Predictors of outcome in diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome. METHODS: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014). CONCLUSIONS: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group.

Single Intraosseous Simvastatin Application Induces Endothelial Progenitor Cell Mobilization and Therapeutic Angiogenesis in a Diabetic Hindlimb Ischemia Rat Model.

BACKGROUND: Endothelial progenitor cells have shown the ability to enhance neovascularization. In this study, the authors tested whether intraosseous delivery of simvastatin could mobilize endothelial progenitor cells and enhance recovery in a hindlimb ischemia model. METHODS: There are eight groups of rats in this study: normal control; type 1 diabetes mellitus control group control without drug intervention; and type 1 diabetes mellitus rats that randomly received intraosseous simvastatin (0, 0.5, or 1 mg) or oral simvastatin administration (0, 20, or 400 mg). All type 1 diabetes mellitus rats had induced hindlimb ischemia. The number of endothelial progenitor cells in peripheral blood, and serum markers, were detected. The recovery of blood flow at 21 days after treatment was used as the main outcome. RESULTS: The authors demonstrated that endothelial progenitor cell mobilization was increased in the simvastatin 0.5- and 1-mg groups compared with the type 1 diabetes mellitus control and simvastatin 0-mg groups at 1, 2, and 3 weeks. Serum vascular endothelial growth factor levels were significantly increased at 2 weeks in the simvastatin 0.5- and 1-mg groups, in addition to the increase of the blood flow and the gastrocnemius weight at 3 weeks. Similar increase can also been seen in simvastatin 400 mg orally but not in simvastatin 20 mg orally. CONCLUSION: These findings demonstrate that a single intraosseous administration of simvastatin mobilized endothelial progenitor cells at a dose one-hundredth of the required daily oral dose in rats, and this potent mobilization of endothelial progenitor cells markedly improved diabetic limb ischemia by means of neovascularization.

Safety and Effectiveness of Paclitaxel Drug-Coated Devices in Peripheral Artery Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. OBJECTIVES: This study assessed DCD safety and effectiveness in LER for PAD. METHODS: VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional hazards models. RESULTS: Among 4,316 patients who underwent LER, 3,478 (80.6%) were treated for claudication, and 1,342 (31.1%) received DCDs. Median follow-up was 31 months, vital status was ascertained in 99.6% of patients, and there were 394 deaths. After weighting, DCDs were not associated with mortality (HR: 0.95; 95% CI: 0.83-1.09) or MALE (HR: 1.08; 95% CI: 0.90-1.30) but were associated with reduced UILR (3-year Kaplan-Meier: 21.5% vs 24.6%; HR: 0.84; 95% CI: 0.76-0.92). Irrespective of DCD use, consistent benefit of rivaroxaban for composite cardiovascular and limb events (Pinteraction = 0.88) and safety of rivaroxaban with respect to bleeding (Pinteraction = 0.57) were observed. CONCLUSIONS: In >4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216).

Contemporary Medical Management of Peripheral Artery Disease.

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. Modifiable risk factors including cigarette smoking, dyslipidemia, diabetes, poor diet quality, obesity, and physical inactivity, along with underlying genetic factors contribute to lower extremity atherosclerosis. Patients with PAD often have coexistent coronary or cerebrovascular disease, and increased likelihood of major adverse cardiovascular events, including myocardial infarction, stroke and cardiovascular death. Patients with PAD often have reduced walking capacity and are at risk of acute and chronic critical limb ischemia leading to major adverse limb events, such as peripheral revascularization or amputation. The presence of polyvascular disease identifies the highest risk patient group for major adverse cardiovascular events, and patients with prior critical limb ischemia, prior lower extremity revascularization, or amputation have a heightened risk of major adverse limb events. Medical therapies have demonstrated efficacy in reducing the risk of major adverse cardiovascular events and major adverse limb events, and improving function in patients with PAD by modulating key disease determining pathways including inflammation, vascular dysfunction, and metabolic disturbances. Treatment with guideline-recommended therapies, including smoking cessation, lipid lowering drugs, optimal glucose control, and antithrombotic medications lowers the incidence of major adverse cardiovascular events and major adverse limb events. Exercise training and cilostazol improve walking capacity. The heterogeneity of risk profile in patients with PAD supports a personalized approach, with consideration of treatment intensification in those at high risk of adverse events. This review highlights the medical therapies currently available to improve outcomes in patients with PAD.

