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.

Gender-related differences in changes of estimated bleeding risk in patients on dual antiplatelet therapy: the RE-SCORE multicenter prospective registry.

The risk of bleeding as predicted by the PRECISE-DAPT score can vary over time after percutaneous coronary intervention (PCI). We sought to compare the predictive ability of the PRECISE-DAPT score calculated at baseline and reassessed during follow-up in male and female patients undergoing PCI. The RE-SCORE was a multicenter, prospective registry including patients undergoing PCI treated with dual antiplatelet therapy (DAPT) for 1 year. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The PRECISE-DAPT score was determined for each patient at the time of PCI and at 1, 4 and 8-month follow-up visits or before the occurrence of an endpoint event. A total of 480 patients undergoing PCI were included. At baseline, median PRECISE-DAPT score was similar in males (23.2 [IQR 20.1-24.2]) and females (23.4 [IQR 20.2-25.3]; p = .22). During follow-up, an increase in the PRECISE-DAPT occurred significantly more often in females (44%) than in males (23%; p < .001). The discrimination of the PRECISE-DAPT score calculated at baseline was marginal in both males (c-index = 0.59, 95% CI: 0.51-0.65) and females (c-index = 0.55, 95% CI: 0.49-0.60). The discriminative ability of the score reassessed at follow-up was excellent in females (c-index = 0.84; 95% CI: 0.77-0.91) but remained modest in males (c-index = 0.61; 95% CI: 0.55-0.70). The bleeding predictive ability of the PRECISE-DAPT score can vary over time, more commonly in females than males. The discrimination of the score calculated during follow-up appeared improved in females but remained modest in males.Clinical Trial Registration - ClinicalTrials.gov Identifier: NCT03526614.

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.

Bi-Atrial Function before and after Percutaneous Closure of Atrial Septum in Patients with and without Paroxysmal Atrial Fibrillation: A 2-D and 3-D Speckle Tracking Echocardiographic Study.

Our aim was to analyze atrial function with 2-D (2-D-STE) and 3-D (3-D-STE) speckle tracking echocardiography in patients with atrial septal devices and paroxysmal atrial fibrillation (PAF). One hundred sixteen patients and a subgroup of 22 patients who developed PAF after device insertion were studied. Left atrial and right atrial peak longitudinal strain and standard deviations of time to peak strain (TPS) were calculated using 2-D-STE. The left atrial/right atrial emptying fraction and expansion index were determined using 3-D-STE. By multivariate analysis, pre-closure 3-D right atrial expansion index, left atrial time to peak strain, and 3-D left atrial expansion index were independently associated with PAF. Compared with the other indices, receiver operating characteristic analysis revealed better diagnostic accuracy for the combination of pre-closure time to peak strain and 3-D expansion index in detecting PAF. Patients with atrial septal devices have pre-existing left and right atrial dilation and dysfunction as assessed by 2-D-STE and 3-D-STE that appear sensitive for the stratification of PAF risk in this population.

The role of Glycoprotein IIb/IIIa inhibitors in acute coronary syndromes and the interference with anemia.

The role played by glycoprotein (GP) IIb/IIIa inhibitors (GPI) has continuously evolved until the most recent Guidelines whereby they were stepped down from class I to class II recommendation for treating acute coronary syndromes (ACS). GPI compete with a wider use of ADP inhibitors and novel anticoagulant drugs although GPI use has greatly narrowed. However, GPI may still have a role. Several criteria were proposed to define post-PCI anemia which is strictly related to bleeding and transfusion. In ACS, it should be important to define anemia in comparative terms versus baseline levels: ≥ 15% of red blood cell decrease should be a practical cut-off value. If one wishes to concentrate on hemoglobin (Hb), a≥2g/dl Hb decrease from baseline should be considered. It is important to recognize post-PCI anemia in the setting of ACS. There are sub-populations exposed to short-term hemorrhagic and/or long-term ischemic risks. Ischemic and hemorrhagic risks need to be carefully evaluated along with thrombocytopenia and its prognostic significance in order to put all these blood and rheological parameters into a clinically oriented perspective on which therapeutical decisions should be based. Definition of high risk procedures (complexity, angiographic characteristics and patient's risk profile, regardless whether STEMI or NSTEMI) may help selecting GPI. There are positive elements in GPI use: efficacy, rapid onset and reversibility of action, absence of pharmacogenomic variability, pharmacoeconomic considerations and the possibility of intracoronary administration. All these elements should be evaluated when selecting these agents for therapeutics.

