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Background Randomized studies have reported low rates of atrial fibrillation (AF) after patent foramen ovale (PFO) closure ( Objective To prospectively determine the incidence, timing, and determinants of supraventricular arrhythmia following PFO closure based on loop recorder monitoring. Methods Cardiac monitoring was proposed to all patients after PFO closure from June 2018 to October 2021 in our center by mean of implantable loop recorder (ILR) monitoring in patients considered at higher risk of AF (age ≥55 years, associated cardiovascular risk factors, prior palpitations, or documented supraventricular ectopic activity) or 4-week external loop recorder (ELR) monitoring in other patients. The primary endpoint was the incidence of AF, flutter, or atrial tachycardia lasting >30 seconds within 28 days of the procedure. Determinants of the primary endpoint were assessed with stepwise logistic regression model. Results A total of 225 patients were included. The primary endpoint occurred in 47/225 (20.9%) patients, including n=13 (9.9%) and n=24 (28.9%) among ELR- and ILR-monitored patients, respectively. Among ILR-monitored patients, median follow-up was 428 (211–752) days, and four more cases of supraventricular arrhythmia were diagnosed beyond 28 days (Figure 1). Overall, median delay from procedure to arrhythmia was 14.0 (6.5–19.0) days and half of these patients reported symptomatic episodes. Determinants of the primary endpoint were older age (adjusted odds ratio [aOR]: 1.67, 95% confidence interval [CI]: 1.18–2.36, per 10-year increase), device left disc diameter ≥25mm (aOR: 2.67, 95% CI: 1.19–5.98) and male sex (aOR: 4.78, 95% CI: 1.96–11.66) (Figure 2). Conclusion Using prolonged loop recorder monitoring, supraventricular arrhythmia was diagnosed in one patient out of five with a median delay of 14 days suggesting that this post-procedural event has been so far, underestimated. Funding Acknowledgement Type of funding sources: None.

Aims To compare the safety and efficacy of antithrombotic regimens following transcatheter aortic valve replacement (TAVR) in patients without having an indication for chronic oral anticoagulation Methods and results We conducted a Prospero-registered systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVR antithrombotic regimens up to March 2021. We estimated the relative risk and 95% confidence intervals using a fixed effect model in a frequentist pairwise and network metanalytic approach. We included 6 studies comprising of 3,777 patients with a mean weighted follow-up of 13.3 months. Single antiplatelet therapy (SAPT) was associated with a significant reduction of life-threatening, disabling, or major bleeding compared to dual antiplatelet therapy (DAPT) (Risk Ratio [RR] 0.44, 95% confidence interval [CI]: 0.28–0.69), apixaban (RR: 0.47, 95% CI 0.26–0.84) and low-dose rivaroxaban + 3-month SAPT (RR: 0.30, 95% CI: 0.16–0.57). Risk of all-cause death was significantly reduced with DAPT compared to low-dose rivaroxaban + 3-month SAPT (RR: 0.60, 95% CI: 0.41–0.88) and a consistent reduction was observed with SAPT and DAPT compared to apixaban (RR: 0.60, 95% CI: 0.31–1.16 and RR: 0.58, 95% CI: 0.32–1.04, respectively). There were no differences between the various regimens with respect to myocardial infarction and stroke. Apixaban significantly reduced the risk of pulmonary embolism, valve thrombosis and grade 3 or 4 reduced leaflet motion. Conclusion Following TAVR in patients without an indication for chronic oral anticoagulant, SAPT was associated with the lowest risk of bleeding compared to DAPT and direct oral anticoagulant-based regimens without significant ischemic offset. Funding Acknowledgement Type of funding sources: None.

Resume Le syndrome coronaire aigu est le centre d’une recherche scientifique importante depuis des decennies. Les recommandations de la societe europeennes de 2020 sur le syndrome coronaire aigue sans elevation du segment ST ont inclus les resultats d’essais scientifiques recents portant sur le diagnostic et la prise en charge du SCA ST-. Dans cette mise au point, nous detaillons et expliquons les donnees dernieres les nouveautes en matiere de recommandations, notamment sur la strategie diagnostique de troponine a H0 et H1/H2, la place du coroscanner, le delai d’exploration invasive en fonction du profil de risque et la gestion du traitement antithrombotique de ces patients.

