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Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after re-perfusion with clinical outcomes after anterior STEMI.Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had re-gression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/ or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave re-gression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 +/- 2784 IU/l vs. 3814 +/- 2595 IU/l vs. 1733 +/- 1583 IU/l respectively, p b 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).Conclusion: Ina population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.(c) 2019 Elsevier Inc. All rights reserved.

Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

International audience; No abstract available

Summary Background How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. Aims To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non-ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018–2019 and for an unavoidable emergency, i.e. birth. Methods Based on the national hospitalisation database [Programme de medicalisation des systemes d’information (PMSI)], all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. Results Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018–2019 by less than 10%; after the start of lockdown, it decreased by 31% compared to the corresponding time window in 2018–2019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. Conclusion This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.

Introduction Myocardial infarction affects more than 120,000 people every year in France. Despite the increasing effectiveness of patient management, the morbi-mortality of this condition remains high. Peripheral blood mononuclear cells (PBMC) have been recently shown to present a phenotype characteristic of a pathology, providing prognostic and/or diagnostic information. Objective We aim to develop a protocol for inflammatory and calcium phenotyping of human PBMC by flow cytometry. Methods After thawing PBMC from healthy patients, cell viability is followed by Trypan blue staining to define the optimal time for use. Regarding cell phenotyping, lymphocytes are Methods distinguished from monocytes according to their morphological criteria. Using the CD14, CD16, CCR2, and CX3CR1 markers, pro-inflammatory monocytes are further differentiated from anti-inflammatory monocytes. To analyze Ca2+ fluxes, different cell compartments are marked with chemical probes measuring the Ca2+ present in each compartment: FuraRedAM for cytosol, Rhod2AM for mitochondria, and MagFluo4AM for the reticulum. Dose-response study is performed to determine the optimal concentrations of each probe. Correct addressing of the probes in each compartment is verified by confocal microscopy. Using a pharmacological approach, the optimal conditions for measuring Ca2+ exchange between the different cell compartments will be determined. Results Cell viability remains stable during 8 hours but drops at 24 hours. Therefore, cytometer analyzes are carried out on the same day of thawing. Dose–response experiments and development of the multi-labeling protocol to phenotype the different PBMC populations are ongoing. Conclusion Once the protocol will be set up, PBMC from an existing cohort of post-myocardial infarction patients will be analyzed to better define the molecular signature of myocardial ischemia-reperfusion lesions by correlating the inflammatory/calcium PBMC profile with cytokines profile.

Resume Les coronariens ont un risque plus eleve de complications cardiaques en postoperatoire d’une chirurgie non cardiaque. Un coronarien est considere a haut risque postoperatoire lorsqu’il a presente recemment un syndrome coronarien aigu recent ou est symptomatique pour un faible niveau d’effort. Le coronarien stable asymptomatique est a faible risque de complications postoperatoires. La mortalite des infarctus postoperatoires est beaucoup plus elevee que dans un contexte non chirurgical. En cas de STEMI, une occlusion coronaire aigue est probable. La priorite est a la reperfusion coronaire. Le patient doit etre transfere pour une coronarographie et une angioplastie. Un pretraitement par aspirine est recommande. L’indication des autres antiagregants sera decidee au cours de la coronarographie en fonction de la procedure. En cas de syndrome coronarien aigu sans sus-decalage du segment ST, la rupture de plaque n’est pas le mecanisme le plus frequent. Leur cause premiere est un desequilibre entre les apports et les besoins du myocarde. Ce mismatch est cause par d’autres complications perioperatoires : hypo- ou hypertension, hypoxie, sepsis, anemie, troubles du rythme. Il n’y a pas a envisager un traitement antithrombotique, ni une coronarographie. Neanmoins, une instabilite hemodynamique primitivement cardiaque, un angor, des troubles du rythme ventriculaires ou des modifications dynamiques du segment ST doivent conduire a une coronarographie en urgence. Parmi les facteurs de NSTEMI de type 2, la fibrillation auriculaire est particulierement frequente. Elle est souvent en lien avec inotropes, anemie, hypoxie, embolie pulmonaire, pneumothorax, sepsis, epanchement pericardique. En cas de mauvaise tolerance une cardioversion electrique en urgence est necessaire. Pour reduire la cadence ventriculaire, Les betabloquants et tout particulierement l’esmolol IV sont a considerer en premier dans ce contexte d’hyperactivite sympathique perioperatoire. Les NSTEMI de type 2 et les NIMS marquent une vulnerabilite myocardique, pas necessairement coronarienne, que revele le stress postoperatoire. Un bilan cardiologique est toujours a envisager a distance de la chirurgie pour au moins une echocardiographie et une evaluation et le cas echeant une prise en charge du risque cardiovasculaire global et souvent une evaluation non invasive de l’ischemie.

