Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs

To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1β increased NO production in both clones, and TNF-α had a synergistic effect on IL-1β-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clones similarly located in the lungs of syngeneic mice 48 h after injection. However, EMT-6H cells were significantly more tumorigenic than EMT-6 J cells as assessed at later time points. Injection of EMT-6 J cells and simultaneous treatment of mice with aminoguanidine (AG), a NOS II inhibitor, significantly increased tumour formation. Injection of EMT-6H and EMT-6 J cells into NOS II-deficient mice resulted in a significant survival increase as compared with wild-type animals. Simultaneous administration of AG increased the death rate of NOS II-deficient mice injected with EMT-6 J cells. These results demonstrate that: (i) NO does not influence the early stages of tumour metastasis to the lungs and (ii) NOS II expression in tumour cells reduces, while NOS II expression in host cells enhances, tumour nodule development. In conclusion, the cellular origin and the local NO production are critical in the metastatic proces

Utility of Cardiac Magnetic Resonance to assess association between admission hyperglycemia and myocardial damage in patients with reperfused ST-Segment Elevation Myocardial Infarction

International audienceAbstract: Aims: to investigate the association between admission hyperglycemia and myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) using Cardiac Magnetic Resonance (CMR). Methods: We analyzed 113 patients with STEMI treated with successful primary percutaneous coronary intervention. Admission hyperglycemia was defined as a glucose level >= 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP), providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE), reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores. Results: Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and < 0.001), multivessel disease (p = 0.02 for both) and hyperglycemia (p < 0.001). Moreover, they were characterized by higher levels of HbA(1c) (p = 0.01 and 0.04), peak plasma Creatine Kinase (p < 0.001), left ventricular end-systolic volume (p = 0.005 and < 0.001), and lower left ventricular ejection fraction (p = 0.001 and < 0.001). In a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores. Conclusion: Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR

0132: Identifying familial hypercholesterolemia from registries of patients with acute myocardial infarction: an algorithm-based approach

International audienc

0134 : Atrial fibrillation is associated with a marker of endothelial function and oxidative stress in patients with acute myocardial infarction

International audienc

0482: Silent AF in acute myocardial infarction severely impairs long term prognosis

BackgroundSilent Atrial Fibrillation (AF) has recently been shown to be common in acute myocardial infarction (AMI) and to dramatically increase in-hospital death. However, the long term prognosis of silent AF in AMI remains unknown.MethodsFrom the 1st May 2011 and the 31st January 2013 all the consecutive patients were prospectively analyzed by continuous ECG monitoring (CEM) during the first 48 hours after admission for an AMI. Silent AF was defined as asymptomatic episodes lasting at least 30 sec. Patients discharged alive and with a follow-up at 1 year were included in the present study. Patients who developed silent AF were compared with symptomatic AF and No AF group.ResultsAmong the 737 patients included, 96 (13.0%) developed silent AF and 56 (7.6%) developed symptomatic AF during their hospital stay. Compared with the no AF group, patients with silent AF were markedly older 80 (64-84) vs. 61 (53-75) years; p<0.001), more frequently women (42% vs. 30%); p=0.069), and less frequently smoker (24% vs. 37%; p<0.001).GRACE risk score was significantly higher in silent AF group (131(101-148)) than in no AF group (98(75-); p<0.001). They also had a significant left atrial (LA) enlargement with LA surface indexed at 10.1 (8.5-12.6) vs. 9.2 (7.4-10.9)cm²/ m²; p<0.001 and LA volume indexed 29.4 (21.0-43.1) vs. 24.1 (18.1-32.9)cm3/m²; p<0.001. At one year follow-up, rehospitalizations for heart failure were more frequent after silent AF (4.2%) or symptomatic AF (8.9%) than in no AF group (1.4%), (p<0.001). One year mortality was dramatically higher in silent AF group (9.4%) and in symptomatic AF group (17.9%) than in no AF group (3.8%) (p<0.001).ConclusionSilent AF in AMI severely impairs long term prognosis, including rehospitalization for heart failure and death. Our large prospective study suggests that silent AF screening should be improved after AMI in order to identify patients at high risk for long term events

