TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction

Background: Current STEMI guideline recommendations limit the use of prasugrel to clopidogrel-naïve patients. However, in daily clinical practice a considerable proportion of STEMI patients undergoing primary PCI are preloaded with clopidogrel. Whether the use of prasugrel in clopidogrel pretreated STEMI patients is safe remains unknown. Similarly, the efficacy of a combined loading dose regimen has not been evaluated. Methods: Between 1 September 2009 and 15 October 2012, a total of 1,157 STEMI patients were included in the randomized COMFORTABLE AMI trial (NCT 00962416) and 891 STEMI patients in the SPUM ACS registry (NCT 01000701) at 12 centers. Patients were divided into three groups according to type of peri-procedural antiplatelet loading: (1) Clopidogrel and subsequent Prasugrel loading dose [CP], (2) Prasugrel loading dose alone [P] (3) Clopidogrel loading dose alone [C]; 23 patients were excluded because they were not exposed to Clopidogrel and Prasugrel. The primary safety endpoint was the rate of BARC type 3, 4 and 5 bleeding at 30 days. The primary efficacy endpoint was the composite of cardiac death, nonfatal MI and nonfatal stroke at 30 days. Outcomes were analyzed using Cox's Regressions (crude) and multinomial ITPW weighted Cox's Regressions. Results: A total of 2,025 patients were analysed of whom 428 (21.1%) had received CP, 447 (22.1%) patients P alone, and 1,150 (56.8%) patients C alone. The primary safety endpoint was observed among 1.2% of CP, 1.6% of P, and 1.5% of C patients (CP vs C ad. HR 0.99 (0.36-2.72), PC vs P ad. HR 0.73 (0.22-2.41). The primary safety endpoint occurred less frequently among CP (1.9%) compared with C patients (5.0%, adjusted HR 0.47 (0.22-1.00), but with similar frequency among P and C patients (2.9% vs 5.0%, ad. HR 0.68 (0.27-1.73). The net clinical benefit outcome parameter tended to be lower among CP (2.8%) compared with C patients (6.3%, ad. HR 0.56 (0.30-1.05), whereas no significant difference was observed between P and C patients (3.8% vs 6.3%, ad. HR 0.85 (0.39-1.86). Conclusions: Among STEMI patients preloaded with Clopidogrel, the concurrent administration of a Prasugrel loading dose appears safe and potentially more effective than Clopiogrel alone

Effect of Timing of Staged Percutaneous Coronary Intervention on Clinical Outcomes in Patients With Acute Coronary Syndromes.

Background Complete revascularization reduces cardiovascular events in patients with acute coronary syndromes (ACSs) and multivessel disease. The optimal time point of non-target-vessel percutaneous coronary intervention (PCI) remains a matter of debate. The aim of this study was to investigate the impact of early (<4 weeks) versus late (≥4 weeks) staged PCI of non-target-vessels in patients with ACS scheduled for staged PCI after hospital discharge. Methods and Results All patients with ACS undergoing planned staged PCI from 2009 to 2017 at Bern University Hospital, Switzerland, were analyzed. Patients with cardiogenic shock, in-hospital staged PCI, staged cardiac surgery, and multiple staged PCIs were excluded. The primary end point was all-cause death, recurrent myocardial infarction and urgent premature non-target-vessel PCI. Of 8657 patients with ACS, staged revascularization was planned in 1764 patients, of whom 1432 patients fulfilled the eligibility criteria. At 1 year, there were no significant differences in the crude or adjusted rates of the primary end point (7.8% early versus 10.8% late, hazard ratio [HR], 0.72 [95% CI, 0.47-1.10], P=0.129; adjusted HR, 0.80 [95% CI, 0.50-1.28], P=0.346) and its individual components (all-cause death: 1.5% versus 2.9%, HR, 0.52 [95% CI, 0.20-1.33], P=0.170; adjusted HR, 0.62 [95% CI, 0.23-1.67], P=0.343; recurrent myocardial infarction: 4.2% versus 4.4%, HR, 0.97 [95% CI, 0.475-1.10], P=0.924; adjusted HR, 1.03 [95% CI, 0.53-2.01], P=0.935; non-target-vessel PCI, 3.9% versus 5.7%, HR, 0.97 [95% CI, 0.53-1.80], P=0.928; adjusted HR, 1.19 [95% CI, 0.61-2.34], P=0.609). Conclusions In this single-center cohort study of patients with ACS scheduled to undergo staged PCI after hospital discharge, early (<4 weeks) versus late (≥4 weeks) staged PCI was associated with a similar rate of major adverse cardiac events at 1 year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291

Progression of cardiac allograft vasculopathy assessed by serial three-vessel quantitative coronary angiography.

