PAD4-Induced NETosis Via Cathepsin G-Mediated Platelet-Neutrophil Interaction in ChAdOx1 Vaccine-Induced Thrombosis-Brief Report.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome characterized by platelet anti-PF4 (platelet-activating antiplatelet factor 4)-related thrombosis. Platelet-neutrophil interaction has been suggested to play a role, but the underlying mechanism has not been fully elucidated. METHODS: The study included 10 patients with VITT after ChAdOx1 (chimpanzee adenovirus Oxford 1) nCoV-19 (Oxford-AstraZeneca) vaccine administration, 10 patients with ischemic stroke (IS), 10 patients with acute deep vein thrombosis, and 10 control subjects in whom blood levels of neutrophil extracellular traps (NETs), soluble TF (tissue factor), and thrombin generation were examined. Furthermore, we performed in vitro studies comparing the effect of serum from patients and controls on NETs formation. Finally, immunohistochemistry was performed in cerebral thrombi retrieved from a patients with VITT and 3 patients with IS. RESULTS: Compared with patients with IS, patients with deep vein thrombosis, controls, and patients with VITT had significantly higher blood values of CitH3 (citrullinated histone H3), soluble TF, D-dimer, and prothrombin fragment 1+2 (P<0.0001). Blood CitH3 significantly correlated with blood soluble TF (Spearman rank correlation coefficient=0.7295; P=0.0206) and prothrombin fragment 1+2 (Spearman rank correlation coefficient=0.6809; P<0.0350) in patients with VITT. Platelet-neutrophil mixture added with VITT plasma resulted in higher NETs formation, soluble TF and thrombin generation, and platelet-dependent thrombus growth under laminar flow compared with IS and deep vein thrombosis plasma; these effects were blunted by PAD4 (protein arginine deiminase 4) and cathepsin G inhibitors, anti-FcγRIIa (Fc receptor for IgG class IIa), and high doses of heparin. Immunohistochemistry analysis showed a more marked expression of PAD4 along with more diffuse neutrophil infiltration and NETs formation as well as TF and cathepsin expression in VITT thrombus compared with thrombi from patients with IS. CONCLUSIONS: Patients with VITT display enhanced thrombogenesis by PAD4-mediated NETs formation via cathepsin G-mediated platelet/neutrophil interaction.

Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial.

BACKGROUND: Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events. AIMS: We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI). METHODS: This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with the reference arm (12-month aspirin monotherapy following 12-month DAPT) after PCI. Patient-oriented composite endpoints (POCEs: all-cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time-dependent covariate in patients with the experiment or reference antiplatelet arm. RESULTS: Among 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12-1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92-1.19; pinteraction = 0.035). During the second-year follow-up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27-1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83-1.28; pinteraction = 0.008). CONCLUSIONS: In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov.

Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: implication for myocardial infarction.

AIMS: Low-grade endotoxaemia is detectable in human circulation but its role in thrombosis is still unclear. METHODS AND RESULTS: We measured serum lipopolysaccharide (LPS) concentration, soluble P-selectin (sP-selectin), a marker of platelet activation, and zonulin, a marker of gut permeability, in peripheral circulation, coronary thrombi, and intracoronary blood of patients with ST-elevation myocardial infarction (STEMI, n = 50) and stable angina (SA) (n = 50), respectively, and in controls (n = 50). Experimental study was carried out in mice to assess if Escherichia coli-LPS (E. coli-LPS) possess thrombotic property. Coronary thrombi from STEMI showed higher concentrations of LPS, sP-selectin vs. intracoronary blood of SA and peripheral blood of controls (P < 0.001). Zonulin was higher in STEMI compared to the other two groups [4.57 (3.34-5.22); 2.56 (0.41-4.36); 1.95 (1.22-2.65) ng/mL; P < 0.001] and correlated with LPS (Rs = 0.585; P < 0.001). Escherichia coli DNA was positive in 34% of STEMI vs. 12% of SA and 4% of controls (P < 0.001). In a subgroup of 12 STEMI, immunohistochemical analysis of coronary thrombi showed positivity for leucocyte Toll-like receptor 4 (TLR4), cathepsin G, and LPS from E. coli in 100%, 80%, and 25% of samples, respectively. E. coli-LPS injected in mice to reach LPS concentrations like those detected in coronary thrombi was associated with enhanced artery thrombosis and platelet activation, an effect blunted by TLR4 inhibitor co-administration. In vitro study demonstrated that LPS from E. coli enhanced platelet aggregation via TLR4-mediated leucocyte cathepsin G activation. CONCLUSION: ST-elevation myocardial infarction patients disclose an enhanced gut permeability that results in LPS translocation in human circulation and eventually thrombus growth at site of artery lesion via leucocyte-platelet interaction.

Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial.

AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial.

BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77). INTERPRETATION: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. FUNDING: AstraZeneca, Biosensors, and The Medicines Company.

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial.

BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. METHODS: The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). INTERPRETATION: The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. FUNDING: Abbott Vascular.

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial.

BACKGROUND: Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up. METHODS: In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively). INTERPRETATION: The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent. FUNDING: Abbott Vascular.

A Case Report of an Unusual Acute Intramural Hematoma Disguise as Pulmonary Embolism.

Aortic intramural hematoma (IMH) is characterized by an aortic wall hematoma without intimal flap and it is a variant of acute aortic syndromes (AAS). This entity may represent 10%-25% of the AAS involving the ascending aorta and aortic arch (Stanford Type A) in 10%-30% of cases and the descending thoracic aorta (Stanford Type B) in 60%-70% of cases. IMH impairs the aortic wall and may progress to either inward disruption of the intima, which finally induces typical dissection or outward rupture of the aorta. The literature describes some clinical reports where Type A aortic dissection mimics a pulmonary embolism but is not described as a case provoked by IMH with outward rupture of the aorta.

Acute iatrogenic aortic coarctation after balloon-expandable prosthesis pop-out during transcatheter aortic valve implantation intervention.

An 80-year-old man was referred to our cath-lab for transcatheter aortic valve implantation (TAVI) due to symptomatic severe aortic valve stenosis. The intervention utilized a balloon-expandable prosthesis (Edwards Sapien 3 Ultra n°26, Edwards Lifesciences).

[An unexpected case of right heart dilation in the elderly]. / Una insolita causa di dilatazione delle sezioni destre nell'anziano.

Atrial septal defects (ASD) represent the most common congenital heart defect diagnosed in adulthood. Adults with an ASD are often asymptomatic, but sometimes may present with non-specific symptoms such as dyspnea on exertion or exercise intolerance. Isolated sinus venosus atrial defect is an extremely rare anomaly. Sinus venosus defects occur more commonly in the superior (rather than inferior) portion of the embryologic sinus venosus and commonly occur with partial anomalous pulmonary venous return, particularly of the right upper pulmonary vein. We describe the case of an 80-year-old man with an undiagnosed, hemodynamically significant superior sinus venosus type of ASD who presented with persistent dyspnea and hypoxia after COVID-19 disease. Although cardiac magnetic resonance represents the gold standard for the morpho-functional evaluation of ASDs, transesophageal echocardiography is an accessible method for diagnosing the superior sinus venosus type of ASD and three-dimensional transesophageal echocardiography is useful for obtaining an "en face" view of the ASD and important surrounding structures.

Early and prolonged glutathione infusion favorably impacts length of hospital stay in ST-elevation myocardial infarction patients: a subanalysis of the GSH2014 Trial.

BACKGROUND: Developing strategies aimed to shorten the length of stay (LOS) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) is a healthcare goal to be pursued. We carried out a subanalysis of the GSH 2014 Trial to assess the potentiality of glutathione sodium salt infusion to impact on LOS. METHODS: 100 consecutive patients with STEMI, aged more than 18 years and referred to the three enrolling centers for primary angioplasty (p-PCI), were asked to participate to the GSH 2014 Trial. Fifty patients were randomized to treatment group and fifty to placebo; treatment consisted into an intravenous infusion of glutathione sodium salt over 10 minutes before p-PCI; after interventions, glutathione was infused at the same doses at 24, 48 and 72 h elapsing time. A stepwise linear multivariate model was built in order to assess independent predictors of LOS. RESULTS: Subjects receiving infusion of glutathione sodium salt had a significantly lower LOS than subjects receiving placebo (8.6±3 vs. 10.8±4 days, P=0.006). At multivariate analysis, the randomization to GSH group was negatively associated with length of stay (ß±SEß -1.64±0.74, cumulative R2 0.43, P=0.03) independently from age, sex, cardiovascular risk factors, number of treated vessels, infarct-related coronary artery (left anterior descending artery as reference) and enrolment hospital. CONCLUSIONS: Results from this subanalysis support the hypothesis that an early and prolonged glutathione sodium salt administration, as antioxidant therapy to patients with STEMI, may favorably impact on LOS. Further studies with larger sample size are necessary to confirm these data.

