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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. We aim to develop a protocol for inflammatory and calcium phenotyping of human PBMC by flow cytometry. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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 < 0.0001; r = 0.57, p < 0.0001; r = 0.53, P < 0.0001; r = 0.35, P = 0.0004) and inversed correlated with LVEF (respectively r = −0.38, P = 0.0002; r = −0.50, P < 0.0001; r = −0.41, P < 0.0001; r = −0.23, P = 0.02) assessed by CMR. 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. [ABSTRACT FROM AUTHOR]

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. 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). 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. A small fraction (< 14%) of STEMI patients were diabetic and did not show a bigger infarct size when compared to non-diabetic ones. HFHSD mice had bigger infarct size compared to SD (HFHSD 47.8 [43.5, 49.0] vs. SD 37.3 [33.5, 43.6] %, n = 8–9/group, P < 0.05). Metformin treatment reduced cell death after H/R in the HFHSD cardiomyocytes, to a similar extent as in SD cells. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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]. These results suggest that leptin might be an early prognosis marker in STEMI patients. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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 < 0.0001, and r = 0.29, P = 0.0001) and inversely correlated with LVEF (respectively r = −0.42, P < 0.0001 and r = −0.26, P = 0.0003). Patients with IL-10/IL-6 ratio ≥ 1 had smaller IS compared to patients with IL-10/IL-6 ratio < 1 (respectively 9.0% IQR [2.4–15.4] of LV versus 17% IQR [8.7–29.3] of LV, P < 0.0001) and they had higher LVEF (58.0% IQR [52.0–62.3] versus 49.0% IQR [41.5–56.0], P < 0.0001). Patients with IL-10/IL-6 ratio < 1 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 compared to patients with IL-10/IL-6 ratio ≥ 1 (HR = 2.7 95% CI [1.2–5.5], P = 0.04). Serum IL-10/IL-6 > 1 was associated with a poor outcome after STEMI and might be a valuable prognostic marker. [ABSTRACT FROM AUTHOR]

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). Our hypothesis was that the serum levels of sTNFR1 and sTNFR2 might be a marker of the severity of STEMI. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. Our objective was to define the kinetics of basophils within the first month in patients admitted for STEMI and to assess their prognostic value. 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. 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 < 0.001) and was back to baseline level at H48. Basophils at H48 were not associated with IS assessed by CMR (r = −0.08, P = 0.32), LVEF (r = −0.12, P = 0.08) or LV end diastolic volume (r = −0.03, P = 0.68). Patients with H48 basophil level below the median value of the population were more likely to have an adverse clinical event (MI, stroke, hospitalization for heart failure and all-cause death) during the 18 months follow-up compared to patients with basophil level above the median (hazard ratio at 6.1 [2.5–15.0], P = 0.005). In a multivariable Cox regression analyses with models including peak troponin I, LVEF and age, low levels of basophils at H48 remained associated with an increased risk of adverse clinical event. Area under the receiver operating curve was 0.68 (0.57–0.78), P = 0.005 (Fig. 1). Basophil count at H48 in STEMI patients is an independent prognosis marker to predict clinical outcome. [ABSTRACT FROM AUTHOR]

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. To describe the prevalence, the management and the 12-month follow-up of LVT in a contemporary acute STEMI population. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. We investigated whether inflammation in the acute phase MI could influence LLT effect on LDL-c reduction at 1-month follow-up. 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 naïve 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 < 1.4 mmol/l and % decreasing over 50%). 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 naïve 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 < 1.4 mmol/L at 1-month (Fig. 1). 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. [ABSTRACT FROM AUTHOR]

The HIBISCUS-STEMI BIOBANK (coHort of patients to Identify Biological and Imaging markerS of CardiovascUlar outcomes in ST elevation myocardial infarction) is based on a prospective cohort of 500 patients with ST elevation myocardial infarction (STEMI), supported by the RHU MARVELOUS (ANR-16-RHUS-0009). Its primary objective is to identify new biomarkers of clinical outcomes with specific attention to heart failure. All patients with suspicion of STEMI have given written consent and clinical, laboratory and imaging information has been recorded in the database of the Lyon Clinical Investigation Center (CIC). Blood sampling (taken 24/7) (24 mL) was repeated 5 times: before PCI (Percutaneous Coronary Intervention), at 4-24-48 hours and 1 month after PCI. Blood was immediately transferred to the local biobank to be processed in serum, plasma or peripheral blood mononuclear cells (PBMC), and cryopreserved at −80 °C or in liquid nitrogen. Total blood was also stored for future genetic studies. The biobank has been certified for NF S96-900 French norm and assure traceability and quality of samples and storage. More than 36,000 high quality biological samples associated with clinical and MRI (magnetic resonance imaging) data are already available and several projects are ongoing with new biomarkers being identified, e.g. to explore the role of inflammation in myocardial ischemia-reperfusion damage and development of LV remodeling and heart failure within 1 year after AMI. The HIBISCUS-STEMI Biobank is a powerful tool for biomarkers research, available for academic or industrial collaboration. This will help to better understand the mechanisms of AMI and, to improve our assessment of individual prognosis after acute myocardial infarction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

