Publications by authors named "Sébastien Armero"

25 Publications

  • Page 1 of 1

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 12;74(22):2728-2739

Paris Cardiovascular Research Center, INSERM Unit 970, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Cardiology Department, Paris, France.

Background: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.

Objectives: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.

Methods: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed.

Results: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.

Conclusions: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.
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http://dx.doi.org/10.1016/j.jacc.2019.09.054DOI Listing
December 2019

Impact of left atrial appendage closure on circulating microvesicles levels: The MICROPLUG study.

Int J Cardiol 2020 May 18;307:24-30. Epub 2019 Oct 18.

Department of Cardiology, Institut Mutualiste Montsouris, Paris, France.

Background: Left atrial appendage occlusion (LAAO) has emerged as a valid alternative to oral anticoagulation therapy for the prevention of systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Microvesicles (MVs) are shed-membrane particles generated during various cellular types activation/apoptosis that carry out diverse biological effects. LAA has been suspected to be a potential source of MVs during AF, but the effects its occlusion on circulating MVs levels are unknown.

Methods: N = 25 LAAO and n = 25 control patients who underwent coronary angiography were included. Blood samples were drawn before and 48 h after procedure for all. A third sample was collected 6 weeks after procedure in LAAO patients. In N = 10 extra patients, samples were collected from right atrium, LAA and pulmonary vein during LAAO procedure. Circulating AnnV + procoagulant, endothelial, platelets, red blood cells/RBC and leukocytes derived-MVs were measured using flow cytometry methods.

Results: In the LAAO group, AnnV+, platelets, RBC, and leukocytes MVs were significantly increased following intervention, whereas only AnnV + MVs levels significantly rose in controls. The 6-w analysis showed that RBC-MVs and AnnV + MVs levels were still significantly elevated compared to baseline values in LAAO patients. The in-site analysis revealed that leukocytes and CD62e + endothelial-MVs were significantly higher in left atrial appendage compared to pulmonary vein, suggesting a local increased production. No major adverse event was observed in any patient post procedural course.

Conclusions: LAAO impacts circulating MVs and might create mild pro-coagulant status and potential erythrocytes activation due to the device healing during the first weeks following intervention.
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http://dx.doi.org/10.1016/j.ijcard.2019.10.026DOI Listing
May 2020

[Abnormality location of the circumflex artery].

Rev Prat 2019 May;69(5):526

Hôpital européen, radiologie, Marseille, France.

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May 2019

Device-Related Thrombus After Left Atrial Appendage Occlusion With the Amulet Device.

Heart Lung Circ 2019 Nov 27;28(11):1683-1688. Epub 2018 Sep 27.

Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (APHM), Department of Cardiology, Nord Hospital, Chemin des Bourrelly, 13915 Marseille, Cedex, France; MARS Cardio, Mediterranean Association for Research and Studies in Cardiology, Nord Hospital, Chemin des Bourrelly, 13915 Marseille, Cedex, France.

Background: Left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation who are considered unsuitable for a lifelong oral anticoagulant regimen. Recently, a single-centre study reported device-related thrombus formation in 16.7% of patients treated with the second-generation Amulet device (St. Jude Medical, St. Paul, MN, USA), presenting a potential major safety concern. As "real-world" data on device-related thrombus formation following LAAO with the Amulet occluder are scarce, we aimed to evaluate this outcome in a retrospective registry.

Methods: Clinical and tranosesophageal echocardiography data after LAAO with the Amulet in consecutive patients from three centres were collated.

Results: Among 38 patients (mean age 75.8 years), mean (standard deviation) CHADS-VASc and HAS-BLED scores were 4.4 (1.2) and 3.4 (0.9), respectively. All patients underwent successful device placement without procedure-related adverse events. The antithrombotic regimen at discharge consisted of dual antiplatelet therapy (DAPT) in 27 patients (71.1%), single antiplatelet therapy in 10 patients (26.3%), and no antithrombotic therapy in one patient (2.6%). Device-related thrombus was observed in one patient (2.6%) despite DAPT regimen. The outcome of this patient was uncomplicated after adjustment of oral anticoagulant therapy. No patients presented with a thromboembolic event following LAAO during a mean (standard deviation) follow-up of 15 (5) months.