In April 2020, in response to the high thrombotic risk associated with COVID-19, the GIHP and GFHT published proposals for the prevention of venous thromboembolism (VTE) and haemostasis monitoring in patients with COVID-19 [1]. In February 2021, six authors from the proposals (CT, AM, AlG, AnG, SS, YG, PA) decided to update them. This update was justified by several points: - The epidemiology of thrombotic complications has been described. - Different anticoagulation regimens have been reported, and retrospective studies have suggested that higher-than-standard prophylactic anticoagulation may be beneficial. - Initially underestimated, bleeding complications have emerged as a limitation of increased-dose anticoagulation and occur later than thrombotic events. - The first results of large-scale randomised controlled studies on increased doses of anticoagulation have been published. - Immunomodulatory therapies (corticosteroids, interleukin-6 receptor antagonists) are now widely used, but their effect on the thrombotic risk is unknown. - Despite improved survival, thrombotic complications remain a concern [2].

Aortic stenosis remains one of the most frequent valvulopathy worldwide, burdened with great mortality and morbidity, and for which there is not yet an effective preventive approach, although the pathophysiological mechanisms involved in its development are better understood nowadays. Its cure, however, has been revolutionized in the last decade by the advent of transcatheter aortic valve implantation, or TAVI (also named transcatheter aortic valve replacement or TAVR). The technique of TAVI has been refined and its indications has been extended, following the publication of large randomized controlled trials where it was compared to surgical aortic valve replacement with favorable results. Consequently, transfemoral TAVR has become the first line of treatment in case of symptomatic severe aortic valve stenosis. In this review, we describe the pathophysiological mechanisms leading to severe aortic stenosis and the main ongoing randomized controlled trials targeting them. We describe the indication for surgical or percutaneous aortic valve replacement and the main complications following the procedure.

International audience; BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.

Background Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP). However, the prognosis value of IL-1β level in acute myocardial infarction patients has never been evaluated. We aim to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death. Methods IL-1β concentration was measured among 1398 STEMI patients enrolled in a prospective cohort study. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were also analyzed. Results In a STEMI population, IL-1β concentration measured at admission was independently associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.43 per 1SD increase; 95% CI, 1.12 to 1.83; p10 pg/mL that was markedly associated with higher mortality rates at 90 days (adjHR: 2.80; 95% CI: 1.63–4.80, p=0.0002) and one-year (adjHR: 1.75; 95% CI: 1.09–2.78, p=0.019), regardless of the hs-CRP concentration. The relationship was even stronger when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.31; 95% CI: 1.30–4.10, p=0.004 and 2.17; 95% CI: 1.24–3.80, p=0.006) and at one year (adjHR: 2.26; 95% CI: 1.31–3.87, p=0.03 and 2.25; 95% CI: 1.33–3.79, p=0.004). Conclusion IL-1β measured at admission in acute MI patients is associated with the risk of mortality and recurrent major cardiovascular events, regardless of the CRP level. A threshold of 10 pg/mL identifies patients at higher risk of events. Survival Funding Acknowledgement Type of funding source: None

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.

Atrioventricular block (AVB) is common after transcatheter aortic valve replacement (TAVR) and permanent pacemaker (PPM) implantation is needed in up to 30% of patients. Main predictors of long term AVB are electrocardiographic. The purpose of this study is to assess the prognostic value of serial HV intervals measured before and after TAVR to shorten the timing of PPM implantation.His bundle recordings were performed before (HV1), immediately after TAVR (HV2) and at day 2 for Edwards Sapien (ES) and 5 for Medtronic CoreValve (CV) (HV3). PPM indications were high degree AVB before day 5 or prolonged HV interval ≥80ms at the last recording. High degree AVB after discharge was evaluated from the pacemaker memories and ECG at 1 and 6months.Data were obtained in 84 patients (33% CV and 67% ES). HV values were not associated with early or late AVB. PPM were implanted in 27 patients (34%) for documented AVB (n=17, 24%), prolonged HV interval (n=9) or sick sinus syndrome (n=1). Persistent complete AVB during the procedure and postoperative high degree AVB were the only perioperative factors associated with further long term occurrence of high degree AVB (p=0.001 and p0.001). On multivariate analysis, only postoperative high degree AVB was significant (p=0.001).Pre- and post-operative HV measurements were not correlated with late AVB after TAVR. Perioperative persistent complete AVB and postoperative high degree AVB are the only factors to predict late AVB and should be considered for the decision of PPM implantation.