We read with interest the paper by Psotka et al. ([1][1]) showing that the mean 1-year rates of heart failure clinical trial publication or reporting are low (

Introduction Leptin, an adipocyte derived hormone, plays a central role in food intake regulation but also in inflammation regulation. Leptin level is increased after myocardial infarction but its relationship with clinical prognosis is unknown. Objective The study objective was to evaluate, in a cohort of patients admitted for ST elevation myocardial infarction (STEMI), the one-month serum kinetics of leptin and its potential relationship with infarct size, left ventricular function and clinical outcome. Methods We prospectively enrolled 251 consecutive STEMI patients. Leptin was assessed in the serum at admission (H0), 4 h, 24 h and 48 hours (H4, H24 and H48) and 1 month (M1) after admission. Patients underwent cardiac magnetic resonance imaging at M1 for measurement of infarct size (IS) and left ventricular ejection fraction (LVEF). Clinical outcomes were recorded over 24 months after STEMI. Results We demonstrated that leptin level reaches a peak 24 hours after the admission. Leptin level at H24 was correlated with IS (r = 0.19, P = 0.02) and inversely correlated with LVEF (r = −0.16, P = 0.04). Leptin serum level was associated with an increased risk of experiencing the composite endpoint during the 24 months of follow-up [adjusted HR = 2.3 CI (1.1–4.8), P = 0.03]. Conclusion These results suggest that leptin might be an early prognosis marker in STEMI patients.

Introduction Due to the failure of the translation of cardioprotective drugs against myocardial infarction from bench to bedside, revising animal models has become a necessity. Owing to its current growing incidence, type 2 diabetes (T2D) represents one of the main risk factors of co-morbidities in myocardial infarction, yet discrepancies exist between reported animal and human studies. Objective We aimed to compare the impact of diabetes on infarct size after cardiac ischemia-reperfusion in a human cohort of ST elevation myocardial infarction (STEMI) patients with a diet-induced mouse model of T2D, using a high-fat high-sucrose diet for 16 weeks (HFHSD). Methods Infarct size was evaluated by MRI in a cohort of 250 STEMI patients after primary percutaneous intervention. For mouse study, T2D was induced by 16 weeks of HFHSD versus a standard diet (SD) then in vivo 45 mins ischemia followed by 24 hrs of reperfusion were performed to compare myocardial infarct size. To mimic the diabetic medication regimen, 6 weeks of oral gavage with Metformin was performed in the HFHSD group: cell death upon in vitro 70 min hypoxia-2 h reoxygenation (H/R) on isolated cardiomyocytes was analysed by propidium-iodide staining. Results A small fraction ( Conclusion Our data highlight that anti-diabetic medications may have a protective effect, thus they should be included in the pre-clinical studies of cardioprotective approaches in diabetic models. However, the relatively low number of diabetic patients in the STEMI population should also lead us to think about the inclusion of other risk factors in our animal models, notably aging.