Effectiveness of a novel biodegradable polymer, sirolimus-eluting stent platform in percutaneous coronary intervention.

BACKGROUND: The purpose of this registry is to report the immediate and long-term safety and efficacy of the Biotronik Orsiro stent in an unselected population during everyday practice. METHODS: Between May 2012 and June 2013, 246 consecutive coronary angioplasty procedures were performed using at least one Orsiro drug-eluting stent, in 225 patients and 303 lesions. RESULTS: Diabetes was present in 34.7% of patients. Procedures were non-elective percutaneous coronary intervention (PCI) in 17.1% of cases and acute coronary syndromes were 55.1%. Radial vascular access was used in 78% of cases, multivessel PCI was performed in 19.5% of the procedures. In 81.6% of cases lesions were B2/C type, 20.7% of procedures had bifurcation lesions. Procedural success was 99.6%. No acute thrombosis occurred. Clinical follow-up median period was 24.3 (±8.28) months and FU was available in 93.7% of patients. Death for any cause occurred in 11 patients (5.2%), 6 of them were non cardiac-related. Cardiac-related death rate was 2.4%. Two patients had in-stent restenosis. The overall target lesion failure rate was 3.3%. CONCLUSIONS: This observational data regards our experience with Biotronik Orsiro stent in an unselected population. This initial data, although limited by a mainly clinical follow-up and restricted number of patients, confirms the good clinical performance of this sirolimus-eluting stent with a biodegradable polymer in everyday practice, including complex lesions, according to current larger studies in the literature.

Assessment of Biventricular Function by Three-Dimensional Speckle-Tracking Echocardiography in Secondary Mitral Regurgitation after Repair with the MitraClip System.

BACKGROUND: The goal of this study was to determine changes in left ventricular (LV) and right ventricular (RV) function with three-dimensional (3D) speckle-tracking echocardiography (STE) after percutaneous mitral valve repair with the MitraClip system in high-risk surgical patients with moderate to severe or severe secondary mitral regurgitation (MR). METHODS: Thirty-two patients with MR undergoing MitraClip were prospectively included. Patients underwent two-dimensional (2D) and 3D transthoracic echocardiography before clip implantation and after 6-month follow-up. LV and RV longitudinal strain was obtained by 2D STE and 3D STE. LV circumferential, radial, and area strain was calculated by 3D STE. Data analysis was performed offline. RESULTS: At 6-month follow-up, significant improvements were seen in LV 2D global longitudinal strain (P < .005), 3D global longitudinal strain (P = .0002), and 3D area strain (P = .0001). Overall, significant improvements were also seen in 3D RV ejection fraction (P < .05) and 3D RV free-wall longitudinal strain (P < .05). A poor increase in LV strain after clip implantation (P = NS) occurred in patients with pronounced preexisting RV dysfunction. The areas under the receiver operating characteristic curves for LV and RV 3D speckle-tracking echocardiographic parameters showed high discriminative values (range, 0.87-0.91) in predicting unfavorable outcomes with persistent symptoms (New York Heart Association class > II) after the procedure. CONCLUSIONS: Three-dimensional STE showed overall LV and RV strain improvement after clip implantation as well as lower postprocedural LV strain values in patients with worse preexisting RV function. These findings could help in guiding MR treatment strategies, suggesting different therapies in the presence of marked RV impairment or anticipating the procedure in case of evolving RV dysfunction.

Global and regional left ventricular strain indices in post-myocardial infarction patients with ventricular arrhythmias and moderately abnormal ejection fraction.