Background The respective ischemic and bleeding risks of early aspirin discontinuation following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains uncertain. Objectives To evaluate the safety and efficacy of early aspirin discontinuation in ACS or PCI patients treated with P2Y12 inhibitors with or without anticoagulants. Methods We performed a review of randomized controlled trials (RCTs) comparing a P2Y12 inhibitor-based single antiplatelet strategy following early aspirin discontinuation to a strategy of sustained dual antiplatelet therapy (DAPT) in ACS or PCI patients requiring or not anticoagulation for another indication. The primary safety endpoint was major bleeding while non-major bleeding and all bleeding were secondary safety endpoints. The primary efficacy endpoint was all-cause mortality while secondary efficacy endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), definite stent thrombosis (ST) or any stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. The study is registered in PROSPERO (CRD42019139576). Results We included 9 RCTs comprising 40,621 patients.Compared to prolonged DAPT, major bleeding (2.2% vs. 2.8%; RR 0.68; 95% CI: 0.54 to 0.87; p=0.002; I2: 63%), non-major bleeding (5.0% vs. 6.1%; RR: 0.66; 95% CI: 0.47 to 0.94; p=0.02; I2:87%) and all bleeding (7.4% vs. 9.9%; RR: 0.65; 95% CI: 0.53 to 0.79; p Conclusions In patients on DAPT after an ACS or a PCI, early aspirin discontinuation prevents bleeding events with no effect on the ischemic risk or mortality. Figure 1. Central illustration Funding Acknowledgement Type of funding source: None

The performance and indications of transvalvular aortic valve implantation or TAVI has considerably expanded and is now the first therapeutic line option in the management of severe aortic stenosis. The targeted population shares both high risk of ischemic complications, particularly stroke or subclinical leaflet thrombosis of the bioprothesis, as well as hemorrhagic complications, strongly correlated to death. Based on previous experience with intracoronary stents, a dual antiplatelet therapy has been recommended by experts' consensus. This paradigm is now challenged by the observed increased risk of hemorrhagic complications without a reduction of ischemic events. Moreover, the role of non-vitamin K oral anticoagulant in patients undergoing TAVI remains to be determined. Several large ongoing randomized controlled trials will likely change our practice within the next coming year.

Background Left Ventricular Thrombus (LVT) is associated with a high risk of thromboembolic complications such as stroke. Contemporary data are lacking on the management, prognosis and treatment of LVT, particularly with the emergence of the non-vitamin K antagonist anticoagulants (NOACs). Purpose To study the time and predictive factors associated with thrombus regression on treatment and its association with survival, embolic and bleeding complications. Methods From January 2011 to January 2018, a computerized case sensitive search of LVT was performed on 90 065 consecutive echocardiogram reports. All patients with a confirmed LVT were included in this analysis after imaging review by two independent experts. Repeated echocardiographic data, treatment management and clinical outcomes were collected during follow-up. Major adverse cardiac events (MACE), defined as the composite of death, ischemic stroke or transient ischemic attack (TIA), myocardial infarction (MI) or embolic peripheral artery occlusion were analyzed as well as major bleeding events (BARC ≥3) and the predictive factors and impact of LVT regression. Results We identified 174 patients with a suspected LVT of whom 159 had confirmed LVT on two different cardiac imaging exams. Ischemic cardiomyopathy was the main cause of LVT (n=125, 78.6%) including 56 (35.2%) patients with an acute ST segment elevation MI. The mean left ventricular ejection fraction was 31.9±12.5% with predominant (98.1%) apical location of the LVT. Anticoagulation therapy was achieved with vitamin K antagonists, NOACs and parenteral heparins in 48.7%, 22.8% and 27.8% of patients, respectively. Concomitant antiplatelet therapy was prescribed in 67.9% of patients. Total LVT regression was reached in two third of patients (62.3%, n=99) within a median time of 103 [32–392] days. Independent predictors of total LVT regression were an ischemic cardiomyopathy (HR: 0.36 [0.19–0.70], p=0.002), a larger baseline thrombus area (HR=0.66 [0.45–0.96], p During a median follow-up of 632 [187–1126] days, MACE occurred in 59 (37.1%) patients with a 18.9% rate of mortality and 13.2% of major bleeding. Patients with a total LVT regression had a non-significant lower rate of MACE as compared with patients without total LVT regression (35.4% vs. 40.0%; HR=0.71 [0.42–1.21]; p=0.20), and a significant lower rate of mortality (15.2% vs. 25.0%; HR=0.48 [0.23–0.98]; p=0.039). Occurence of mortality (A) and MACE (B) Conclusions The prognosis of LVT remains severe with a high risk of major cardiovascular event and mortality. Total LVT regression, mostly reached in 3 months, can be obtained with both vitamin K antagonists and NOACs and is associated with a better prognosis.

