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.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

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.

Intraprocedural continuous saline infusion lines significantly reduce the incidence of acute kidney injury during endovascular procedures for stroke and myocardial infarction: evidence from a systematic review and meta-regression.

BACKGROUND: Contrast media used in mechanical therapies for stroke and myocardial infarction represent a significant cause of acute kidney injury (AKI) in acute medical scenarios. Although the continuous saline infusion line (CSIL) is a standard procedure to prevent thrombus formation within the catheter during neurovascular interventions of mechanical thrombectomy (MT), it is not utilized in percutaneous coronary interventions (PCI). METHODS: A systematic review of the incidence of AKI after MT for stroke treatment was performed. These data were compared with those reported in the literature regarding the incidence of AKI after PCI for acute myocardial infarction. A random-effect model meta-regression was performed to explore the effects of CSIL on AKI incidence, using clinical details as covariates. RESULTS: A total of 18 and 33 studies on MT and PCI were included, respectively, with 69,464 patients (30,138 [43.4%] for MT and 39,326 [56.6%] for PCI). The mean age was 63.6 years±5.8 with male 66.6%±12.8. Chronic kidney disease ranged 2.0-50.3%. Diabetes prevalence spanned 11.1% to 53.0%. Smoking status had a prevalence of 7.5-72.0%. Incidence of AKI proved highly variable (I2=98%, Cochrane's Q 2985), and appeared significantly lower in the MT subgroup than in the PCI subgroups (respectively 8.3% [95% confidence interval: 4.7-11.9%] vs. 14.7 [12.6-16.8%], P<0.05). Meta-regression showed that CSIL was significantly associated with a decreased incidence of AKI (OR=0.93 [1.001-1.16]; P=0.03). CONCLUSIONS: Implementation of CSIL during endovascular procedures in acute settings was associated with a significant decrease in the risk of AKI, and its safety should be routinely considered in such interventions.

Statistical primer: individual patient data meta-analysis and meta-analytic approaches in case of non-proportional hazards.

Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples.

European Association of Cardio-Thoracic Surgery (EACTS) expert consensus statement on perioperative myocardial infarction after cardiac surgery.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Effect of traditional or heat-not-burn cigarette smoking on circulating miRNAs in healthy subjects.

BACKGROUND: Traditional combustion cigarette (TCC) smoking is an established risk factor for several types of cancer and cardiovascular diseases. Circulating microRNAs (miRNAs) represent key molecules mediating pathogenetic mechanisms, and potential biomarkers for personalized risk assessment. TCC smoking globally changes the profile of circulating miRNAs. The use of heat-not-burn cigarettes (HNBCs) as alternative smoking devices is rising exponentially worldwide, and the circulating miRNA profile of chronic HNBC smokers is unknown. We aimed at defining the circulating miRNA profile of chronic exclusive HNBC smokers, and identifying potentially pathogenetic signatures. METHODS: Serum samples were obtained from 60 healthy young subjects, stratified in chronic HNBC smokers, TCC smokers and nonsmokers (20 subjects each). Three pooled samples per group were used for small RNA sequencing, and the fourth subgroup constituted the validation set. RESULTS: Differential expression analysis revealed 108 differentially expressed miRNAs; 72 exclusively in TCC, 10 exclusively in HNBC and 26 in both smoker groups. KEGG pathway analysis on target genes of the commonly modulated miRNAs returned cancer and cardiovascular disease associated pathways. Stringent abundance and fold-change criteria nailed down our functional bioinformatic analyses to a network where miR-25-3p and miR-221-3p are main hubs. CONCLUSION: Our results define for the first time the miRNA profile in the serum of exclusive chronic HNBC smokers and suggest a significant impact of HNBCs on circulating miRNAs.

Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts.

Rheumatoid arthritis (RA) is an idiopathic, autoimmune connective tissue disorder that primarily affects the synovial joints, causing symmetric, erosive-deforming polyarthritis. It is also associated with extra-articular manifestations, particularly cardiovascular (CV) diseases (CVD). CV risk modification in RA remains unsolved despite recent advances in the management of RA. RA is an independent risk factor for atherosclerosis. RA and atherosclerosis share similar pathophysiological features (such as the pro-inflammatory cascade activation including interleukin-6) and risk factors (such as microflora dysbacteriosis and smoking). Patients with RA experience an exacerbation of atherogenesis, with atheromas destabilization, endothelial dysfunction, vasculitis, and hypercytokinemia. Consequently, the inflammatory response associated with RA is the basis for CVD development. The treat-to-target strategy not only improved RA control but also had a favorable effect on the morpho-functional state of the CV system in patients living with RA. Thus, disease-modifying antirheumatic drugs (DMARDs) - in particular methotrexate - may have a beneficial effect on the prevention of CV events in RA. It must be mentioned that RA is a serious multi-system disease, not only because of a window period during which the course of RA can be reversed, but also due to early damage to the heart and blood vessels. For this reason, a thorough cardiological assessment must be performed for all patients with RA, regardless of sex, age, disease stage, and disease activity score.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial.

