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We sought to improve the risk prediction of 3-month left ventricular remodeling (LVR) occurrence after myocardial infarction (MI), using a machine learning approach.Patients were included from a prospective cohort study analyzing the incidence of LVR in ST-elevation MI in 443 patients that were monitored at Angers University Hospital, France. Clinical, biological and cardiac magnetic resonance (CMR) imaging data from the first week post MI were collected, and LVR was assessed with CMR at 3 month. Data were processed with a machine learning pipeline using multiple feature selection algorithms to identify the most informative variables.We retrieved 133 clinical, biological and CMR imaging variables, from 379 patients with ST-elevation MI. A baseline logistic regression model using previously known variables achieved an AUC of 0.71 on the test set, with 67% sensitivity and 64% specificity. In comparison, our best predictive model was a neural network using seven variables (in order of importance): creatine kinase, mean corpuscular volume, baseline left atrial surface, history of diabetes, history of hypertension, red blood cell distribution width, and creatinine. This model achieved an AUC of 0.78 on the test set, reaching a sensitivity of 92% and a specificity of 55%, outperforming the baseline model.These preliminary results show the value of using an unbiased data-driven machine learning approach. We reached a higher level of sensitivity compared to traditional methods for the prediction of a 3-month post-MI LVR.

IntroductionCurrent guidelines for patients presenting to the emergency department (ED) with chest pain without ST-segment elevation myocardial infarction (STEMI) on ECG are based on serial troponin measurements. A clinical tool able to identify very low-risk patients who could forgo a troponin test and low-risk patients requiring only one troponin measurement would be of great interest. To do so, the HEAR and HEART score, standing for history, ECG, age, risk factors±troponin were prospectively assessed, but not combined and implemented in clinical practice. The objective of the eCARE study is to assess the impact of implementing a diagnostic strategy based on a HEAR score Methods and analysisStepped-wedge cluster-randomised control trial in 10 EDs. Patients with non-traumatic chest pain and no formal diagnosis were included and followed for 30 days. In the interventional phase, the doctor will be asked not to perform a troponin test to look for an acute coronary if the HEAR score is Ethics and disseminationThe study was approved by an institutional review board for all participating centres. If successful, the eCARE study will cover a gap in the evidence, proving that it is safe and efficient to rule out the hypothesis of an acute myocardial infarction in some selected very low-risk patients or based on a single troponin measurement in some low-risk patients.Trial registration numberNCT04157790.

Aims: Periprocedural myocardial infarctions have been reported in the setting of planned percutaneous coronary intervention (PCI). We assessed the prevalence of nonculprit artery acute myocardial infarction (NCAMI) and its relationship with coronary artery characteristics, final infarct size, and 1-year adverse clinical outcomes in a population of anterior ST-elevated myocardial infarction (STEMI) patients. Methods and Results: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) studies were performed within 7 days of admission in 129 anterior STEMI patients from the CIRCUS trial treated by primary PCI. Infarct in the noninfarct artery territory (circumflex, right coronary) was assessed on LGE-CMR and T2-weighted images. Eleven (8.5%) patients exhibited NCAMI. The only independent characteristic significantly associated with NCAMI was the presence of multiple complex coronary lesions (odds ratio = 12.9, 95% confidence interval [3.1–53.4]; p < 0.001). There was a significantly increased infarct size in NCAMI patients compared to patients without NCAMI (45.8 ± 20.4% of the left ventricle [LV] vs. 31.0 ± 15.1% of LV, respectively; p = 0.02), with lower LV ejection fraction (46 ± 10% vs. 34 ± 8%, respectively; p < 0.001). Conclusion: NCAMIs are present in 8.5% of anterior STEMI patients and are significantly associated with multiple complex coronary lesions without significant relationship to any revascularization procedural technique. NCAMI was associated with a greater infarct size and reduced LVEF but not worse clinical outcomes at 1 year.

New treatments are needed to protect the myocardium against the detrimental effects of acute ischaemia/reperfusion (IR) injury following an acute myocardial infarction (AMI), in order to limit myocardial infarct (MI) size, preserve cardiac function and prevent the onset of heart failure (HF). Given the critical role of mitochondria in energy production for cardiac contractile function, prevention of mitochondrial dysfunction during acute myocardial IRI may provide novel cardioprotective strategies. In this regard, the mitochondrial fusion and fissions proteins, which regulate changes in mitochondrial morphology, are known to impact on mitochondrial quality control by modulating mitochondrial biogenesis, mitophagy and the mitochondrial unfolded protein response. In this article, we review how targeting these inter‐related processes may provide novel treatment targets and new therapeutic strategies for reducing MI size, preventing the onset of HF following AMI.

