Different Oxidative Stress and Inflammation Patterns of Diseased Left Anterior Descending Coronary Artery versus Internal Thoracic Artery.

BACKGROUND: Oxidative stress and inflammation are typically implied in atherosclerosis pathogenesis and progression, especially in coronary artery disease (CAD). Our objective was to investigate the oxidative stress and inflammation burden directly associated with atherosclerotic plaque in patients with stable coronary disease undergoing coronary artery bypass graft (CABG) surgery. Specifically, markers of oxidative stress and inflammation were compared in blood samples obtained from the atherosclerotic left anterior descending artery (LAD) and blood samples obtained from the healthy left internal thoracic artery (LITA), used as a bypass graft, within the same patient. METHODS: Twenty patients scheduled for off-pump CABG were enrolled. Blood samples were collected from the LITA below anastomosis and the LAD below the stenosis. Samples were analysed for oxidative stress (sNOXdp, H2O2, NO) and inflammation markers (TNFα, IL-6, IL-1ß, IL-10). RESULTS: The analysis showed a significant increase in oxidative stress burden in the LAD as compared to LITA, as indicated by higher sNOX2-dp and H2O2 levels and lower NO levels (p < 0.01). Also, pro-inflammatory cytokines were increased in the LAD as compared to the LITA, as indicated by higher TNFα and IL-6 amounts (p < 0.01). On the other hand, no significant differences could be seen regarding IL-1ß and IL-10 levels between the two groups. CONCLUSIONS: The oxidative stress and inflammatory burden are specifically enhanced in the LAD artery of stable coronary patients compared to systemic blood from the LITA of stable coronary patients.

Invasive and conservative management of elderly patients presenting with acute coronary syndrome: A meta-analysis of randomized controlled trials and adjusted observational studies.

BACKGROUND: Elderly patients are often under-represented in studies about coronary revascularization in acute coronary syndromes (ACS) and undertreated in clinical practice. We sought to evaluate differences in outcomes between an initial invasive or conservative strategy in this subset of patients, METHODS: The analysis was performed following PRISMA guidelines. Randomized controlled trials (RCTs) and adjusted observational studies comparing an invasive and conservative strategy in old patients with ACS were systematically identified. Random or fixed effect model was used accordingly to heterogeneity testing results. Short-term mortality was the primary outcome. 30-day and longer-term re-infarction, MACE and all-cause mortality were secondary endpoints. Sensitivity analysis including RCTs only were performed for the primary endpoint and 1 year mortality and another analysis, stratifying NSTEMI and STEMI studies, was performed for short-term mortality. RESULTS: Invasive management was associated with lower short and long-term mortality (30 days OR 0.64, 95 % CI 0.54-0.76, p < 0.001; 1 year HR 0.60, 95 % CI 0.52-0.78, p < 0.001; Long-term HR 0.62, 95 % CI 0.55-0.71, p < 0.001) compared to a conservative strategy. In the short-term follow-up, the benefit was preserved when differentiating for NSTEMI or STEMI studies but not when considering only RCTs. Major bleedings were more frequent in the invasive group (30 days OR 1.61, 95 % CI 1.39-1.87, p < 0.001). The mean difference in length of stay was not significantly different between the two strategies (mean difference in days 0.14, 95 % CI -0.79 to 1.06, p = 0.77). CONCLUSION: An initial invasive strategy might lead to reduced short and long-term mortality in elderly patients presenting with acute coronary syndrome but it is associated with increased bleeding events rate. No difference in hospital stay length was observed. Results were mainly driven by non-randomized studies.

Exposure to serum from exclusive heated tobacco product smokers induces mTOR activation and fibrotic features in human cardiac stromal cells.