Background Hyperglycemia is a well-known prognostic marker in patients with acute myocardial infarction (AMI), associated with higher mortality compared with normoglycemia. Whether the prognostic impact of glycemic status at the acute stage of AMI is similar in patients with chronic dysglycemia has not been extensively explored. Aims and methods Using data from the nationwide French FAST-MI cohorts (2005, 2010 and 2015), we analysed the association between glycemia at entry and 30-day death, according to HbA1c level. From the 13,130 patients included, 5,452 had both glycemia and HbA1c assessed at entry. Of those, 1173 (21.5%) had an HbA1c ≥7%. Results In patients with HbA1c 180 mg/dl); a graded association between admission glycemia and 30-day mortality was observed, ranging from 0.7% in normoglycemic patients to 6.3% in patients with admission glycemia >180 mg/dl. In contrast, in patients with HbA1c ≥7%, LVEF was not correlated with glycemia (180 mg/dl 49±12%), and mortality was the highest in patients with normoglycemia (9.2%) and the lowest in patients with glycemia between 140 and 180 mg/dl (3.1%) (Figure). In multivariate analyses adjusting for baseline characteristics and early management, normoglycemia was associated with a decreased risk of 30-day mortality in patients with HbA1c Figure 1. 30-day death Conclusion In AMI patients with high HbA1c levels on admission, normoglycemia is associated with higher early mortality than hyperglycemia. In contrast, a graded correlation is observed between admission glycemia and early mortality in patients with HbA1c Acknowledgement/Funding Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier

Background Recent studies have emphasized the prognostic value of mild left ventricular ejection fraction (LVEF) impairment in severe aortic stenosis. However, despite adaptive mechanisms to pressure overload, subtle impaired systolic function could be worsened by increased afterload and partly reversible immediately after its correction. Objectives The aim was to evaluate the short terms effects of transcatheter aortic valve replacement (TAVR) on LV systolic function assessed by global longitudinal strain (GLS). We hypothesized that abrupt decrease of LV afterload after TAVR could lead to immediate improvement of LV systolic function. Methods Patients referred to our Department for TAVR were included from January 2018 to July 2018 in this observational prospective single center study. Transthoracic echocardiography (TTE) was performed immediately before and 1–5 days after TAVR by the same operator and reviewed in a blind fashion. Results 35 symptomatic patients with severe aortic stenosis referred for TAVR (age 84±5 y, 18 male, NYHA 2–3, orifice area 0.7±0.2 cm2, LVEF 66±13%, GLS −15.1±4.7%) were included. Only 9/35 (26%) had a LVEF ≤60%. Overall, no significant change in LVEF (65±14%; p=0.55) or GLS (−16.1±4.8%; p=0.11) occurred immediately after TAVR despite a dramatic decrease in transoartic mean pressure gradient (44±15 mm Hg versus 6±3 mmHg; p Improvement in GLS according to the LVEF Conclusion Following TAVR, an early improvement in LV systolic function assessed by GLS was observed only in patients with pre-existing mild LV systolic dysfunction. Further studies should evaluate whether this improvement is associated with better long term outcome.

Background Incidence and correlates of readmission for heart failure in all-comers, after successful transcatheter aortic valve replacement (TAVR) remain unclear. Objective We sought to evaluate the incidence, risk factors and clinical impact of readmission for HF after successful TAVR in an unselected patient population. Methods All patients who underwent successful TAVR in two high-volume French tertiary centers from February 2010 to December 2016 were prospectively included and followed-up for one year. Cox multivariate model was used to assess risk factors of readmission for heart failure, evaluated a time-updated covariate and mortality. Results A total of 1139 patients (mean age 82.4±7.7 years, 52.2% male) were included. Readmission for heart failure occurred in 99 (8.7%) patients. Risk factors of readmission for HF were chronic pulmonary disease (adjHR 1.8; 95% CI [1.2–2.8], p=0.008), chronic kidney disease (adjHR 1.7; 95% CI [1.1–2.6], p=0.01), diabetes mellitus (adjHR 1.7; 95% CI [1.1–2.5], p=0.01), prior atrial fibrillation (adjHR 1.6; 95% CI [1.1–2.4], p=0.02) and post-TAVR left ventricular ejection fraction (LVEF) ≤35% (adjHR 2.1 95% CI 1.2–3.7, p=0.009). Readmission for HF was strongly associated with mortality (Figure) along with increased STS score (adjHR 1.07 95% CI 1.03–1.12, p=0.002), prior atrial fibrillation (adjHR 2.13 95% CI 1.53–2.96, p Figure 1 Conclusion Readmission for heart failure occurs in one out of ten patients after successful TAVR and is strong risk factor of mortality. Comorbidities and post-TAVR LVEF≤35% are the main correlates of readmission for heart failure. Acknowledgement/Funding ACTION study group