Isquemia arterial aguda de membros superiores em pacientes diagnosticados com COVID-19: série de casos / Acute upper limb arterial ischemia in patients diagnosed with COVID-19: case series

Resumo A infecção pelo coronavírus 2 causador da síndrome respiratória aguda grave (SARS-CoV-2) em humanos foi detectada pela primeira vez em Wuhan, na China, em 2019 e dispersada mundialmente ao longo de 2020. As diferentes manifestações clínicas, com amplo espectro de apresentação, desde infecções assintomáticas até formas graves que podem levar a óbito, são desafiadoras. Este trabalho objetiva descrever uma série de quatro casos de isquemia arterial aguda dos membros superiores em pacientes diagnosticados com COVID-19, os quais foram manejados clinicamente com anticoagulação, antiagregação plaquetária e uso de prostanoides. Dois pacientes receberam alta hospitalar com regressão e delimitação da área isquêmica, sem necessidade de intervenção cirúrgica, e dois pacientes faleceram em decorrência de complicações pulmonares. Uma adequada compreensão da fisiopatologia dessa doença pode favorecer um melhor manejo clínico de suas complicações.

Abstract Infection by coronavirus 2, cause of the severe acute respiratory syndrome (SARS-CoV-2) in humans, was detected for the first time in Wuhan, China, in 2019, and spread globally over the course of 2020. Its different clinical manifestations are challenging, with a wide spectrum of presentations, ranging from asymptomatic infections to severe forms that can result in death. The objective of this study is to describe a series of four cases of acute arterial ischemia involving the upper limbs in patients diagnosed with COVID-19, which were managed clinically with anticoagulation, platelet antiaggregation, and prostanoids. Two patients were discharged from hospital with regression and delimitation of the ischemic zone, without needing surgical intervention, while two patients died from pulmonary complications. Adequate understanding of the pathophysiology of this disease could support better clinical management of its complications.

Alprostadil associated with low molecular weight heparin to treat limb ischemia caused by SARS-CoV2 / Alprostadil associado a heparina de baixo peso molecular para o tratamento da isquemia de membros causada por SARS-CoV2

Abstract The current coronavirus pandemic has already taken a great toll globally, causing massive morbidity and mortality. One of its severe forms is a thrombophilic state that can damage several systems. This article reports the case of 60-year-old female patient who presented with mild flu symptoms, which turned out to be a SARS-CoV2 infection, and ended up developing arterial thrombosis with limb ischemia in a private care hospital in Sorocaba, São Paulo, Brazil. Considering this progression, we decided to intervene with low molecular weight heparin and Alprostadil, achieving a good clinical outcome. Our description aims to identify key points and clinical signs that offer evidence of the therapeutic window and a treatment option for coagulatory presentations of COVID-19.

Resumo A atual pandemia de coronavírus já gerou danos profundos ao redor do mundo, causando grande quantidade de morbidades e mortes. Uma das manifestações das formas graves da doença é o estado trombofílico, que pode provocar danos em vários sistemas. Este artigo relata o caso de uma paciente do sexo feminino, 60 anos de idade, que foi internada em um serviço hospitalar privado com sintomas gripais inespecíficos leves, mas que progrediu com trombose arterial e isquemia de membros causada pelo SARS-CoV2. Devido à essa evolução, foi optada pela administração concomitante de heparina de baixo peso molecular e Alprostadil, com bom desfecho clínico. Nossa descrição objetiva identificar pontos-chave e sinais clínicos que evidenciem essa janela terapêutica, bem como uma opção de tratamento para as apresentações coagulatórias da COVID-19.