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.

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.

Posterior mitral leaflet cleft in nonobstructive hypertrophic cardiomiopathy.

A 43-year-old nigerian woman presented to cardiac intensive care unit for acute pulmonary edema with severe mitral regurgitation in a hypertrophic non obstructive cardiomyopathy for prevalent hypertrophy of posterior and lateral walls. A transesophageal echocardiography showed the isolated cleft of posterior mitral leaflet. In literature deep and multiple mitral valve clefts are described in patients with hypertrophic obstructive cardiomyopathy undergoing septal myectomy, including possible true posterior clefts, but they are not associated with the premyectomy severity of mitral regurgitation or jet direction, and do not result in surgical MV intervention. The hypertrophic cardiomyopathy is not confined to cardiac muscle but rather involves the mitral valve with structural abnormalities. In this case surgical correction of cleft was the solution for several mitral regurgitation.

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).

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.

Ascending aorta dilatation is associated to hard cardiovascular events, follow-up from multicentric ARGO-Perspective project.

Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension. Four hundred forty-five hypertensive patients from six Italian hospitals were recruited as part of ARGO-SIIA study1. For all centers, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was defined through absolute sex-specific thresholds as in previous studies (41 mm for males, 36 mm for females). Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE (HR = 4.07 [1.81-9.17], p < 0.001). This result was confirmed after correction for main demographic characteristics such as age, sex and BSA (HR = 2.91 [1.18-7.17], p = 0.020). At penalized Cox regression, age, left atrial dilatation, left ventricular hypertrophy and AAD were identified as best predictor of MACEs and AAD resulted a significant predictor of MACEs even after correction for these confounders (HR = 2.43 [1.02-5.78], p = 0.045). The presence of AAD was found to be associated with an increased risk of MACE independently of for major confounders, including established HMODs. AAD ascending aorta dilatation, LAe left atrial enlargement, LVH left ventricular hypertrophy, MACEs major adverse cardiovascular events, SIIA Società Italiana dell'Ipertensione Arteriosa (Italian Society for Arterial Hypertension).

Acute Left Ventricle Free-Wall Rupture Post Primary PCI: In Vivo Imaging.

A 69-year-old male was referred to our cath lab for primary percutaneous coronary intervention due to acute anterior ST-segment elevation myocardial infarction. Left coronary angiography revealed acute occlusion of the proximal left anterior descending artery. After several additional diagnostic procedures and implantation of a drug-eluting stent, an abrupt clinical deterioration manifested with sudden hypotension. There was evidence of cardiac tamponade, and the constant supply of blood from the pericardium along with the development of cardiogenic shock state led us to suspect cardiac laceration. This imaging series illustrates a heart team operating in vivo on a rare acute myocardial infarction mechanical complication, which occurred soon after primary percutaneous coronary intervention.

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.

Importance of central BP assessment in ISH of the young. Which devices are best suited for practical use?

Isolated systolic hypertension (ISH), defined as brachial systolic blood pressure (bSBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg, is highly prevalent among young subjects and in the elderly. The prognostic significance of ISH in young individuals remains the object of large debate which might be solved, at least in part, if considering the prognostic role of central BP. For any given value of pBP, the cardiovascular (CV) risk is better defined by central BP (cBP). Young individuals with ISH have long been considered at low CV risk, given the assumption that a "spurious hypertension" phenotype characterized by elevated peripheral (brachial) BP (pBP), normal cBP, and elevated BP amplification was often found in this population. However, this remains to be proven, because many other studies found no differences in BP amplification between ISH and sisto-diastolic hypertension. Despite numerous attempts, methodologies for cBP assessment by non-invasive devices are currently not standardized. As a result, different devices could provide different cBP values despite using the same biological signals. Devices providing accurate estimates of BP amplification as a dimensionless ratio between amplitudes of central and peripheral arterial waveforms might be well suited for clinical purposes in young individuals with ISH. There is urgent need of well-designed prospective studies aiming at longitudinally evaluating the amount of CV risk associated with elevated cBP in young subjects with ISH and their related incremental prognostic value.

Protective Biomolecular Mechanisms of Glutathione Sodium Salt in Ischemia-Reperfusion Injury in Patients with Acute Coronary Syndrome-ST-Elevation Myocardial Infarction.

Ischemia-Reperfusion Injury (IRI) is responsible for adverse outcomes in patients with ST-Elevation Myocardial Infarction (STEMI). Oxidative stress, resulting from the production of Reactive Oxygen Species (ROS) and low availability of Glutathione (GSH), are the two main mediators of IRI. The effectiveness of exogenous antioxidant therapy in this scenario is still debated, since the encouraging results obtained in animal models have not been fully reproduced in clinical studies. In this review we focus on the role of GSH, specifically on the biomolecular mechanisms that preserve myocardial cells from damage due to reperfusion. In this regard, we provide an extensive discussion about GSH intrinsic antioxidant properties, its current applications in clinical practice, and the future perspectives.

Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

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.

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.

Left atrial volume indexed for height2 is a new sensitive marker for subclinical cardiac organ damage in female hypertensive patients.