Introduction: We sought to improve the risk prediction of 3-month left ventricular remodeling (LVR) occurrence after myocardial infarction (MI), using a state-of-the-art machine learning approach. Methods: We retrieved 135 variables, ranging from clinical, biological and cardiac magnetic resonance data, from 379 patients with ST-elevated myocardial infarction and processed them with a machine learning pipeline using advanced feature selection and modelling algorithms such as gradient boosting, neural networks or recurrent neural networks. Results: A baseline logistic regression model using known variables such as infarct size, creatine kinase peak, no reflow and cardiovascular risk factors, achieved an AUC of 0.71 on the test, with 67% sensitivity and 64 % specificity. In comparison, our best predictive model was a neural network using seven variables (in order of importance): creatine kinase, mean corpuscular volume, baseline left atrial surface, history of diabetes, history of hypertension, red blood cell distribution width, and creatinine. This model achieved an AUC of 0.78 on the test set, reaching a sensitivity of 92% and a specificity of 67%, outperforming the baseline model. Conclusions: We were able to achieve state-of-the-art performance with a high level of sensitivity for the prediction of a 3-month post-MI LVR. Our unbiased data-driven machine learning approach highlights the role of classical parameters alongside unexpected variables such as left atrial dilation at baseline, mean corpuscular volume and red blood cell distribution width whose role in the pathophysiology of post-MI cardiac remodeling remain to be clarified. The relative simplicity and the good availability of these parameters make our new approach suitable for clinical testing.

Supplemental Digital Content is available in the text., Background: Inflammation is a key factor of myocardial damage in reperfused ST-segment–elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment–elevation myocardial infarction. Methods: In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment–elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes. Results: We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement–defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16–44] versus 28.4 IQR [14–40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, –8.3% to 11.1%) versus –1.1% (IQR, –8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10–28] versus 18 IQR [10–27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002). Conclusions: In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.

International audience; Background: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided.Methods: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected.Findings: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p

Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. © Published on behalf of the European Society of Cardiology. All rights reserved.

Summary Background Intra-aortic balloon pumps (IABPs) have been used routinely since the 1970s. Recently, large randomized trials failed to show that IABP therapy has meaningful benefit, and international recommendations downgraded its place, particularly in cardiogenic shock. Aims The aim of this registry was to describe the contemporary use of IABP therapy, in light of these new data. Methods This prospective multicentre registry included 172 patients implanted with an IABP in 19 French cardiac centres in 2015. Baseline characteristics, aetiologies leading to IABP use, and IABP-related and disease-related complications were assessed. In-hospital and 1-year mortality rates were studied. Results A total of 172 patients were included (mean age 65.5 ± 12.0 years; 118 men [68.6%]). The reasons for IABP implantation were mainly haemodynamic (n = 107; 62.2%), followed by bridge to revascularization (n = 34; 19.8%) and four other “rare” aetiologies (n = 29 patients; 16.8%). In-hospital and 1-year mortality rates were 40.7% and 45.8%, respectively. Fourteen patients (8.1%) experienced ischaemic or haemorrhagic complications, which were directly related to the IABP in seven patients (4.1%). Conclusions Despite current international guidelines regarding the place of IABPs in ischaemic cardiogenic shock without mechanical complications, this aetiology remains the leading cause for its utilization in the contemporary era.

Mitochondrial dynamics is a possible modulator of myocardial ischemia/reperfusion injuries (IRI). We previously reported that mice partially deficient in the fusion protein OPA1 exhibited higher IRI. Therefore, we investigated whether deficiency in the fission protein DRP1 encoded by Dnm1l gene would affect IRI in Dnm1l+/- mouse. After baseline characterization of the Dnm1l+/- mice heart, using echocardiography, electron microscopy, and oxygraphy, 3-month-old Dnm1l+/- and wild type (WT) mice were exposed to myocardial ischemia/reperfusion (I/R). The ischemic area-at-risk (AAR) and area of necrosis (AN) were delimited, and the infarct size was expressed by AN/AAR. Proteins involved in mitochondrial dynamics and autophagy were analyzed before and after I/R. Mitochondrial permeability transition pore (mPTP) opening sensitivity was assessed after I/R. Heart weight and left ventricular function were not significantly different in 3-, 6- and 12-month-old Dnm1l+/- mice than in WT. The cardiac DRP1 protein expression levels were 60% lower, whereas mitochondrial area and lipid degradation were significantly higher in Dnm1l+/- mice than in WT, though mitochondrial respiratory parameters and mPTP opening did not significantly differ. Following I/R, the infarct size was significantly smaller in Dnm1l+/- mice than in WT (34.6±3.1% vs. 44.5±3.3%, respectively; pDnm1l+/- mice only. Altogether, data indicates that increasing fusion by means of Dnm1l deficiency was associated with protection against IRI, without alteration in cardiac or mitochondrial functions at basal conditions. This protection mechanism due to DRP1 haploinsufficiency increases the expression of autophagic markers.