Introduction Tumor necrosis factor-α (TNF-α) interacts with two soluble receptors: TNFR1 and TNFR2. Little is known about the role of sTNFR1 and sTNFR2 in patients with acute ST-segment elevation myocardial infarction (STEMI). Hypothesis Our hypothesis was that the serum levels of sTNFR1 and sTNFR2 might be a marker of the severity of STEMI. Methods We prospectively enrolled 230 consecutive STEMI patients who underwent PCI revascularization in our hospital into a prospective cohort. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month after admission (H4, H24, H48, M1). sTNFR1 and sTNFR2 serum levels were assessed using an ELISA assay. Patients underwent cardiac magnetic resonance imaging at M1. Clinical outcomes were recorded over 18 months after STEMI. Results Mean age of the study population was 59 ± 12 years and 48.5% patients exhibited anterior STEMI. sTNFR1 level significantly increased at H24 with a median of 601.2 pg/mL (interquartile range [IQR] [397.1–896.7]). sTNFR2 level significantly increased at H48 with a median of 2262.3 pg/mL (IQR [1659.6–2862.4]). Patients with sTNFR1 and sTNFR2 peak levels greater than the population median value displayed significantly larger final infarct size and lower LVEF. Patients with peak levels of sTNFR1 and sTNFR2 higher than the population median value were more likely to have an adverse clinical event (MI, stroke, hospitalization for heart failure and all-cause death) during the first 18 months after STEMI (hazard ratio [HR] at 9.0 [3.7–22.2], P = 0.0003 for sTNFR1 and 5.5 [2.1–14.3], P = 0.002 for sTNFR2). Patients with high level of both sTNRF1 and sTNFR2 were at higher risk of adverse clinical event compared to patients with low level (HR = 13.1 [4.4–38.7], P = 0.0005). Conclusion High levels of circulating sTNFR1 and sTNFR2 were associated with larger infarct size, impaired recovery of LVEF and adverse clinical event in STEMI patients. sTNFR1 and 2 might be useful prognosis markers.

Introduction IL-6 and IL-10 are two major cytokines secreted at the acute phase of myocardial infarction (MI). IL-6 has a pro-inflammatory effect whereas IL-10 has anti-inflammatory effect. Objective Our objective was to assess the prognosis value of IL-6, IL-10 and IL-10/IL-6 ratio serum level at the acute phase of ST elevation MI (STEMI). Methods We prospectively enrolled 247 patients admitted for acute STEMI from 2016 to 2019. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month (H4, H24, H48, M1). IL-6 and IL-10 were assessed using ELISA. Patients underwent cardiac magnetic resonance imaging at one month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were prospectively recorded over 18 months. Results Patient mean age was 59±12 years. IL-6 reached a peak at H24 at 5.4 pg/mL interquartile range (IQR) [2.1–11.0] and IL-10 peaked as early as admission at 5.6 pg/mL IQR [8.7–29.3] followed by a decrease within the first month. Median IL-10/IL-6 ratio at admission was 4.2 [1.4–8.6] with a strong decrease at H24 (0.5 [0.2–1.3]). IL-6 and IL-10 levels at H24 were correlated with IS (respectively r=0.44, p Conclusion Serum IL-10/IL-6 >1 was associated with a poor outcome after STEMI and might be a valuable prognostic marker. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospices Civils de Lyon, Fédération Française de Cardiologie

Background White blood cell count (lymphocyte, neutrophil, eosinophil) have been shown to be independently and incrementally associated with clinical events after acute myocardial infarction (MI). However, the prognostic value of basophil has never been studied at the acute phase of MI. Objective Our objective was to define the kinetics of basophils within the first month in patients admitted for STEMI and to assess their prognostic value. Methods We prospectively enrolled 243 patients admitted for acute ST elevated MI (STEMI) from 2016 to 2019. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month after admission (H4, H24, H48, M1). Patients underwent cardiac magnetic resonance imaging at one month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were prospectively recorded over 18 months. Results Patient mean age was 59 ± 12 years. Basophil count significantly decreased at H24 with a median of 30.0 Mega/L (interquartile range [IQR] [20.0–50.0]) compared to admission (40.0 M/L IQR [30.0–60.0], P Fig. 1 ). Conclusion Basophil count at H48 in STEMI patients is an independent prognosis marker to predict clinical outcome.