Chronic smokers have increased risk of fibrosis-related atrial fibrillation. The use of heated-tobacco products (HTPs) is increasing exponentially, and their health impact is still uncertain. We aim to investigate the effects of circulating molecules in exclusive HTP chronic smokers on the fibrotic behavior of human atrial cardiac stromal cells (CSCs). CSCs were isolated from atrial tissue of elective cardiac surgery patients, and exposed to serum lots from young healthy subjects, stratified in exclusive HTP smokers, tobacco combustion cigarette (TCC) smokers, or nonsmokers (NS). CSCs treated with TCC serum displayed impaired migration and increased expression of pro-inflammatory cytokines. Cells cultured with HTP serum showed increased levels of pro-fibrotic markers, and reduced expression of connexin-43. Both TCC and HTP sera increased collagen release and reduced secretion of angiogenic protective factors from CSCs, compared to NS serum. Paracrine support to tube-formation by endothelial cells and to viability of cardiomyocytes was significantly impaired. Treatment with sera of both smokers groups impaired H2O2/NO release balance by CSCs and reduced early phosphorylation of several pathways compared to NS serum, leading to mTOR activation. Cotreatment with rapamycin was able to reduce mTOR phosphorylation and differentiation into aSMA-positive myofibroblasts in CSCs exposed to TCC and HTP sera. In conclusion, the circulating molecules in the serum of chronic exclusive HTP smokers induce fibrotic behavior in CSCs through activation of the mTOR pathway, and reduce their beneficial paracrine effects on endothelial cells and cardiomyocytes. These results point to a potential risk for cardiac fibrosis in chronic HTP users.

Prediction of 30-day mortality after surgery for infective endocarditis using risk scores: Insights from a European multicenter comparative validation study.

BACKGROUND: It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS: Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and 5 specific risk scores for early mortality after surgery for IE-(1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intracardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intracardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa)-was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS: A total of 1,012 patients from 5 European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs 0.693 or less, P = .01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION: EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than 5 established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.

Transcatheter Aortic Valve Replacement in Low Surgical Risk Patients: An Updated Metanalysis of Extended Follow-Up Randomized Controlled Trials.

The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients who underwent TAVR or SAVR. We calculated odds ratio (OR) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for permanent pacemaker implantation and paravalvular leaks. Three randomized controlled trials were included with a total of 2,611 low surgical risk patients (Society of Thoracic Surgeons score <4%). Compared with SAVR, the TAVR group had similar rates of all-cause mortality (OR 0.94,95% CI 0.65 to 1.37, p = 0.75) and disabling stroke (OR 0.84, 95% CI 0.52 to 1.36, p = 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95% CI 0.67 to 1.38, p = 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p = 0.31), valve thrombosis (OR 3.11, 95% CI 0.29 to 33.47, p = 0.35), endocarditis (OR 0.71,95% CI 0.35 to 1.48, p = 0.36), aortic valve reintervention (OR 0.93, 95% CI 0.52 to 1.66, p = 0.80), and rehospitalization (OR 0.80, 95% CI 0.52 to 1.02, p = 0.07) compared with SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95% CI 4.18 to 16.14, p <0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95% CI 0.17 to 0.30, p <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95% CI 0.88 to 1.97, p = 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm2/m2, 95% CI 0.05 to 0.15, p = 0.0001), but similar transvalvular mean gradients (0.60, 95% CI 3.94 to 2.73, p = 0.72). In conclusion, TAVR patients had similar long-term outcomes compared with SAVR, except for an elevated risk of paravalvular leaks in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort.

A Meta-Analysis of Short-Term Outcomes of TAVR versus SAVR in Bicuspid Aortic Valve Stenosis and TAVR Results in Different Bicuspid Valve Anatomies.