Conclusions: In this retrospective study, device-related thrombus formation with the second-generation Amulet device was rare and occurred at a rate similar to that of the previous device. Importantly, no patient experienced a device-related thromboembolic event during follow-up. Larger real-life studies are required to confirm the safety profile of this increasingly used device.
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http://dx.doi.org/10.1016/j.hlc.2018.08.022DOI Listing
November 2019

Multimodality imaging guidance for percutaneous paravalvular leak closure: Insights from the multi-centre FFPP register.

Arch Cardiovasc Dis 2018 Jun - Jul;111(6-7):421-431. Epub 2018 Jun 22.

Faculté de médecine Paris-Sud, hôpital Marie-Lannelongue, université Paris-Sud, Paris-Saclay, 92350 Le Plessis-Robinson, France.

Background: Percutaneous paravalvular leak (PVL) closure has emerged as a palliative alternative to surgical management in selected high-risk patients. Percutaneous procedures are challenging, especially for mitral PVL. Accurate imaging of the morphologies of the defects is mandatory, together with precise guidance in the catheterization laboratory to enhance success rates.

Aims: To describe imaging modalities used in clinical practice to guide percutaneous PVL closure and assess the potential of new imaging tools.

Methods: Data from the 'Fermeture de Fuite paraprothétique' (FFPP) register were used. The FFPP register is an international multi-institutional collaborative register started in 2017 with a retrospective and a prospective part. A descriptive analysis of multimodality imaging used to guide PVL closure in clinical practice was performed.

Results: Data from 173 procedures performed in 19 centres from three countries (France, Belgium and Poland) were collected, which included eight cases of PVL following transcatheter valve replacement. Transoesophageal echocardiography was used in 167 cases (96.5%) and 3D echocardiography in 87.4% of cases. In one case, 3D-echocardiography was fused with fluoroscopy images in real time using echonavigator software. Details about multimodality imaging were available from a sample of 31 patients. Cardiac computed tomography (CT) was performed before 10 of the procedures. In one case, fusion between preprocedural cardiac CT angiography data and fluoroscopy data was used. In two cases, a 3D model of the valve with PVL was printed.

Conclusion: Echocardiography, particularly the 3D mode, is the cornerstone of PVL imaging. Other imaging modalities, such as cardiac CT and cardiac magnetic resonance imaging, may be of complementary interest. New techniques such as imaging fusion and printing may further facilitate the percutaneous approach of PVLs.
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http://dx.doi.org/10.1016/j.acvd.2018.05.001DOI Listing
October 2018

Feasibility and acceptability of a self-measurement using a portable bioelectrical impedance analysis, by the patient with chronic heart failure, in acute decompensated heart failure.

Geriatr Psychol Neuropsychiatr Vieil 2018 Jun;16(2):145-154

Service de cardiologie, Fondation Hôpital Ambroise Paré/Hôpital Européen, Marseille, France, Institut SIlvermed, Centre gérontologique départemental, Marseille, France.

Chronic heart failure (CHF) is a major public health matter. Mainly affecting the elderly, it is responsible for a high rate of hospitalization due to the frequency of acute heart failure (ADHF). This represents a disabling pathology for the patient and very costly for the health care system. Our study is designed to assess a connected and portable bioelectrical impedance analysis (BIA) that could reduce these hospitalizations by preventing early ADHF.

Methods: This prospective study included patients hospitalized in cardiology for ADHF. Patients achieved 3 self-measurements using the BIA during their hospitalization and answered a questionnaire evaluating the acceptability of this self-measurement. The results of these measures were compared with the clinical, biological and echocardiographic criteria of patients at the same time.