Left atrial enlargement (LAe) is a subclinical marker of hypertensive-mediated organ damage, which is important to identify in cardiovascular risk stratification. Recently, LA indexing for height was suggested as a more accurate marker of defining LAe. Our aim was to test the difference in LAe prevalence using body surface area (BSA) and height2 definitions in an essential hypertensive population. A total of 441 essential hypertensive patients underwent complete clinical and echocardiographic evaluation. Left atrial volume (LAV), left ventricular morphology, and systolic-diastolic function were evaluated. LAe was twice as prevalent when defined using height2 (LAeh2) indexation rather than BSA (LAeBSA) (51% vs. 23%, p < 0.001). LAeh2, but not LAeBSA, was more prevalent in females (p < 0.001). Males and females also differed in left ventricular hypertrophy (p = 0.046) and left ventricular diastolic dysfunction (LVDD) indexes (septal Em/Etdi: p = 0.009; lateral Em/Etdi: p = 0.003; mean Em/Etdi: p < 0.002). All patients presenting LAeBSA also met the criteria for LAeh2. According to the presence/absence of LAe, we created three groups (Norm = BSA-/h2-; DilH = BSA-/h2+; DilHB = BSA+/h2+). The female sex prevalence in the DilH group was higher than that in the other two groups (Norm: p < 0.001; DilHB: p = 0.036). LVH and mean and septal Em/Etdi increased from the Norm to the DilH group and from the DilH to the DilHB group (p < 0.05 for all comparisons). These results show that LAeh2 identified twice as many patients as comparing LAe to LAeBSA, but that both LAeh2 and LAeBSA definitions were associated with LVH and LVDD. In female patients, the LAeh2 definition and its sex-specific threshold seem to be more sensitive than LAeBSA in identifying chamber enlargement.

Dipyridamole versus verapamil for treatment of no-reflow during primary angioplasty.

BACKGROUND: No previous study has assessed the possible role of dipyridamole for treatment of no-reflow during acute myocardial infarction (AMI). METHODS AND RESULTS: Forty-six consecutive patients (age 64 ± 13 years, 37 men) with no reflow during primary percutaneous coronary intervention were randomized to initial treatment with either dipyridamole (0.56 mg/kg i.c.) or verapamil (1 mg i.c.). Patients with unsuccessful response to the first drug were then switched to the second one (from dipyridamole to verapamil and vice versa). Angiographic end-points were similar in the two groups: TIMI flow was 2.9 ± 0.3 versus 2.8 ± 0.4 (P = 0.28), corrected TIMI frame count (cTFC) 26.4 ± 8.8 versus 31.6 ± 11.4 (P = 0.14) and TIMI myocardial perfusion grade (TMPG) 2.1 ± 1.2 versus 1.7 ± 1.2 (P = 0.12) in dipydidamole and verapamil group, respectively. Optimal myocardial perfusion (TMPG-3) was achieved by 56% of patients with dipyridamole and 39% with verapamil (P = 0.38). In patients with persistent no-reflow administration of dipyridamole on top of verapamil resulted in a significant further improvement of cTFC (from 31.6 ± 11.4 to 24.6 ± 5.7 P = 0.009) and of TMPG (from 1.7 ± 1.2 to 2.6 ± 0.7, P = 0.007). Conversely, verapamil did not induce a significant improvement in coronary flow (cTFC changed from 26.4 ± 8.8 to 24.5 ± 8.5, P = 0.28 and TMPG from 2.1 ± 1.2 to 2.4 ± 1.2, P = 0.13). There were no significant side effects induced by dipyridamole, while verapamil caused AV block in 9% of cases. CONCLUSIONS: Dipyridamole is a safe and effective first-line drug for treatment of no-reflow. Dipyridamole can also be successfully used in patients with incomplete response to verapamil.

Operators' radiation exposure reduction during cardiac catheterization using a removable shield.

Cardiac catheterization through radial access is associated with significant ionizing radiation exposure for the operator. We aimed at evaluating whether a removable shield placed upon the patient could impact favorably on annual radiation exposure for the operator. We designed a pre-post study comparing radiation exposure in a total of five operators under standard protection procedures (first period) and after applying a removable shield (second period). Each period included all the procedures performed in 1 year. Radiation exposure was measured through three dosimeters on each operator. A total of 1610 procedures were performed during the first period, and 1670 during the second period. For each operator, Fluoroscopy Time (FT) per exam did not differ between the two periods (13.1 ± 1 vs 12.9 ± 2 min/exam, p = 0.73), whereas Dose-Area Product (DAP) per procedure was slightly higher in the second period (5.247 ± 651 vs 6.374 ± 967 mGy/cm2, p < 0.01). The use of a removable shield significantly reduced operators' radiation dose at the left bracelet (64.3 ± 13.3 µSv/exam vs 23.8 ± 6.0 µSv/exam, p = 0.003). This remained significant even after adjustment for DAP per procedure (p = 0.015) and number of operators participating to each procedure (p = 0.013), whereas no significant difference was observed for card (5.6 ± 10.5 µSv/exam vs 0.9 ± 0.3 µSv/exam, p = 0.36) and neck bands (3.3 ± 4.5 µSv/exam vs 2.0 ± 2.0 µSv/exam, p = 0.36) dosimeters. The use of a removable shield during cardiac catheterization reduces radiation exposure at the level of the operator's upper limb, whereas no difference was found for other body parts. This may help in reducing radiation exposure of operator's hand. DAP increase merits further investigation.

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H2O2) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H2O2 generation on myocardium. METHODS: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H2O2 production, 8-iso-prostaglandin F2α (PGF2α) formation, H2O2 breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. RESULTS: Following acute reperfusion, a significant reduction of H2O2 production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H2O2 persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). CONCLUSION: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H2O2 generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding. TRIAL REGISTRATION NUMBER: EUDRACT 2014-00448625; Pre-results.