BACKGROUND:The purpose of the present study was to assess the short- and long-term progression of cardiac allograft vasculopathy (CAV) using serial 3-vessel quantitative coronary angiography (QCA). METHODS:CAV progression was assessed using serial 3-vessel QCA analysis at baseline, 1-year and long-term angiographic follow-up (8.5±3.7 years) after heart transplantation. The change in minimal lumen diameter (MLD) and percent diameter stenosis (%DS) was serially assessed within matched segments. Patients were graded according to the ISHLT-CAV classification and grouped as ISHLT-CAV0 and ISHLT-CAV1-3. The primary endpoint was mean change in MLD and %DS. RESULTS:A total of 41 patients and 520 matched segments were available for serial 3-vessel QCA. Overall, MLD decreased non-significantly from baseline to 1-year follow-up and significantly from 1-year to the long-term angiographic follow-up (Δ-0.08mm/year [95%CI -0.11 to -0.05], P<0.001). %DS increased significantly from baseline to 1-year (Δ+0.96%/year [95%CI 0.04 to 1.88], P = 0.041) and from 1-year to long-term angiographic follow-up (Δ+0.61%/year [95%CI 0.33 to 0.88], P<0.001). ISHLT-CAV1-3 at 1 year and at long-term angiographic follow-up was observed in 22% and 61%, respectively. Between baseline and long-term angiographic follow-up, a significant reduction in MLD was observed within both groups without a significant difference in the reduction between the two groups (ISHLT-CAV0: median -0.49mm [IQR -0.54 to -0.43] vs. ISHLT-CAV1-3: median -0.40mm [IQR -0.44 to -0.35], P = 0.4). CONCLUSION:The current data suggest that QCA can't predict CAV beyond 1 year, but, QCA affirmed that CAV progresses to a similar extent in patients who do not develop visual CAV during long-term follow-up

Copolymerization of ethylene with propylene and higher α-olefins catalyzed by (imido)vanadium( iv ) dichloride complexes

International audienceWe have synthesized and characterized a series of dimethylamine–imido V(=NR)Cl2(NHMe2)2 [R = tBu (1a), CPh3 (1b), 2,6-CHPh2-4-Cl-C6H2 (1c)], and pyridine–imido V(=NR)Cl2(Py)3 [R = tBu (2a), CPh3 (2b), 2,6-CHPh2-4-Cl-C6H2 (2c)] complexes. The solid-state structures of 1a–1c, and 2c were determined by X-ray crystallography. Complexes 1a and 2a–2c, in combination with Et2AlCl and Cl3CCO2Et, have been screened as catalysts for the copolymerization of ethylene with various α-olefins (i.e., propylene, 1-hexene, 1-octene, and 4-methyl-1-pentene). The results are compared with the known PMe2Ph–imido V(=NR)Cl2(PMe2Ph)2 [R = tBu (3a), 2,6-iPr2-C6H3 (3d)] complexes. Differences in the (co)polymerization regarding the activity and reactivity toward the target comonomers are investigated to probe the effect of imido ligand substitution, and of the coligand. With the exception of dimethylamine 1a, 2 and 3 are instantaneously activated and exhibit good activity, affording copolymers with a moderate comonomer content (4.2 < mol% < 13.7), from low to high molecular weight (36 < Mw × 103 g mol−1 < 270), and unimodal molecular weight distribution (2.1 < Mw/Mn < 2.7), strongly depending on the type of comonomer, copolymerization temperature, and, to a lesser extent, the type of ligand set employed. 13C NMR spectra of poly(ethylene-co-propylene)s have been fully interpreted as a result of uninterrupted methylene sequence distribution, the ethylene–propylene sequence, and inverted propylene units. In addition, the copolymers were characterized by DSC, TGA, and successive self-nucleation and annealing (SSA). A preliminary investigation of the tensile behavior of the copolymers was performed by uniaxial stretching until failure

Vanadium-Catalyzed Terpolymerization of α,ω-Dienes with Ethylene and Cyclic Olefins: Ready Access to Polar-Functionalized Polyolefins

