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.

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.

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.

[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.

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.

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.

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.

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.

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.

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 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.

Glutathione Infusion Before and 3 Days After Primary Angioplasty Blunts Ongoing NOX2-Mediated Inflammatory Response.

Background Glutathione is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesized that glutathione administration immediately before and after primary angioplasty (primary percutaneous coronary intervention) could be effective in modulating immune cell activation, thereby preventing infarct expansion. Methods and Results One hundred consecutive patients with ST-segment-elevation myocardial infarction, scheduled to undergo primary percutaneous coronary intervention were randomly assigned before the intervention to receive an infusion of glutathione (2500 mg/25 mL over 10 minutes), followed by drug administration at the same doses at 24, 48, and 72 hours elapsing time or placebo. Total leukocytes, NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2) activation, NO bioavailability, cTpT (serum cardiac troponin T), hsCRP (high-sensitivity C-reactive protein), and TNF-α (tumor necrosis factor α) levels were measured. Left ventricular size and function were assessed within 120 minutes, 5 days, and 6 months from percutaneous coronary intervention. Following reperfusion, a significant reduction of neutrophil to lymphocyte ratio (P<0.0001), hsCRP generation (P<0.0001), NOX2 activation (P<0.0001), TNF-α levels (P<0.001), and cTpT release (P<0.0001) were found in the glutathione group compared with placebo. In treated patients, blunted inflammatory response was linked to better left ventricular size and function at follow-up (r=0.78, P<0.005). Conclusions Early and prolonged glutathione infusion seems able to protect vital myocardial components and endothelial cell function against harmful pro-oxidant and inflammatory environments, thus preventing maladaptive cardiac repair and left ventricular adverse remodeling. Registration URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2014-004486-25.

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.

Comparison of Investigator-Reported and Clinical Event Committee-Adjudicated Outcome Events in GLASSY.

BACKGROUND: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. METHODS: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. RESULTS: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. CONCLUSIONS: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.

Endothelial shear stress and vascular remodeling in bioresorbable scaffold and metallic stent.

BACKGROUND AND AIMS: The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up. METHODS: In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks. RESULTS: Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Post-procedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling. CONCLUSIONS: In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES.