Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial

International audienceChronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage >= 3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy

Antiplatelet Drug Regimen in Patients With Stent Thrombosis ― Insights From the PESTO French Optical Coherence Tomography Registry ―

International audienceThrombosis) French multicenter prospective observational registry reported that a stent mechanical abnormality was present in 97% of subjects with ST explored by intracoro-nary optical coherence tomography (OCT) imaging. 5 Premature discontinuation and incomplete individual response to APT have previously been reported as major risk factors for ST. 6,7 However, the interactions between APT regimen and potential underlying stent abnormalities remain largely unknown, even though different mechanical substrates could favor a rheological environment that might promote thrombosis. For example, uncovered/poorly healed struts behave as foreign bodies that induce platelet A lthough its frequency has decreased over the recent past years, stent thrombosis (ST) remains a major complication of percutaneous coronary interventions (PCI) and still carries a high mortality. 1 ST is a mul-tifaceted process that can be triggered by different factors such as the patient's clinical characteristics, efficacy of anti-platelet therapy (APT) or underlying mechanical stent abnormalities. 2 However, coronary angiography has limited sensitivity to correctly identify these latter mechanisms and recent studies suggest that intracoronary imaging is a valuable option to achieve this purpose. 3,4 Therefore, the PESTO (Morphological Parameters Explaining Sten

Characteristics of stent thrombosis in bifurcation lesions analysed by optical coherence tomography

International audienceAIMS:This work aimed to investigate a cohort of patients presenting with stent thrombosis (ST) explored by optical coherence tomography (OCT) to identify the underlying mechanical abnormalities in case of bifurcation lesions.METHODS AND RESULTS:The PESTO study was a prospective national registry involving 29 French catheterisation facilities. Patients with acute coronary syndromes were prospectively screened for presence of definite ST and analysed by OCT after culprit lesion reopening. The cohort involved 120 subjects, including 21 patients (17.5% of the global PESTO group; median age: 62.6 yrs; 76% male) with bifurcation lesions. The clinical presentation was acute or subacute ST in 34%, late ST in 5% and very late ST in 62% of the patients. The main underlying mechanisms were strut malapposition in 33%, stent underexpansion in 19% and isolated strut uncoverage in 19% of the cases. The proximal main branch was involved in 71%, distal main branch in 52% and jailed side branch in 5% of the patients.CONCLUSIONS:In this cohort, bifurcation lesions represented a limited number of all ST cases. Different sections of the bifurcation could be involved. Although the underlying mechanisms were various, strut malapposition was the most frequently observed cause

Mechanical abnormalities associated with first- and second-generation drug-eluting stent thrombosis analyzed by optical coherence tomography in the national PESTO French registry

International audienc

Indications actuelles de la contre-pulsion par ballonnet intra-aortique : le registre CP-GARO

International audienceBACKGROUND: 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

Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy

International audienceIn the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00827411

Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study

International audienceBACKGROUND:The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a conventional strategy without monitoring and drug adjustment. No significant improvement in clinical outcomes with platelet function monitoring was observed.OBJECTIVE:The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome.METHODS AND RESULTS:In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of-function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6%, p = 0.0112) and 14 days later (23.8 vs. 10.4%, p < 0.0001) and more frequently on prasugrel (11.5 vs. 8.1%, p = 0.039) as compared with rapid metabolizers (n = 935). Intensification of antiplatelet treatment did not differ between slow and rapid metabolizers according to the study algorithm based on platelet function only. The primary study outcome defined as the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation did not differ between slow and rapid metabolizers (HR 0.988, 95% CI [0.812;1.202], p = 0.90). Likewise, the primary safety outcome did not differ between rapid and slow metabolizer phenotype.CONCLUSIONS:The genetic clopidogrel profile was a good marker of platelet function response on clopidogrel but was not related to clinical outcome suggesting that the genetic added little to the pharmacodynamic information used in the study to adjust antiplatelet therapy. ClinicalTrials.gov: NCT00827411

Incidence, delays, and outcomes of STEMI during COVID‐19 outbreak: Analysis from the France PCI registry

International audienceObjectivesThe aim of this study was to assess the impact of the coronavirus disease 2019 (COVID‐19) outbreak on incidence, delays, and outcomes of ST‐elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) in France.MethodsWe analyzed all patients undergoing PPCI <24 hours STEMI included in the prospective France PCI registry. The 2 groups were compared on mean monthly number of patients, delays in the pathway care, and in‐hospital major adverse cardiac events (MACE: death, stent thrombosis, myocardial infarction, unplanned coronary revascularization, stroke, and major bleeding).ResultsFrom January 15, 2019 to April 14, 2020, 2064 STEMI patients undergoing PPCI were included: 1942 in the prelockdown group and 122 in the lockdown group. Only 2 cases in the lockdown group were positive for COVID‐19. A significant drop (12%) in mean number of STEMI/month was observed in the lockdown group compared with prelockdown (139 vs 122, P < 0.04). A significant increase in “symptom onset to first medical contact” delay was found for patients who presented directly to the emergency department (ED) (238 minutes vs 450 minutes; P = 0.04). There were higher rates of in‐hospital MACE (7.7% vs 12.3%; P = 0.06) and mortality (4.9% vs 8.2%; P = 0.11) in the lockdown group but the differences were not significant.ConclusionAccording to the multicenter France PCI registry, the COVID‐19 outbreak in France was associated with a significant decline in STEMI undergoing PPCI and longer transfer time for patients who presented directly to the ED. Mortality rates doubled, but the difference was not statistically significant

Comparison of Immediate With Delayed Stenting Using the Minimalist Immediate Mechanical Intervention Approach in Acute ST-Segment-Elevation Myocardial Infarction: The MIMI Study.

International audienceDelayed stent implantation after restoration of normal epicardial flow by a minimalist immediate mechanical intervention aims to decrease the rate of distal embolization and impaired myocardial reperfusion after percutaneous coronary intervention. We sought to confirm whether a delayed stenting (DS) approach (24-48 hours) improves myocardial reperfusion, versus immediate stenting, in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.In the prospective, randomized, open-label minimalist immediate mechanical intervention (MIMI) trial, patients (n=140) with ST-segment-elevation myocardial infarction ≤12 hours were randomized to immediate stenting (n=73) or DS (n=67) after Thrombolysis In Myocardial Infarction 3 flow restoration by thrombus aspiration. Patients in the DS group underwent a second coronary arteriography for stent implantation a median of 36 hours (interquartile range 29-46) after randomization. The primary end point was microvascular obstruction (% left ventricular mass) on cardiac magnetic resonance imaging performed 5 days (interquartile range 4-6) after the first procedure. There was a nonsignificant trend toward lower microvascular obstruction in the immediate stenting group compared with DS group (1.88% versus 3.96%; P=0.051), which became significant after adjustment for the area at risk (P=0.049). Median infarct weight, left ventricular ejection fraction, and infarct size did not differ between groups. No difference in 6-month outcomes was apparent for the rate of major cardiovascular and cerebral events.The present findings do not support a strategy of DS versus immediate stenting in patients with ST-segment-elevation infarction undergoing primary percutaneous coronary intervention and even suggested a deleterious effect of DS on microvascular obstruction size.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01360242