Le printemps de la cardiologie

2010 Archives of Cardiovascular Diseases Supplements  
Patient receiving oral anticoagulation (OAC) with vitamin K Antagonists (VKA) are patients with higher risk of both ischemic and bleeding complications when bridging therapy is performed. Trans-radial approach has been shown to dramatically decrease the rate of bleeding complications after coronary angiography. We, therefore, designed a study to assess the safety and feasibility of trans-radial coronary angiography with uninterrupted strategy with VKA in selected patients eligible for radial
more » ... roach. Methods and results: Consecutive patients receiving OAC and scheduled for coronary angiography were prospectively included between December 2008 and September 2009. Patients were eligible and included if the Allen's Test Manoeuvre was positive and the radial pulse suitable according to an experienced operator, and coronary angiography was performed by radial approach with uninterrupted oral anticoagulantion.100 consecutive patients were included. Major and Minor bleeding according to the TIMI classification and ischemic Cardiovascular events (death, myocardial infarction, target vessel revascularization, and stent thrombosis) were recorded. Among the 100 patients included, trans-radial Coronary angiography was feasible in 95 patients, and femoral access was used in 5 patients. Among the 95 patients, we did not observe any major and minor bleeding or ischemic CV events. Among the 5 "femoral access" patients, closure device was used in all patients and no patients suffered from major bleeding. Conclusion: In patient receiving OAC, screening of patients suitable for radial approach is an effective tool to identify patients eligible for a strategy of uninterrupted therapy with VKA. This strategy is feasible and safe in a large majority of patients with good probability of radial access if performed by trained operator from a "radial group". Introduction: Thrombi in contact with non re-endothelialized stent struts are associated with drug-eluting stents (DES) thrombosis. Hence, detection of thrombi in DES could help to evaluate the risk of DES thrombosis. Annexin V radio-labelled with 99m Technetium ( 99m Tc) is a radiotracer with a high affinity for activated platelets. Objectives: Our objectives were: 1) to develop an animal model of nonocclusive thrombosis of stents, 2) to evaluate the ability of annexin V 99m Tc for the detection of in-stent thrombi using scintigraphy. Methods: Right carotid arteries of NZW rabbits (n=14) fed a high cholesterol diet were implanted with overlapping DES (n=7) or bare-metal stents (BMS; n=7). Four weeks after stent implantation, rabbits underwent a first scintigraphy 3 hours after injection of 200 MBq of radio-labelled annexin V 99m Tc. At the end of the first scintigraphy, a suture was placed surgically proximal to the injured carotid arteries in order to induce a thrombus-prone flow limiting stenosis. Four days later, a second scintigraphy was performed. After the second scintigraphy, stents were excised and fixed for histological examination and scanning electron microscopy (SEM). Results: Activities measured in vivo in the stented carotid arteries after injection of annexin V 99m Tc increased on the second scintigraphy after creation of a surgical stenosis as compared to the first scintigraphy (0.24 vs. 0.15 counts/pixel/ MBq, respectively; p<0.05). On the second scintigraphy, activities were higher in DES vs. BMS (0.26 vs. 0.19 counts/pixel/ MBq, respectively; p<0.005). High activities measured in stents were associated with the detection of thrombi on corresponding histological sections and SEM. Conclusions: In this study, we developed a rabbit model of non-occlusive thrombosis of stents in carotid arteries. In this model, in-stent thrombi could be detected using annexin V 99m Tc scintigraphy. Myocardial infarctions or strokes are due to atherothrombosis, i.e. thrombosis occurring at the surface of atherosclerotic plaques. Atherosclerotic plaques are chronic inflammatory lesions of the vascular wall, but the role of inflammation in atherothrombosis is not clear. Our lab has been the first to clearly show a link between the inflammatory mediator prostaglandin E2 (PGE2) produced in plaques and atherothrombosis, due to the ability of PGE2 to activate its EP3 receptor on platelets. Our current project is to find whether PGE2 production is under the control of a pathway that modulates the plaque thrombogenicity. PTGS-2 is the gene coding for cyclooxygenase 2, needed for PGE2 biosynthesis, and contains a peroxisome proliferator activated receptor (PPAR) responsive element. Macrophages are predominant into the plaque, and express PPARγ. Therefore, PPARγ might modulate the PGE2 production in atherosclerotic plaques. To test this hypothesis, we stimulated freshly isolated peritoneal macrophages in vitro with