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.

Introduction While left ventricular (LV) remodeling lead to heart failure and mortality after a myocardial infarction (MI), left atrial dilatation remain poorly described. We sought to evaluate left atrial ejection fraction (LAEF) after MI and its impact on prognosis. Method Out of 477 patients presenting a first ST-segment elevation MI with successful revascularization, LAEF was measurable in 374 patients who constituted the population study. Cardiac magnetic resonance imaging (CMR) was performed at baseline and after a 3-month follow-up. Results A reduced LAEF represented its lower quartile (LAEF Fig. 1 ). More, we found an interaction between redLAEF and age on its effect on heart failure during follow-up (OR = 0.47, P = 0.022), with the effect of redLAEF being more prominent amongst > 65 years old patients. Overall, LAEF improved from 40.9 ± 10.3% to 42 ± 11.2% (P = 0.038) but did not differ amongst non-redLAEF patients (P = 0.77). LAEF improved over time in redLAEF patients (n = 75) who did not suffer from cardiovascular outcomes (from 27.7 ± 6.5% to 34.2 ± 13.3, P Conclusion LAEF was a good predictor of cardiovascular outcomes in patients after an myocardial infarction, independently of LVEF and infarct size, and more specifically amongst > 65 years old patient.

Postinfarction adverse left ventricular (LV) remodelling is strongly associated with heart failure events. Conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR).To assess the predictive value of the new indexes for 1-year adverse LV remodelling in patients with anterior ST-segment elevated myocardial infarction (STEMI).CMR studies were performed in 129 patients with anterior STEMI (58±12 years; 78% men) from the randomized CIRCUS trial (CMR substudy) treated with primary percutaneous coronary intervention and followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). Conicity index, sphericity index, LVGFI, infarct size and microvascular obstruction (MVO) were assessed by CMR performed 5±4 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume of ≥15% by transthoracic echocardiography at 1 year.Adverse LV remodelling occurred in 27% of patients at 1 year. Infarct size and MVO were significantly predictive of adverse LV remodelling: odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05 (P0.001) and OR 1.12, 95% CI 1.05-1.22 (P0.001), respectively. Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR 1.10, 95% CI 1.03-1.16; P=0.001). In multivariable analysis, infarct size remained an independent predictor of adverse LV remodelling at 1 year (OR 1.05, 95% CI 1.02-1.08; P0.001). LVGFI and infarct size were associated with occurrence of MACE: OR 1.21, 95% CI 1.08-1.37 (P0.001) and OR 1.02, 95% CI 1.00-1.04 (P=0.018), respectively. Conicity and sphericity indexes were not associated with MACE.LVGFI was associated with adverse LV remodelling and MACE 1 year after anterior STEMI.

Background The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic. Methods In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956. Findings Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51–0·70]). Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62–0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55–0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19. Interpretation A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics. Funding Recherche Hospitalo-Universitaire en Santé iVasc.

This study sought to identify parameters that could guide towards an ischemic origin in patients hospitalized for myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). MINOCA is challenging in clinical practice, as the pathophysiology is multifaceted. A total of 135 patients with MINOCA who underwent cardiovascular magnetic resonance imaging (CMR) in a single tertiary University Hospital, were retrospectively included. The study cohort was classified into 4 groups according to the CMR diagnosis (i.e., myocarditis, myocardial infarction, Takotsubo cardiomyopathy, normal or uncommon diagnosis). According to the CMR, 62% had myocarditis, 14.1% myocardial infarction, 4.4% of Takotsubo and 19.3% showed a normal CMR or uncommon diagnoses. In the multivariate analysis, three criteria were independently correlated with the underlying diagnosis of myocardial infarction: (1) the absence of inflammatory response (HR: 5.71 IC95% [1.79–18.28]; p = 0.002), (2) the presence of coronary atheroma in invasive coronary angiography (HR: 6.56 IC95% [2.27–18.92]; p = 0.001) and (3) a peak of troponin ratio elevated than normal levels of 150 (HR: 4.12 IC95% [1.45–11.65]; p = 0.01). The prevalence of myocardial infarction in MINOCA was 4.9% in the absence of these three criteria, 3.4% with one of the criteria present, 34.5% with two criteria present and 71.4% with all three criteria. The negative predictive value for MI was 96% in the presence of at least two criteria. Our study shows that the absence of inflammatory response, a high troponin and the presence of angiographic coronary atheroma are independently correlated with a myocardial infarction underlying cause of MINOCA.

Infarct size is a major prognostic factor in ST-segment elevation myocardial infarction (STEMI). It is often assessed using repeated blood sampling and the estimation of biomarker area under the concentration versus time curve (AUC) in translational research. We aimed at developing limited sampling strategies (LSS) to accurately estimate biomarker AUC using only a limited number of blood samples in STEMI patients. This retrospective study was carried out on pooled data from five clinical trials of STEMI patients (TIMI blood flow 0/1) studies where repeated blood samples were collected within 72 h after admission to assess creatine kinase (CK), cardiac troponin I (cTnI) and muscle-brain CK (CK-MB). Biomarker kinetics was assessed using previously described biomarker kinetic models. A number of LSS models including combinations of 1 to 3 samples were developed to identify sampling times leading to the best estimation of AUC. Patients were randomly assigned to either learning (2/3) or validation (1/3) subsets. Descriptive and predictive performances of LSS models were compared using learning and validation subsets, respectively. An external validation cohort was used to validate the model and its applicability to different cTnI assays, including high-sensitive (hs) cTnI. 132 patients had full CK and cTnI dataset, 49 patients had CK-MB. For each biomarker, 180 LSS models were tested. Best LSS models were obtained for the following sampling times: T4–16 for CK, T8–T20 for cTnI and T8–T16 for CK-MB for 2-sample LSS; and T4–T16–T24 for CK, T4–T12–T20 for cTnI and T8–T16–T20 for CK-MB for 3-sample LSS. External validation was achieved on 103 anterior STEMI patients (TIMI flow 0/1), and the cTnI model applicability to recommended hs cTnI confirmed. Biomarker kinetics can be assessed with a limited number of samples using kinetic modelling. This opens the way for substantial simplification of future cardioprotection studies, more acceptable for the patients.

International audience; The actual protective mechanisms underlying cardioprotection with remote ischemic conditioning (RIC) remain unclear. Recent data suggest that RIC induces kynurenine (KYN) and kynurenic acid synthesis, two metabolites derived from tryptophan (TRP), yet a causal relation between TRP pathway and RIC remains to be established. We sought to study the impact of RIC on the levels of TRP and its main metabolites within tissues, and to assess whether blocking kynurenine (KYN) synthesis from TRP would inhibit RIC-induced cardioprotection. In rats exposed to 40-min coronary occlusion and 2-h reperfusion, infarct size was significantly smaller in RIC-treated animals (35.7 ± 3.0% vs. 46.5 ± 2.2%, p = 0.01). This protection was lost in rats that received 1-methyl-tryptophan (1-MT) pretreatment, an inhibitor of KYN synthesis from TRP (infarct size = 46.2 ± 5.0%). Levels of TRP and nine compounds spanning its metabolism through the serotonin and KYN pathways were measured by reversed-phase liquid chromatography–tandem mass spectrometry in the liver, heart, and limb skeletal muscle, either exposed or not to RIC. In the liver, RIC induced a significant increase in xanthurenic acid, nicotinic acid, and TRP. Likewise, RIC increased NAD-dependent deacetylase sirtuin activity in the liver. Pretreatment with 1-MT suppressed the RIC-induced increases in NAD-dependent deacetylase sirtuin activity. Altogether, these findings indicate that RIC mechanism is dependent on TRP–KYN pathway activation.