BACKGROUND: To provide a comprehensive analysis of the current literature comparing the outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS), with particular attention to BAV morphology in patients undergoing TAVR. METHODS: Following PRISMA guidelines, all relevant articles with no design restrictions from PubMed, CCTR (Cochrane Controlled Trials Register), and Google Scholar were screened for inclusion. Studies were included if they reported clinical endpoints for SAVR and TAVR or, in BAS treated with TAVR, for type 1 and non-type 1 morphology. Odds ratio and Cohen's D were considered as effect size measurements for qualitative and quantitative variables, respectively. RESULTS: A total of eight studies comparing short-term outcomes between SAVR and TAVR and nine studies with outcomes data between type 1 and non-type 1 BAS treated with TAVR were considered for the final analysis. No statistically significant difference was found for what concerns the rates of death, stroke, and acute kidney injury between SAVR and TAVR. In comparison to patients undergoing SAVR, the incidence of PPI (permanent pacemaker implantation) was greater in the TAVR group (OR 0.35, 95% CI 0.15-0.79, p = 0.01), and the frequency of bleeding events was found to be higher among patients undergoing SAVR (OR 4.3, 95% CI 2.9-6.4, p < 0.001). The probabilities of 30-day mortality, stroke, and any bleeding were not significantly affected by bicuspid valve morphology in TAVR patients. PPI or development of new conduction anomalies was found to be more frequent in type 1 anatomies (OR 0.46, 95% CI 0.30-0.70, p <0.001). Mildly lower post-procedural transprothesic gradients were found in patients with type 1 morphology. CONCLUSIONS: In BAS patients, TAVR has comparable short-term outcomes rates with SAVR, but higher PPI rates and lower incidence of bleeding events. In patients undergoing TAVR, type 1 BAS is associated with lower postoperative transvalvular gradients but higher PPI rates and conduction abnormalities.

Vacuum-assisted wound closure with instillation followed by nitinol clips application to treat deep sternal wound infections after cardiac surgery: evolution of a two-step approach.

INTRODUCTION: DSWI, or mediastinitis, is a life-threatening complication following cardiac surgery. Although infrequent, it can cause significant morbidity and mortality, often requires multiple procedures, and increases health care costs. Different treatment approaches have been used. OBJECTIVE: This article compares closed catheter irrigation with the currently used 2-stage approach using a proprietary vacuum-assisted wound closure with instillation system followed by sternal synthesis with nitinol clips. MATERIALS AND METHODS: The records of 34 patients with DSWI who underwent cardiac surgery between January 2012 and December 2020 were retrospectively analyzed. Patients received either closed catheter irrigation or vacuum-assisted wound closure with instillation for decontamination and subsequent closure with pectoralis major flaps (with or without the modified Robicsek technique), or more recently, with nitinol clips. RESULTS: Wound healing was achieved in all patients treated with vacuum-assisted wound closure with instillation. In this group, no patients died and the mean hospital stay was reduced. CONCLUSIONS: These findings suggest that use of vacuum-assisted wound closure with instillation along with nitinol clips for sternal closure decreases mortality and reduces the length of hospital stay, making it a safer, effective, and less invasive technique for the management of DSWI after cardiac surgery.

Acute type A aortic dissection in bicuspid versus tricuspid aortic valve patients: focus on geometrical features of the aorta.

OBJECTIVES: This retrospective observational study aimed to assess the geometrical features, including diameters, length and angulation, of the ascending aorta with bicuspid and tricuspid aortic valve and to identify imaging markers potentially predicting whether aortopathy is likely to evolve chronically or to complicate with acute type A dissection. METHODS: Angio-computed-tomography scans of 354 patients (from 3 centres) with non-dilated (n = 97), aneurysmal (n = 100) or dissected aorta (n = 157) were reviewed. Diameters were measured at root, sinotubular junction, ascending, brachio-cephalic trunk origin; centreline lengths of the root and tubular tract and ascending-arch angle (between the ascending tubular tract axis and the proximal arch axis) were also measured. For 12 dissection patients, pre-dissection scans were available to investigate predisposing aortic geometry. Statistical analysis included: tricuspid versus bicuspid comparisons in each subgroup; univariate and multivariate analyses of the predictors of ascending-arch angle narrowing; and estimation of diagnostic accuracy of the angle parameter. RESULTS: Diameters and lengths were similar between aneurysms and dissections, whereas dissections showed a significant ascending-arch angle narrowing (117 ± 13° in tricuspid, 115 ± 14° in bicuspid) compared to non-dilated and aneurysmal aortas (all P < 0.001). The best angle cut-off to discriminate dissection patients was 131° (96% sensitivity). In patients with a pre-dissection scan, Asc-Arch narrowing was already present before dissection. In non-dissected aortas over-angulation was predicted by root phenotype dilatation both in bicuspid and tricuspid patients. Bicuspid patients with non-dilated aorta showed elongated root (P = 0.027), a feature significantly correlated with Asc-Arch angle narrowing (P = 0.008). CONCLUSIONS: The ascending-arch angle is promising as a risk marker for dissection to be used along with diameter. Its narrowing seems to be associated with elongation of the root, a feature that bicuspid patients can show even without significant dilatation. Root phenotype aortopathy may be at higher risk also with tricuspid aortic valve.