Background Thrombolysis In Myocardial Infarction (TIMI) flow is a prognostic factor which assessment is complex in life-threatening situations. Because TIMI flow evaluation by site investigator (SI) is subject to bias, independent Core-Laboratory (CL) adjudication is the reference standard in clinical trials. Purpose To evaluate the concordance between CL and SI in the evaluation of the culprit artery TIMI flow, and the associated prognosis in the CULPRIT-SHOCK trial. Methods All patients of the CULPRIT-SHOCK trial with CL adjudications were included in this analysis. CL adjudicators were blinded to patient's characteristics and outcomes: pre and post-PCI TIMI flows were solely evaluated on the basis of coronary angiograms. SI determined the TIMI flow before and immediately after PCI of the culprit lesion. The concordance was determined by Cohen's κ coefficient. A multivariate analysis was used to evaluate 1) factors of discordance 2) the association between each method of evaluation and the mortality at 30 days and 1 year. Results Among CULPRIT-SHOCK patients, 663 patients were eligible for this analysis. Of the 214 patients adjudicated TIMI flow 3 by CL before PCI, SI over-estimated the obstruction to TIMI flow 0–1-2 in 121 (56.5%). Of the 139 patients scored TIMI flow 0–1-2 by CL after PCI, SI over-graded their results to TIMI flow 3 in 79 (56.8%). Overall, the K coefficient of agreement was 0.44, 95% CI [0.36; 0.51] before PCI and 0.44, 95% CI [0.35; 0.53] after PCI. Mechanical circulatory support and culprit left main were the main factors of discordance of TIMI flow after PCI. The association between TIMI flow 0–1-2 after PCI and 30-days mortality was significant, whether adjudicated by SI or CL (figure). Post-PCI TIMI-flow 0–1-2 was associated to 1-year mortality only when evaluated by SI (figure). Association between TIMI and mortality Conclusions In comparison to the independant CL evaluation, SI overestimated the severity of coronary slow flow before PCI, and the success of PCI in improving coronary flow. The level of agreement between CL and SI was moderate. While both evaluations predicted 30-days mortality, only SI scoring was associated to 1-year mortality. Acknowledgement/Funding European Union Seventh Framework Program, the German Heart Research Foundation, German Cardiac Society.

Background Alirocumab and evolocumab, two proprotein convertase subtilisin–kexin type 9 inhibitors, have both been associated with improved outcomes in patients with atherosclerotic cardiovascular disease in addition to standard lipid-lowering therapies. However, their comparative safety and efficacy profiles are unknown. Purpose To compare the safety and efficacy of alirocumab versus evolocumab. Methods We conducted a systematic review and network meta-analysis of placebo-controlled randomized trials available up to November 2018 evaluating the safety and efficacy of alirocumab and evolocumab. We estimated risk ratio and 95% confidence intervals using fixed effect model in a frequentist pairwise and network metanalytic approach. The primary safety endpoints were any adverse events leading to treatment-discontinuation, injection site reaction, systemic allergic reaction, neurocognitive events, ophthalmologic events and new-onset of diabetes mellitus (DM) or worsening of pre-existing DM. The primary efficacy endpoints were all-cause and cardiovascular (CV) death, myocardial infarction (MI) and stroke. This study was registered in PROSPERO (CRD42018090768). Results A total of 30 trials, enrolling 59,026 patients were included in this analysis, of whom 13,607 received alirocumab and 17,931 received evolocumab. Mean weighted follow-up time was 2.5 years, with an exposure time of 144,907 patients-years. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. There were no significant differences between alirocumab and evolocumab in terms of safety endpoints, except for injection site reaction with a 27% increased risk of injection site reaction with alirocumab compared to evolocumab (Figure). Compared with evolocumab, alirocumab was associated with a reduction of all-cause death but not CV death. There were no significant differences in MI or stroke between alirocumab and evolocumab. Conclusion Alirocumab and evolocumab share a similar safety profile. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to heterogeneity of the studied populations between the two drugs.