Introduction In secondary prevention, the 2019 ESC guidelines recommend achieving LDL cholesterol below 1.4 mmol/l and decreasing over 50% of its baseline value. After myocardial infarction (MI), it has been debated whether MI inflammation could influence lipid profile and thus response to lipid lowering therapy. Objective We investigated whether inflammation in the acute phase MI could influence LLT effect on LDL-c reduction at 1-month follow-up. Method We retrospectively included consecutive patients admitted for an acute ST-elevation MI (STEMI) between October 2014 and December 2017. Clinical characteristics, lipid profile and CRP were collected at baseline within the first 24 h and lipid profile at 1-month follow-up. We compared in LLT naive patients the LLT response variability according to baseline median CRP (low-CRP vs. high-CRP group) and the percentages of patients achieving goals and targets according to 2019 guidelines (% achieving an LDL-c Results We included 209 STEMI patients. Baseline and 1-month LDL-c was 3.3 ± 0.9 and 1.8 ± 0.6 mmol/L respectively. Baseline median CRP was 4.0 [1.9–9.4] mg/L, and baseline LDL-c was not different according to CRP group. More than 95% of patients were discharged with atorvastatin 80 mg or rosuvastatin 20 mg, but ezetimibe in only 8 patients. In 187 LLT naive patients, LLT response profile was not different according to baseline median CRP (figure) with a mean LDL-c decrease of 42 ± 20% in low-CRP and 37 ± 25% in high-CRP patients (P = 0.1). The number of patients achieving a LDL-c reduction over 50% was 35 (38%) and 34 (37%) (P = 0.1). Only 41(20%) patients achieved a LDL-c Fig. 1 ). Conclusion After STEMI, 1-month LDL-c reduction by mainly high-dose statin was not significantly modified by early inflammation when baseline LDL measured at admission. LDL-c control at 1-month remains scarce according to the 2019 ESC guidelines.

Introduction Left ventricular thrombus (LVT) is a rare complication of ST-elevation myocardial infarction (STEMI) and its management is based on low-evidence recommendations. LVT is also underdiagnosed because of low routine use of cardiac Myocardial Resonance (CMR) imaging after STEMI. Objective To describe the prevalence, the management and the 12-month follow-up of LVT in a contemporary acute STEMI population. Method Consecutive STEMI patients were enrolled in a monocentric, observational, prospective study (HIBISCUS cohort). They all underwent a trans-thoracic echocardiography (TTE) at Intensive Care Unit (ICU) discharge and at one month. A CMR was also performed at one month. All CMR were re-analyzed a posteriori by a core lab, this assessment was the gold standard for LVT diagnosis. Medical treatment, follow-up by medical imaging and adverse events were collected at 12 months prospectively. Results A total of 247 STEMI patients were included. LVT was present in 30 (12.1%) patients. For eight of them clinicians were not aware of the diagnosis as LVT was not seen upon first CMR reading. LVT was diagnosed before ICU discharge in 16.7% of cases. In patients with initial diagnosis (n = 22), vitamin K Antagonist (VKA) treatment was prescribed in (n = 15) 76.7% and a direct oral anticoagulant (DOAC) in (n = 7) 23.3%. A LVT follow-up imaging was specifically requested in 77.8% cases within 12-months. It was based on TTE in n = 9 (64.3%), CMR in n = 3 (21.4%) and MDCT in n = 2 (14.3%). Follow-up imaging showed a persistent LVT in 28.6% of cases. At 12 months follow-up there was no ischemic stroke but one (3%) severe hemorrhage and one (3%) stent thrombosis. Conclusion This observational study shows a 12% prevalence of LVT in a contemporary STEMI population and confirms the significant underdiagnosis by TTE. There was an important heterogeneity in the management and monitoring of LVT with a low rate of ischemic or hemorrhagic events.