Aim: to evaluate the impact of a nationwide lockdown in France on acute myocardial infarction (AMI) admissions, by patient characteristics and regional prevalence of the pandemic. Methods and Results: We collected data from 21 centres participating in the on-going FRENCHIE registry (NCT04050956), which collects data from all patients admitted for STEMI or NSTEMI within 48 hours of symptom onset. We compared weekly admissions in the 4 weeks preceding and the 4 weeks following institution of the lockdown. We observed a brutal 30% decrease in AMI admissions (24% for STEMI and 36% for NSTEMI, P=0.14) following institution of the lockdown, with similar trends according to gender (30% decrease in both men and women), risk factors, and regional prevalence of COVID-19. The decrease was numerically greater in patients aged 80 years or more (44% vs 27%, P=0.10). Patient characteristics, including time to hospital admission in STEMI patients, did not differ between the 2 periods. In-hospital mortality was numerically higher following institution of the lockdown (5.2% vs 3.4%, P=0.12), with similar trends for STEMI and NSTEMI. Conclusion: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message in case of a second wave of the pandemic or future major epidemics. Funding Statement: The FRENCHIE registry is supported by Recherche Hospitalo-universitaire en sante (RHU) iVasc within the programme "Investissements d'avenir", and sponsored by Assistance Publique – Hopitaux de Paris (Delegation a la Recherche Clinique et a l'Innovation). Declaration of Interests: YC reports research Grants to the Institution or Consulting/Lecture Fees from : Novartis , Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Coste reports having received fees from Amgen, AstraZeneca, Bayer and Servier, outside the submitted work G. Lemesle reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BristolMyers Squibb, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, and The Medicine Co, outside the submitted work. FS reports personal fees from Amgen, Astra Zeneca, Bayer, BMS, MSD, Pfizer, and Sanofi, outside the submitted work D. Angoulvant reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Sanofi, Amgen, Novartis, Novo-Nordisk, Servier and MSD, outside the submitted work C. Bouleti reports receiving consulting and lecture fees from Novartis and AstraZeneca, outside the submitted work. G. Cayla has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Goube reports receiving consulting and lecture fees from AMGEN, SANOFI, BMS, ABBOT, outside the submitted work. T. Lhermusier has received research grants/consultant fees/lectures fees from AstraZeneca, Boston scientifics and Abbott, outside the submitted work A. Saib reports lectures fees from Novartis, outside the submitted work JG Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, BoehringerIngelheim, Bristol-Myers Squibb/Pfizer, Sanofi, and Daiichi-Sankyo and grants from Bayer, BristolMyers Squibb/Pfizer and Biosensors, outside the submitted work. F. Boccara reports research grants from Amgen; lecture fees from Janssen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. And personal consultant or lecture fees from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Intercept, MSD, Novartis, Pfizer, Sanofi, and Servier, outside the submitted work. T. Simon reports grants from Astrazeneca, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi, and personal fees for board membership and/or consultancy and/or lectures from AstraZeneca, BMS, Sanofi, and Novartis, outside the submitted work. N. Danchin has received research grants, or speaking and consulting fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli-Lilly, Intercept, MSD, Novartis, Novo-Nordisk, Pfizer, Sanofi, Servier, outside the submitted work. The other authors have nothing to report. Ethics Approval Statement: FRENCHIE has been approved by the Comite de Protection des Personnes and by the French data regulatory authority (Commission Nationale de l'Informatique et des Libertes).

The ability of remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN) following percutaneous coronary angiography in at-risk patients is controversial. No evidence exists regarding potential RIPC positive effects on renal function and clinical outcomes in the long-term. The PREPARE study was a randomized, prospective, multicenter, and double-blinded trial. A total of 222 patients scheduled for coronary angiography and/or percutaneous transluminal coronary angioplasty with an estimated glomerular filtration rate (eGFR) 2, or eGFR between 40 and 60 mL/min/1.73 m2 and two further risk factors were allocated to RIPC or control groups. Preventive measures were applied to all patients, including continuous intravenous saline infusion, withdrawal of nephrotoxic drugs, and limited volume of contrast medium. The primary endpoint, namely incidence of CIN, was 3.8% in the control group and 5.1% in the RIPC group (p = 0.74). The secondary endpoints, i.e., changes in serum creatinine and eGFR levels from baseline to 48 hours and from baseline to 12 months following contrast medium exposure, did not differ between both groups. The incidences of all major clinical events at 12 months were similar in both groups. In this population at risk of CIN, preventive strategies were associated with low CIN incidence. RIPC impacted neither the CIN incidence nor both the renal function and clinical outcomes at 1-year follow-up.

Introduction Post-infarction adverse left ventricular (LV) remodelling is strongly associated with subsequent heart failure events. The conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR). The aim of our study was to assess their predictive value on one-year adverse LV remodelling in patients with anterior myocardial infarction. Methods CMR studies were performed in 129 anterior ST-elevated myocardial infarction (STEMI) patients (58 ± 12 years, 78%men) from the randomized CIRCUS trial (CMR sub-study) treated with the primary percutaneous coronary intervention (PCI) and were followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). The conicity index, sphericity index, LVGFI, infarct size (IS) and microvascular obstruction (MVO) were assessed by CMR performed 5 ± 2 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 15% by transthoracic echocardiography at 1 year. Results Adverse LV remodeling occurred in 27% of patients in one year. IS and MVO were significantly predictive of adverse LV remodelling (OR = 1.03, CI 95% [1.02–1.05], P Fig. 1 ). Conclusion LVGFI was associated with adverse LV remodelling and MACE at one year after anterior STEMI. However, this relationship and its predictive value in on top of infarct size remain hypothesis-generating at this stage. Further studies are needed to explore the relationship of all these remodelling indices with adverse outcomes in larger populations of MI patients.