268 Impact of age on clinical periodontal parameters in patients with acute myocardial infarction

AimTo evaluate the periodontal status in patients with acute myocardial infarction (AMI) and to determine whether there was a specific profile according to age.MethodsA total of 197 consecutive patients with AMI were included and the oral examination included the number of teeth, endodontically treated teeth, periodontal screening index (PSI), clinical attachment level, and radiographic apical lesions (radiography examination). Patients were classified according to tertiles of age.ResultsThe table below summarizes the specific profile according to age. The study demonstrated that patients with AMI exhibited an unfavourable dental state of health. No relationship was found between C-reactive protein levels and periodontitis.ConclusionThis work demonstrates specific profiles of dental status according to age. In younger patients, the dental status was poor, and although no relationship with CRP was shown, further studies are needed to include a more specific assessment of coronary lesions and their evolution in this context of poor dental health.(Voir tableau ci-dessous)Tertile 1Tertile 2Tertile 3pN666665Mean age, y47.7 ± 0.459.5 ± 0.372.5 ± 0.4<0.001Men83%89%75%0.104CRP > 3mg/L,52%41%54%0.205Current smoker72%63%47%0.017Periodontal statusPresence of caries50%28%45%0.037Presence of Inflammation64%71%67%0.731Teeth lost8 ± 810 ± 815 ± 80.019Alteration of chewing24%34%67%<0.001Bone Loss55%71%86%0.00

New insights into symptomatic or silent atrial fibrillation complicating acute myocardial infarction

International audienceAtrial fibrillation (AF) is the most frequent heart rhythm disorder in the general population and contributes not only to a major deterioration in quality of life but also to an increase in cardiovascular morbimortality. The onset of AF in the acute phase of myocardial infarction (MI) is a major event that can jeopardize the prognosis of patients in the short-, medium- and long-term, and is a powerful predictor of a poor prognosis after MI. The suspected mechanism underlying the excess mortality is the drop in coronary flow linked to the acceleration and arrhythmic nature of the left ventricular contractions, which reduce the left ventricular ejection fraction. The principal causes of AF-associated death after MI are linked to heart failure. Moreover, the excess risk of death in these heart failure patients has also been associated with the onset of sudden death. Whatever its form, AF has a major negative effect on patient prognosis. In recent studies, symptomatic AF was associated with inhospital mortality of 17.8%, to which can be added mortality at 1year of 18.8%. Surprisingly, silent AF also has a negative effect on the prognosis, as it is associated with an inhospital mortality rate of 10.4%, which remains high at 5.7% at 1year. Moreover, both forms of AF are independent predictors of mortality beyond traditional risk factors. The frequency and seriousness of silent AF in the short- and long-term, which were until recently rarely studied, raises the question of systematically screening for it in the acute phase of MI. Consequently, the use of continuous ECG monitoring could be a simple, effective and inexpensive solution to improve screening for AF, even though studies are still necessary to validate this strategy. Finally, complementary studies also effect of oxidative stress and endothelial dysfunction, which seem to play a major role in triggering this rhythm disorder

0128: CHA2DS2-VASc score estimates in-hospital mortality beyond GRACE score after acute myocardial infarction