Results: Twenty-three patients were included, the self-measurement during the overall duration of the hospitalization was conducted autonomously by more than 80% of the patients. The acceptability (90%) for the use of the portable BIA was excellent. Some correlations were statistically significant, such as the total water difference to the weight difference (p=0.001). There were common trends between the variation of impedance analysis measures and other evaluation criteria.

Conclusion: The feasibility and acceptability of a self-measurement of bioelectrical impedance analysis by the patient in AHF opens up major prospects in the management of monitoring patients in CHF. The interest of this tool is the prevention of ADHF leading to hospitalization or re-hospitalizations now requires to be presented by new studies.
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http://dx.doi.org/10.1684/pnv.2018.0730DOI Listing
June 2018

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

Clin Cardiol 2018 Jan 22;41(1):5-12. Epub 2018 Jan 22.

Aix-Marseille Université, AP-HM, Unité INSERM 1076, Unité de Soins Intensifs Cardiologiques, Department of Cardiology, Hôpital Nord, Marseille, France.

According to recent literature, pretreatment with a P2Y ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y ADP receptor antagonist pretreatment.
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http://dx.doi.org/10.1002/clc.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490048PMC
January 2018

The safety of cardiac resynchronization therapy pacemaker implantation in octogenarians: a monocentric experience.

Int J Cardiol 2013 Oct 24;168(3):2969-70. Epub 2013 May 24.

Division of Cardiology, Hôpital Nord, Aix-Marseille Université, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.04.118DOI Listing
October 2013

Clinical impact of genetically determined platelet reactivity.

J Cardiovasc Transl Res 2013 Jun 13;6(3):398-403. Epub 2012 Nov 13.

Département de Cardiologie, Centre Hospitalo-Universitaire Nord, Chemin des Bourrely, Marseille, France.

Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the rate of major adverse cardiac events following percutaneous coronary intervention. Clopidogrel is a prodrug which requires a two-step hepatic biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered clopidogrel metabolism is a major cause of high on-treatment platelet reactivity (HTPR), which translates into thrombotic events in stented patients. Studies demonstrated that HTPR could be overcome in poor metabolizers thanks to increased loading doses or maintenance doses of clopidogrel or with the use of more potent antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials with clinical endpoints remain necessary to determine the optimal antiplatelet therapy in patients carrying genetic polymorphism associated with HTPR and thrombotic events.
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http://dx.doi.org/10.1007/s12265-012-9421-4DOI Listing
June 2013

Tailoring antiplatelet therapy: a step toward individualized therapy to improve clinical outcome?

Curr Pharm Des 2012 ;18(33):5392-401

Département de cardiologie, Hopital universtaire nord de Marseille, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille univ. France, Marseille, France.

P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP receptor antagonists correlates with thrombotic recurrences. Recent studies observed a relationship between excessive platelet reactivity inhibition and bleedings. Together these data support the potential of platelet reactivity measurement to prevent thrombotic events without increasing bleeding. In the present review we aimed to summarize evidences of a therapeutic window for P2Y12-ADP receptor antagonists and the potential of platelet reactivity monitoring and individualized antiplatelet therapy to optimize the clinical outcome in patients suffering from an acute coronary syndrome or undergoing percutaneous coronary intervention.
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http://dx.doi.org/10.2174/138161212803251934DOI Listing
April 2013

Biological efficacy of a 600 mg loading dose of clopidogrel in ST-elevation myocardial infarction.

Thromb Haemost 2012 Jul 26;108(1):101-6. Epub 2012 Apr 26.

Département de Cardiologie, Hôpital Universitaire Nord, Aix-Marseille University, Marseille, France.