Introduction Myocardial infarction (MI) is followed by an intense inflammatory response which is necessary for the healing of the infarcted area, but which can also have deleterious effect by increasing infarct size (IS). A good knowledge of this inflammatory response is necessary to develop new treatments targeting this phase. Objective Our study aims at describing the temporal kinetic of inflammatory biomarkers in ST-elevation MI (STEMI) patients and to evaluate their correlation with IS and left ventricular ejection fraction (LVEF). Method We included 100 patients of our HIBISCUS cohort (STEMI patients cohort) with blood samples collected at admission (H0), then 4 (H4), 24 (H24), 48 hours (H48) and 1 month (M1) after reperfusion. C-reactive protein (CRP), interleukin(IL)-1β, IL-1α, IL-6, IL-8, IL-10, tumor necrosis factor (TNFα), Growth Differentiation Factor 15 (GDF15) and interleukin 1 receptor-like 1 (ST2) were assessed in the serum by ELISA. All patients underwent a cardiac magnetic resonance imaging (CMR) at 1 month. Results Patient were aged of 57 ± 10 years. Contrary to other biomarkers, IL-1β, IL-1α and TNFα were weakly detectable in the serum. CRP reached a peak at H48 with a median of 11.7 mg/L interquartile range (IQR) [2.3–29.1]. IL-6 peaked at H24 with 4.8 pg/mL IQR [1.9–14.3], IL-8 at H24 with 2.6 pg/mL IQR [1.3–4.7], IL-10 at H0 with 5.7 pg/mL IQR [2.9–11.3], GDF15 at H0 with 203.7 pg/mL IQR [106.0–301.6] and ST2 at H24 with 25.6 pg/mL IQR [16.8–37.7]. Only CRP, IL-6, IL-10 and ST2 were significantly corelated with IS (respectively r = 0.51, P Conclusion During STEMI, we observed a specific kinetic for each biomarker with variable peak time. CRP, IL-6, IL-10 and ST2 were significantly correlated with IS and inversely correlated with LVEF.

Introduction The prognosis after a myocardial infarction is now importantly linked to the reperfusion injury, which consists in cellular death due to reperfusion by itself. This ischemia/reperfusion phenomenon is mediated by the inflammatory response to myocardial infarction, mainly through the secretion of pro-inflammatory and anti-inflammatory cytokines by macrophages. Many treatments has been developed to target that inflammatory response, but the effects of standard treatments of the myocardial infarction, as recommended in the guidelines, has never been studied. Objective To examine the effects of standard treatments of the myocardial infarction on the secretion of the most important ischemia/reperfusion cytokines. Method We used a murin macrophage model of inflammation (BMDM) to quantify the secretion of the main cytokines of ischemia/reperfusion (TNF-α, IL-6, IL-1α, IL-1β and IL-10). These macrophages were incubated alone, along with a treatment of each main class given after a myocardial infarction or with an association of pre-hospital phase treatments (aspirine, ticagrelor and unfractionned heparin). Secretion of the different cytokines was quantified using an ELISA testing. Results The standard treatments impact mostly IL-1β, which is known to be the most deleterious cytokine during ischemia/reperfusion. Its secretion is lowered by aspirin, the anti-Gp2b3a abciximab, and unfractionned heparin. The other treatments tested, including the low-weight molecular heparin enoxaparin, have no effect on IL-1β secretion. The standard treatments have only few effects on the secretion of the other cytokins. Conclusion Aspirin, abciximab and unfractionned heparin have an important anti-IL-1β effect, reducing its secretion. This could explain the lack of efficacy of the specific anti-IL-1β treatments during the acute phase of myocardial infarction. These results should be confirmed using an in vivo murin model and a human in vitro model.