The performance and indications of transvalvular aortic valve implantation or TAVI has considerably expanded and is now the first therapeutic line option in the management of severe aortic stenosis. The targeted population shares both high risk of ischemic complications, particularly stroke or subclinical leaflet thrombosis of the bioprothesis, as well as hemorrhagic complications, strongly correlated to death. Based on previous experience with intracoronary stents, a dual antiplatelet therapy has been recommended by experts' consensus. This paradigm is now challenged by the observed increased risk of hemorrhagic complications without a reduction of ischemic events. Moreover, the role of non-vitamin K oral anticoagulant in patients undergoing TAVI remains to be determined. Several large ongoing randomized controlled trials will likely change our practice within the next coming year.

International audience; Background Elderly patients are at high-risk of bleeding, particularly in the setting of acute coronary syndrome treated with an invasive strategy. Treatment adjustment by platelet function testing (PFT) failed to improve clinical outcomes in the randomized ANTARCTIC trial. Purpose This prespecified substudy aims at determining the predictive factors of bleeding and their relation to ischemic events and mortality. Methods We analyzed the 877 patients over the age of 75 years from the ANTARCTIC trial and randomized to a strategy of dose or drug antiplatelet therapy adjustment or a conventional strategy without PFT. In the monitoring group, patients received prasugrel 5 mg daily after coronary stenting and treatment was adjusted according to PFT. Correlation between occurrence of bleeding and major cardiovascular adverse events (MACE) defined as the composite of cardiovascular death, myocardial infarction and stroke was analyzed at one year. Results Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n = 181 patients) with one third occurring in the first month. MACE occurred more frequently at one year in patients with a bleeding (16.6% vs. 7.6%, adj.HR: 2.04(1.24;3.38); P = 0.005). Rates of myocardial infarction and stroke were higher at one year after bleeding (9.9% vs. 4.5%, adj.HR: 2.40(1.24;4.66); P = 0.0093 and 6.6% vs. 1%, adj.HR: 5.55(2.04;15.06); P = 0.0008 respectively) without significant difference in death (6.6% vs. 4.0%; HR: 1.20(0.57;2.51); P = 0.63). Predictive factors of major bleedings in the multivariate model were age > 85 years [adj.HR: 2.48(1.25;4.91); P = 0.0093] and hemoglobin level (per gram of decrease) [adj.HR: 1.45(1.18;1.79); P = 0.0004]. Conclusions Clinically relevant bleedings were frequently observed in elderly patients and strongly associated with myocardial infarction and stroke. Age itself remained a predictive factor of bleeding in this population over the age of 75 years.

Introduction Serum cholesterol efflux capacity, a biomarker of the early step of the reverse cholesterol transport, has been associated with atherosclerosis independently of high-density lipoprotein (HDL) cholesterol level. Objective To evaluate the prognostic impact of serum cholesterol efflux capacity on mortality in a large cohort of patients hospitalized for an acute myocardial infarction (MI). Method Serum cholesterol efflux capacity was measured in 1,609 consecutive patients admitted with an acute MI. Results In a fully adjusted model that included age, sex, traditional cardiovascular risk factors including lipid levels, and prognostic factors of MI, serum cholesterol efflux capacity was a strong predictor of survival (adjusted hazard ratio for mortality per 1-SD increase in serum cholesterol efflux capacity, 0.79; 95% confidence interval: 0.66 to 0.95; P = 0.0132). Patients displaying an elevated serum cholesterol efflux capacity had a marked lower rate of mortality at 6 years (adjusted hazard ratio: 0.54 [0.32 to 0.89]; P = 0.0165) as compared with patients with reduced serum cholesterol efflux capacity. Conclusion Serum cholesterol efflux capacity, an integrative marker of reverse cholesterol transport pathway and efficacy, was inversely associated with all-cause mortality in MI patients independently of HDL cholesterol level and other risk factors.

International audience

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery., SCOPUS: ar.j, info:eu-repo/semantics/published

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.

