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Heart rhythm: the official journal of the Heart Rhythm Society 05/2013; · 4.56 Impact Factor
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ABSTRACT: Although our understanding of vascular pathology has greatly improved in recent years, the cellular and molecular mechanisms underlying the enhanced thrombotic propensity in type 2 diabetes mellitus (T2DM) remain incompletely characterized. Detrimental interactions between activated vascular cells (i.e., platelets, leukocytes, endothelial cells) and the vulnerable atheromatous plaque are a major determinant of the increased atherothrombotic burden in T2DM patients. Endothelial damage and accelerated senescence, impairment of the endothelial progenitor cell repair system, plaque neovascularization and inflammation, decreased clearance of detrimental molecules within the plaque, and increased expression of matrix metalloproteinases may collectively contribute to intraplaque hemorrhage and subsequent rupture. Notably, recent data demonstrates the central importance of the tissue factor-microparticle-mediated pathway in diabetic thrombophilia and cardiovascular complications. Acting as detrimental amplifiers of various biological responses (including thrombogenicity and plaque remodeling), microparticles have also emerged as a key marker of global vascular damage in T2DM patients. Available evidence suggests that targeting the tissue factor-microparticle pathway may be a promising approach for reducing the burden of the atherosclerotic complications of diabetes.
Seminars in Thrombosis and Hemostasis 04/2013; · 4.52 Impact Factor
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ABSTRACT: Patients with chronic kidney disease (CKD) represent an increasing proportion of the population undergoing percutaneous coronary intervention (PCI) and up to 40% of the patients treated for acute coronary syndrome (ACS). Several studies and registries in the setting of ACS and elective PCI have reported a negative association between CKD and mortality, stent thrombosis, post-procedural ischaemic events and bleeding events. Pharmacological inhibition of the adenosine diphosphate receptor by thienopyridines or ticagrelor and disruption of the cyclooxygenase pathway by aspirin constitute the current standards of care to prevent thrombotic complications following stent-based PCI. In CKD patients, the avoidance of anti-platelet therapy may be driven by the lack of clinical trial data to support its efficacy, by errors or omissions, or by a reluctance to use this therapy in a population characterized by its enhanced bleeding risk. However, there is growing evidence to suggest that a severely decreased glomerular filtration rate per se, independent of the presence of diabetes mellitus, is an important determinant of high residual platelet reactivity under a clopidogrel maintenance dose. Recent reports have emphasized that the impact of impaired platelet inhibition by thienopyridines is of paramount importance in CKD patients, with an enhanced mortality rate in low-responder patients. Pharmacodynamic studies indicate the phosphodiesterase 3 inhibitor, cilostazol, the third generation thienopyridine prasugrel and the reversible P2Y12 antagonist ticagrelor to be potent strategies to overcome this biological resistance. In clinical practice, platelet function testing should be considered in CKD patients undergoing PCI, especially in those who experience thrombotic events despite dual therapy. Newer agents should be contemplated in patients who display higher residual platelet aggregability after standard treatment. Among these, the non-thienopyridine P2Y12 receptor antagonist ticagrelor, which does not require biotransformation, could be the drug of choice in CKD patients with ACS. In this population, ticagrelor has been found to reduce mortality and ischaemic events with an acceptable bleeding risk.
Nephrology Dialysis Transplantation 03/2013; · 3.40 Impact Factor
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International journal of cardiology 10/2012; · 7.08 Impact Factor
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ABSTRACT: The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood.
In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days).
126 consecutive patients categorized by estimated GFR: stages 1-2 (>60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (<15 mL/min/1.73 m(2); n = 36) were prospectively enrolled.
Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) ≥61% and in the VerifyNow turbidimetric-based assay as a value >235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition <15%.
We examined factors associated with low response to clopidogrel using logistic regression.
A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI ≥61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU >235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition <15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P < 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity.
Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded.
GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus.