The aim of the study described here was to compare myocardial strains in ischemic heart patients with and without sustained ventricular tachycardia (VT) and moderately abnormal left ventricular ejection fraction (LVEF) to investigate which index could better predict VT on the basis of the analysis of global and regional left ventricular (LV) dysfunction. We studied 467 patients with previous myocardial infarction and LVEF >35%. Fifty-one patients had documented VT, and 416 patients presented with no VT. LV volumes and score index were obtained by 2-D echocardiography. Longitudinal, radial and circumferential strains were determined. Strains of the infarct, border and remote zones were also obtained. There were no differences in standard LV 2-D parameters between patients with and those without VT. Receiver operating characteristic values were -12.7% for global longitudinal strain (area under the curve [AUC] = 0.72), -4.8% for posterior-inferior wall circumferential strain (AUC = 0.80), 61 ms for LV mechanical dispersion (AUC = 0.84), -10.1% for longitudinal strain of the border zone (AUC = 0.86) and -9.2% for circumferential strain of the border zone (AUC = 0.89). In patients with previous myocardial infarction and moderately abnormal LVEF, peri-infarct circumferential strain was the strongest predictor of documented ventricular arrhythmias among all strain quantitative indices. Additionally, strain values from posterior-inferior wall infarctions had a higher association with arrhythmic events compared with global strain.

Echocardiographic findings in simple and complex patent foramen ovale before and after transcatheter closure.

AIMS: Percutaneous closure of patent foramen ovale (PFO) in cryptogenic cerebrovascular events is an alternative to medical therapy. The interpretation of residual shunts after implantation of different devices for PFO with different morphologies is controversial. METHODS AND RESULTS: Transcatheter PFO closure was performed in 123 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer (n = 46), Figulla Occlutech (n = 41), and Atriasept Cardia (n = 36). Fifty-six patients presented with simple PFO and 67 patients had complex morphologies. All patients were studied with contrast enhanced transesophageal echocardiography (TEE) before interventional procedure and thereafter at 1 and 6 months and every 6-12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive TEE studies. Various PFO morphologies were identified by TEE before device implantation. The device size to PFO diameter ratio was significantly increased in patients with complex PFO compared with those patients with a simple PFO morphology (P < 0.05). The difference between the closure rate of S-PFO and C-PFO concerning each device type was significant (Amplatzer P = 0.0027, Figulla P = 0.0043, and Atriasept P < 0.01). The mean follow-up period was 3.4 years (median 2.7 years) with a cerebrovascular re-event rate of 2.4% per year. In three patients, thrombi were detected in the 6-month TEE controls and resolved after medical therapy. In three other patients, the implantation of an adjunctive device was necessary for residual shunt. CONCLUSION: In our series of patients, the closure rate was dependent on PFO morphology more than occluder size and type. An adjunctive device was implanted in selected cases.

Aspirin reload before elective percutaneous coronary intervention: impact on serum thromboxane b2 and myocardial reperfusion indexes.

BACKGROUND: Microvascular obstruction seems to predict poor outcome in patients undergoing elective percutaneous coronary intervention (PCI), but the underlying mechanism is still unclear. We analyzed whether serum thromboxane B2, a stable metabolite of thromboxane A2, may be implicated in post-PCI microvascular obstruction. METHODS AND RESULTS: We enrolled 91 patients (74 males, 66±10 years) on chronic low-dose aspirin therapy (aspirin, 100 mg daily) scheduled for elective PCI and randomly assigned to receive aspirin reload (325 mg orally, n=46) or no reload (control group, n=45) ≥1 hour before elective PCI. Serum levels of thromboxane B2, reperfusion indexes (corrected Thrombolysis In Myocardial Infarction frame count and myocardial blush grade), and serum cardiac troponin I were assessed before and after PCI. Serum thromboxane B2 significantly increased after 120 minutes (P=0.0447) from PCI in control but not in aspirin reload group. After PCI, both groups showed a statistically significant reduction in corrected Thrombolysis In Myocardial Infarction frame count more evident in aspirin reload group (P=0.0023). Moreover, after PCI, 61% of patients allocated to aspirin reload and only 32% of patients allocated to control group reached normal microcirculatory reperfusion (myocardial blush grade=3); patients with myocardial blush grade=3 exhibited lower values of serum thromboxane B2 compared with those with myocardial blush grade <3 (P=0.05). Periprocedural cardiac troponin I significantly increased (F=3.64; P=0.01334) and correlated with serum thromboxane B2 (ρ=0.31; P=0.0413) in control but not in aspirin reload group. In addition, left ventricular ejection fraction significantly increased after PCI only in the aspirin reload group (P=0.0005). CONCLUSIONS: Aspirin loading dose before elective PCI improves myocardial reperfusion and injury indexes, suggesting a possible role of platelet thromboxane A2 in microvascular occlusion. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01374698.