Optimal platelet reactivity (PR) inhibition is critical to prevent thrombotic events in primary percutaneous coronary intervention (PCI). We aimed to determine the relationship between high on-treatment platelet reactivity (HTPR) and ST-elevation myocardial infarction (STEMI) following a 600 mg loading dose (LD) of clopidogrel. We performed a prospective monocentre study enrolling patients on clopidogrel undergoing PCI. The VASP index was used to assess PR inhibition after clopidogrel LD. HTPR was defined according to the consensus as a VASP index ≥50%. The present study included 833 patients undergoing PCI. Most patients had PCI for an acute coronary syndrome (58.7%). The mean VASP index was 50 ± 23% with a large inter-individual variability (range: 1-94%). Patients with a VASP index ≥50% were significantly older (p= 0.03), with a higher body mass index (BMI) (p<0.001), more often diabetic (p=0.03), taking omeprazole (p=0.03), admitted for an acute coronary syndrome (ACS) and with a high fibrinogen level compared to good responders (VASP <50%). In multivariate analysis BMI, omeprazole use, ACS and high fibrinogen level (p<0.001) remained significantly associated with HTPR. Of importance, in this analysis STEMI was independently associated with HTPR when compared with the other forms of ACS (NSTEMI and unstable angina) with an odd ratio of 2.14 (95% CI: 1.3 -3.5; p=0.003). In conclusion, STEMI is associated with high on-treatment platelet reactivity following 600 mg of clopidogrel. The present results suggest that 600 mg of clopidogrel may not be able to achieve an optimal PR inhibition in STEMI patients undergoing PCI and more potent drugs may be preferred.
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http://dx.doi.org/10.1160/TH12-02-0125DOI Listing
July 2012

Rate of nuisance bleedings and impact on compliance to prasugrel in acute coronary syndromes.

Am J Cardiol 2011 Dec 8;108(12):1710-3. Epub 2011 Sep 8.

Département de Cardiologie, Hôpital Universitaire Nord, Faculté De Médecine, Université de la Méditerranée, Marseille, France.

Antiplatelet agents are critical to prevent thrombotic events in patients with acute coronary syndromes, particularly those who undergo percutaneous coronary intervention. Prasugrel is a potent P2Y(12)-adenosine diphosphate receptor antagonist that is superior to clopidogrel in such patients. Previous studies have observed that nuisance and internal bleedings were relatively frequent in patients under clopidogrel therapy and were associated with noncompliance. Furthermore, premature drug discontinuation is associated with thrombotic recurrences. The aim of the present study was to investigate the rate of nuisance or internal bleedings in patients receiving prasugrel and its relation with compliance. This prospective multicenter study included 396 patients. Bleeding events were recorded and classified as alarming, nuisance, or internal according. Compliance with prasugrel therapy was assessed. Almost half of the patients (48.5%) were included for ST-segment elevation acute coronary syndromes. During the 1-month follow-up period, 54 patients (13.6%) had bleeding events. Most bleeding events were classified as internal or nuisance (96%). Internal and nuisance bleedings were associated with high rates of prasugrel discontinuation (16.6% and 14.7%, respectively). Nuisance and internal bleedings were significantly associated with prasugrel discontinuation in multivariate analysis (odds ratio 3.1, 95% confidence interval 1.01 to 9.2, p = 0.04). The rate of major adverse cardiovascular events was 2.3%. No relation was observed between minor bleeds, compliance, and major adverse cardiovascular events. In conclusion, in the present study, minor bleedings were common during the first month after percutaneous coronary intervention and were significantly associated with prasugrel withdrawal.
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http://dx.doi.org/10.1016/j.amjcard.2011.07.038DOI Listing
December 2011

Differential 1-year clinical outcomes for ST-segment elevation myocardial infarction related to stent thrombosis or saphenous vein graft thrombosis.

Catheter Cardiovasc Interv 2013 Aug 7;82(2):193-200. Epub 2013 May 7.

Interventional Cardiology Division, Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Qc H1T 1C8, Canada.

Aim: Thrombosis of stents and of saphenous vein grafts (SVG) remains a severe complication of either revascularization techniques that often are present as ST elevation myocardial infarction (STEMI). The aim of this longitudinal cohort study was to compare the 1-year clinical outcomes among STEMI patients requiring primary PCI due to stent thrombosis and graft occlusion presenting with STEMI.