BACKGROUND: In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. OBJECTIVES: The authors analyzed separately the outcomes of INV patients treated with PCI or CABG. METHODS: Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. RESULTS: Among INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). CONCLUSIONS: In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

Features and outcomes of bailout repeat transcatheter aortic valve implantation (TAVI): the Bailout Acute TAVI-in-TAVI to Lessen Events (BATTLE) international registry.

AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic stenosis in patients with intermediate to prohibitive surgical risk. When a single TAVI device fails and cannot be retrieved, TAVI-in-TAVI must be performed acutely, but outcomes of bailout TAVI-in-TAVI have been incompletely appraised. We aimed at analyzing patient, procedural and outcome features of patients undergoing bailout TAVI-in-TAVI in a multicenter registry. METHODS: Details of patients undergoing bailout TAVI-in-TAVI, performed acutely or within 24 h of index TAVI, in 6 international high-volume institutions, were collected. For every case provided, 2 same-week consecutive controls (prior TAVI, and subsequent TAVI) were provided. Outcomes of interest were procedural and long-term events, including death, myocardial infarction, stroke, access site complication, major bleeding, and reintervention, and their composite (i.e. major adverse events [MAE]). RESULTS: A total of 106 patients undergoing bailout TAVI-in-TAVI were included, as well as 212 controls, for a total of 318 individuals. Bailout TAVI-in-TAVI was less common in younger patients, those with higher body mass index, or treated with Portico/Navitor or Sapien devices (all p < 0.05). Bailout TAVI-in-TAVI was associated with higher in-hospital rates of death, emergency surgery, MAE, and permanent pacemaker implantation (all p < 0.05). Long-term follow-up showed that bailout TAVI-in-TAVI was associated with higher rates of death and MAE (both < 0.05). Similar findings were obtained at adjusted analyses (all p < 0.05). However, censoring early events, outlook was not significantly different when comparing the two groups (p = 0.897 for death, and p = 0.645 for MAE). CONCLUSIONS: Bail-out TAVI-in-TAVI is associated with significant early and long-term mortality and morbidity. Thus, meticulous preprocedural planning and sophisticated intraprocedural techniques are of paramount importance to avoid these emergency procedures.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

Bayesian interpretation of non-inferiority in transcatheter versus surgical aortic valve replacement trials: a systematic review and meta-analysis.

OBJECTIVES: The concept of non-inferiority is widely adopted in randomized trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). However, uncertainty exists regarding the long-term outcomes of TAVR, and non-inferiority may be difficult to assess. We performed a systematic review and meta-analysis of randomized trials comparing TAVR and SAVR, with a specific emphasis on the non-inferiority margin for 5-year all-cause mortality. METHODS: A systematic search was applied to 3 electronic databases. Randomized trials comparing TAVR and SAVR were included. Bayesian methods were implemented to evaluate the posterior probability of non-inferiority at different trial non-inferiority margins under either a vague, Cauchy, or a literature-based prior. Primary outcomes were 5-year actuarial all-cause mortality, and the probability of non-inferiority at various transformed trial non-inferiority margins. Secondary outcomes were long-term survival and 1- and 2-year actuarial survival. RESULTS: Eight trials (n = 8698 patients) were included. Kaplan-Meier-derived 5-year survival was 61.6% (95% CI 59.8-63.5%) for TAVR, and 63.7% (95% CI 61.9-65.6%) for SAVR. Six trials (n = 6370 patients) reported all-cause mortality at 5-year follow-up. Under a vague prior, the posterior median relative risk for all-cause mortality of TAVR was 1.14, compared to SAVR (95% credible interval 1.06-1.22, probability of relative risk <1.00 = 0.01%, I2 = 0%). Similar results in terms of point estimate and uncertainty measures were obtained using frequentist methods. Based on the various trial non-inferiority margins, the results of the analysis suggest that non-inferiority at 5 years is no longer likely. CONCLUSIONS: It is unlikely that TAVR is still non-inferior to SAVR at 5 years in terms of all-cause mortality.