Introduction Left ventricular thrombus (LVT) is a frequent complication after an acute myocardial infarction (MI) and is associated with systemic thromboembolism. Cardiovascular magnetic resonance imaging (CMR) is the diagnostic gold-standard, but its limited availability makes screening tools necessary. This study sought to identify the clinical and imaging determinants of LVT early and late after an acute MI. Method The study grouped the data of 2 observational cohorts of patients with reperfused ST-segment elevation MI patients, including a longitudinal and prospective CMR assessment at baseline, and 3 to 6 months after the inaugural event. Results An LVT was found in 51 patients out of the 700 (7.3%) baseline CMR scans, and in 26 out of the 607 (4.3%) at follow-up. LVT patients presented higher rates of anterior infarction, greater infarct size and left ventricular (LV) volumes, and lower LV ejection fraction (LVEF), but similar age, cardiovascular risk factors, and MVO prevalence. At baseline Multivariable analysis showed anterior infarction (OR = 5.216 [1.156-23.538] P 50% had a NPV of 98.26% [96.06-99.29] and a specificity of 58.44% {54.30-62.47] ( Fig. 1 ). Conclusion The prevalence of left ventricular thrombus reached 10.6% of STEMI patients. We identified an anterior infarction and greater LV end-systolic volume to be the best determinants of LV thrombus occurrence at baseline, while LVEF was the best predictor at follow-up.

AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and non-obstructive coronary arteries (MINOCA) with normal ejection fraction (EF). METHODS This is an observational analysis of 131 MINOCA patients with normal EF. Three cardiac magnetic resonance (CMR) diagnosis classes were recognized according to the late gadolinium enhancement (LGE) pattern: Myocardial infarction (MI) (n = 34), myocarditis (n = 47), and “no LGE” (n = 50). Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year. RESULTS Ventricular arrhythmia was observed in 18 (13.8%) patients during hospitalization. The “no LGE” patients experienced fewer ventricular events than the MI and myocarditis patients [4.0% vs 26.5% and 14.9%, respectively (P = 0.013)]. There was no significant difference between the MI and myocarditis groups. On multivariate analysis, LGE transmural extent [OR = 1.52 (1.08-2.15), P = 0.017] and ST-segment elevation [OR = 4.65 (1.61-13.40), P = 0.004] were independent predictors of ventricular arrhythmic events, irrespective of the diagnosis class. Finally, no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year. CONCLUSION MINOCA patients with normal EF presented no 1-year cardiovascular events, irrespective of the CMR diagnosis class. LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.

International audience; In recent years, the number of investigations based on nontargeted metabolomics has increased, although often without a thorough assessment of analytical strategies applied to acquire data. Following published guidelines for metabolomics experiments, we report a validated nontargeted metabolomics strategy with pipeline for unequivocal identification of metabolites using the MSMLS molecule library. We achieved an in-house database containing accurate m/z values, retention times, isotopic patterns, full MS, and MS/MS spectra. A UHPLC-HRMS Q-Exactive method was developed, and experimental variations were determined within and between 3 experimental days. The extraction efficiency as well as the accuracy, precision, repeatability, and linearity of the method were assessed, the method demonstrating good performances. The methodology was further blindly applied to plasma from remote ischemic pre-conditioning (RIPC) rats. Samples, previously analyzed by targeted metabolomics using completely different protocol, analytical strategy, and platform, were submitted to our analytical pipeline. A combination of multivariate and univariate statistical analyses was employed. Selection of putative biomarkers from OPLS-DA model and S-plot was combined to jack-knife confidence intervals, metabolites' VIP values, and univariate statistics. Only variables with strong model contribution and highly statistical reliability were selected as discriminated metabolites. Three biomarkers identified by the previous targeted metabolomics study were found in the current work, in addition to three novel metabolites, emphasizing the efficiency of the current methodology and its ability to identify new biomarkers of clinical interest, in a single sequence. The biomarkers were identified to level 1 according to the metabolomics standard initiative and confirmed by both RPLC and HILIC-HRMS.

