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.
The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35–6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07–5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17–4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.
Despite cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) being the current gold standard for non-invasive myocardial characterization and fibrosis quantification, its accessibility is limited, particularly in acute settings and in certain patient populations with contraindications to magnetic resonance imaging. Late iodine enhancement (LIE) in computed tomography (CT) imaging has emerged as a potential alternative, capitalizing on the similarities in the contrast kinetics between gadolinium and iodinated contrast agents. Studies have investigated LIE-CT’s effectiveness in myocardial infarction (MI) detection, revealing promising outcomes alongside some disparities compared to LGE-CMR. LIE-CT also proves beneficial in diagnosing non-ischemic heart diseases such as myocarditis, hypertrophic cardiomyopathy, and sarcoidosis. While LIE-CT demonstrates good accuracy in detecting certain myocardial pathologies, including acute MI and chronic fibrotic changes, it has limitations, such as the inability to detect diffuse myocardial enhancement. Nonetheless, thanks to the availability of optimized protocols with minimal radiation doses and contrast medium administration, integrating LIE-CT into cardiac CT protocols could enhance its clinical utility, particularly in acute settings, providing valuable prognostic and management insights across a spectrum of cardiac ischemic and non-ischemic conditions.
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.
The increasing interest in tricuspid regurgitation (TR) is due to the deep link between mortality and the severity of TR, as well as the limited application of surgical solutions in a setting marked by high in-hospital mortality, attributed to the late presentation of the disease. This delay in intervention is likely associated with a limited understanding of valvular and ventricular anatomy as well as the pathophysiology of the disease, leading to an underestimation of TR severity. With the rapid development of transcatheter solutions showing early safety and efficacy, there is a growing necessity to accurately understand and diagnose the valvular disease process to determine suitable management strategies. This review will outline the normal and pathological anatomy of the tricuspid valve, classify the anatomical substrates of TR, and present new risk stratification methods to determine the appropriate timing for both medical and surgical treatment.
Median sternotomy and steel wires for sternal closure are the standard approach for cardiac surgery. An incomplete repair associated with chest wall motion, especially in the presence of predisposing factors, can lead to life-threatening deep sternal wound infection, also known as mediastinitis, in 2–5% of cases. Despite current antibiotic and surgical treatments, mediastinitis is associated with a 10–40% mortality rate and a significant increase in morbidity and hospital stay. High mortality and difficult treatment appear to be due to bacterial biofilm, a self-produced extracellular polymeric product that incorporates host tissue and is responsible for the failure of immune defenses and standard antimicrobial therapies. Nanostructures are an effective strategy to enhance the healing process, as they establish a favorable environment for the neosynthesis of the extracellular matrix, supporting tissue development. Synthetic polymers have been proven to exhibit suitable biodegradable and mechanical properties, and their biofunctionalization to enhance cell attachment and interaction with the extracellular matrix is being widely investigated. The use of antibiotic treatments suspended in poly-D,L-lactide and polyethylene oxide and electrospun into nanofibers, or in sponges, has been shown to inhibit bacterial biofilm production. Additionally, growth factors can be incorporated into 3D bioresorbable scaffolds with the aim of constituting a structural and biological framework to organize and expedite the healing process. Therefore, these combined approaches may change the treatment of mediastinitis in the near future.