American Journal of Kidney Diseases 03/2012; 59(6):777-85. · 5.43 Impact Factor
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Claudia Herrera Siklódy,
Thomas Arentz,
Jan Minners, Laurence Jesel,
Christian Stratz,
Christian M Valina,
Reinhold Weber,
Dietrich Kalusche,
Florence Toti,
Olivier Morel,
Dietmar Trenk
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ABSTRACT: Experimental data suggest that use of cryoablation in pulmonary vein isolation (PVI) is associated with less cell damage and less thrombus formation compared to radiofrequency (RF) energy.
The purpose of this study was to test the hypothesis that cryoablation significantly reduces markers of cell damage, platelet activation, and inflammation in patients undergoing PVI for treatment of atrial fibrillation (AF).
Sixty patients with symptomatic drug-resistant AF (age 56 ± 9 years, 48 males, 38 with paroxysmal AF) were randomly assigned to undergo PVI using either an open irrigated-tip RF catheter or a cryoballoon. Markers of cell damage (high-sensitive troponin T [hs-TnT], microparticles), platelet activation (platelet reactivity by aggregometry, expression of platelet surface proteins P-selectin and activated glycoprotein [GP] IIb/IIIa), and inflammatory response (high-sensitive C-reactive protein [hs-CRP]) were determined before and up to 48 hours after the procedure.
PVI resulted in a significant rise in hs-TnT, microparticles, markers of platelet activation, and hs-CRP over time, with distinct temporal patterns for each parameter. However, after Bonferroni correction for repeated measurements, no significant differences were noted in these parameters between patients treated with cryoablation or RF energy. Procedural time was significantly shorter in patients treated with cryoballoon (177 ± 30 minutes vs 200 ± 46 minutes, P = .03), with no differences in fluoroscopic time, periprocedural complications, or success rate.
Cryoablation and RF energy result in a comparable rise of markers of cell damage, platelet activation and inflammatory response. The data do not support the concept of an improved safety profile for cryoablation in PVI.
Heart rhythm: the official journal of the Heart Rhythm Society 09/2011; 9(2):189-96. · 4.56 Impact Factor
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ABSTRACT: Plasma membrane remodeling characterized by phosphatidylserine exposure and consecutive microparticle (MP) shedding is an ubiquitous process enabling the clearance of senescent cells and the maintenance of tissue homeostasis. MPs are released as fragments from the budding plasma membrane of virtually all eukaryotic cell types undergoing stimulation or apoptosis and may be considered a broad primitive response to stress. MP release is dependent on cytoskeleton degradation pathways involving caspases, requires a sustained increase in intracellular calcium triggering K+ and Cl- efflux and is possibly tuned by mitochondria permeability changes. Because they convey a broad spectrum of bioactive molecules, circulating MPs may serve as shuttles promoting cellular cross talk in various pathological settings such as inflammation or immunity-induced thrombotic disorders. If the drastic shedding of procoagulant MPs appears clearly noxious in thrombotic disorders or in some models of inflammation-induced coagulopathy, this does not necessarily endorse their invariably harmful nature. In the vessel, endothelial cytoprotection reported in the early regulation of inflammation-induced coagulopathy is emblematic of the beneficial effects provided by MPs. In addition, MPs would prove beneficial in the prevention of blood leakage. Because of their multiple properties that are characteristic of a private response of the parental cell, MPs could act as cytoprotective and anti-inflammatory agents through the delivery of activated protein C or annexin 1 and could contribute to the limitation of vascular hyporeactivity. Owing to their ability to cargo bioactive signals, MPs could be viewed as an integrated communication network enabling the coordination of complex cellular responses in biological fluids and the maintenance of the homeostasis equation. A better understanding of the molecular mechanisms involved in MP shedding would pave the way of a new pharmacological approach aiming at the control of MP-driven cellular responses.