agonists for PPARs. We show that PGE2 production by cultured macrophages was increased only by rosiglitazone, a PPARγ agonist. Using a specific inhibitor for PPARγ, we showed that the stimulating effect of rosiglitazone on PGE2 production is indeed due to its April 15 th , effect on PPARγ. We then confirmed that PPARγ mRNA and protein level are clearly up regulated in ApoE-/-vascular wall. These data strongly suggest that PPARγ modulate the plaque PGE2 production. We are currently investigating the mechanism involved: PPARγ could modulate the level of one of the different enzyme of the arachidonic acid cascade leading to PGE2. In vivo studies are currently under way to test whether rosiglitazone impacts the PGE2 production in vivo and thereby modulates atherothrombosis. Our results could unveil a mechanism explaining the cardiovascular toxicity of rosiglitazone evidenced by clinical trials in patients treated for mellitus diabetes. Optimal management of coronary artery disease in very old patients -over eighty years of age -remains unclear due to the absence of large randomized trials in this high-risk subgroup and the benefit/risk ratio of percutaneous coronary intervention (PCI) is difficult to assess in clinical practice. Data from registries are therefore valuable to assess the benefit/risk ratio of reperfusion strategies. Aim: The aim of our study was to evaluate the in-hospital and two year outcome of PCI in elderly patients aged ≥ 80 years old in a prospective registry including patients with clinical presentation ranging from stable angina to cardiogenic shock. Methodes and Results: Between 2004 and 2009, a coronary angiogram was performed in 554 patients aged ≥ 80 years of age. PCI was performed in 232 patients. Mean age was 82 ± 2.6 and 38% were women. The procedures were unplanned due to ST elevation myocardial infarction (STEMI) 32.8%), cardiogenic shock complicating STEMI (9%), and non ST segment elevation myocardial infarction (NSTEMI) (30.6%). 36.6% of procedures were performed for stable angina refractory to optimal medical therapy. Radial access was used in 87% of cases. One vessel disease was found in 32%. Primary success rate was 93%. Stents were implanted in 99% of lesions, with only 1% use of drug eluting stent). Rates of in hospital mortality were respectively 12.5% in all patients; 85.7% in those presenting with cardiogenic shock, 14.5% in those with STEMI without shock, 2.8% in patients with NSTEMI and 2.35% in patients with stable angina. The overall two year mortality rate is 20%. Conclusion: In very old patients over 80 years of age, in hospital outcome is strongly related to the clinical presentation at admission. The prognosis of cardiogenic shock remains poor in this subgroup despite revascularization. In contrast, the in-hospital outcome of PCI in patients admitted with STEMI, NSTEMI and stable angina is encouraging. However, long term mortality remains high. Cardiovascular mortality in chronic kidney disease patients undergoing percutaneous coronary intervention is mainly related to impaired P2Y12 inhibition by clopidogrel Olivier Objectives: To determine whether low platelet response to the P2Y 12 receptor antagonist clopidogrel as assessed by VAsodilator Stimulated Phosphoprotein flow cytometry test (VASP-FCT) predicts cardiovascular events in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). Background: Whilst both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavourable outcome after PCI, the deleterious impact of their association is unknown. The platelet VASP-FCT is a new assay specific of the P2Y 12 ADP receptor-pathway. In this test, platelet activation is expressed as Platelet Reactivity Index (PRI). Methods: 440 unselected patients (CKD: 126 (CrCl < 60 ml/min), Normal renal function: 314 (CrCl > 60 ml/min)) undergoing urgent (n=336) or planned (n=104) PCI were prospectively enrolled. In each sub-group, patients were classified as low-responders (LR: PRI≥61%) and responders (R: PRI<61%) to clopidogrel Results: At follow-up (9±2 months), total, cardiac mortality, probable and possible stent thrombosis rates were higher in CKD patients. In this sub-group, cardiac death, total stent thrombosis and MACE were dramatically increased in LR patients. Conversely, in patients with normal renal function, LR was not associated with an adverse cardiovascular outcome. In CKD patients, multivariate analysis identified LR to clopidogrel (HR 4.00 [1.08-14.80]; p=0.025) and BNP > 400 ng/L (HR 9.55 [1.18-77.11]; p=0.034) as independent predictors of cardiac death. Conclusions: In CKD patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cut-off value of ≥61%. Level of PGE2 released by macrophages Cardiac death following PCI Background: Despite the results of recent randomized studies, the systematic use of aspiration techniques in ST-elevation myocardial infarction has not been included in