Differences in Postoperative Atrial Fibrillation Incidence and Outcomes After Cardiac Surgery According to Assessment Method and Definition: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most frequent complication of cardiac surgery. Despite clinical and economic implications, ample variability in POAF assessment method and definition exist across studies. We performed a study-level meta-analysis to evaluate the influence of POAF assessment method and definition on its incidence and association with clinical outcomes. METHODS AND RESULTS: A systematic literature search was conducted to identify studies comparing the outcomes of patients with and without POAF after cardiac surgery that also reported POAF assessment method. The primary outcome was POAF incidence. The secondary outcomes were in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay. Fifty-nine studies totaling 197 774 patients were included. POAF cumulative incidence was 26% (range: 7.3%-53.1%). There were no differences in POAF incidence among assessment methods (27%, [range: 7.3%-53.1%] for continuous telemetry, 27% [range: 7.9%-50%] for telemetry plus daily ECG, and 19% [range: 7.8%-42.4%] for daily ECG only; P>0.05 for all comparisons). No differences in in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay were found between assessment methods. No differences in POAF incidence or any other outcomes were found between POAF definitions. Continuous telemetry and telemetry plus daily ECG were associated with higher POAF incidence compared with daily ECG in studies including only patients undergoing isolated coronary artery bypass grafting. CONCLUSIONS: POAF incidence after cardiac surgery remains high, and detection rates are variable among studies. POAF incidence and its association with adverse outcomes are not influenced by the assessment method and definition used, except in patients undergoing isolated coronary artery bypass grafting.

Management of Coronary Artery Disease in Older Adults: Recent Advances and Gaps in Evidence.

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults.

Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study.

BACKGROUND AND AIMS: Trehalose, spermidine, nicotinamide, and polyphenols are natural substances that exert pro-autophagic and antioxidant properties. Their role in blood pressure (BP) regulation and preservation of vascular function in essential hypertension is unknown. The aim of this study was to evaluate the effect of a mixture of these agents on BP level, markers of oxidative stress, autophagy, endothelial function, and vascular stiffness in outpatients with grade 1 uncomplicated essential hypertension. METHODS AND RESULTS: A single-centre, open-label, case-control, pilot study was conducted in adult outpatients (aged ≥18 years) receiving or not the mixture for two months along with the standard therapies. Both at baseline and at the end of the treatment the following clinical parameters were evaluated: brachial seated office BP level, central aortic pressure, pulse wave velocity, augmentation index (AI@75). Both at baseline and at the end of the treatment, a blood sample was drawn for the measurement of: H2O2, HBA%, levels of sNOX2-dp, Atg 5, P62, endothelin 1, and NO bioavailability. The mixture of nutraceuticals did not influence BP levels. Patients receiving the mixture showed a significant decrease of oxidative stress, stimulation of autophagy, increased NO bioavailability and no increase of the AI@75, in contrast to what observed in hypertensive patients not receiving the mixture. CONCLUSIONS: The supplementation of the trehalose, spermidine, nicotinamide, and polyphenols mixture counteracted hypertension-related arterial stiffness through mechanisms likely dependent on oxidative stress downregulation and autophagy stimulation. These natural activators of autophagy may represent favourable adjuvants for prevention of the hypertensive cardiovascular damage.

Treatment with gentamicin-impregnated collagen sponges in reducing infection of implantable cardiac devices: 10-year analysis with propensity score matching.

INTRODUCTION AND OBJECTIVES: The incidence of device infection has increased over time and is associated with increased mortality in patients with cardiac implantable electronic devices (CIEDs). Gentamicin-impregnated collagen sponges (GICSs) are useful in preventing surgical site infection (SSI) in cardiac surgery. Nevertheless, to date, there is no evidence concerning their use in CIED procedures. Our study aims to determine the effectiveness of treatment with GICSs in preventing CIED infection. METHODS: A total of 2986 adult patients who received CIEDs between 2010 and 2020 were included. Before device implantation, all patients received routine periprocedural systemic antibiotic prophylaxis. The study endpoints were the CIED infection rate at one year and the effectiveness of the use of GICSs in reducing CIED infection. RESULTS: Among 1524 pacemaker, 942 ICD and 520 CRT implantations, CIED infection occurred in 36 patients (1.2%). Early reintervention (OR 9 [95% CI 3.180-25.837], p<0.001), pocket hematoma (OR 11 [95% CI 4.195-28.961], p<0.001), diabetes (OR 2.9 [95% CI 1.465-5.799], p=0.002) and prolonged procedural time (OR 1.02 [95% CI 1.008-1.034], p=0.001) were independent risk factors for CIED infection. Treatment with GICSs reduced CIED infections significantly ([95% CI -0.031 to -0.001], p<0.001). CONCLUSIONS: The use of GICSs may help in reducing infections associated with CIED implantation.