Medical adjunctive therapy for patients with chronic limb-threatening ischemia:a systematic review

INTRODUCTION: To systematically review the literature on medical adjunctive therapy for patients with chronic limb-threatening ischemia (CLTI). EVIDENCE ACQUISITION: MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched for studies published between January 1, 2009, and June 1, 2019. Articles that studied medical treatment of CLTI patients and reported clinical outcomes were eligible. Main exclusion criteria were case reports <20 patients, incorrect publication type, and CLTI caused by Buerger disease. The primary end point was major amputation (above the ankle) in studies with a follow-up of ≥6 months. Secondary end points were other clinical end points such as death and wound healing. Study quality was assessed according to the Downs and Black checklist. EVIDENCE SYNTHESIS: Included were 42 articles; 4 focused on antiplatelet therapy, 5 on antihypertensive medication, 6 on lipid-lowering therapy, 16 on stem cell therapy, 3 on growth factors, 5 on prostanoids, and 1 study each on cilostazol, glucose-lowering therapy, spinal cord stimulation, sulodexide, and hemodilution. Calcium channel blockers, iloprost, cilostazol, and hemodilution showed significant improvement of limb salvage, but data are limited. Stem cell therapy showed no significant improvement of limb salvage but could potentially improve wound healing. Antiplatelets, antihypertensives, and statins showed significantly lower cardiovascular events rates but not evident lower major amputation rates. The quality of the studies was fair to good. CONCLUSIONS: Certain medical therapies serve to improve limb salvage next to revascularization in CLTI patients, whereas others are important in secondary prevention. Because high quality evidence is limited, further research is needed

Development of a Prediction Model for the Occurrence of Stenosis or Occlusion after Percutaneous Deep Venous Arterialization

Percutaneous deep venous arterialization (pDVA) is a promising treatment option in patients with chronic limb-threatening ischemia. Stenosis and occlusions, which are the Achilles' heel of every revascularization procedure, can be treated when detected early. However, frequent monitoring after pDVA is required because when stenosis or occlusions develop is unknown. Therefore, patients currently need to visit the hospital every 2 weeks for surveillance, which can be burdensome. Accordingly, we aimed to develop a model that can predict future stenosis or occlusions in patients after pDVA to be able to create tailor-made follow-up protocols. The data set included 343 peak systolic velocity and 335 volume flow measurements of 23 patients. A stenosis or occlusion developed in 17 patients, and 6 patients remained lesion-free. A statistically significant increase in the risk of stenosis or occlusion was found when duplex ultrasound values decreased 20% within 1 month. The prediction model was also able to estimate a patient-specific risk of future stenosis or occlusions. This is promising for the possibility of reducing the frequency of follow-up visits for low-risk patients and increasing the frequency for high-risk patients. These observations are the starting point for individual surveillance programs in post-pDVA patients. Future studies with a larger cohort are necessary for validation of this model

Організаційно-економічні передумови та особливості формування сфери фінансових послуг в економічній системі

Glucocorticoids (GCs) are widely used anti-inflammatory drugs well known to cause many adverse effects. Still, there is a dearth of data on the long-term cardiovascular effects of GCs in patients with established cardiovascular disease and the effect on atherosclerotic plaque composition. A total of 1894 patients who underwent carotid endarterectomy (CEA), of whom 40 patients received systemic GCs, were included in the Athero-Express Biobank. Atherosclerotic plaque samples and peripheral blood samples were obtained during CEA. Cardiovascular events during 3 years of follow-up were investigated using Cox regression modeling to adjust for possible confounding. Atherosclerotic plaque composition was examined using immunohistochemical staining. Use of GCs at inclusion was associated with markedly increased incidences of ischemic stroke (15.2% vs. 5.9%), composite events (48.5% vs. 26.9%), and cardiovascular death (21.2% vs. 5.7%), as well as an increased risk of cardiovascular death (hazards ratio 2.7, 95% confidence interval, 1.1-6.7) and all-cause death (hazards ratio 2.3, 95% confidence interval, 1.1-4.8) after 2.6 years of follow-up. None of the histological features of atherosclerotic plaques were significantly different in patients using GCs. After CEA, the use of systemic GCs is independently associated with an increased incidence of cardiovascular events and an increased risk of cardiovascular and all-cause death, but not atherosclerotic plaque compositio

Long-Term Stroke Risk in Patients With New Ischemic Brain Lesions on MRI After Carotid Revascularization

BACKGROUND: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. METHODS: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). RESULTS: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. CONCLUSIONS: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ISRCTN 25337470.</p

Clinical Response to Procedural Stroke Following Carotid Endarterectomy:A Delphi Consensus Study

Objective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree. Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 – 9 (most adequate response) was given, IQR ≤ 2. Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%). Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended

Atherosclerotic Plaque Biomarkers: Beyond the Horizon of the Vulnerable Plaque

Cardiovascular disease (CVD) is the number one cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic inflammatory disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability, leading to thrombus formation and cardiovascular events. Due to the burden of cardiovascular disease, identification of patients at risk for cardiovascular events and treatment stratification is needed. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Imaging modalities have focused on the characteristics of the vulnerable plaque. However, it has become evident that not all so-called vulnerable plaques lead to rupture and subsequent thrombosis. The latter obviously limits the positive predictive value for imaging assessment of plaques and patients at risk. Serum biomarkers have also been studied extensively, but have very limited application in a clinical setting for risk stratification. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future cardiovascular events, also in other territories of the vascular tree. Results look promising and plaque markers can be used to develop imaging modalities to identify patients at risk, or to monitor treatment effect. Plaque biomarker studies do not challenge the definition of the vulnerable plaque, but use its concept in favor of prediction improvement for vascular patients