Methods And Results: We prospectively collected data on all patients undergoing primary PCI at the Montreal Heart Institute between April 1, 2007 and March 30, 2008. Study patients were grouped according to the etiology of the STEMI: stent thrombosis, graft thrombosis, or atherosclerosis-related STEMIs (control group). The primary combined end-point, major adverse cardiac events (MACE), was defined as death, myocardial infarction, and target vessel revascularization within 12 months as primary end point. Of the 489 STEMI patients included in the study, 23 were due to stent thrombosis, 22 to graft thrombosis, and 444 in the control group. Stent and graft thromboses were associated with a higher MACE rates, 26.1 and 22.7%, respectively, compared to the control group, 9.3% (P = 0.004). Moreover, only stent thrombosis was associated with an increased risk of MACE (HR 2.57, confidence interval 95% 1.08-6.08.

Conclusion: Patients with stent thrombosis present with higher rate of reinfarction while graft thrombosis is associated with an increase in 1-year cardiac mortality. Using multivariate analysis, higher MACE rates were associated with stent thrombosis as compared to graft thrombosis.
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http://dx.doi.org/10.1002/ccd.23300DOI Listing
August 2013

Clopidogrel loading dose adjustment according to platelet reactivity monitoring in patients carrying the 2C19*2 loss of function polymorphism.

J Am Coll Cardiol 2010 Nov 12;56(20):1630-6. Epub 2010 Aug 12.

Département de cardiologie, Hôpital Universitaire Nord, Faculté de médecine, Université de la méditerranée, Marseille, France.

Objectives: We aimed to investigate the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19*2 loss-of-function polymorphism undergoing percutaneous coronary intervention for an acute coronary syndromes.

Background: CYP2C19*2 polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after percutaneous coronary intervention.

Method: A prospective multicenter study enrolling 411 patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥ 50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP2C19 was determined by allele-specific polymerase chain reaction. In patients carrying CYP2C19*2 and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 600 mg LDs to obtain a VASP index <50%.

Results: One hundred thirty-four patients (35.3%) carried at least one 2C19*2 allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19*2 carriers exhibiting HTPR to reach a VASP index <50%.

Conclusions: Increased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of-function CYP2C19*2 polymorphism.
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http://dx.doi.org/10.1016/j.jacc.2010.07.004DOI Listing
November 2010

Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy.

Platelets 2010 ;21(7):503-7

Pôle de Cardiologie, Service de Cardiologie Interventionnelle, Hôpital Universitaire Nord, AP-HM, Faculté de Médecine, Université Aix-Marseille II, France.

Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 –VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.
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http://dx.doi.org/10.3109/09537104.2010.499483DOI Listing
February 2011

Early and late outcomes of clopidogrel and coumadin combination for patients on oral anticoagulants undergoing coronary stenting.

Cardiovasc Revasc Med 2010 Jul-Sep;11(3):159-62

Department of Cardiology, Centre Hospitalo-Universitaire Nord, Chemin des Bourrelys, 13015 Marseille, France.

Background: In patients under oral anticoagulant requiring percutaneous coronary intervention (PCI) with stent implantation, the optimal association between aspirin, clopidogrel and oral anticoagulant (OAC) remains cumberstome. Triple therapy and dual therapy using aspirin and OAC have been evaluated and are associated with a high frequency of major bleedings. The combination of clopidogrel and OAC has never been evaluated.

Objective: We aimed to investigate the safety and efficacy of clopidogrel and OAC in patients requiring OAC undergoing PCI for acute coronary syndrome.

Methods: A monocenter retrospective study was undertaken between 2000 and 2006 and included all patients undergoing PCI with stent implantation on OAC. On discharge dual therapy with clopidogrel and OAC was prescribed. The primary end-point was the frequency of major TIMI bleedings. Secondary end-points were major cardiovascular event (MACE). Results are reported as rate of events with 95% confidence intervals (CI).