Modified Risk Tobacco Products and Cardiovascular Repair: Still Very "Smoky".

Smoking habits represent a cardiovascular risk factor with a tremendous impact on health. Other than damaging differentiated and functional cells of the cardiovascular system, they also negatively affect reparative mechanisms, such as those involved in cardiac fibrosis and in endothelial progenitor cell (EPC) activation. In recent years, alternative smoking devices, dubbed modified tobacco risk products (MRPs), have been introduced, but their precise impact on human health is still under evaluation. Also, they have not been characterized yet about the possible negative effects on cardiovascular reparative and regenerative cells, such as EPCs or pluripotent stem cells. In this perspective, we critically review the still scarce available data on the effects of MRPs on molecular and cellular mechanisms of cardiovascular repair and regeneration.

Current knowledge on the association between cardiovascular and periodontal disease: an umbrella review.

INTRODUCTION: Periodontal disease (PD) and cardiovascular diseases (CVD) are among the most common pathologies in the world and their relationship has long been studied. Both conditions lead to a chronic inflammatory process with degenerative characteristics and their biunivocal correlation is now well established. The aim of this umbrella review on cardiovascular and periodontal disease was to evaluate the real degree of association between these two pathological conditions. EVIDENCE ACQUISITION: We conducted a comprehensive literature search on PubMed/Medline and in the Cochrane Library for systematic reviews focused on clinical evidence regarding the relationship between PD and CVD. The internal validity of systematic reviews and meta-analyses was formally analyzed using the Overview Quality Assessment Questionnaire (OQAQ) Tool. The umbrella review was planned in accordance with current international recommendations and was described as specified by the PRISMA Guidelines. EVIDENCE SYNTHESIS: Thirty-one systematic reviews, including 8 meta-analyses for a total of 507 clinical studies and over 3,549,966 patients were included. PD resulted to be associated with a higher risk of developing CVD (acute coronary syndrome, acute myocardial infarction) and cerebrovascular diseases (ischemic stroke); however, if the treatment of periodontitis reduces the risk of CVD events related is yet to be investigated. CONCLUSIONS: To date, the relationship between CVD and PD provides heterogeneous data. There is an association between PD and CVD, but a causal relationship cannot be established. Further research with properly designed long-term follow-up studies are needed in order to examine various physiopathological aspects of their association.

Different Techniques of Surgical Left Atrial Appendage Closure and Their Efficacy: A Systematic Review.

Background: Atrial fibrillation has been identified as an independent risk factor for thromboembolic events. Since 1948 different surgical techniques have described the feasibility and the rationale of left atrial surgical appendage closure. The aim of this systematic review is to evaluate the reported patency rates of different surgical techniques. Methods: This systematic review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Two independent investigators searched the PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and OVID® (Wolters Kluwer, Alphen aan den Rijn, Netherlands) to identify relevant studies. Consecutively, a PICO (Population, Intervention, Comparison and Outcomes) strategy assessment of literature was performed to search eventual other relevant studies that may have been ignored. Results: A total of 42 studies were included in our analysis. The total number of patients who underwent surgical left atrial appendage closure was 5671, and in 61.2% an imaging follow up was performed, mostly with transesophageal echocardiographic evaluation. Success rate for the different techniques was: Clip deployment 98%; Lariat procedure 88%; Surgical amputation 91%; Endocardial suture 74.3%, Epicardial suture 65%; Left atrial appendage closure (LAAC) ligation 60.9%; Stapler technique with excision of left atrial appendage (LAA) 100%; Stapler without excision 70%. Conclusions: To date, data on surgical left atrial appendage closure are poor and not standardized, even if reported rates are acceptable and comparable to transcatheter procedures. If validated on large-scale non-retrospective and multicentric studies, these promising developments may offer a valuable alternative for patients with atrial fibrillation (AF) and ineligible for oral anticoagulation therapy.