Seminars in Immunopathology 08/2011; 33(5):469-86. · 6.27 Impact Factor
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ABSTRACT: Microparticles (MPs) derived from platelets, monocytes, endothelial cells, red blood cells, and granulocytes may be detected in low concentrations in normal plasma and at increased levels in atherothrombotic cardiovascular diseases. The elucidation of the cellular mechanisms underlying the generation of circulating MPs is crucial for improving our understanding of their pathophysiological role in health and disease. The flopping of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the key event that will ultimately lead to the shedding of procoagulant MPs from activated or apoptotic cells. Research over the last few years has revealed important roles for calcium-, mitochondrial-, and caspase-dependent mechanisms leading to PS exposure. The study of Scott cells has unraveled different molecular mechanisms that may contribute to fine-tuning of PS exposure and MP release in response to a variety of specific stimuli. The pharmacological modulation of MP release may have a substantial therapeutic impact in the management of atherothrombotic vascular disorders. Because PS exposure is a key feature in pathological processes different from hemostasis and thrombosis, the most important obstacle in the field of MP-modulating drugs seems to be carefully targeting MP release to relevant cell types at an optimal level, so as to achieve a beneficial action and limit possible adverse effects.
Arteriosclerosis Thrombosis and Vascular Biology 01/2011; 31(1):15-26. · 6.37 Impact Factor
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Olivier Morel,
Soraya El Ghannudi, Laurence Jesel,
Bogdan Radulescu,
Nicolas Meyer,
Marie-Louise Wiesel,
Sophie Caillard,
Umberto Campia,
Bruno Moulin,
Christian Gachet,
Patrick Ohlmann
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ABSTRACT: We sought to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) differentially affects outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).
Although both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavorable outcome after PCI, the impact of their association is unknown. The platelet VASP-FCT assay is specific for the P2Y(12) ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI).
Four-hundred forty unselected patients (CKD: 126, estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2)), no-CKD: 314 eGFR >60 ml/min/1.73 m(2)) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: PRI ≥ 61%) or responders (R: PRI <61%) to clopidogrel.
At a mean follow-up of 9 ± 2 months, all-cause mortality, cardiac death, and possible stent thrombosis were higher in CKD than in no-CKD patients. Within the CKD group, the LR status was associated with higher rates of all-cause mortality (25.5% vs. 2.8%, p < 0.001), cardiac death (23.5% vs. 2.8%, p < 0.001), all stent thrombosis (19.6% vs. 2.7%, p = 0.003), and MACE (33.3% vs. 12.3%, p = 0.007). Conversely, in no-CKD patients, the LR status did not affect outcomes. Multivariate analysis identified Killip class ≥ 3, drug-eluting stent implantation, and the interaction between LR and CKD (hazard ratio: 11.96, 95% confidence interval: 1.22 to 116.82; p = 0.033) as independent predictors of cardiac death.
In CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI.
Journal of the American College of Cardiology 01/2011; 57(4):399-408. · 14.16 Impact Factor
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ABSTRACT: Membrane remodeling, phosphatidylserine (PS) exposure, and subsequent microparticle (MP) shedding regulation is a critical step in maintaining vascular homeostasis. Shed MP, more particularly those of platelet origin, could be viewed as a way to increase the catalytic procoagulant surface relying on the essential presence of PS for optimal hemostatic response. Whether "flip-flop" is mandatory for the release of MP is suggested from the phenotype of Scott's syndrome, a rare bleeding disorder in which both PS exposure and MP shedding are deficient. PS exposure results from a specific cytoskeleton degradation pathway involving caspases, tuned by mitochondria permeability changes, and requiring a sustained increase in intracellular calcium. The actual roles of transmembrane ion transport or transient transmembrane pores in PS exposure remain to be more firmly established. Considering that an excess of plasma membrane procoagulant activity is associated with an increased risk of thrombosis, the identification of effectors of PS exposure and MP release appear relevant targets in thrombosis research and focused drug design. In this view, animal models of Scott's syndrome should prove of primary importance for the characterization of the genetic trait(s) accounting for the associated defect that would provide an important hint toward the control of PS exposure and subsequent MP release.