Results: Two hundreds and nine patients were followed for 71 +/- 22 months. The indication for oral anticoagulation was atrial fibrillation in 80% of patients, a valvular prothesis in 18% and a history of pulmonary embolism in 5%. The rate (95%CI) of major bleeding was 2.4% (0.9%-5.8%) 2.87% (1.17%-6.44%) and 3.8% (1.79%-7.68%) at 1 month, 12 months and 71 months respectively, which represent 8 events among which 2 were fatal. The MACE rate (95%CI) was low: 0% at one month, 3.8% (1.79%-7.68%) at 12 months and 24.4% (19.07%-30.65%) at 71 months of follow up. Only one stent thrombosis was recorded at the ninth month. The overall rate of death was 9.5% (6.28%-14.32%) among which 2.87% (1.17%-6.44%) were of cardiovascular origin.

Conclusion: The use of clopidogrel and OAC combination in patients on OAC undergoing coronary stenting is safe and efficient at the short-term. At the long-term, this combination is probably not safe, with a relatively high incidence of fatal stroke.
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http://dx.doi.org/10.1016/j.carrev.2009.05.002DOI Listing
October 2010

A pitfall of fractional flow reserve measurement.

J Invasive Cardiol 2010 Jun;22(6):E110-1

Hopital Universitaire Nord de Marseille, Departement de Cardiologie, Marseille, France.

Fractional flow reserve is a simple and efficient tool to assess the severity of an intermediate lesion in order to determine the optimal therapy. However there are some limitations to its use. We observed that in patients with an occluded artery, FFR measurements in the vessel supplying collaterals can be underestimated leading to inappropriate therapy.
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June 2010

Predictors of B-type natriuretic peptide and left atrial volume index in patients with preserved left ventricular systolic function: an echocardiographic-catheterization study.

Arch Cardiovasc Dis 2010 Jan 12;103(1):3-9. Epub 2010 Jan 12.

Department of Cardiology, Centre Hospitalo-Universitaire Nord, Marseille, France.

Background: B-type natriuretic peptide (BNP) and left atrial volume index (LAVi) are used as surrogate measures for global myocardial function and are recommended for the diagnosis of heart failure with normal ejection fraction. Little is known, however, about predictors in patients with preserved systolic function.

Aims: To identify factors that influence the relation of BNP and left atrial size to invasively determined left ventricular end-diastolic pressure in stable patients with preserved left ventricular systolic function.

Methods: Fifty-nine consecutive patients were included prospectively. Clinical, biological, Doppler echocardiographic and invasive variables were collected simultaneously.

Results: BNP was predicted independently by left ventricular ejection fraction, diastolic function and age (p<0.05). LAVi was predicted independently by left ventricular mass index and invasive left ventricular end-diastolic pressure (p<0.01). BNP predicted increased left ventricular end-diastolic pressure greater than 16 mmHg (p=0.004); the optimal cut-off value was 33 pg/mL (area under the receiver-operating characteristic curve [AUC] 0.74 [0.6-0.84], p<0.001, sensitivity 72%, specificity 70%). LAVi predicted increased left ventricular end-diastolic pressure (p<0.001); the optimal cut-off value for LAVi was 26 mL/m(2) (AUC 0.87 [0.75-0.94], p<0.001; sensitivity 85%, specificity 80%). Unlike BNP (p=0.1), LAVi performed well in patients with abnormal relaxation at mitral filling (p<0.01).

Conclusion: BNP is influenced by age in stable patients with preserved systolic function and should be interpreted cautiously. LAVi is a powerful surrogate for invasively determined left ventricular end-diastolic pressure regardless of age and mitral filling.
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http://dx.doi.org/10.1016/j.acvd.2009.10.005DOI Listing
January 2010

Relation of body mass index to high on-treatment platelet reactivity and of failed clopidogrel dose adjustment according to platelet reactivity monitoring in patients undergoing percutaneous coronary intervention.

Am J Cardiol 2009 Dec;104(11):1511-5

Département de Génétique Médicale, Hôpital de la Timone enfant, Marseille, France.