Natural Activators of Autophagy Increase Maximal Walking Distance and Reduce Oxidative Stress in Patients with Peripheral Artery Disease: A Pilot Study.

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H2O2 production, H2O2 break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H2O2 (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070.

Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes.

Smoking is still a major cardiovascular risk factor, despite many public awareness campaigns and dedicated interventions. Recently, modified risk products (MRP), e.g., heat-not-burn cigarettes (HNBCs), have been introduced as surrogates of traditional combustion cigarettes (TCCs). Although these products are promoted as healthier than TCCs, few studies have been conducted to assess it. This work is a sex-focused sub-study of a prospective observational study in which apparently healthy chronic TCC smokers were age-matched with regular HNBC users. Blood samples were collected for biochemical assays and blood pressure and flow-mediated dilation (FMD) were measured. Out of 60 subjects, 33 (55%) were women, and 27 (45%) men, with 11 (33%) vs. 9 (33%) non-smokers, respectively, 10 (30%) vs. 10 (37%) TCC smokers, and 12 (36%) vs. 8 (30%) HNBC smokers (p = 0.946). Bivariate and multivariable analyses showed no statistically significant between-sex differences in NO, H2O2, sCD40L, sNox2-dp, sP-selectin, platelet aggregation, cotinine or FMD, overall, in non-smokers, in TCC smokers, or in HNBC smokers (all p > 0.05). HNBCs appeared safer than TCCs when focusing on Nox2-dp (p = 0.026) and sP-selectin (p = 0.050) but had similar levels of the other measured markers. In conclusion, HNBCs have similar detrimental effects on women and men's oxidative stress (H2O2: p = 0.49; sNox2-dp: p = 0.31) and platelet activation (sP-selectin: p = 0.33; platelet aggregation p = 0.87).

Acute thrombotic occlusion of a brachiocephalic branch graft and pseudoaneurysm formation after debranching surgery for a "non-A non-B" aortic dissection.

Non-A non-B aortic dissection is a pathology with potentially life-threatening consequences, and aortic debranching followed by thoracic endovascular aortic repair is one of the possible treatment options. Branch graft occlusion is an infrequent complication and no definite guidelines exist about postoperative antithrombotic therapy nor preoperative evaluation of individual anatomical characteristics-in particular regarding cerebral circulation-in such patients. We present the case of a 54-year-old man undergoing an aortic debranching procedure for a thoracoabdominal aortic dissection originating in the aortic arch, complicated by thrombotic occlusion of the brachiocephalic branch of the prosthesis and pseudoaneurysm of the ascending aorta, with our management and considerations.

Platelet Activation Favours NOX2-Mediated Muscle Damage in Elite Athletes: The Role of Cocoa-Derived Polyphenols.

Mechanisms of exercise-induced muscle injury with etiopathogenesis and its consequences have been described; however, the impact of different intensities of exercise on the mechanisms of muscular injury development is not well understood. The aim of this study was to exploit the relationship between platelet activation, oxidative stress and muscular injuries induced by physical exercise in elite football players compared to amateur athletes. Oxidant/antioxidant status, platelet activation and markers of muscle damage were evaluated in 23 elite football players and 23 amateur athletes. Compared to amateurs, elite football players showed lower antioxidant capacity and higher oxidative stress paralleled by increased platelet activation and muscle damage markers. Simple linear regression analysis showed that sNOX2-dp and H2O2, sCD40L and PDGF-bb were associated with a significant increase in muscle damage biomarkers. In vitro studies also showed that plasma obtained from elite athletes increased oxidative stress and muscle damage in human skeletal muscle myoblasts cell line compared to amateurs' plasma, an effect blunted by the NOX2 inhibitor or by the cell treatment with cocoa-derived polyphenols. These results indicate that platelet activation increased muscular injuries induced by oxidative stress. Moreover, NOX2 inhibition and polyphenol extracts treatment positively modulates redox status and reduce exercise-induced muscular injury.