La myocardite aiguë, complication habituelle des infections virales chez l'adulte jeune, se manifeste le plus souvent sous la forme d'un épisode unique, totalement résolutif. La persistance d'une inflammation myocardique chronique à distance d'une myocardite aiguë fait suspecter une pathologie sous-jacente, comme une maladie systémique ou une cardiomyopathie d'origine génétique. Cependant, les causes des myocardites chroniques (MC) et le profil évolutif de ces patients sont aujourd'hui largement méconnus. Nous avons mené une étude de cohorte rétrospective de patients atteints de MC, afin d'en préciser les caractéristiques étiologiques et les principaux profils évolutifs. Une cohorte de 45 patients atteints de MC suivis au CHU de Lyon entre 2007 et 2023 a été constituée. Les myocardites chroniques étaient définies par (i) la survenue de myocardites aigues récidivantes (MAR) et/ou (ii) la persistance de la troponinémie et/ou des anomalies de l'IRM cardiaque au moins 3 mois après la myocardite aigue initiale, suggérant une myocardite aigue de résolution incomplète (MARI). Les données clinico-biologiques, histologiques, morphologiques, thérapeutiques et du suivi ont été colligées. Une cause sous-jacente a été identifiée dans 12 (27 %) cas de MC. Une cardiomyopathie arythmogène génétique a été recherchée chez 12 patients, et identifiée chez 5 d'entre eux, représentant la première cause de MC au sein de notre cohorte (MC d'origine génétique [MCg]). Une maladie de système (MC d'origine systémique [MCs]) a été identifiée chez 8 patients (2 sarcoïdoses, 3 connectivites, 1 vascularite à ANCA, 1 syndrome des antiphospholipides et 1 maladie de Behçet). Il n'a pas été retrouvé de cause chez les 33 (73 %) cas restants (MC idiopathique [MCi]). Les patients atteints de MCg étaient significativement plus jeunes que ceux atteints de MCs (18 [18–22] vs 44 [37-49] ans ; p = 0,006) et présentaient une troponinémie plus élevée lors du premier épisode de myocardite (2,000 [540–47 000] ng/L vs 323 [197,5–6716] ng/L ; p = 0,03). Deux profils évolutifs distincts de MC ont été dégagés : 28 (62 %) patients ont présenté des MAR, tandis que les 15 (33 %) patients ont présenté une MARI. Les patients présentant une MCi avaient davantage tendance à présenter un profil récidivant que les patients atteint de MCs ou de MCg (76 % vs 38 % et 40 % respectivement). Un traitement immunosuppresseur a été davantage utilisé au cours des MCs par rapport MCi (100 % vs 18 % ; p < 0,001), associant une corticothérapie à de l'hydroxychloroquine (n = 3), du méthotrexate (n = 2), de l'azathioprine (n = 2), du mycophenolate mofetil (n = 3), du cyclophosphamide (n = 1) ou de l'anakinra (n = 2). Deux patients atteints de MCg (40 %) ont également bénéficié d'un traitement immunomodulateur par méthotrexate ou anakinra. Après un suivi médian de 4,6 ans, une altération de la FEVG < 50 %, un événement cardiovasculaire majeur ou le recours à un pacemaker/défibrillateur sont survenus dans 20 %, 22 % et 20 % des MC respectivement, avec des taux supérieurs au cours des MCg suggérant un pronostic plus défavorable. Le taux de transplantation cardiaque ou de décès au cours de l'étude était de 4,4 % et 2,2 % respectivement. Cette étude décrit les causes prédominantes et les profils évolutifs principaux des patients atteints de myocardite chronique. Elle souligne la faible rentabilité des explorations paracliniques à la recherche d'une maladie de système et appuie l'importance du diagnostic génétique. [ABSTRACT FROM AUTHOR]