Repeated Glutathione Sodium Salt Infusion May Counteract Contrast-Associated Acute Kidney Injury Occurrence in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Randomized Subgroup Analysis of the GSH 2014 Trial.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is still a major concern for referring physicians, especially in the setting of ST-elevation myocardial infarction (STEMI) patients undergoing primary-PCI (pPCI). To evaluate whether glutathione sodium salt (GSS) infusion impacts favorably on CA-AKI, an unplanned exploratory data analysis of the GSH 2014 trial was performed. METHODS: One hundred patients with STEMI were assigned at random to an experimental group (No. 50) or to a placebo group (No. 50). Treatment consisted of an intravenous infusion of GSS lasting over 10 min before p-PCI. The placebo group received the same quantity of normal saline solution. After the interventions, glutathione was administered in the same doses to both groups at 24, 48 and 72 h. RESULTS: CA-AKI occurred in 5 out of 50 patients (10%) allocated to the experimental group (GSS infusion) and in 19 out of 50 patients (38%) allocated to the placebo group (p between groups < 0.001). No patients in either group required renal replacement therapy. After allowing for multiple confounders, GSS administration (OR 0.17, 95% CI 0.04-0.61) and door-to-balloon time (in hours) (OR 1.61, 95% CI 1.01-2.58) have been the only independent predictors of CA-AKI. CONCLUSIONS: the results of this sub-study, which show a significant trend towards an improved nephroprotection in the experimental group, led to the hypothesis of a possible new prophylactic approach to counteract CA-AKI using repeated GSS infusion. Subsequent studies with specific clinical outcomes would be necessary to confirm these data.

The Combined Treatment of Glutathione Sodium Salt and Ascorbic Acid for Preventing Contrast-Associated Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Hypothesis to Be Validated.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses.

[Barlow's disease with arrhythmic phenotype: a case report]. / Un caso di malattia di Barlow a fenotipo aritmico.

Barlow disease represents the extreme form of the degenerative mitral valve spectrum described by Carpentier. The myxoid degeneration of the mitral valve may result in a billowing leaflet or in a prolapse and myxomatous degeneration of the mitral leaflets. There are increasing evidences of the association between Barlow disease and sudden cardiac death. It is common in young women. Symptoms include anxiety, chest pain and palpitation. In this case report, the markers of risk for sudden death such as typical ECG changes, complex ventricular ectopy, a spiked configuration of the lateral annular velocities, mitral annular disjunction and evidence of myocardial fibrosis were assessed.

Left radial versus right radial approach for coronary artery catheterization: a prospective comparison.

BACKGROUND: Despite several advantages of the transradial over the transfemoral approach, the use of transradial access for coronary interventions in daily practice is still low. Major limitations are the technical and anatomical issues related with right radial artery access. The left radial approach may have an advantage from the point of view of the vascular anatomy. The aim of this study was to evaluate the safety and feasibility of routinely using the left radial compared to the right radial approach. METHODS: This is a prospective single center study comparing left radial to right radial access for coronary artery catheterization. The overall in-hospital major adverse cardiac and cerebral events (MACCE), procedural success rate, bleeding, vascular and procedural complications, fluoroscopy time, number of catheters, and amount of contrast agent used were assessed. RESULTS: A total of 1,032 coronary angiograms were performed: 420 were performed using the right radial artery and 612 the left radial artery. No differences were observed in MACCE and success rate between the two groups. No cases of major or minor bleeding and vascular complications requiring surgical intervention were reported. Fluoroscopy time and the number of catheters used were significantly less in the left radial group (P = 0.001 and P = 0.007, respectively), while the volume of contrast was similar (P = 0.264). CONCLUSIONS: The left radial approach in our series was demonstrated to be safe and feasible in daily practice, and in this study was associated with a reduction in fluoroscopy time and number of catheters used.

Manual Coronary Thrombectomy in Primary PCI: What a Satisfaction it is Sometimes to Look Into the Catheter.