Seminars in Thrombosis and Hemostasis 11/2010; 36(8):833-44. · 4.52 Impact Factor
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Olivier Morel,
Frédérique Sauer,
Alessio Imperiale,
Sébastien Cimarelli,
Cyrille Blondet, Laurence Jesel,
Annie Trinh,
Fabien De Poli,
Patrick Ohlmann,
André Constantinesco,
Pierre Bareiss
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ABSTRACT: To gain more insight into the involvement of inflammatory response and neurohumoral activation in Takotsubo cardiomyopathy (TTC), we investigated C-reactive protein (CRP), leukocytes, plasma catecholamines levels, iodine 123 meta-iodobenzylguanidine (123I-mIBG) myocardial uptake, myocardial perfusion (thallium 201 [201Tl] or technetium [Tc] 99m-tetrofosmin myocardial single photon emission computed tomography [SPECT]), and metabolism (fluorine 18-fluorodeoxyglucose positron emission tomography).
Inflammatory status and brain natriuretic peptide (BNP) levels in 17 patients with TTC were compared with 14 age-matched patients. In TTC, elevated levels of CRP were evidenced on admission, reaching a peak in the following days (P < .01). CRP levels were correlated to baseline left ventricular ejection fraction (LVEF) and BNP levels (P < .05). Leukocytes were correlated to BNP and noradrenaline levels. Myocardial 123I-mIBG SPECT showed a reduced activity in the midventricle and apex corresponding to 35% +/- 23% of the total myocardial mass, partially reversible at follow-up. An identical pattern was retrieved when assessing myocardial glucose metabolism. At rest, no relevant abnormalities of myocardial perfusion could be evidenced at the subacute phase.
Inflammatory status in TTC was related to LVEF impairment and to the extent of neurohormonal activation. The hypothesis of a catecholamine-induced myocardial "stunning" is emphasized by the evidence of a reduced 123I-mIBG myocardial activity, impairment of myocardial glucose metabolism, and wall motion kinetic after the same temporospatial distribution.
Journal of cardiac failure 05/2009; 15(3):206-13. · 3.25 Impact Factor
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Patrick Ohlmann,
Antoine Faure,
Olivier Morel,
Michel Kindo, Laurence Jesel,
Bogdan Radulescu,
Philippe Billaud,
Nicolas Meyer,
Hélène Petit,
Annie Trinh,
Eric Epailly,
Gérald Roul,
Michel Chauvin,
Jean-Philippe Mazzucotelli,
Bernard Eisenmann,
Pierre Bareiss
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ABSTRACT: To compare the diagnostic value of circulating Sta-Liatest D-Di levels in classic acute aortic dissection (AAD) and in aortic intramural hematoma (AIH), a variant of AAD without a patent false lumen.
Single-center retrospective case-control study.
University Hospital of Strasbourg, France.
Ninety-four consecutive patients with both confirmed AAD and d-dimer measurements at entry were included. d-dimer levels were assayed by the immunoturbidimetric method Sta-Liatest D-Di (Diagnostica Stago, Asnieres sur Seine, France).
Patient characteristics and clinical evolution were analyzed.
Eighty-four patients (89%) presented a classic AAD with patent false lumen and ten (11%) presented an AIH. Clinical presentation did not differ between the two groups. The mortality rate was 0% in AIH and 26% in classic AAD. d-dimer levels were significantly lower in patients with AIH (median, 1230 ng/mL; interquartile range, 685-2645 ng/mL) than in patients with AAD with patent false lumen (median value, 9290 ng/mL; interquartile range, 3890-20,000 ng/mL; p = 0.008). All patients with AAD and patent false lumen had d-dimer levels above the threshold of 400 ng/mL (sensitivity 100%). However, one patient with AIH presented d-dimer levels below the threshold. Therefore, the sensitivity of the d-dimer test in detecting AIH was 90%.
Sta-Liatest D-Di levels are lower in AIH than in AAD with patent false lumen. This test can quite possibly be negative in the case of intramural hematoma. This feature must be considered when interpreting d-dimer levels in patients with acute aortic syndrome.
Critical care medicine 04/2009; 37(3):899-901. · 6.37 Impact Factor
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ABSTRACT: To assess the extent of endothelium, platelet, and leukocyte damage and coagulation activation induced by radiofrequency catheter ablation (RF) of atrial flutter. In the vasculature, procoagulant microparticles (MPs) are reliable markers of vascular damage. They provide an additional phospholipidic surface, enabling the assembly of the enzyme complexes of blood coagulation and consequent thrombin generation.
