Giulia Benedetti

Thrombus Aspiration During Primary Percutaneous Coronary Intervention Improves Myocardial Reperfusion and Reduces Infarct Size. The EXPIRA (Thrombectomy With Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention) Prospective, Randomized Trial

OBJECTIVES The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND PPCI may cause thrombus dislodgment, leading to microvascular damage. METHODS One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST-segment resolution >70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size. RESULTS Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months. CONCLUSIONS Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

Impact of Thrombectomy With EXPort Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention (EXPIRA Trial) on Cardiac Death

In ST-segment elevation myocardial infarction (STEMI) impairment of microcirculatory function is a negative independent predictor of myocardial function recovery. In the Impact of Thrombectomy with EXPort Catheter in Infarct-Related Artery during Primary Percutaneous Coronary Intervention (PCI; EXPIRA) trial we found that manual thrombectomy resulted in a better myocardial reperfusion expressed by an improved procedural outcome and a decrease of infarct size compared to conventional PCI. The aim of the present study was to investigate whether the early efficacy of thrombus aspiration translates into very long-term clinical benefit. We randomized 175 patients with STEMI with occlusive thrombus at baseline undergoing primary PCI to thromboaspiration with a manual device (Export Medtronic, n = 88) or standard PCI (n = 87). No differences in baseline, clinical, and angiographic preprocedural findings were observed between the 2 groups except for incidence of hypertension and cholesterol levels. After 24 months major adverse cardiac events were 13.7% versus 4.5% (p = 0.038, log-rank test) and cardiac death was 6.8% versus 0% (p = 0.012, log-rank test). A strict correlation was observed between cardiac death incidence and tissue reperfusion parameters (postprocedural myocardial blush grade and ST-segment resolution). In conclusion, manual thrombus aspiration before stenting of the infarct-related artery in selected patients with STEMI improving myocardial reperfusion significantly decrease cardiac death and major adverse cardiac events at 2 years.

Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel The RESET GENE Trial

Background—High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs. Methods and Results—Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003). Conclusions—HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01465828.

Incidence of contrast-induced acute kidney injury associated with diagnostic or interventional coronary angiography

BACKGROUND Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-acquired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. METHODS For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical analysis was completed using Students t-test, chi-square or Fisher exact test, and multivariate logistic regression. RESULTS Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were significantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. CONCLUSIONS The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabetes. Lower levels of basal hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media volume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

Integrin β2-chain (CD18) over-expression on CD4+ T cells and monocytes after ischemia/reperfusion in patients undergoing primary percutaneous revascularization

β2-integrin subunit (CD18) plays an essential role in leukocyte recruitment and adhesion in sites of endothelial injury. We analyzed the surface expression of CD18 on T lymphocytes and monocytes in a series of patients presenting acute coronary syndrome (ACS) who underwent primary percutaneous intervention (PCI) for coronary artery revascularization. We found that basal CD18 expression on peripheral blood-derived CD4+ (but not CD8+) T lymphocytes was significantly increased in ACS patients as compared with age-matched healthy volunteers. During primary PCI, a significant increase in CD18 molecule density was detected immediately after balloon deflation (reperfusion) on both CD4+ T cells and monocytes obtained from the right atrium (RT) as compared with basal values. These data suggest that upregulation of CD18 molecules plays an important role in local recruitment of CD4+ T cells and monocytes to the site of endothelial damage after ischemia/reperfusion, therefore being responsible, at least in part, for the inflammatory-mediated complications associated with primary PCI.

A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale.

Background Percutaneous coronary intervention (PCI) is a highly effective therapy for acute ST-elevation myocardial infarction. Adjunctive therapy with platelet glycoprotein (GP) IIb/IIIa inhibitor can result in increased vessel patency and improved outcomes in ST-elevation myocardial infarction patients undergoing PCI. The investigation of novel dosing and delivery strategies of this therapy may help to further improve outcomes. Methods IC-Clearly is a randomized, open-label, multicenter trial, with the purpose of evaluating the effectiveness of an intracoronary bolus dose of abciximab delivered using the ClearWay RX catheter vs. an intravenous bolus of abciximab for ST-elevation myocardial infarction with angiographically visible thrombus (thrombus grade ≥2). A total of 150 patients will be randomized 1: 1 to treatment of the culprit artery with intracoronary abciximab (75 patients) or intravenous abciximab (75 patients) in addition to a maintenance infusion regimen of abciximab administered intravenously for 12 h after PCI. The number of patients included in this study is based on the estimation of sample size needed to identify a statistically significant difference in the primary endpoints between the two groups. The primary endpoint chosen to evaluate this hypothesis is infarct size assessed by cardiac magnetic resonance. Clinical outcomes will be assessed for each patient through hospital discharge and at 30-day follow-up. Conclusion The purpose of this study is to evaluate whether an intracoronary bolus of abciximab delivered with the ClearWay RX catheter prior to the 12 h post-PCI intravenous infusion regimen of abciximab will result in significant additional clot resolution in vivo and improved myocardial perfusion when compared with an intravenous bolus of abciximab on top of the 12 h post-PCI intravenous infusion regimen of abciximab as per standard practice. The primary endpoint chosen to evaluate this hypothesis is infarct size as assessed by cardiac magnetic resonance.