the new guidelines. To date, there have been very few bench tests of the different systems and the aim of our study was to test two catheters on different models of arteries with thrombi at 6 and 12 hours. Methods: The test apparatus consisted of 3-mm diameter glass tubes of 150 mm in length. The thrombi were left for either 6 or 12 hours and ten models of tubes were used: straight, with a single bend and with two bends. Two types of catheter were tested: the Export ® aspiration catheter (EAC) and the Proxis ® embolic protection system (PES). The main assessment criterion was total thrombectomy. Results: Total thrombectomy was achieved in only 55.3% of the tests and no difference appeared between the two systems. Total thrombectomy was achieved more frequently with 6-h thrombi than 12-h thrombi for the two techniques, 62.5% vs. 42.5% (p=0.018) and 67.5% vs. 48.7% (p=0.025) for EAC and PES catheter, respectively. In contrast, total thrombectomy were more frequent in straight tubes and in tubes with a single bend than in tubes with double bends, respectively for EAC (64% vs. 44.8%, p=0.028) and for PES (85.9% vs. 35.4%, p<0.001). Conclusion: The use of thrombectomy in the invasive management of acute coronary syndromes is growing. Our work on a "laboratory bench" reveals important technical differences. In consequence, in clinical practice, we speculate that the catheter system must be chosen according to both the artery anatomy and the delay between chest pain and PCI. 0123 In-hospital complications after PCI for non ST-segment elevation myocardial infarction in old women as compared to young men Background: To analyze the in-hospital complication rate in women suffering from NSTEMI treated with PCI compared to men. Methods: 479 consecutive patients (133 women and 346 men) suffering from a NSTEMI between January 1st 2006 and March 21st 2009 were retrospectively analyzed. Data were analyzed using nonparametric tests and reported as median unless otherwise specified. Results : As compared to men, women were significantly older (p<.005). All cardiovascular risk factors but tobacco and hypertension were similar between the groups. No difference was noticed for pre-hospital cardiovascular drug treatment. However women were slightly more severe at entry (more Killip class IV; p=.0023; higher GRACE score for in-hospital death -p=.008 and CRUSADE score for bleedingp < .0001). All the patients underwent PCI of the infarct-related artery after 24 or 48 hrs post admission without any sex-related difference. During hospitalization, 130 complications were recorded. Though the event rate was slightly higher in women (30% vs. 26% -p=NS), no single event was significantly gender related. The logistic regression identified age and CRP concentration as the only predictive variables in the whole group. After splitting for genders, these parameters were still predictive of events in men. In women however, CRP was the only one with a borderline p value. Conclusions: Our study does not support any gender difference for in-hospital adverse events in patients treated invasively for a Non-STEMI. 0444 Shear stress induced-endothelial microparticles release: role of MAPK and NF-κ κ κ κB pathways. Endothelial Microparticles (EMPs) are bioactive submicron membrane vesicles released upon cell activation and may contribute to the pathogenesis of atherosclerosis. Laminar shear stress is known to protect against plaque formation contrarily to oscillatory and low shear stress. We thus investigated whether shear stress could modulate the release of EMPs and whether these effects would be mediated by the MAPK and NF-κB pathways. Endothelial cells (HUVECs, Passage 2-3) were subjected to low (1.5dyn/ cm 2 ), high (15dyn/cm 2 , physiologic) laminar shear stress or maintained under static conditions for 24 hours. EMPs were isolated from the cell culture medium by centrifugation, and characterized by annexinV labelling using flow cytometry. Endothelial exposure to low shear stress stimulated EMP release by 4-fold as compared to physiologic shear stress conditions ; TNFα or IL1β (10nM), also increased EMP release by 50% over static conditions. The effects of low shear stress was decreased by 40% by ERK1/2 and JNK inhibitor (PD98059 and SP600125, 10 -5 M) and was only impared by 5% following exposure to NF-κB inhibitor (PDTC, 10 -5 M). However, NF-κB inhibition by PDTC decreased both actin filaments polymerization (F-actin), known to determine EMP formation at the plasma membrane, and subsequent EMP release (40% decrease) following endothelial stimulation with TNFα or IL1β. Altogether, these findings indicate that multiple mechanisms can lead to EMP release among which, NF-κB seems to play an important role by acting on actin polymerization. The MAPK pathway seems to further participate in vesiculation under low shear stress. Our results might help to explain the