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Microplastics are particles smaller than five millimeters deriving from the degradation of plastic objects present in the environment. Microplastics can move from the environment to living organisms, including mammals. In this study, six human placentas, collected from consenting women with physiological pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments (ranging from 5 to 10 μm in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4 in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in terms of morphology and chemical composition. All of them were pigmented; three were identified as stained polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments, which were all used for man-made coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics and personal care products.

Background and Aims: Preclinical evidence suggests that proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors hold anti-inflammatory properties independently of their ability to lower LDL-cholesterol (C). However, whether PCSK9 inhibitors exert anti-inflammatory effects within the atherosclerotic plaque in humans is unknown. We explored the impact of PCSK9 inhibitors, used as monotherapy, compared with other lipid-lowering drugs (oLLD) on the expression of inflammatory markers within the plaque, assessing also the subsequent incidence of cardiovascular events., Methods: In an observational study, we recruited 645 patients on stable therapy for at least six months and undergoing carotid endarterectomy, categorizing patients according to the use of PCSK9 inhibitors only (n = 159) or oLLD (n = 486). We evaluated the expression of NLRP3, caspase-1, IL-1β, TNFα, NF-kB, PCSK9, SIRT3, CD68, MMP-9, and collagen within the plaques in the two groups through immunohistochemistry, ELISA, or immunoblot. A composite outcome including non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality was assessed during a 678 ± 120 days follow-up after the procedure., Results: Patients treated with PCSK9 inhibitors had a lower expression of pro-inflammatory proteins and a higher abundance of SIRT3 and collagen within the plaque, a result obtained despite comparable levels of circulating hs-CRP and observed also in LDL-C-matched subgroups with LDL-C levels <100 mg/dL. Patients treated with PCSK9 inhibitors showed a decreased risk of developing the outcome compared with patients on oLLD, also after adjustment for multiple variables including LDL-C (adjusted hazard ratio 0.262; 95% CI 0.131-0.524; p < 0.001). The expression of PCSK9 correlated positively with that of pro-inflammatory proteins, which burden was associated with a higher risk of developing the outcome, independently of the therapeutic regimen., Conclusions: The use of PCSK9 inhibitors is accompanied by a beneficial remodelling of the inflammatory burden within the human atheroma, an effect possibly or partly independent of their LDL-C lowering ability. This phenomenon might provide an additional cardiovascular benefit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users)., Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization., Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33-0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21-0.98; p = 0.041)., Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI., Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT., Clinicaltrials: gov Identifier: NCT05261867., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling., Background: adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy., Methods: miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users., Results: At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p > 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p < 0.01) and miR-181 levels (p < 0.01) and higher values of miR-18 (p < 0.01)and miR-145 (p < 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p < 0.01) and 6MWT (p < 0.01) along with a more significant reduction of LVESv (p < 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users., Conclusions: ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications., Methods: EVs were recovered from plasma of 19 ACS patients and 50 healthy subjects (HS). Flow cytometry, qRT-PCR, and Western blot (WB) were performed to evaluate both intra-vesicular and intra-cellular signals. ShinyGO, PANTHER, and STRING tools were used to perform GO and PPI network analyses., Results: ACS-derived EVs showed increased levels of DNA methyltransferases (DNMTs) (p<0.001) and Ten-eleven translocation (TET) genes reduction. Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B, were significantly increased in plasma ACS-EVs. DNA methylation analysis on PBMCs from healthy donors treated with HS- and ACS-derived EVs showed an important role of DNMTs carried by EVs. PPI network analysis evidenced that ACS-EVs induced changes in PBMC methylome. In the most enriched subnetwork, the hub gene SRC was connected to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, BAIAP2 genes that were showed to have many molecular effects on various cell types into onset of several CVDs. Modulation in gene expression after ACS-EVs treatment was confirmed for SRC, NOTCH1, FOXO3, RXRA, DGKG and BAIAP2 (p<0.05)., Conclusions: Our data showed an important role for ACS-derived EVs in gene expression modulation through de novo DNA methylation signals, and modulating signalling pathways in target cells., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Admission hyperglycemia is common in subjects with acute myocardial infarction (AMI). Reperfusion therapy with primary percutaneous coronary intervention (PPCI) represents the leading therapeutic choice, in particular in ST-segment elevation myocardial infarction (STEMI). Despite this, mortality, re-hospitalizations and complications remain a relevant problem. Adenosine, a purine nucleoside, may reduce no-reflow. Therefore, whe studied the effects of intravenous infusion of adenosine in addition to primary percutaneous coronary intervention (PPCI) in hyperglycemic patients with STEMI., Methods: We evaluated 836 patients with STEMI and admission hyperglycemia (glycemia >140 mg/dL). At the end, 399 patients were entered into the database. Patients were grouped on the basis of whether they received adenosine or not., Results: A total of 199 patients received intravenous adenosine infusion and PPCI and 200 patients did not. Kaplan-Meier analysis demonstrated significant differences in all death, cardiac death, re-hospitalization for heart failure and for acute coronary syndrome in the adenosine treated group., Conclusions: The effects of intravenous infusion of adenosine and PPCI on clinical outcomes are significant but we need future larger studies with larger follow-up and statistical analysis to confirm our results., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Bioresorbable scaffolds have emerged as a potential breakthrough for the treatment of coronary artery lesions. The need for drug release and plaque scaffolding is temporary, and leaving a permanent stent once the process of plaque recoil and vessel healing has ended might be superfluous or even deleterious exposing the patient to the risk of very late thrombosis, eliminating vessel reactivity, impairing non-invasive imaging and precluding possible future surgical revascularization. This long-term potential limitation of permanent bare metal stents might be overcome by using a resorbable scaffold. The metallic and antithrombotic properties make the resorbable magnesium scaffold an appealing technology for the treatment of coronary artery lesions. Notwithstanding this, its mechanical properties substantially differ from those of conventional bare metal stents, and previous experience using polymer-based scaffolds has shown that a standardized implantation technique and optimal patient and lesion selection are key factors for a successful implantation. A panel of expert cardiologists gathered to find a consensus on the best practices for Magmaris implantation in a selected patient population and to discuss the rationale for new potential future indications., Competing Interests: Declaration of competing interest All the authors have no major conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The efficacy of novel nonvitamin K antagonist oral anticoagulants (NOACs) in nonvalvular atrial fibrillation (AF) to prevent stroke is well assessed, but NOACs use in AF that occurs after bioprosthetic aortic valve replacement (AVR) is not endorsed. This retrospective real-world study evaluated the efficacy and safety of NOACs prescribed no earlier than 4 months after AVR as an alternative to warfarin in patients with AF., Methods: We pooled 1032 patients from the databases of 5 centers. Ischemic/embolic events and major bleeding rates were compared between 340 patients assuming NOACs and 692 prescribed warfarin. Propensity score matching was performed to avoid the bias between groups., Results: The NOACs vs warfarin embolic/ischemic rate was 13.5% (46 of 340) vs 22.7% (157 of 692), respectively, (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.37-0.75; P < .001), and the incidence rate was 3.7% vs 6.9% patients/year, respectively (log-rank test P = .009). The major bleeding rate was 7.3% (25 of 340) vs 13% (90 of 692) (HR, 0.5; 95% CI, 0.33-0.84; P = .007), and the incidence rate was 2% vs 4% patients/year (log-rank test P = .002.) After propensity score matching, the NOACs vs warfarin embolic/ischemic rate was 13.1% (42 of 321) vs 21.8% (70 of 321) (HR, 0.6; 95% CI, 0.4-0.9; P = .02), and the incidence rate was 4.1% vs 6.7% patients/year (log rank test P = .01). The major bleeding rate was 7.8% (25 of /321) vs 13.7% (44 of 321) (HR, 0.5; 95% CI, 0.31-0.86; P = .01), and the incidence rate was 2.4% vs 4.2% patients/year (log-rank P = .01)., Conclusions: In a real-word study, NOACs use overcomes the indications provided by guidelines. This study evidenced that NOACs use in patients who developed AF after bioprosthetic AVR was more effective in prevention of thromboembolism and safe in reduction of major bleeding events compared with warfarin., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: To describe the contemporary management by cardiologists