Introduction Cardioprotection methods have been developed to protect the heart against deleterious effects of ischemia reperfusion (IR), among them, postconditioning (PC) was shown to decrease infarct size (IS). Thus, it was shown that deacetylation, a post-translational modification, was crucial for PC success. Our lab recently shown that modification on acetylation level of cyclophilin D (CypD) by sirtuin 3 (SIRT3), a mitochondrial deacetylase, modifies the efficiency of ischemic-postconditionning (IPC). Indeed, it was shown that in absence of SIRT3, CypD is hyperacetylated leading to mPTP opening and cell death and inefficacy of IPC. Moreover, numerous studies have linked the lack of SIRT3 with aging associated pathologies. Objective The goal of this study was to decipher the impact of CypD deacetylation mediated by SIRT3 in PC in the aging context. Methods We submitted young (2 months) and old (≤ 12 months) mice, WT and SIRT3 KO, to IR and IPC. IS were quantified, and mitochondrial protein acetylation was evaluated. In parallel, basal mitochondrial functions and protein acetylation were assessed, as well as deacetylase activity, to estimate the impact of aging. Results Our results enlightened the importance of SIRT3 for PC success in young mice (25% IS reduction), that is lost in the old mice. We reported no more modification of the acetylation profile neither after IR or IPC in old mice. Moreover, we quantified a significant decrease in deacetylase activity with age (25%), associated to a significant decrease in NAD+ content (60%) with no basal mitochondrial function modification in old mice that could be associated to the loss of IPC efficiency. Conclusion In accordance with what we demonstrated in young mice, the failure of IPC in old mice could be explained by a lack of CypD deacetylation following IPC stimulus, linked with an alteration of the deacetylase mitochondrial activity associated to a significant decrease in NAD+ mitochondrial content.

Introduction and objective Although early reperfusion, ST-elevation myocardial infarction (STEMI) remain a major cause of mortality and heart failure. Reperfusion is commonly associated with persistent micro-vascular obstruction (MVO), edema and intramyocardial hemorrhage (IMH) which are detected using cardiovascular magnetic resonance (CMR) imaging. Furthermore, STEMI is associated with an important inflammatory reaction. So far, the correlation between CMR parameters and inflammation remain unclear. Methods and results This study aims at deciphering the correlation between adverse events and inflammatory biomarkers. This is a prospective study including 21 STEMI patients referred for a primary percutaneous coronary intervention. Seven blood samples were collected at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion. The presence of inflammatory markers including fibrinogen, inteleukin-10, interleukine-6, C reactive protein (CRP), interleukine-8, and neutrophils count was assessed by enzyme-linked immunosorbent assay (ELISA) technique. At day 7 after reperfusion, CMR was performed to determine infarct size, MVO, IMH and edema. The study compares the expression level of each biomarker with CMR measures. MVO was present in 55% of patients and IMH in 33.3%. We observed a correlation between IL-6, CRP, fibrinogen, neutrophil levels and IMH (P = 0.033; P = 0.05; P = 0.0085; P = 0.0046 respectively). Patients with persistent MVO present a significantly higher rate of CRP (P = 0.0125). No significant difference was found for other markers and edema was not significantly correlated with inflammation. Conclusion Following acute myocardial infarction in human patient, IMH appears to be strongly correlated with inflammatory biomarkers. Targeting the couple IMH/inflammation could be a novel strategy in future adjunctive STEMI treatment.