International audienceα,ω-Dienes are an important class of monomers due to their utility in the synthesis of cyclopolyolefins and reactive polyolefin intermediates. In this contribution, the terpolymerization of two α,ω-dienes (i.e., 1,5-hexadiene and 1,7-octadiene) with ethylene and various cyclic olefins [i.e., norbornene (NB), 5-ethylidene-2-norbornene (ENB), and dicyclopentadiene (DCPD)] catalyzed by a chelated imido vanadium complex has been examined. The ENB and DCPD diene termonomers provide additional sites for post-polymerization functionalization. Vanadium-catalyzed terpolymerization of the investigated α,ω-dienes yields polyolefins with a high molecular weight (Mw up to 200 × 103 g mol–1), unimodal and narrow molecular weight distribution, subambient glass transition temperatures (−30 < Tg °C < −3), and a proper content of C═C bonds. Comprehensive NMR investigation of the obtained polymers revealed that subtle changes in the α,ω-diene size have important effects on the numerous combinations of insertion paths (ring closure vs ring opening), from which different repeating units with a C═C bond in the side or main polymer chain and cyclic units are installed. Finally, the poly(ethylene-ter-1,5-hexadiene-ter-NB) was subjected to thiol-ene addition using thioglycolic acid, methyl thioglycolate, and N-acetyl-l-cysteine to access polar-functionalized polyolefins with a degree of functionalization and properties dependent on the thiol substitution

Aorta Related and All-cause Mortality in Patients with Aortic Intramural Haematoma.

OBJECTIVES The prognosis of patients with intramural haematoma (IMH) of the aorta beyond the first year after diagnosis remains largely unknown. In particular, patients that do not undergo interventions are lost to follow-up. The aim was to assess medium-term outcome in IMH patients. METHODS Post hoc analysis of 63 consecutive patients presenting with IMH between 1999 and 2013 was performed. Patients meeting imaging criteria at the first presentation were included even if follow-up imaging showed evidence of intimal disruption or false lumen flow. RESULTS Eighteen patients presented with type A and 45 with type B IMH (29% vs. 71%, p < .001). The mean age was 71 ± 9.2 years, range 42-88 years. Follow-up was completed in 97% of patients by May 2017 and represents a mean follow-up of 6.3 ± 3.6 years. Freedom from intervention in patients with type B IMH was 40%. TEVAR was performed in 47% because of development, unmasking of an entry tear (57%), progression to acute type B dissection (24%), or subsequent dilation of the affected aortic segments (19%). Open repair was performed in 13% of type B IMH patients because of dilation of the descending aorta. In type A IMH, 89% underwent open repair. Aorta related 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 9.5%, respectively, for all IMH patients. All-cause 30 day, 6 month, 1 year, and late mortality were 1.6%, 6.3%, 6.3%, and 47.6%, respectively, for all IMH patients. Late mortality in type B IMH did not differ whether patients underwent TEVAR, open repair, or received best medical treatment only (26% vs. 22%, p = 1.0). CONCLUSIONS Late aorta related mortality in IMH was low whereas all-cause mortality was substantial. Aorta related mortality in IMH patients only occurs during the first year after diagnosis. Interventions after the first year are rarely necessary

Shear Stress Estimated by Quantitative Coronary Angiography Predicts Plaques Prone to Progress and Cause Events.

OBJECTIVES This study examined the value of endothelial shear stress (ESS) estimated in 3-dimensional quantitative coronary angiography (3D-QCA) models in detecting plaques that are likely to progress and cause events. BACKGROUND Cumulative evidence has shown that plaque characteristics and ESS derived from intravascular ultrasound (IVUS)-based reconstructions enable prediction of lesions that will cause cardiovascular events. However, the prognostic value of ESS estimated by 3D-QCA in nonflow limiting lesions is yet unclear. METHODS This study analyzed baseline virtual histology (VH)-IVUS and angiographic data from 28 lipid-rich lesions (i.e., fibroatheromas) that caused major adverse cardiovascular events or required revascularization (MACE-R) at 5-year follow-up and 119 lipid-rich plaques from a control group that remained quiescent. The segments studied by VH-IVUS at baseline were reconstructed using 3D-QCA software. In the obtained geometries, blood flow simulation was performed, and the pressure gradient across the lipid-rich plaque and the mean ESS values in 3-mm segments were estimated. The additive value of these hemodynamic indexes in predicting MACE-R beyond plaque characteristics was examined. RESULTS MACE-R lesions were longer, had smaller minimum lumen area, increased plaque burden (PB), were exposed to higher ESS, and exhibited a higher pressure gradient. In multivariable analysis, PB (hazard ratio: 1.08; p = 0.004) and the maximum 3-mm ESS value (hazard ratio: 1.11; p = 0.001) were independent predictors of MACE-R. Lesions exposed to high ESS (>4.95 Pa) with a high-risk anatomy (minimal lumen area 70%) had a higher MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS who had high- (20.0%) or low-risk anatomy (7.1%; p < 0.001). CONCLUSIONS In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information, and, in combination with lesion anatomy, enabled more accurate identification of MACE-R lesions