD) is approximately 50%. The presence of PAD is associated with non-healing ulcers, major amputation, cardiovascular morbidity, and mortality. It is estimated that persons with diabetes, foot ulceration and PAD have 50% of 5-years mortality rate. Therefore, subjects with ischemic diabetic foot ulcers (DFUs) should be considered a special group of patients with specific clinical characteristics, general health status and prognosis. In persons with ischemic DFUs, an early diagnosis and treatment are mandatory to reduce the risk of worse outcomes such as major amputation. Revascularization of occluded lower extremity arteries is the main treatment to restore blood flow in the foot and promote wound healing. Nonetheless, there are several unmet needs in the management of diabetic subjects with PAD and foot ulceration as medical therapy, diagnostic criteria and indications for revascularization, revascularization strategy and technical approach as well as the management of no-option critical limb ischemia patients. It is a common opinion that there is an evolution of PAD features in diabetic persons, which seems to present a more aggressive pattern. This may be related to the frequent presence of concomitant comorbidities such as renal failure which could influence the characteristics of atherosclerotic plaques and their distribution. The aim of this review is to commence a complete overview and state of the art in the treatment of patients with diabetes, PAD, and foot ulceration and to describe the current challenges and future perspectives.

Heterogeneity of Age and Its Associated Features in Patients with Critical Limb Ischemia.

Aim: Critical limb ischemia (CLI) has a wide age distribution. We aimed here to reveal age-associated clinical features in CLI patients.Materials and Methods: We analyzed 531 Japanese CLI patients referred to vascular centers. The three-year mortality risk by age was compared to that for the Japanese nationals, derived from Japan’s national life table data. Clinical characteristics associated with age in CLI patients were also explored.Results: Mean age was 73±10 years. Whereas 27.9% were aged ≥80 years, 19.2% were aged <65 years. Mortality risk was increased with age, but its risk ratio relative to the same-aged nationals was higher in younger patients. Incidence of major amputation was higher in a younger population. Receiving welfare, smoking, increased body mass index, diabetes with hemoglobin A1c ≥7.0%, non-high density lipoprotein cholesterol ≥190 mg/dL, renal failure, and the Wound, Ischemia, and foot Infection classification stage 4 were associated with younger age, whereas non-ambulation and institutionalization were associated with older age.Conclusion: Patients aged <65 years, belonging to the working-age population, reached almost one fifth of the CLI population. Younger patients had a lower mortality risk in the population, but had a higher risk ratio relative to the same-aged nationals. Socioeconomic disadvantage, poor cardiovascular risk control, and wound severity were associated with younger age.

Characteristics and outcomes of patients with peripheral artery disease undergoing endovascular revascularization: A community hospital perspective.

There are limited data on outcomes for patients with peripheral artery disease undergoing endovascular revascularization by multi-disciplinary teams in a community hospital setting. From January 2015 through December 2015, we assembled a multi-disciplinary program comprised of cardiologists, surgeons, radiologists, nurses, and administrative staff for managing patients with peripheral artery disease undergoing endovascular revascularization. Demographic, procedural, and outcomes data were collected with use of a template from the Society for Vascular Surgery Vascular Quality Initiative database. We compared characteristics and outcomes of patients with intermittent claudication and critical limb ischemia. We used Kaplan-Meier methods to estimate the rate of overall survival and freedom from rehospitalization between groups. After excluding patients with acute limb ischemia (n = 5), peripheral intervention to the upper extremity (n = 6), or abdominal aorta (n = 11), there were 82 patients in the study cohort; 45 had intermittent claudication and 37 had critical limb ischemia. Baseline and procedural characteristics were similar between groups, although critical limb ischemia patients were more likely to have hyperlipidemia (75.7% vs. 53.3%, P = .42). Procedural success was achieved in 91.3% of cases. Actionable access site bleeding occurred in 2.4% of patients. High rates of aspirin (91.5%) and statin (87.8%) were noted at discharge. After two years of post endovascular revascularization, survival was 57.5% for critical limb ischemia patients and 94.4% for intermittent claudication patients (P < .001). Freedom from rehospitalization was 32.7% for critical limb ischemia patients and 83.5% for intermittent claudication patients (P < .001). We found that favorable outcomes may be achieved with a multi-disciplinary peripheral artery disease program at community hospitals. The incorporation of quality improvement practices may further help to develop standardized and regionalized approaches to care delivery for patients with peripheral artery disease.

PFKFB3-mediated glycolysis rescues myopathic outcomes in the ischemic limb.

Compromised muscle mitochondrial metabolism is a hallmark of peripheral arterial disease, especially in patients with the most severe clinical manifestation — critical limb ischemia (CLI). We asked whether inflexibility in metabolism is critical for the development of myopathy in ischemic limb muscles. Using Polg mtDNA mutator (D257A) mice, we reveal remarkable protection from hind limb ischemia (HLI) due to a unique and beneficial adaptive enhancement of glycolytic metabolism and elevated ischemic muscle PFKFB3. Similar to the relationship between mitochondria from CLI and claudicating patient muscles, BALB/c muscle mitochondria are uniquely dysfunctional after HLI onset as compared with the C57BL/6 (BL6) parental strain. AAV-mediated overexpression of PFKFB3 in BALB/c limb muscles improved muscle contractile function and limb blood flow following HLI. Enrichment analysis of RNA sequencing data on muscle from CLI patients revealed a unique deficit in the glucose metabolism Reactome. Muscles from these patients express lower PFKFB3 protein, and their muscle progenitor cells possess decreased glycolytic flux capacity in vitro. Here, we show supplementary glycolytic flux as sufficient to protect against ischemic myopathy in instances where reduced blood flow–related mitochondrial function is compromised preclinically. Additionally, our data reveal reduced glycolytic flux as a common characteristic of the failing CLI patient limb skeletal muscle.

Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease

BackgroundMalnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization. MethodsWe explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values. ResultsIn addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log–rank p < 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log–rank p < 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96–0.98, p < 0.001] and IC (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001). ConclusionsPreprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.