Atherosclerosis-related coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. This requires effective primary and secondary prevention in reducing the complications related to CAD; the regression or stabilization of the pathology remains the mainstay of treatment. Statins have proved to be the most effective treatment in reducing adverse effects, but there are limitations related to the administration and achievement of effective doses as well as side effects due to the lack of target-related molecular specificity. The implemented technological steps are polymers and nanoparticles for the administration of statins, as it has been seen how the conjugation of drug delivery systems (DDSs) with statins increases bioavailability by circumventing the hepatic–renal filter and increases the related target specificity, enhancing their action and decreasing side effects. Reduction of endothelial dysfunction, reduced intimal hyperplasia, reduced ischemia–reperfusion injury, cardiac regeneration, positive remodeling in the extracellular matrix, reduced neointimal growth, and increased reendothelialization are all drug-related effects of statins enhanced by binding with DDSs. Recent preclinical studies demonstrate how the effect of statins stimulates the differentiation of endogenous cardiac stem cells. Poly-lactic-co-glycolic acid (PLGA) seems to be the most promising DDS as it succeeds more than the others in enhancing the effect of the bound drug. This review intends to summarize the current evidence on polymers and nanoparticles for statin delivery in the field of cardiovascular disease, trying to shed light on this topic and identify new avenues for future studies.

Peripheral arterial disease (PAD) is an increasingly pathological condition that commonly affects the femoropopliteal arteries. The current fashionable treatment is percutaneous transluminal angioplasty (PTA), often with stenting. However, the in-stent restenosis (ISR) rate after the stenting of the femoropopliteal (FP) district remains high. Many techniques have been proposed for the treatment of femoropopliteal ISR, such as intravascular brachytherapy, laser atherectomy, second stenting and drug-coated balloons angioplasty (DCB). DCB showed a significantly lower rate of restenosis and target lesions revascularization (TLR) compared to conventional PTA. However, further studies and multi-center RCTs with dedicated long-term follow-up are needed to verify the true efficiency of this approach. Nowadays, the correlation between PAD and inflammation biomarkers is well known. Multiple studies have shown that proinflammatory markers (such as C-reactive proteins) and the high plasma levels of microRNA could predict the outcomes after stent placement. In particular, circulating microRNA-320a, microRNA-3937, microRNA-642a-3p and microRNA-572 appear to hold promise in diagnosing ISR in patients with PAD, but also as predictors of stent patency. This narrative review intends to summarize the current knowledge on the value of circulating biomarkers as predictors of ISR and to foster the scientific debate on the advantages of using DCB in the treatment of ISR in the FP district.

Surgical bypass is the gold standard treatment in patients affected by chronic limb-threatening ischemia in advanced GLASS stages, according to the Global Vascular Guidelines. For patients in whom an autologous graft is not available, a prosthesis could be used with the adjunct of a distal arteriovenous fistula interposition. The aim of this study was to examine the long-term results of below-the-knee surgical revascularization using a prosthesis with the distal adjunct mentioned above. From 2010 to 2020, we performed 159 lower limb below-the-knee surgical revascularizations using a prosthesis with the creation of an arteriovenous fistula interposition on the distal anastomosis. The GLASS stage was 3 in 100% of patients. The primary patency rates were as follows: 86.7% at 1 year, 57.2% at 3 years, and 12.6% at 5 years. The graft thrombosis rates were 17.4% at 1 year, 42.1% at 3 years, and 64.5% at 5 years. The amputation-free survival rates were 79% at 1 year, 76% at 3 years, and 64% at 5 years. PTFE prosthetic bypass for below-the-knee arteries using an arteriovenous fistula interposition is a good solution in patients without an autologous conduit. This technique offers reasonable graft patency and limb salvage rates.

