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.

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.

[Temporal evolution of antithrombotic therapy use in patients with acute coronary syndromes undergoing percutaneous coronary intervention in Italy: comparison between the EYESHOT and SCOPE registries]. / Analisi della recente evoluzione temporale dell'impiego della terapia antitrombotica nei pazienti con sindrome coronarica acuta sottoposti ad angioplastica coronarica in Italia: confronto dei registri EYESHOT e SCOPE.

BACKGROUND: Few data exist on temporal evolution of antithrombotic agent use in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) in Italy. We sought to compare data from the most recent prospective, multicenter, nationwide registries conducted in Italy, namely EYESHOT and SCOPE. METHODS: EYESHOT enrolled 2585 consecutive ACS patients, both ST-segment elevation myocardial infarction (STEMI) and non-ST elevation ACS (NSTE-ACS), admitted to 203 Italian coronary care units over a 3-week period (2-22 Dec 2013 and 27 Jan-16 Feb 2014). Among patients enrolled in EYESHOT, 1755 (67.9%) underwent PCI (52.6% with STEMI and 47.4% with NSTE-ACS). In the SCOPE registry, a total of 1363 patients undergoing PCI were enrolled over 3 months (15 Feb-15 Apr 2016) in 39 Italian cath lab centers at medium to high PCI volume: 331 (24.3%) with a diagnosis of STEMI and 1032 (75.7%) with a diagnosis of NSTE-ACS. RESULTS: Over 2 years, the use of clopidogrel in the cath lab significantly decreased (from 11% to 8% in STEMI; p=0.06 and from 9% to 5% in NSTE-ACS; p=0.0002), while the administration of ticagrelor dramatically increased (from 14% to 37%; p<0.0001 in STEMI and from 7% to 44%; p<0.0001 in NSTE-ACS). At discharge, a significant decrease in the use of clopidogrel (from 32% to 21% in STEMI; p=0.02, and from 47% to 24% in NSTE-ACS; p<0.0001) and a concomitant increase in the novel P2Y12 receptor inhibitor prescription occurred, particularly among NSTE-ACS patients (from 8% to 14% for prasugrel; p=0.002 and from 43% to 58% for ticagrelor; p=0.03). CONCLUSIONS: From the present analysis on ACS patients undergoing PCI enrolled in EYESHOT and SCOPE registries, a significant increase in the use of novel P2Y12 receptor inhibitors was observed, both at the time of PCI and at discharge.

Distal left circumflex coronary artery flow reserve recorded by transthoracic Doppler echocardiography: a comparison with Doppler-wire.

BACKGROUND: Coronary flow reserve (CFR) recording by means of transthoracic echocardiography (TTDE) in all the main distal coronary arteries is a challenge for advanced echocardiography. Validation studies of TTDE versus Doppler-wire (DW) recordings are available for Left Anterior Descending artery (LAD) and the Posterior Descending coronary artery (PD), but lacking for the more technically challenging Left Circumflex coronary artery (LCx). AIM: To evaluate the reliability of TTDE in assessing CFR in LCx when compared to the intracoronary Doppler flow-wire gold standard. METHODS: we evaluated 5 patients (age = 60 +/- 9 years, 5 males) on LCx by TTDE and invasive CFR assessment. TTDE recording was performed using a low-frequency probe, with a four-chamber as a guiding 2D view. The 2 tests were performed on different days and in random order within 48 hours in a blind fashion. Vasodilator stimulus was adenosine, intravenously (140 gamma/kg/min x 3-6 min) for TTDE and intracoronary (40 gamma bolus) for DW recordings. RESULTS: CFR values on LCx ranged from 1.9 to 2.8 for DW, and from 2.0 to 3.0 for TTDE, with an overall correlation of R = 0,85 (p = 0,06); normal (CFR > 2.5) or abnormal (CFR < 2.5) value was concordantly identified by the 2 techniques in 4 out 5 cases (80%). CONCLUSION: CFR of LCx artery can be obtained noninvasively with TTDE.

[Severe aortic stenosis successfully treated with percutaneous aortic valve implantation]. / Stenosi aortica severa inoperabile trattata con successo mediante impianto di valvola aortica per via percutanea.

Patients with severe calcific aortic stenosis are occasionally not amenable to surgery because of advanced age or severe co-morbidities. Percutaneous aortic valve dilation is used but has only limited time relief. While preclinical evidence on percutaneous aortic valve replacement seems promising, only very limited clinical data are available worldwide. We hereby present the first case of percutaneous aortic valve replacement successfully performed in Italy in a 74-year-old high-risk female. This case emphasizes the technical challenges inherent to this procedure and its promising role in selected very high-risk patients with severe aortic stenosis, notwithstanding the early and long-term risk of adverse events.

A uncommon cause of angina during upper limb exercise.

Subclavian artery stenosis or occlusion may be a cause of myocardial ischemia in patients treated using an internal mammary artery graft. Subclavian stenosis may cause myocardial ischemia during arm exercise by a coronary-subclavian steal phenomenon, with flow inversion in the graft from the coronary tree to the left subclavian artery. We here describe a case of a patient developing left subclavian occlusion after coronary artery bypass grafting with the left internal mammary artery. The lesion was successfully treated with a carotid-subclavian bypass. The article underscores the importance of an early diagnosis (possibly before bypass surgery) and discusses possible treatments. Percutaneous interventions with stent implantation appear the treatment of choice, but surgery has an important role in case of total occlusion.