High on-treatment platelet reactivity (HTPR) after a clopidogrel loading dose predicts the risk of thrombotic events after percutaneous coronary intervention. We have demonstrated that HTPR could be overcome in most cases using dose adjustment according to PR monitoring resulting in an improved clinical outcome. However, this strategy failed in nearly 10% of patients with HTPR. Cytochrome P450 (CYP) 2C19 polymorphism was a major determinant of the response to clopidogrel and could be responsible for a failure of dose adjustment. We aimed to determine the clinical and genetical predictors of a failure of the dose-adjustment strategy. Seventy-three patients undergoing percutaneous coronary intervention were included in this prospective multicenter study. A vasodilator phosphoprotein index >or=50% after a 600-mg loading dose of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a vasodilator phosphoprotein index <50%. Genetic polymorphism of CYP2C19 was determined by direct sequencing. Clinical predictors of HTPR were body mass index (BMI; p = 0.01), diabetes mellitus (p = 0.03), and acute coronary syndrome (p = 0.02). The mutant 2 allele of CYP2C19 681A > G loss of function polymorphism was also significantly associated with HTPR (p = 0.04). The rate of successful dose adjustment was similar in carriers of the CYP2C19 2 allele and carriers of the wild-type allele. The only independent predictor of a failed dose adjustment was a high BMI (p = 0.01). In conclusion, high BMI, acute coronary syndrome, diabetes mellitus, and CYP2C19 2 are associated with HTPR after a 600-mg loading dose of clopidogrel. Dose adjustment overcomes HTPR in carriers of the CYP2C19 2 allele. BMI is the only independent predictor of failed dose adjustment. Thus, drug underdosage seems to be the main determinant of HTPR.
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http://dx.doi.org/10.1016/j.amjcard.2009.07.015DOI Listing
December 2009

Impact of P2Y12-ADP receptor polymorphism on the efficacy of clopidogrel dose-adjustment according to platelet reactivity monitoring in coronary artery disease patients.

Thromb Res 2010 Apr 14;125(4):e167-70. Epub 2009 Nov 14.

Département de cardiologie, Hôpital Universitaire Nord, faculté de médecine, Marseille, France.

Introduction: High on-treatment platelet reactivity (HTPR) after clopidogrel loading dose (LD) is associated with a high risk of thrombotic events after percutaneous coronary intervention(PCI). We have demonstrated that HTPR could be overcome in the majority of cases using LD adjustment resulting in an improved clinical outcome. However this strategy failed in nearly 10% of patients with HTPR. We aimed to determine if P2Y12-ADP receptor polymorphisms were associated with failed dose adjustment.

Material And Method: Forty-three patients undergoing PCI were included in this prospective study. A VASP index >or=50% after a 600 mg LD of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a VASP index <50%. Genetic polymorphism of the P2Y12-ADP receptor was determined by direct sequencing.

Results: Patients with successful dose-adjustment (SDA) (n=33) and failed (FDA) (n=10) dose-adjustment groups were compared. The 2 groups were similar in terms of cardiovascular risk factors including diabetes mellitus (SDA vs FDA: 42 vs 20%; p=0.3). The prevalence of the H2 allele of the P2Y12-ADP receptor was also similar between the 2 groups (p=0.3). The H2 allele was found in 6 patients which are all included in the SDA group. After the first 600 mg loading dose of clopidogrel, patients carrying at least one H2 allele had similar VASP index compared to those carrying two copies of the wild type allele (H1) (SDA vs FDA: 44.9+/-14.9 vs 43.5+/-10%; p=0.8).

Conclusion: The present study suggests that the H2 allele of the P2Y12-ADP receptor is not involved in clopidogrel failed dose adjustment according to platelet reactivity monitoring.
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http://dx.doi.org/10.1016/j.thromres.2009.10.014DOI Listing
April 2010

Impact of loading dose adjustment on platelet reactivity in homozygotes of the 2C19 2* loss of function polymorphism.

Int J Cardiol 2010 Nov 26;145(1):165-6. Epub 2009 Aug 26.