Introduction Circadian rhythm modulates many physiological functions. Some studies suggest a circadian variation of infarct size (IS) in experimental models and in human. It is also known that inflammation is modulated according to circadian rhythm. Inflammation has a central role in post-MI remodeling and final IS. Circadian variation of IS and inflammation response after MI are unknown. Objective Our objective was to evaluate the modulation of IS according to the reperfusion time of the day and to assess if post-MI inflammation was also modulated by circadian rhythm. Method In our biobank, we selected 115 patients who presented with a ST-elevated Myocardial Infarction (STEMI). Two groups were done according to the reperfusion time of day. The morning group (MG) was reperfused between 6:01 am and 12:00 and the afternoon group (AG) was reperfused between 12:01 and 6:00 pm. Each patient had a blood sample upon admission and 4 hours after reperfusion. IS was assessed using cardiac magnetic resonance (MRI) imaging. Main inflammatory markers as interleukin (IL)-6, IL-8, IL-10 and C-reactive protein (CRP) were dosed using ELISA. Results There were 53 patients in the MG and 62 patients in the AG. Patients characteristics were similar in the two groups, especially ischemia time (median of 165 min in both groups). We observed that IS assessed by MRI was significantly reduced by 23.2% in the AG compared to the MG (P = 0.04). Furthermore, patients reperfused the afternoon showed a less intense inflammation reaction post-MI with a 54% decrease of CRP (P = 0.004) and 30% decrease of IL-6 (P = 0.047) compared to the MG. IL-8 and IL-10 levels were similar in the 2 groups. Conclusion We confirmed a circadian variation of myocardial IS in STEMI reperfused patients according to the reperfusion time of the day. The largest IS was observed in the MG. CRP and IL-6 were also modulated according to circadian rhythm with a higher level the morning compared to the afternoon.

Introduction Acute myocardial infarction (MI) leads to an intense inflammatory response with endothelial cell activation. Vascular cell adhesion protein 1 (VCAM-1), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) promote the adherence of leucocytes especially monocytes, in the infarcted area which may increase infarct size (IS). Objective Our objective was to evaluate the kinetic of endothelial cell activation markers at the acute phase of ST-elevated MI (STEMI) and their relationship with IS and Major Adverse Cardiac Event (MACE). Method Blood sample of 182 STEMI patients were collected at admission and four hours after reperfusion. Infarct Size (IS) was assessed in all patients using cardiac Magnetic Resonance Imaging (cMRI) one month after discharge. We performed ELISA quantification of the main markers of endothelial cell activation in serum: VCAM-1, E-selectin, ICAM-1 and MCP-1. Results Patients mean age was 58 ± 11 years with 77% males. Median levels of each marker at admission reached 165.3 ng/mL interquartile range (IQR) [127.0–193.3] for VCAM-1, 140.6 ng/mL IQR [104.6–196.6] for ICAM-1, 15.3 ng/mL IQR [10.2–23.3] for E-selectin and 53.8 pg/mL IQR [34.7–90.5] for MCP-1. VCAM-1 and MCP-1 serum levels significantly increased four hours after admission (respectively +6% and +32%). E-selectin and ICAM-1 levels did not change four hours after admission compared to admission. Only VCAM-1 was significantly correlated with IS assessed by cMRI (r = 0.26, P = 0.0004) and inversely correlated with left ventricular ejection fraction (r = −0.16, P = 0.04). However, VCAM-1 level and other markers were not associated with MACE. Conclusion MI is associated with endothelial cell activation. VCAM-1 and MCP-1 significantly increased at the acute phase of MI whereas E-selectin and ICAM-1 levels are stable. Only VCAM-1 serum level was correlated with IS. However, none of these markers was associated with the occurrence of MACE.