Comparison between balloon angioplasty and additional coronary stent implantation for the treatment of drug-eluting stent restenosis: 18-Month clinical outcomes

Objective To evaluate the long-term outcomes after different modalities of treatment of drug-eluting stent (DES) in-stent restenosis (ISR) in a ‘real world’ setting. Methods Actually, few and conflicting data are available about the management of in-stent restenosis (ISR) after DES implantation. In our ‘real world’ registry 1082 consecutive patients who received a DES implantation were included. At 9-month angiographic follow-up, 93 patients presented a DES ISR that was treated with ‘homo-DES’ (HMD) (N = 27), ‘hetero-DES’ (HTD) (N = 19) and conventional balloon angioplasty (POBA) (N = 47). We evaluated the clinical outcomes in terms of major adverse cardiac event (MACE) (death, myocardial infarction and target vessel revascularization) at 18 months. Results There was no difference for clinical and angiographic characteristics between the three groups, except for the presence of silent ischaemia as clinical presentation (7.7 HMD vs. 2.2% POBA; P = 0.0001). No late stent thrombosis was found. At 18-month clinical follow-up patients treated with HMD, HTD and POBA presented a rate of MACE of 10.2, 0 and 8.7%, respectively (P = NS). Kaplan–Meier survival probability showed that HTD and POBA treatment tended to have more favourable outcomes at 18 months than the HMD treatment. Conclusion In our registry, POBA seems to be as effective as other DES implantations in cases of DES ISR, especially in cases of focal type (Mehran classification IA, IC), in terms of long-term outcomes.

Computed-Tomography and Magnetic Resonance Imaging Assessment of Traumatic Left Anterior Descending Coronary Dissection Causing Acute Myocardial Infarction

![Figure][1] ![Figure][1] [![Graphic][3] ][3] A 16-year-old healthy boy involved in a car accident sustained a blunt chest trauma. He was admitted to the emergency department because of severe chest pain associated with remarkable elevation of the ST-segment in the anterior

Role of the central endogenous opiate system in patients with syndrome X

BACKGROUND To evaluate the role of the endogenous opioid system (EOS) in abnormal pain perception in patients with syndrome X, we used a neuroendocrine approach, evaluating plasmatic luteinizing hormone (LH) changes after naloxone, a competitive antagonist of opioid receptors able to unblock tonic EOS inhibition on gonadotropin release. Thus LH response to naloxone test indicates the central EOS activity on hypothalamic luteinizing hormone-releasing hormone (LH-RH) inhibitory opioid receptors. METHODS Ten patients with syndrome X, 10 age-matched male patients with coronary artery disease (CAD), and 10 normal subjects were analyzed. Naloxone tests were performed between 8 and 9 am. Basal beta-endorphin and LH levels were determined on 4 blood samples at 20-minute intervals; after naloxone (0.1 mg/kg intravenously in 4 minutes), LH was measured on 8 samples at 15-minute intervals. In all patients the test was also performed after LH-RH administration. Anginal pain on exercise testing was subjectively scored on a 1 to 10 analogic scale and wall motion abnormalities were quantified by a wall motion score index. RESULTS Significant differences were found in LH release after naloxone (CAD 260.3 +/- 42.6 vs syndrome X 151.6 +/- 48.5 mIU/mL, P <.05), angina score (CAD 5.5 +/- 1.3 vs syndrome X 7.2 +/- 1.7, P <.05), and wall motion abnormalities (CAD 3.6 +/- 1. 2 vs syndrome X 2.8 +/- 1.9, P <.05). CONCLUSIONS The reduced LH release after naloxone in syndrome X, with a normal LH-RH response, suggests a lower central EOS activity, which may be related to the higher anginal pain perception.

Endogenous opioid system modulation in anginal pain: Demonstration of its central activity

Plasma beta-endorphin levels provide controversial results on the role of endogenous opioid system in modulation of anginal pain. As an alternative, the action of plasmatic luteinizing hormone after administration of naloxone was investigated: naloxone blocks the tonic endogenous opioid system inhibition of gonadotropin release; thus, the level of luteinizing hormone after naloxone administration is an index of central endogenous opioid system activity. Twenty patients with coronary artery disease and positive results of stress tests were selected: 10 had angina (group I) and 10 did not (group II). Ten healthy subjects were also studied as a control group (group III). In all patients basal plasma beta-endorphin levels, basal luteinizing hormone plasma levels (every 15 minutes for 1 hour) and luteinizing hormone plasma levels after administration of 0.1 mg/kg naloxone over 4 minutes (every 15 minutes for 2 hours) were determined. In 15 patients the test was performed after luteinizing hormone releasing hormone was given. The integral concentration time of luteinizing hormone plasma level during baseline (LHiB) and after administration of naloxone (LHiN) or luteinizing hormone releasing hormone (LHiRH), the ratio (LHiN:LHiB and LHiRH:LHiB) and the differences (LHiN-LHiB and LHiRH-LHiB) between the postinfusion period and baseline were calculated. No difference was found in beta-endorphin plasma levels and luteinizing hormone response after luteinizing hormone releasing hormone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)