An 89-year-old woman was referred to our cath lab for a primary percutaneous coronary intervention following electrocardiographic evidence of inferior ST-segment elevation myocardial infarction. A coronary angiography revealed single- vessel disease with complete occlusion of the right coronary artery. After crossing the occlusion with a guidewire, we proceeded with manual thrombectomy using the Eliminate Aspiration Catheter (Terumo Europe). To our knowledge, this is the longest coronary thrombus ever reported to be removed in its entirety.

The Utility of Paraspinal Acoustic Windows for the Evaluation of Acute Dissection of Descending Thoracic Aorta in the Emergency Setting.

Acute aortic dissection (AAD) is the prevalent acute aortic syndrome characterized by rapid onset and progression with time-dependent prognosis. When suspecting AAD of descending thoracic aorta in the context of the emergency department setting, computed tomography scanning and trans-esophageal echocardiography are the most useful imaging modalities. The sensitivity of transthoracic echocardiography in diagnosing for type B dissection is only 31%-55% when compared with other modalities. We describe the case of a 62-year-old female with a clinical history of Marfan syndrome where the low sensitivity of the transthorac approach in the detection of descending aortic dissection was overcomed by the posterior thoracic approach with the posterior paraspinal window (PPW). In the literature, are described just few reports where echocardiography via the PPW makes it possible to diagnose acute descending aortic syndrome.

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT. CONCLUSION: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.

The impact of UEFA Euro 2020 football championship on Takotsubo Syndrome: Results of a multicenter national registry.

Objectives: The UEFA 2020 European Football Championship held in multiple cities across Europe from June 11 to July 11, 2021, was won by Italy, providing an opportunity to examine the relationship between emotional stress and the incidence of acute cardiovascular events (ACE). Methods and results: Cardiovascular hospitalizations in the Cardiac Care Units of 49 hospital networks in Italy were assessed by emergency physicians during the UEFA Euro 2020 Football Championship. We compared the events that occurred during matches involving Italy with events that occurred during the remaining days of the championship as the control period. ACE was assessed in 1,235 patients. ACE during the UEFA Euro 2020 Football Championship semifinal and final, the most stressful matches ended with penalties and victory of the Italian team, were assessed. A significant increase in the incidence of Takotsubo Syndrome (TTS) by a factor of 11.41 (1.6-495.1, P < 0.003), as compared with the control period, was demonstrated during the semifinal and final, whereas no differences were found in the incidence of ACS [IRR 0.93(0.74-1.18), P = 0.57]. No differences in the incidence of ACS [IRR 0.98 (0.87-1.11; P = 0.80)] or TTS [IRR 1.66(0.80-3.4), P = 0.14] were found in the entire period including all matches of the UEFA Euro 2020 compared to the control period. Conclusions: The data of this national registry demonstrated an association between the semifinal and final of UEFA Euro 2020 and TTS suggesting that it can be triggered by also positive emotions such as the victory in the European Football Championship finals.

Association Between Air Pollution and Acute Coronary Syndromes During Lockdown for COVID-19: Results From the Terni Hub Center.

Background: During the lockdown for COVID-19, a massive decrease in hospital admissions for acute coronary syndrome (ACS) and a drop in air pollution were both detected in Italy. Our aim was to investigate the possible association between these two events at the Province of Terni, one of the most polluted urban and industrial area in Central Italy. Methods: We analyzed data of daily 24-h urban air concentrations of particulate matter (PM)10 and PM2.5 from fixed station monitoring network located in the main city centers of the Terni province, and accesses for ACS at the catheterization laboratory of the Cardiological Hub Center of the Terni University Hospital during lockdown. A comparison was made with data corresponding to the same lockdown time period of years 2019, 2018, and 2017. Results: Invasive procedures for ACS decreased in 2020 (n = 49) as compared with previous years (n = 93 in 2019, n = 109 in 2018, and n = 89 in 2017, p < 0.001). Conversely, reductions in average PM10 (20.7 µg/m3) and PM2.5 (14.7 µg/m3) in 2020 were consistent with a long-term decreasing trend, being comparable to those recorded in 2019 and 2018 (all p > 0.05) and slightly lower than 2017 (p < 0.05). The Granger-causality test demonstrated the lack of association between time-varying changes in air pollution and the number of procedures for ACS. Conclusions: Our results did not support the hypothesis that reduction in invasive procedures for ACS during lockdown was linked to an air cleaning effect. Reasons other than reduced air pollution should be sought to explain the observed decrease in ACS procedures.