Background: The surgical treatment of chronic limb-threatening ischemia and optimal conduit choice are extensively debated. The presence of suboptimal autologous material, such as varicosities or venous aneurysms, might impair long-term outcomes. Therefore, kink-resistant external supports have been advocated in the recent literature to improve the conduit quality and outcomes. This study analyzes the FRAME external support in venous ectasic grafts in patients with chronic limb-threatening ischemia. Methods: From September 2017 to September 2023, a total of sixteen patients underwent CLTI surgery with FRAME external support for venous grafts. The inclusion criteria for FRAME applications were varicose or ectasic autologous material with a diameter ≥ 4.5 and ≤ 8 mm in an isolated segment or in the entire vein and a higher risk of bypass extrinsic compression (e.g., extra-anatomical venous bypass course). Results: Technical success and intraoperative patency were achieved in all cases. At 30 days, the limb salvage and survival rates were 100%. The primary bypass patency was 93.7% due to an early graft occlusion. No graft infection was registered. In one case, dehiscence of the surgical wound was treated by surgical debridement and antibiotic therapy. Minor amputation was required in four patients. Over a median follow-up of 32 months, two occlusions were observed; one was treated with reoperation and the other with major amputation. The primary patency was 68.7% and the assisted primary patency was 75%. Limb salvage rates observed during the entire follow-up period were 87.5%. No graft infections or dilatation of the reinforced veins were registered. Conclusions: For patients with CLTI undergoing infrainguinal bypass, satisfactory results in terms of patency and limb salvage rates were achieved using the autologous venous material, even if ectasic or varicose, with the vascular external support FRAME.

Objective: To report early and mid-term outcomes of the arterialization of the deep venous system in no-option critical limb-threatening ischemia (CLTI) using duplex ultrasound and angiographic evaluation to improve limb perfusion. Methods: A single-center prospective study of patients with no-option CLTI treated with hybrid surgical arterialization of the deep venous circulation and staged endovascular embolization of the venous collateral. Embolization was performed using a controlled-release spiral, within two weeks after bypass surgery. Patients were assessed for clinical status, wound healing, median transcutaneous partial pressure of O₂ (TcPO₂), and post-operative duplex ultrasound evaluating peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) to assess foot perfusion and bypass features. Primary endpoint analysis was primary technical success, limb salvage, patency rates, and clinical improvement. Secondary endpoints were 30-day and long-term mortality, major cardiovascular events (MACE), including myocardial infarction or stroke, and serious adverse events (SAE). Results: Five patients with no-option CLTI were treated at our center using the hybrid deep vein arterialization technique. Clinical stage was grade 3 in one patient and grade 4 in the remaining four. Mean age was 65.8 years (range 49–76 years), and two patients were affected by Buerger’s disease. Primary technical success was achieved in all patients, and all the bypasses were patent at the angiographic examination. At 30-day and at average follow-up of 9.8 months (range 2–24 months), mortality, major cardiovascular events (MACE), and serious adverse events (SAE) were not reported, with a primary patency and limb salvage rates of 100%. Three patients required minor amputation. Clinical improvement was demonstrated in all patients with granulation, resolution of rest pain, or both. Median TcPO₂ values rose from 10 mm Hg (range 4–25) before the procedure to 35 (range 31–57) after surgery, and to 59 mm Hg (range 50–76) after the staged endovascular procedure. Conclusions: In our initial experience, the arterialization of the deep venous circulation, with subsequent selective embolization of the venous escape routes from the foot, seems a feasible and effective solution for limb salvage in patients with no-option CLTI and those in the advanced wound, ischemia, and foot infection (WIfI) clinical stage.

Deep vein arterialization (DVA) is a therapeutic option in “no option” for revascularization chronic limb-threatening ischemia patients, creating an arteriovenous bypass between a proximal artery and a distal deep venous target at the ankle. Imaging plays a crucial role in peripheral arterial disease (PAD) patient management. We present the case of a 71-year-old PAD patient (Rutherford class 5) with focal gangrene of the first and second toes of the right foot, who was admitted to the vascular surgery department to undergo revascularization surgery by femoro-tibial artery bypass. During surgery a DVA was performed because of an unsatisfactory distal artery target. The post-operative computed tomography angiography showed the saphenous graft patency and opacification of distal foot veins. Subsequent angiography documented the presence of a large venous collateral, responsible for extensive early wash-out to leg venous vessels, which was then embolized. After two months, the patient underwent amputation of the right first and second necrotic toes at the level of the metatarsophalangeal joints. The post-operative course was excellent, with disappearance of pain at rest and good trophism of the surgical wound.