Publications by authors named "Omar Ait-Mokhtar"

12 Publications

  • Page 1 of 1

Assessment for Pulmonary Artery Hypertension Using Clinical and Echocardiographic Criteria in Patients With Systemic Sclerosis.

Am J Med Sci 2016 Oct 16;352(4):343-347. Epub 2016 Jul 16.

Department of Cardiology, service de cardiologie A2, CHU Mustapha Alger, and Cardiology Oncology Research Collaborative Group, University of medicine of Algiers Benyoucef Benkhedda, Algiers, Algeria.

Background: Prognosis of systemic sclerosis (SSc) is affected by pulmonary artery hypertension (PAH).

Methods: Among 202 patients (mean age: 46.1 ± 13.3 years; 177 women) with SSc, those with a tricuspid regurgitation (TR) jet maximal velocity at 2D-echocardiography (2DE) < 2.8m/second were not considered at high risk for PAH, whereas those with a TR velocity >3m/second or between 2.8 and 3m/second and associated with dyspnea were.

Results: Among 22 patients at risk, 15 (mean age: 50.4 ± 14.3 years) had definite precapillary PAH on right heart catheterization (RHC). The delay period between recognitions of SSc and PAH was 12.9 ± 5.2 years. Dyspnea was present in all 15 patients, 11 (73.3%) being in the New York Heart Association class III or IV. The 2DE showed normal left ventricular geometrics and function (n = 15), enlargement of the right-sided cardiac chambers (n = 12), increased pulmonary arterial resistances with a TR velocity to pulmonary time-velocity integral ratio of > 0.2 (n = 15) and impaired right ventricle function (n = 15). RHC showed severe PAH in all 15 patients (mean pulmonary artery pressure: 48 ± 17mmHg and mean right atrial pressure: 11.8 ± 4.4mmHg) and a reduced cardiac index (2.2L/m²). There was no statistical difference between patients with and without PAH regarding age, sex ratio, duration from onset of disease, diffuse or cutaneous limited type of SSc, Rodnan severity score and presence of digital ulcerations or autoantibodies. Telangiectasia (P = 0.01) and New York Heart Association class III or IV heart failure (P = 0.001) were more frequent in patients with PAH.

Conclusion: A combined clinical and Doppler-coupled 2DE screening of PAH risk in patients with SSc is useful to select those who can undergo RHC.
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October 2016

Pleiotropic effects of ticagrelor: Myth or reality?

Arch Cardiovasc Dis 2016 Aug-Sep;109(8-9):445-8. Epub 2016 Jun 21.

Aix Marseille University and Department of Cardiology, North Hospital, chemin des Bourrely, 13008 Marseille, France. Electronic address:

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January 2017

High on treatment platelet reactivity.

Heart Lung Circ 2012 Jan 13;21(1):12-21. Epub 2011 Oct 13.

Department of Cardiology, Centre Hospitalier Universitaire Nord, Marseille 13015, France.

The addition of clopidogrel to aspirin for patients undergoing percutaneous coronary intervention (PCI) had significantly reduced cardiovascular events. However, despite dual antiplatelet therapy ischaemic events still occur, especially stent thrombosis, which is associated with a high mortality rate. Inter-individual response to clopidogrel is highly variable. It was shown that 4-46% could be considered as high on treatment platelet reactivity (HTPR). Recent studies had demonstrated a relationship between HTPR and ischaemic events in the setting of PCI. Actually the assessment of platelet reactivity in routine practice and its interpretation to make a decision is a debatable issue.
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January 2012

High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

J Am Coll Cardiol 2011 Jul;58(5):467-73

Département de Cardiologie, Hôpital Universitaire Nord, Faculté de Médecine, Chemin des Bourrely, Marseille, France.

Objectives: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events.

Background: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR.

Methods: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month.

Results: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70).

Conclusions: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.
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July 2011

Level of adenosine diphosphate receptor P2Y12 blockade during percutaneous coronary intervention predicts the extent of endothelial injury, assessed by circulating endothelial cell measurement.

J Am Coll Cardiol 2010 Sep;56(13):1024-31

Département de Cardiologie, Hôpital Universitaire Nord, Assistance Publique-Hôpitaux de Marseille, Université Aix-Méditerranée, Faculté de Médecine, Marseille, France.

Objectives: We aimed to investigate whether clopidogrel-induced inhibition of platelet reactivity could reduce the level of circulating endothelial cells (CEC), reflecting the endothelial injury induced by percutaneous coronary intervention (PCI).

Background: Clopidogrel loading dose before percutaneous coronary angioplasty (PCI) reduces platelet activation through a selective and irreversible blockade of the adenosine diphosphate (ADP) receptor P2Y(12). The impact of clopidogrel on endothelial cells has been scarcely studied.

Methods: A total of 149 patients undergoing PCI for stable angina were enrolled. Levels of CEC were measured at baseline (H0) and 6 (H6) and 24 (H24) h after the procedure using a CD146-based immunomagnetic separation assay. The CEC delta-change (CEC at H6 - CEC at H0) was analyzed according to ADP receptor P2Y(12) blockade, assessed by a vasodilator-stimulated phosphoprotein (VASP) assay after a 600-mg loading dose of clopidogrel.

Results: The PCI induced a significant rise in CEC levels 6 h after the procedure. The CEC peak value was significantly higher in patients with high on-treatment platelet reactivity (VASP index ≥50%: 59.6 ± 27.5 cells/ml) as compared with good responders (VASP index <50%: 27 ± 22 cells/ml; p = 0.04). The endothelial injury, assessed by CEC delta-change between H6 and H0, was significantly higher in the high on-treatment platelet reactivity group compared with the good responders group (52.6 ± 25.6 vs. 18.6 ± 23.5, respectively; p < 0.001) and correlated with the VASP index (r = 0.59; p < 0.001). In multivariate analysis, VASP group, the number of diseased vessels, and the number of implanted stents independently predicted the endothelial injury (p < 0.001).

Conclusions: Optimal ADP receptor P2Y(12) blockade reduces the endothelial injury during PCI. This protective effect of clopidogrel on endothelial cells could add to the clinical benefit associated with this drug.
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September 2010

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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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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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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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

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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April 2010