of patients after an episode of myocardial infarction (MI)., Methods: The EYESHOT Post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients referring to cardiologists 1 to 3 years from the last MI event., Results: Over a 3-month period, 1633 consecutive patients [median 22 (IQR 15-28) months from MI] were enrolled: 1028 (63.0%) at the second and 605 (37.0%) at the third year from MI. During the 12 months prior to enrolment, the majority of patients received a transthoracic echocardiogram (60% and 54%), followed by coronary angiography (24% and 16%, in the second and third year from MI groups, respectively). At the time of enrolment, the majority of patients were prescribed on statins (93%) and beta-blockers (82%), without significant differences between the 2 groups. A dual antiplatelet therapy (DAPT) was used more frequently among patients presenting during the second compared to the third year from MI (40% vs 24%; p < 0.0001). At multivariable analysis, the time interval from last MI (2 vs 3 years: OR 2.27; 95% CI 1.79-2.88; p < 0.0001) and a previous percutaneous coronary intervention with multiple stents (OR 3.46; 95% CI 2.19-5.47; p < 0.0001) resulted as the major independent predictors of DAPT persistence at the time of enrolment., Conclusions: This contemporary registry provides unique insights into the current management of post-MI patients and represents an opportunity to further improve the long-term treatment of this high-risk population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring., Methods and Results: 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040)., Conclusions: The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration., Clinical Trial Registration: URL: http://clinicaltrials.gov/ Identifier: NCT02173028., (Copyright © 2017. Published by Elsevier B.V.)

Background: Transradial approach (TRA) for percutaneous coronary procedures is associated with improved patient outcome and is being increasingly adopted worldwide. We surveyed Italian interventional cardiologists in order to take a snapshot of the current practice of TRA., Methods: A web-based questionnaire was emailed to all members of the Italian Society of Interventional Cardiology., Results: The survey was taken by 508 respondents. Cardiogenic shock and chronic total occlusions represented the principal limitations to TRA. Right TRA was the default approach for 81% of respondents. Both diagnostic and interventional procedures were routinely performed through 6 Fr sheaths (83% and 93%, respectively); dedicated TRA curves were used in 11% of diagnostic and in about 3% of interventional procedures. Almost 70% of the operators did not assess dual hand circulation. In case of crossover, the contralateral radial artery was the preferred site (57%). Radial artery hemostasis was mostly achieved by pneumatic bracelet (64%) and patency of the radial artery during hemostasis was ensured in 60% of cases. Pre-discharge patency of the radial artery was routinely assessed by almost 60% of respondents. For diagnostic procedures, adequate heparin anticoagulation (5000IU) was only given by 45% of operators. Most respondents believed that TRA is associated with greater radiation exposure for both the patient (82%) and the operator (98%) as compared to transfemoral approach., Conclusions: This survey provides contemporary data about the adoption of TRA in Italy and gives interesting insights about several technical and clinical issues related to the practice of this vascular approach for coronary procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance., Methods: From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients., Results: ALA administration improved MIBG defect size at 12 months compared to placebo., Conclusions: Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: We examined the effects of peri-procedural intensive glycemic control during early percutaneous coronary intervention (PCI) on the number and differentiation of endothelial progenitor cells (EPCs) and myocardial salvage (MS) in hyperglycemic patients with first ST-elevation myocardial infarction (STEMI)., Methods and Results: We conducted a randomized, prospective, open label study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients (glucose ≥140 mg/dl) were randomized to intensive glycemic control (IGC) for almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7 days after STEMI) and myocardium salvaged by therapy (6 months after STEMI). Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1 levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean plasma glucose during peri-procedural period was greater in CGC group than in IGC group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1 levels were significantly higher in IGC group than in CGC, peaking after 24 h (P < 0.01). In the IGC group, the salvage index was greater than in patients treated with CGC (P < 0.001)., Conclusions: Optimal peri-procedural glycemic control, by increasing EPC number and their capability to differentiate, may improve the myocardial salvage., (© 2013. Published by Elsevier Ireland Ltd. All rights reserved.)