Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

Background: while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. Aim: To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Methods: Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Results: Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. Conclusions: post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

[Aortic stenosis: An update]. / Rétrécissement aortique : mise au point.

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.

[COVID-19 and mechanical circulatory support]. / COVID-19 et assistance circulatoire.

Extracorporeal membrane oxygenation (ECMO) is mainly used as a rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). More rarely, COVID-19 can be complicated by hemodynamic failure due to fulminant myocarditis or massive pulmonary embolism necessitating the implantation of venous-arterial ECMO. The management of ECMO during the COVID-19 pandemic is challenging due to some specificities related to the disease characteristics, such as the management of anticoagulation in patients with a hypercoagulable state and an increased risk of venous thromboembolism. In large retrospective cohorts, survival of ECMO-rescued COVID-19 patients with ADRS was reported to be similar to that reported in previous studies on ECMO support for severe ARDS. Full consideration of ECMO candidacy is crucial for appropriate allocation of resources.

[What antithrombotic treatment should we prescribe after transvalvular aortic valve implantation?] / Quel traitement antithrombotique après un remplacement valvulaire aortique percutané ?

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.

Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.

[Coronary thrombosis: Physiopathology and treatment in the era of tailored medicine]. / Thrombose coronaire : physiopathologie et traitement à l'ère de la médecine personnalisée.

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.

Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 p<0.001). On multivariate analysis, only postoperative high degree AVB was significant (p=0.001). CONCLUSION: 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.

Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity.

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

OBJECTIVE: Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. SETTING AND METHODS: A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. RESULTS: 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). CONCLUSIONS: A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.

Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay.

A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.

Optimal time for catheterization in NSTE-ACS patients with impaired renal function: insights from the ABOARD Study.

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 <60 mL/min defined IRF. The primary endpoint was the in-hospital peak troponin I value; the secondary endpoints were a) the composite of death, myocardial infarction, urgent revascularization or recurrent ischemia (death/MI/UR/RI) and b) STEEPLE major bleeding (MB) at 1-month follow-up. 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.

[Management of ST-elevation myocardial infarction in 2012]. / Prise en charge de l'infarctus du myocarde en 2012.

Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with ST-elevation myocardial infarction.

Current antiplatelet options for NSTE-ACS patients.

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.

[Reducing the risk of vascular complications during percutaneous aortic valve replacement]. / Comment réduire le risque de complication vasculaire lors des procédures de remplacement valvulaire percutané (TAVI) réalisées par voie fémorale ?

The percutaneous aortic valve replacement (TAVI) is the most recent and promising procedure in the area of interventional cardiology with a rapidly growing number of interventions worldwide. The transfemoral approach being less invasive, it has become the predominant access for the device delivery. The prevention of vascular complications by an optimal risk stratification using appropriate imaging techniques (vascular CT scan and angiography), optimised techniques for femoral puncture (active control of the arterial punction, crossover...) and skilled teams for peripheral angioplasty and percutaneous arterial closure devices (Prostar) has become mandatory given the fragile target population for TAVI. Vascular complications remain indeed one of the most frequent complication although the trend toward reduced sheeths size led to significant reduction This is mandatory regarding the needed size of the vascular arterial access - itself with constant improvement by minimising the initial 24 French with mandatory real chirurgical closure to the actual 18-19 French and soon 16 French. The improvement of the implanted devices is due to the recent evidence of the promising future of this technique and the important technological effort realised by the industry not only on the implanted aortic prosthesis but also on their delivering catheters.

Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study.

BACKGROUND: The development of standardized acute kidney injury (AKI) definitions has allowed for a better understanding of AKI epidemiology, but the long-term renal outcomes of AKI in the pediatric critical care setting have not been well established. This study was designed to: (1) determine the incidence of chronic kidney disease (CKD) in children 1-3 years after an episode of AKI at a tertiary-care pediatric intensive care unit (ICU), (2) identify the proportion of patients at risk of CKD, and (3) compare ICU admission characteristics in those with and without CKD. DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients admitted to the British Columbia Children's Hospital pediatric ICU from 2006-2008 with AKI, as defined by AKI Network (AKIN) criteria. Surviving patients, most with short-term recovery from their AKI, were assessed at 1, 2, or 3 years after AKI. PREDICTORS: Severity of AKI as defined by AKIN and several ICU admission characteristics, including demographics, diagnosis, severity of illness, and ventilation data. OUTCOMES & MEASUREMENTS: CKD was defined as the presence of albuminuria and/or glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased GFR (60-90 mL/min/1.73 m2), hypertension, and/or hyperfiltration (GFR ≥ 150 mL/min/1.73 m2). RESULTS: The proportion of patients with AKI stages 1, 2, and 3 were 44 of 126 (35%), 47 of 126 (37%), and 35 of 126 (28%), respectively. The number of patients with CKD 1-3 years after AKI was 13 of 126 (10.3% overall; 2 of 44 [4.5%] with stage 1, 5 of 47 [10.6%] with stage 2, and 6 of 35 [17.1%] with stage 3; P = 0.2). In addition, 59 of 126 (46.8%) patients were identified as being at risk of CKD. LIMITATIONS: Several patients identified with AKI were lost to follow-up, with the potential of underestimating the incidence of CKD. CONCLUSIONS: In tertiary-care pediatric ICU patients, ∼10% develop CKD 1-3 years after AKI. The burden of CKD in this population may be higher with further follow-up because several patients were identified as being at risk of CKD. Regardless of the severity of AKI, all pediatric ICU patients should be monitored regularly for long-term kidney damage.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

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.

Short-term effects of the smoke-free legislation on haemostasis and systemic inflammation due to second hand smoke exposure. The AERER study.

It was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p<0.01) and a 20% reduction in clot lysis time (p=0.05). No change in fibrin properties was observed in the control group of SHS-unexposed volunteers related to the implementation of the smoke-free legislation. Of interest, neither platelet reactivity nor systemic inflammatory biomarkers were changed in either group. The smoke-free legislation is associated with significant changes in fibrin-rich clot properties toward a less thrombogenic conformation with a better fibrinolysis response while neither platelet reactivity nor systemic inflammatory biomarkers are modified. These improvements may explain the observed reduction in acute coronary syndrome following the implementation of the smoke-free legislation.