Background To compare the effect of stented versus stentless bioprostheses on left ventricular remodeling and assess their impact on long-term survival. Methods From January 2002 to December 2009, 62 severe aortic stenosis patients without coronary artery disease were randomized for bioprosthetic aortic valve replacement. After randomization, a cross-over was possible based on intraoperative data. Ventricular remodeling was studied by cardiovascular magnetic resonance imaging six months after surgery. Long-term survival was assessed by telephone survey. Results Thirty-five patients received a porcine Mosaic® Medtronic bioprosthesis (Stented Group; Medtronic, Minneapolis, MN, USA) inserted using the usual supra-annular technique and 27 received a porcine Freestyle® Medtronic bioprosthesis (Stentless Group) inserted in the subcoronary position. Mean age was 75 ± 3 and 73 ± 4 years in the stentless and stented group, respectively. Nine patients who should have been implanted with a stentless bioprosthesis received a stented bioprosthesis for anatomical reasons. At 6 months, the left ventricular mass (LVM) decreased significantly in both groups (Stentless Group: 214.6 ± 56.1 g and 156.3 ± 23 g and Stented Group: 237 ± 75.7 g and 181 ± 53.3 g, respectively after surgery and at 6 months), this decrease was significantly greater in the stentless group (p = 0.026). Reserve and coronary flow were increased in both groups at 6 months. Mean follow-up duration was 6.6 ± 3.0 years and 7.2 ± 4.0 years in the stentless and stented group, respectively. The 5-year actuarial survival was 87.5 ± 11.7% and 82.5 ± 17.1% for the stentless and stented group, respectively (p = 0.81). Conclusion Porcine stentless prosthesis results in a better LVM regression than a stented valve at 6 months without changing the long-term survival.

Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets.We used a rat model of 40-min coronary ligation followed by reperfusion. RIV (3 mg/kg) was given per os 1 h before reperfusion. Infarct size and myocardial proteic expression of survival pathways were assessed at 120 and 30 min of reperfusion, respectively. Plasmatic levels of P-selectin and von Willebrand factor were measured at 60 min of reperfusion. Cellular RIV effects were assessed using hypoxia-reoxygenation (H/R) models on human umbilical vein endothelial cells and on rat cardiomyoblasts (H9c2 cell line).RIV decreased infarct size by 21% (42.9% vs. 54.2% in RIV-treated rats and controls respectively, P 0.05) at blood concentrations similar to human therapeutic (387.7 ± 152.3 ng/mL) levels. RIV had no effect on H/R-induced modulation of endothelial phenotype, nor did it alter myocardial activation of reperfusion injury salvage kinase and survivor activating factor enhancement pathways at 30 min after reperfusion. However, RIV exerted a cytoprotective effect on H9c2 cells submitted to H/R.RIV decreased myocardial I/R injury in rats at concentrations similar to human therapeutic ones. This protection was not associated with endothelial phenotype modulation but rather with potential direct cytoprotection on cardiomyocytes.

Left ventricular remodeling (LVR) occurring after ST-segment elevation myocardial infarction (STEMI) is frequent and severe. We present a metabolomic approach as an attempt to reveal unknown biomarkers associated with post-STEMI LVR. Out of 192 consecutive patients with successfully revascularized STEMI, 32 presented LVR and were clinically matched with 32 no-LVR patients. They underwent cardiac magnetic resonance at baseline, three months and 12 months. Blood samples were collected during index hospitalization. Creatine kinase (CK) peak and inflammatory markers were higher for LVR patients compared to no-LVR patients (mean 3466 &plusmn, 2211 and 2394 &plusmn, 1615 UI/L respectively, p = 0.005 for CK peak, mean 35.9 &plusmn, 44.3 vs. 21.7 &plusmn, 30.4 mg/L respectively, p = 0.020 for C-reactive protein). Leukocyte and neutrophil counts were also higher for LVR patients (mean 12028 &plusmn, 2593/mL vs. 10346 &plusmn, 3626/mL respectively, p = 0.028 and mean 9035 &plusmn, 3036/mL vs. 7596 &plusmn, 3822/mL respectively, p &lt, 0.001). For metabolomic analysis, sphingomyelin C20:2 and symmetrical dimethylarginine were higher for LVR patients, but did not reach significance after the correction for the alpha risk. The metabolomic approach did not discriminate patients with and without LVR. However, common parameters that focus on infarction severity, such as infarct size and inflammatory markers, differed between the groups.