Background The optimal management of left ventricular thrombus (LVT) is unknown, particularly with the emergence of the non-vitamin K antagonist anticoagulants (NOACs). Purpose To identify the independent correlates of LVT regression and clinical outcomes. Methods A computerized case sensitive search on 90 065 consecutive echocardiograms performed between January 2011 and December 2017 identified patients with a LVT. Repeated echocardiographic data, treatment and major adverse cardiac events (MACE), including death, stroke, myocardial infarction or acute peripheral artery emboli were analyzed as well as major bleeding events (BARC ≥ 3) and all-cause mortality. Results We included 159 patients with an LVT confirmed by two independent experts. Patients were treated by vitamin K antagonists (48.4%), parenteral heparins (27.7%) and NOACs (22.6%) with additional antiplatelet therapy in 67.9% of the population. Total LVT regression was reached in 62.3% of the patients in a median time of 103 [32–392] days. The independent correlates associated with LVT regression were a non-ischemic cardiomyopathy (HR 0.36; 95%CI [0.19–0.69], P = 0.002) and a smaller baseline thrombus area (HR 0.66; 95%CI [0.45–0.96], P = 0.031). Cardiovascular events were frequent with 37.1% of MACE, 18.9% of major bleeding and 13.2% of all-cause mortality during a median follow-up of 632 [187–1126] days. A left ventricular ejection fraction >35% (HR 0.46; 95%CI [0.23–0.93], P = 0.029) and an anticoagulation therapy > 3 months (HR 0.42; 95%CI [0.20–0.88], P = 0.021) were independently associated with less MACE. A reduced risk of mortality was observed among patients that obtained a total LVT regression (HR 0.48; 95%CI [0.23–0.98]; P = 0.039) ( Fig. 1 ). Conclusions The presence of LVT was associated with a very high risk of MACE and mortality. Total thrombus regression, obtained with either vitamin K antagonists or NOACs, led to a better prognosis.

Introduction Recent studies have emphasized the prognostic value of mild left ventricular ejection fraction (LVEF) impairment in severe aortic stenosis. However, despite adaptive mechanisms to pressure overload, subtle impaired systolic function could be worsened by increased after load and partly reversible immediately after its correction. The aim was to evaluate the short terms effects of transcatheter aortic valve replacement (TAVR) on LV systolic function assessed by global longitudinal strain (GLS). We hypothesized that abrupt decrease of LV after load after TAVR could lead to immediate improvement of LV systolic function. Method Patients referred to our Department for TAVR were included from January 2018 to July 2018 in this observational prospective single center study. Transthoracic echocardiography (TTE) was performed immediately before and 1–5 days after TAVR by the same operator and reviewed in a blind fashion. Results Thirty-five symptomatic patients with severe aortic stenosis referred for TAVR (age 84 ± 5 y, 18 male, NYHA 2-3, orifice area 0.7 ± 0.2 cm2, LVEF 66 ± 13%, GLS - 15.1 ± 4.7%) were included. Only 9/35 (26%) had a LVEF ≤ 60%. Overall, no significant change in LVEF (65 ± 14%; P = 0.55) or GLS (−16.1 ± 4.8%; P = 0.11) occurred immediately after TAVR despite a dramatic decrease in transoartic mean pressure gradient (44 ± 15 mm Hg versus 6 ± 3 mmHg; P Conclusion Following TAVR, an early improvement in LV systolic function assessed by GLS was observed only in patients with pre-existing mild LV systolic dysfunction. Further studies should evaluate whether this improvement is associated with better long term outcome.

Background To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. Methods We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance Results Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p =0.043) and non-CABG MB (9.3% vs. 2.2%, p =0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p =0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. Conclusion IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.

Resume L’amelioration des strategies de reperfusion avec l’utilisation plus frequente de l’angioplastie primaire, des traitements pharmacologiques et mecaniques adjuvants ont contribue a diminuer spectaculairement la mortalite de l’infarctus du myocarde.

RésuméLa variabilité interindividuelle de réponse au clopidogrel est un phénomène fréquent, bien établi et observé chez une proportion non négligeable de patients. Une avancée rapide des connaissances a permis de comprendre que cette variabilité est principalement liée à la variabilité de production de métabolite actif à partir de la prodrogue qu’est le clopidogrel. Les patients présentant une résistance biologique déterminée par la réalisation de tests fonctionnels plaquettaires ou par des tests génétiques prédisant l’existence d’un faible métabolisme ont un risque accru d’accidents cardiovasculaires permettant de parler de résistance au clopidogrel. À l’inverse, il a été récemment montré que des variants génétiques activateurs du métabolisme hépatique sont associés à une réponse accrue au clopidogrel. Avec l’arrivée de nouvelles thiénopyridines de métabolisme différent et l’accès croissant aux tests fonctionnels ou génétiques, la prise en charge optimale de ces patients reste une question ouverte.AbstractInter-individual variability in the response to clopidogrel is frequent, well established and observed in a fairly large proportion of patients. A rapid advance in the knowledge of this phenomenon has shown that this variability is related mainly to differences in active metabolite production from the prodrug, clopidogrel. Patients presenting biological resistance, determined through platelet function tests or genetic tests predicting the existence of low metabolism, have a higher risk of cardiovascular accidents. In contrast, genetic variants that activate hepatic metabolism are associated with an increased response to clopidogrel. With the arrival of new thienopyridines, with different metabolism, and the growing access to functional and genetic tests, optimal management of these patients remains an open question.