International audienceBackground and aimsCHA2DS2VASc score have recently been suggested to predict death in patients with Atrial Fibrillation (AF). In acute myocardial infarction (AMI), silent AF is more common than symptomatic AF and associated with poor prognosis. In patients with AMI, we aimed to assess the distribution of CHA2DS2VASc score in patients with silent or symptomatic AF and the association of the score with mortality.Methods849 consecutive AMI were prospectively analyzed by continuous ECG monitoring (CEM) 30 sec. Symptomatic AF was defined as any AF occurring on ECG during the hospital stay, resulting in clinical symptoms or need for urgent cardioversion. The population was studied into three groups: No AF, Silent AF, and symptomatic AF. CHA2DS2VASc and GRACE risk score were calculated for risk assessment.ResultsOne hundred and thirty five patients (16%) developed silent AF and 45(5%) had symptomatic AF. Compared with the no AF group, patients with silent AF were markedly older 80 (67-85) vs. 62 (53-75) years; p<0.001), more frequently women (58 (43%) vs. 198 (30%); p=0.006), and less smoker (26 (20%) vs. 242 (36%); with p<0.001). Patients with silent and symptomatic AF, had higher CHA2DS2VASc score than patients without AF (5[4-6] and 5[4-6] vs 3[2-4], p<0.001).CHA2DS2VASc score was similar in patients with silent and symptomatic AF (p=0.550). Mortality was higher in silent AF and symptomatic AF than in patients without AF ((14 (10.4%) and 8 (17.8%) vs 9 (1.3%)), p<0.001). CHA2DS2VASc score was associated with mortality in patients with AF, but not in patients without AF (OR[95% CI]: 1.32[1.02-1.72], p=0.036 and 1.22[0.88-1.71], p=0.236, respectively).In the whole population, optimal threshold for predicting death for GRACE and CHA2DS2VASc risk scores were obtained by Receiver Operating Characteristic (ROC) curve (i.e. 153 and 4, respectively).High CHA2DS2VASc (≥4) and GRACE (≥153) scores independently stratified mortality. By multivariate analysis, high CHA2DS2VASc score was an independent explanatory variable for death after AMI (OR[95% CI): 3.89[1.08-13.93]; p=0.037), beyond GRACE risk score (OR[95% CI]: 9.77[2.74-34.80]; p<0.001).ConclusionPatients with silent AF have level of CHA2DS2VASc risk similar to patients with symptomatic AF. A high CHA2DS2VASc score is associated with mortality, even when adjusted for GRACE risk score. These data suggest that CHA2DS2VASc score could improve risk stratification after AMI

0136 : CHA2DS2VASc score estimates in-hospital mortality beyond GRACE score after acute myocardial infarction

International audienc

0168: Myocardial infarction after kidney transplantation: age related profile. Analysis from a French nationwide hospital medical information database

Cardiovascular disease accounts for 43% of all deaths in patients with endstage renal disease, and CVD continues to remain the leading cause of mortality and morbidity following renal transplantation. However, the characteristics and the hospital mortality of acute myocardial infarction (AMI) in patients with kidney transplantation (KT) remain to be determined in large scale study. From the French nationwide hospital medical information database, all the consecutive patients hospitalized in the 1546 French hospital/clinics for AMI from 1st January 2005 to 31st December 2009 were included. We compared the specific profile and the hospital mortality of patients with KT to patients without renal failure. Patients with personal past history of renal failure and/ or dialysis were excluded.Among the 329 839 patients with AMI included, 404 (0.1%) patients were after KT. Patients with KT were more frequently men (78.7 vs 66.8%, with p<0.001), markedly younger (58±12 vs 68±11, with p<0.001), and les smoker (5.0 vs 9.1%, with p<0.001) than patients without KT. There was also a higher proportion of hypertension (28.5 vs 23.4%, with p0.017) and a lower proportion of STEMI (75.7 vs 82.7%, with p<0.001) in patients after KT. More than two-thirds of AMI complicating post KT period occured before discharge (67.1%) and 91% in the first year after KT. After adjustment for age, sex and STEMI, in-hospital mortality was higher in KT group (4.2 vs 2.9%), but with p=0.210.From our large scale nationwide study, our work demonstrated that patients with KT complicated by AMI are markedly younger with a specific difference for usual risk factors, but transplant-related risk factors explain also this specificity. We highligts that AMI occurs very early after KT, most often before discharge. To decrease the frequency of MI following renal transplantation, screening of coronaropathy and evaluation of risk factors before KT, as well as after KT must be evaluated