Operator exposure to x-ray in left and right radial access during percutaneous coronary procedures: OPERA randomised study.

OBJECTIVE: Left radial access (LRA) and right radial access (RRA) have been shown to be safe and effective for coronary arteries catheterisation. However, the differences between the two approaches in terms of radiation exposure are still unclear. The aim of the present investigation is to evaluate in a randomised study, the dose of radiation absorbed by operators using either LRA or RRA. DESIGN: Randomised, prospective, double arm, single centre study. SETTING: University Hospital. PATIENTS: Male or female subjects with stable, unstable angina and silent ischaemia. INTERVENTIONS: The present study is a comparison of LRA and RRA for coronary artery catheterisation in terms of operators' radiation exposure. MAIN OUTCOME MEASURES: The primary outcome measure was the radiation dose absorbed by operators; secondary outcome measures were fluoroscopy time, dose-area product and contrast delivered. RESULTS: A total of 413 patients were enrolled; 209 were randomly selected to undergo diagnostic procedures with RRA and 204 with LRA. The operator's radiation exposure was significantly lower in the left radial group (LRA 33±37 µSv vs RRA 44±32 µSv, p=0.04). No significant differences were observed in  fluoroscopy time (LRA 349±231s vs RRA 370±246 s p=0.09) and dose-area product (LRA 7011.42±3617.30 µGym(2) vs RRA 7382.38±5226.61 µGym(2), p=0.80), even though in both there was a trend towards a lower level in the LRA. No differences were observed in contrast medium delivered (LRA 89.92±32.55 ml vs RRA 88.88±35.35 ml, p=0.45). CONCLUSIONS: The LRA was associated in the present report with a lower radiation dose absorbed by the operator during coronary angiography.

Idiopathic, serial coronary vessels dissection in a young woman with psychological stress: a case report and review of the literature.

Spontaneous coronary artery dissection (SCAD) is a very rare disease, associated with high mortality rate, whose etiology and pathogenesis are poorly understood. Its sporadic nature and the varied angiographic extent make firm recommendations regarding revascularization impossible. The case described is that of a young, otherwise healthy woman, without a known underlying condition which may lead to SCAD, but with a history of intense psychological stress. We managed the patient with a conservative approach based on watchful waiting, medical therapy, and plain old balloon angioplasty (POBA) with low inflation atmospheres.

Cardiological assessment of cardiac patients undergoing non-cardiac surgery (usefulness of surveys).

AIM OF THE STUDY: The aim of the study was to considerate the effective usefulness of preoperative stress test and echocardiography in adult patients with coronary artery disease, undergoing non-cardiac surgery. MATERIALS AND METHODS: In the last three years, 200 patients aged 58-85, affected by stable ischemic pathology, undergoing non cardiac surgery, and treated with oral drugs, were enrolled for an assessment orotocol including anamnesis, objective examination, blood pressure, RCG, blood chemistry analysis, and was performed a cardiac risk evaluation. A second 50 patients control cohort of the same class was subjected to the same tests, and preoperative and exercise stress test. RESULTS: All patients showed a good hemodynamic compensation and a quick recovery, and the group of 200 patients for whom the risk was closed without further investigation has concluded the process on average three days before the group underwent echocardiography and exercise stress test. DISCUSSION: The clinical evaluation of cardiac patients waiting for non-cardiac surgery, performed through anamnesis, examinations and the ECGs, is the cornerstone of cardiac risk stratification. It also important the type of surgery, as well as some priority conditions like certain neoplastic: diseases, where it seems appropriate to speed up the diagnostic program. CONCLUSIONS: When patients are hemodynamically stable and their conditions controlled by appropriate therapy, it is sufficient to perform first-level tests for the preoperative stratification of cardiovascular risk. It's recommended to perform echocardiogram and stress test when the first level tests are abnormal, when there is a worsening of the conditions prior to admission, or when the patient is not hemodynamically stable.

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.

Very late bare metal stent thrombosis with concomitant patent drug eluting stent in the same vessel: a case for a suggestive hypothesis.

We report a case of very late stent thrombosis of a bare metal stent with a concurrent drug eluting stent's patency in the same coronary vessel, in a patient undergoing primary angioplasty who discontinued his clopidogrel regimen a few weeks after successful deployment of the stents.