With the increasing use of antiplatelet agents (APA), their management during the periendoscopic period has become a more common and more difficult problem. The increase in use is due to the availability of new drugs and the widespread use of drug-eluting coronary stents. Acute coronary syndromes can occur when APA therapy is withheld for noncardiovascular interventions. Guidelines about APA management during the periendoscopic period are traditionally based on assessments of the procedure-related risk of bleeding and the risk of thrombosis if APA are stopped. New data allow better assessment of these risks, of the necessary duration of APA discontinuation before endoscopy, of the use of alternative procedures (mostly for endoscopic retrograde cholangiopancreatography [ERCP]), and of endoscopic methods that can be used to prevent bleeding (following colonic polypectomy). This guideline makes graded, evidence-based, recommendations for the management of APA for all currently performed endoscopic procedures. A short summary and two tables are included for quick reference.

Background Heterozygous Familial Hypercholesterolemia (HeFH) is an underdiagnosed form of dyslipidemia associated with higher risk of myocardial infarction (MI). Identifying patients with possible HeFH would allow family screening and more aggressive treatment. The aim of this study was to assess the prevalence and impact on outcomes of possible HeFH in ST segment Elevation MI (STEMI) patients. Methods Lipid profiling was performed in consecutive STEMI patients admitted at the Pitie-Salpetriere Center, with two measurements, one performed on the arterial blood on arrival in the cath-lab and the second after a fasting period during hospitalization. A possible HEFH was defined by a Dutch Lipid Clinic Score ≥ 3, calculated from medical history and LDL-cholesterol. Major ischemic events and mortality were assessed at one-year. Results Among 1788 consecutive MI patients, the diagnosis of possible HeFH was reached in 12% of patients. There was no significant difference between LDL-cholesterol measured on admission on anticoagulated arterial blood and non-anticoagulated venous blood after a fasting period (1.18 ± 0.41 g/dL vs. 1.17 ± 0.48 g/dL; P = 0.76). HeFH patients were younger (50.6 ± 10.1 vs. 65.5 ± 13.2 years; P Fig. 1 ). Conclusion Possible HeFH is frequent in STEMI patients when screened with the Dutch Lipid Clinic Score that allows characterization of a potentially higher risk population. The better prognosis of these patients may be related to their young age and more aggressive treatment.

Background Elderly patients are at high-risk of bleedings, particularly in the setting of acute coronary syndrome treated with an invasive strategy. Treatment adjustment by platelet function testing (PFT) failed to improve clinical outcomes in the randomized ANTARCTIC trial. Purpose This prespecified substudy aims at determining the predictive value of PFT on occurrence of bleedings. Methods We analyzed the 877 patients over the age of 75 years included in the ANTARCTIC trial and randomized to a strategy of dose or drug antiplatelet therapy adjustment or a conventional “one size fits all” strategy without PFT. In the monitoring group, patients received prasugrel 5 mg daily after coronary stenting and PFT was done 14 days after randomization and repeated 14 days after treatment adjustment. Occurrence of bleedings was collected up to one year and correlated with PFT. Results Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n = 181 patients) with one third occurring in the first month. Cutaneous and gastro-intestinal bleedings were the two predominant complications. There was no significant difference in the final treatment between patients with or without clinically relevant bleedings (respectively, clopidogrel 75 mg: 19.9% and 19.6%, prasugrel 5 mg: 77.3% and 77.9%, prasugrel 10 mg: 2.6% and 2.8%; P = 0.91) The main predictive factors of major bleedings in multivariate model were age > 85 years [adj.HR(95% CI): 2.48(1.25;4.91); P = 0.0093] and hemoglobin level (per gram of decrease) [adj.HR(95% CI): 1.45(1.18;1.79); P = 0.0004]. The last PFT was an independent predictive factor of clinically relevant bleedings (adj.HR(95% CI): 0.95(0.90;0.99); P = 0.017). Conclusion Clinically relevant bleedings were frequent in elderly patients in the setting of acute coronary syndrome. PFT did not improve clinical outcomes but identified the bleeding risk of these patients when the chronic treatment was installed.