Cardioprotection consists in reducing reperfusion injury, by acting before ischemia (preconditioning) or before reperfusion (postconditioning IPC). Sirtuins have been widely studied, and particularly mitochondrial Sirtuin 3 (SIRT3). It has been demonstrated that in the absence of this deacetylase, IPC failed at reducing infarct size (IS) in young mice. We suggested that the absence of SIRT3 lead to hyperacetylation of cyclophilin D (CypD), the major regulator of the mitochondrial permeability transition pore (mPTP), causing a mPTP hypersensitization to Ca2+ overload. To go further, we tested the effect of the absence of SIRT3 on IS in older mice, and sought to clarify the role of SIRT3 in mitochondrial functions. To do so, we used WT and SIRT3 KO mice (129S6/SvEvTac) at 2, 12 and 18 months. Mitochondrial functions were determined by calcium retention capacity (CRC) and oxidative phosphorylation (OxPhos). Mice underwent in vivo acute myocardial ischemia reperfusion, and IS was quantified.Protein expression and acetylation levels were assessed by western blot. We then tested the effect of PC by NMN, a NAD+ precursor and deacetylation enhancer via SIRT3 activation. No evidence was found on SIRT3 implication in cardioprotection in older mice. The major difference found between WT and SIRT3 KO mice was the acetylation level of mitochondrial proteins. Indeed, no significant difference was found between WT and SIRT3 KO mice over 2 m. IS increased with age for both, and IPC failed at reducing infarct size at 18 m. No difference was reported in mitochondrial functions or in protein expression after 2 m. Even a supplementation in NAD+ via NMN injection failed at reducing IS while reducing acetylation levels. Given the absence of effect of SIRT3 knock out on IS, cardioprotection and mitochondrial functions, the absence of effect of acetylation modification using NMN, we wonder what is the relevance of acetylation/de-acetylation status in cardioprotection in old mice? The author hereby declares no conflict of interest

BackgroundAnkle-brachial pressure index (ABI) is an independent predictor of the extent of coronary atherosclerosis and cardiovascular events. To date ABI measurement is not part of the routine examination in patient admitted for coronary angiography. Our objective was to establish ABI measurement as a routine procedure in our interventional cardiology unit to ameliorate the assessment of coronary risk level for patients admitted for scheduled coronary angiography.MethodABI measurement was performed on admission using a doppler ultrasonic instrument. Patients with past medical history of peripheral arteriopathy were excluded. Cardiovascular risk factors and clinical findings were collected. Correlations and multivariate analysis were performed on R software.ResultsIn the pilot study, 40 consecutive patients were included between February and April 2009. 79% were males and the mean age was 66+/-12 years. ABI < 0.9 was found in 6 patients. Significant multivessel disease was found in 10 patients: 6 with ABI

Background Myocardial infarction (MI) is one of the main causes of death in the world. Infarct size (IS) is associated with heart failure and mortality following MI. Early reperfusion is currently the most effective treatment to reduce IS resulting from MI. Although reperfusion reduces infarct size, it can also lead to reperfusion injuries. Recently, it was shown that interleukin- 17A (IL-17A) is involved in the pathophysiology of reperfusion injuries. However, the correlation between IS and the IL-17A level in humans is unknown. Our aim was to evaluate whether the IL-17A serum level and the IL-17A active fraction was correlated with IS in humans. Methods We selected 101 patients who presented with a ST-elevated Myocardial Infarction (STEMI) and 10 healthy controls. For each patient blood samples at admission (H0) and 4 hours after admission (H4) were collected. IL-17A serum levels were assessed using ELISA and the active fraction was assessed with a functional test. IS was determined by peak troponin level and peak CK level for every patient and by cardiac magnetic resonance imaging (CMR) for 20 patients. Results The IL-17A serum level was significantly increased in STEMI patients compared to the healthy controls, showing a median value of 0.9 pg/mL Interquartile Range IQR [0.0-3.2] at H0 and 1.0 pg/mL IQR [0.2-2.8] at H4 versus 0.2 pg/mL IQR [0.0-0.7] for healthy controls. The serum level of IL-17A did not correlate with IS (r=–0.02475, p=0.80 at H0 and r=0.04425, p=0.66 at H4 for peak troponin level; r=–0.03390, p=0.74 at H0 and r=0.02276, p=0.82 at H4 for peak CK level and r=–0.2593, p=0.28 and r= –0.2884, p=0.23 for CMR). As for the serum IL-17A level, no correlation was found between the active fraction of IL-17A and IS. Conclusion Serum IL-17A level is significantly increased in patients at the early phase of acute MI compared to healthy controls. However, the level of IL-17A in the acute phase of MI does not correlate with IS.