proatherogenic effects of low shear stress patterns mediated by EMPs. Background: The atheroprotective properties of estrogens have been clearly demonstrated in all animal models, and appear to be mediated through a direct action on the arterial wall rather than through an effect on the lipoprotein profile. The goal of the present study was to evaluate which cellular target is crucial in this beneficial action of estradiol (E2). Methods and Results: We first confirmed the key role of estrogen receptor α (ERα) in the atheroprotective effect of E2 as this action was completely abolished in mice deficient both in Low Density Lipoprotein receptor (LDLr) and in ERα. Second, using chimeric mice ERα-deficient in the hematopoietic lineage, we showed the persistence of the protective action of E2, suggesting the involvement of extra-hematopoetic ERα. Third, we showed that ERα-floxed mice (ERαflox/flox) bred with the Tie2-Cre+ mice on the LDLr-/-background had a complete inactivation of ERα in most of hematopoietic and in all endothelial cells. Remarkably, in this mouse model, the E2 atheroprotection was completely abolished. Fourth, the atheroprotective effect of E2 remained abolished in Tie2-Cre+ ERαflox/flox LDLr-/-mice transplanted with either Tie2-Cre+ ERαflox/flox or ERα-/-bone marrow, whereas it was present in analogous chimeric Tie2-Cre-ERα flox/flox LDLr-/receivers expressing endothelial ERα. Conclusions: We demonstrate directly and for the first time that endothelial ERα represents a key target of the E2 atheroprotective effect, whereas the hematopoietic ERα is dispensable. Selective estrogen receptor modulators that mimic the E2 endothelial action should now be considered in atheroprotection. 0126 The transactivating function 1 of estrogen receptor alpha is dispensable for the vasculoprotective actions of 17beta-estradiol. Full-length 66-kDa estrogen receptor alpha (ERalpha) stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. Another physiologically expressed 46-kDa ERalpha isoform lacks the N-terminal A/B domains and is consequently devoid of AF-1. Previous studies in cultured endothelial cells showed that the N-terminal A/B domain might not be required for estradiol (E2)-elicited NO production. To evaluate the involvement of ERalpha AF-1 in the vasculoprotective actions of E2, we generated a targeted deletion of the ERalpha A/B domain in the mouse. In these ERal-phaAF-1(0) mice, both basal endothelial NO production and reendothelialization process were increased by E2 administration to a similar extent than in control mice. Furthermore, exogenous E2 similarly decreased fatty streak deposits at the aortic root from both ovariectomized 18-week-old ERalphaAF-1(+/+) LDLr (-/-) (low-density lipoprotein receptor) and ERal-phaAF-1(0) LDLr (-/-) mice fed with a hypercholesterolemic diet. In addition, quantification of lesion size on en face preparations of the aortic tree of 8-month-old ovariectomized or intact female mice revealed that ERalpha AF-1 is dispensable for the atheroprotective action of endogenous estrogens. We conclude that ERalpha AF-1 is not required for three major vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. Thus, selective ER modulators stimulating ERalpha with minimal activation of ERalpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects. Background: Abdominal aortic aneurysms (AAA) is the 4 th localisation of atherosclerosis, occurs in 1 of 19 older men (5.5% of men over 65 years), remains asymptomatic for many years and is the 14th cause of world death, almost from inaugural rupture. Its prevalence in general population implies specific target population screening. Material and Methods: Using small portable cardiac ultrasonography (TTE) equipment we prospectively evaluated the prevalence of AAA (transverse diameter ≥30 mm) in consecutive patients admitted for acute myocadial infarction (AMI) in our intensive care unit. Results: One hundred and fifty two patients were enrolled (mean age 65±14 years old, 78% of male). Feasibility was 93% (10 patients were anechogen) and time duration was 3±1min. Interoobserver variability between cardiologists was good (1.7±1mm). Height patients had an AAA (5.2%). Its prevalence increases with aging and was 8.7% among the people over 60 years old and 10.3% among the people over 65 years old. None patient under 50 years old had AAA. Conclusion: Small TTE is a reliable, quick and simple screening test for AAA. Prevalence of AAA does not seem to be higher in patients with AMI than in general population and increases with aging. Analyse of abdominal aorta should be performed by echocardiographer during the standard echocardiographic exam ("one cardiovascular shot"). 0462 Impact of high fat diet on cardiovascular function and atherosclerosis in female low density lipoprotein receptor deficient mice
doi:10.1016/s1878-6480(10)70356-6 fatcat:nfiqs6ocn5anpmwuxsmb562tsy