International audience; BACKGROUND: Atrial fibrillation (AF) is common in ST-segment elevation myocardial infarction (STEMI), but its influence on prognosis remains controversial.AIM: We examined the 1-year prognostic value of AF in STEMI, distinguishing patients with prior AF from patients with de novo AF.METHODS: Between January 2004 and December 2015, 3173 STEMI patients were enrolled in the RIMA registry (Registre des Infarctus en Maine Anjou). They were divided into 3 groups: (1) AF-free patients; (2) patients with known prior AF; and (3) patients with de novo AF during hospitalization (including admission). We defined 3 primary outcomes at 1-year post-discharge: cardiovascular mortality, readmission for heart failure (HF), and stroke. Temporal onset of de novo AF was also studied.RESULTS: A total 158 patients (5%) had prior AF, and 278 (8.8%) presented de novo AF. Prior AF patients were significantly older [81 (73;86) years] with more comorbidities, but de novo AF patients presented with a greater creatine kinase peak and lower left ventricular ejection fraction [LVEF=44 (35;50)% for de novo AF vs 50 (40;55)% for prior AF, pCONCLUSION: De novo AF was independently associated with 1-year cardiovascular mortality. It should not be considered as an intercurrent event of STEMI, but rather as a strong prognostic marker.

Introduction Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2 h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30 min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels. Methods Wistar male rats were subjected to 40 minutes (min) of myocardial ischemia, followed by 30 min or 2 h of reperfusion. Rats were randomized into four groups: control 30 min (n = 7), FDX 30 min (n = 7), control 2 h (n = 7), and FDX 2 h (n = 7). The FDX groups received 10 mg/kg injection of FDX 10 min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-κB, IκB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX. Results FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2 h of reperfusion. Conclusion The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect.

Objectif Plusieurs etudes recentes suggerent une association du syndrome d’apnees du sommeil (SAS) avec la severite de l’atteinte cardiaque et sa recuperation suite a un infarctus du myocarde (IDM). Notre objectif etait d’evaluer si la presence et la severite des troubles respiratoires nocturnes sont liees a la severite de l’atteinte cardiaque au decours immediat et a 3 mois d’un IDM. Methodes Les patients presentant un premier episode d’IDM etaient inclus et beneficiaient d’une polygraphie ventilatoire dans les 72 h et d’une IRM cardiaque a la phase aigue et a 3 mois. Resultats Cinquante-six patients ont ete inclus. La prevalence du SAS etait de 62,5 % dont 74,3 % de SAS centraux. Les patients desaturateurs avaient une FEVG plus basse a M0 et a M3 (44 % versus 50,9 %a M3, p = 0,031) tout comme les patients hypoxiques (41,7 % versus 49,6 % a M3, p = 0,003). Ces derniers avaient une taille d’IDM plus grande a M0 (30 % versus 18,2 %, p = 0,007) et a M3 (20,7 % versus 13 %, p = 0,004). Il n’a pas ete montre d’effet propre du SAS sur la taille de l’IDM. Il n’y avait pas de relation entre la severite des troubles respiratoires du sommeil et l’evolution des marqueurs d’atteinte cardiaque entre M0 et M3. Conclusion Les troubles respiratoires du sommeil sont frequents a la phase aigue de l’IDM et correles a la severite de l’atteinte cardiaque mais ne semblent pas avoir d’impact sur son evolution a 3 mois.

Background: Inflammation plays a crucial role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. A clinical trial has recently reported a smaller infarct size in a cohort of patients with ST-segment elevation myocardial infarction (MI) treated with a short colchicine course. The mechanism underlying colchicine-induced cardioprotection in the early MI phase remains unclear. We hypothesized that a short pretreatment with colchicine could induce acute beneficial effects by protecting the heart against inflammation in myocardial I/R injury. Methods and Results: Rats were subjected to 40-minute left anterior descending coronary occlusion, followed by 120-minute reperfusion. Colchicine (0.3 mg/kg) or a vehicle was administered per os 24 hours and immediately before surgery. Infarct size was significantly reduced in the colchicine group (35.6% ± 3.0% vs 46.6% ± 3.3%, P < .05). The beneficial effects of colchicine were associated with an increased systemic interleukin-10 (IL-10) level and decreased cardiac transforming growth factor-β level. Interleukin-1β was found to increase in a “time of reperfusion”-dependent manner. Colchicine inhibited messenger RNA expression of caspase-1 and pro-IL-18. Interleukin-1β injected 10 minutes prior to myocardial ischemia induced greater infarct size (58.0% ± 2.0%, P < .05) as compared to the vehicle. Colchicine combined to IL-1β injection significantly decreased infarct size (47.1% ± 2.2%, P < .05) as compared to IL-1β alone, while colchicine alone exhibited a significantly more marked cardioprotective effect than the colchicine-IL-1β association. Conclusion: The cardioprotection induced by a short colchicine pretreatment was associated with an anti-inflammatory effect in the early reperfusion phase in our rat MI model.