The cytochromes 2 C19 2* loss of function polymorphism has recently been shown to be associated with decreased platelet reactivity (PR) inhibition after clopidogrel loading dose (LD) and an excess in thrombotic events following percutaneous coronary intervention (PCI). We aimed to investigate if an optimal PR inhibition could be obtained in patients homozygotes for this alleles using adjusted LD of clopidogrel according to platelet reactivity monitoring. Post-treatment PR was measured using the VASP index. Dose adjustment was performed in order to obtain a PR <50% using additional clopidogrel LD. Direct sequencing was used to select homozygotes for CYP 2C19 2* alleles. Six patients with the loss of function polymorphism were recruited. The mean VASP index was 53.7 ± 16.2% after the first LD of clopidogrel. Four patients had a VASP index >50% and were therefore considered to have high on treatment PR. Using up to 3 additional 600 mg LD of clopidogrel we were able to obtain a VASP <50% in all these patients. The present study is the first to suggest that in homozygotes for CYP 2C19 2* loss of function polymorphism, increased loading dose of 55 clopidogrel is efficient to obtain an optimal level PR inhibition in patients undergoing PCI.
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http://dx.doi.org/10.1016/j.ijcard.2009.07.033DOI Listing
November 2010

Usefulness of basal B-type natriuretic peptide levels for the diagnosis of diastolic heart failure in young patients: an echocardiographic-catheterization study.

Int J Cardiol 2010 Nov 25;145(1):51-2. Epub 2009 Apr 25.

The aim of the present study was to address the diagnostic relevance of B-type natriuretic peptide (BNP) for the diagnosis of diastolic heart failure (DHF) in young patients presenting with chronic, isolated dyspnea. We prospectively included 26 consecutive patients with a left ventricular ejection fraction >50% referred for catheterism. DHF was authenticated in 15 patients with an invasive left ventricular end-diastolic pressure >16 mmHg. By logistic regression analysis, BNP was predictive of DHF (p=0.03). A cut-off value of 31 pg/ml was 67% sensitive and 73% specific for the diagnosis (area under the ROC curve of 0.76 [0.55-0.9], p=0.007).
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http://dx.doi.org/10.1016/j.ijcard.2009.03.127DOI Listing
November 2010

Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis.

Am J Cardiol 2009 Jan 13;103(1):5-10. Epub 2008 Nov 13.

Département de cardiologie, Hôpital universitaire nord, Faculté de médecine, France.

Stent thrombosis remains a significant pitfall of percutaneous coronary intervention (PCI). A recent trial observed that an adjusted loading dose (LD) of clopidogrel according to platelet monitoring decreases the rate of major adverse cardiovascular events after PCI. We investigated if such a strategy of a tailored clopidogrel LD according to platelet reactivity monitoring could decrease the rate of stent thrombosis. This multicenter prospective randomized study included 429 patients with a low clopidogrel response after a 600-mg LD undergoing PCI. Patients were randomized to a control group (n = 214) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 215). In the VASP-guided group, patients received up to 3 additional 600-mg LDs of clopidogrel to obtain a VASP index <50% before PCI. The primary end point was the rate of stent thrombosis at 1 month. Secondary end points were rates of major adverse cardiovascular events and bleeding. Patients in the 2 groups had a high body mass index and were often diabetic (control vs VASP-guided group 28 +/- 5.1 vs 27.9 +/- 4.7 kg/m(2), p = 0.8, and 39% vs 33%, p = 0.2, respectively). PCI was performed in most patients for acute coronary syndrome in the 2 groups (52.3% vs 50.7%, p = 0.8). Despite a 2,400-mg LD of clopidogrel, 8% of patients in the VASP-guided group remained low responders. The rate of stent thrombosis was significantly lower in the VASP-guided group (0.5% vs 4.2%, p <0.01). The rate of major adverse cardiovascular events was also higher in the control group (8.9% vs 0.5%, p <0.001). There was no difference in the rate of bleeding (2.8% vs 3.7%, p = 0.8). In conclusion, a tailored clopidogrel LD according to platelet reactivity monitoring decreases the rate of early stent thrombosis after PCI without increasing bleeding.
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http://dx.doi.org/10.1016/j.amjcard.2008.08.048DOI Listing
January 2009