MPs were measured in the venous blood of 33 patients with isthmus-dependent atrial flutter undergoing RF before (RF(0)), immediately after (RF(1)), and at day 1 (RF(2)) thereafter. Concentrations of PAI-1, vWF, and D-dimers were simultaneously determined. MPs procoagulant activities were determined using a functional prothrombinase assay. RF induces an early rise of platelet-derived MPs (platelet), vWF Ag, and D-dimers levels, which is concomitant with the decrease of PAI-1 concentrations. Conversely, no significant changes in endothelial-derived MPs could be evidenced. At RF(2), sustained elevation of leukocytes-derived MPs, vWF, and D-dimers testified to an ongoing prothrombotic status.
RF ablation of common flutter induces a prothrombotic state and the release of platelet and leukocyte-derived procoagulant microparticles. Whereas this activation of blood coagulation could be viewed as clinically marginal in right-sided procedures, its relevance in left-sided procedures should be established.
Pacing and Clinical Electrophysiology 03/2009; 32(2):193-200. · 1.35 Impact Factor
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Olivier Morel,
Bruno Pereira,
Gerlinde Averous,
Antoine Faure, Laurence Jesel,
Philippe Germain,
Lelia Grunebaum,
Patrick Ohlmann,
Jean-Marie Freyssinet,
Pierre Bareiss,
Florence Toti
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ABSTRACT: During myocardial infarction, platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MPs) in the bloodstream. Few data are available on the potential role played by MPs in coronary atherothrombosis. In the present study, we investigated the levels and cellular origins of MPs within the occluded coronary artery of patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty (PCI).
A total of 12 patients with STEMI treated by primary PCI within 24h of symptom onset were included in this study. MPs procoagulant activity and cellular origin were characterized within the occluded coronary artery before PCI (C(0)), after restoration of the epicardial blood flow (C(1)), and in blood collected from the femoral artery (F).
Levels of leukocyte-derived CD11a(+) MPs, endothelial-derived CD105(+) MPs, and tissue factor (TF)-bearing MPs were significantly higher within the occluded coronary artery than in peripheral blood samples. Restoration of the epicardial blood flow led to a significant reduction of procoagulant CD11a(+) and CD105(+) MPs by 30% and 42%, respectively (p<0.05).
Elevation of procoagulant MPs within the occluded coronary artery of patients with STEMI suggests their pathophysiological role in coronary atherothrombosis.
Atherosclerosis 11/2008; 204(2):636-41. · 3.79 Impact Factor
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Michel Haïssaguerre,
Nicolas Derval,
Frederic Sacher, Laurence Jesel,
Isabel Deisenhofer,
Luc de Roy,
Jean-Luc Pasquié,
Akihiko Nogami,
Dominique Babuty,
Sinikka Yli-Mayry, [......],
Kang Teng Lim,
Sebastien Knecht,
George D Veenhuyzen,
Pierre Bordachar,
Michel Chauvin,
Pierre Jais,
Gaelle Coureau,
Genevieve Chene,
George J Klein,
Jacques Clémenty
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ABSTRACT: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest.
We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects.
Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008).
Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.
New England Journal of Medicine 05/2008; 358(19):2016-23. · 53.30 Impact Factor
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Patrick Ohlmann,
Olivier Morel,
Bogdan Radulescu,
Michel Kindo,
Antoine Faure,
Philippe Billaud,
Hélène Petit,
Nicolas Meyer, Laurence Jesel,
Dominique Desprez,
Jean-Philippe Mazzucotelli,
Bernard Eisenmann,
Pierre Bareiss
European Heart Journal 04/2008; 29(6):828-9; author reply 829. · 10.48 Impact Factor
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Babe Bakouboula,
Olivier Morel,
Antoine Faure,
Fatiha Zobairi, Laurence Jesel,
Annie Trinh,
Michel Zupan,
Matthieu Canuet,
Lelia Grunebaum,
Agnès Brunette,
Dominique Desprez,
François Chabot,
Emmanuel Weitzenblum,
Jean-Marie Freyssinet,
Ari Chaouat,
Florence Toti
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ABSTRACT: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.
We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH).
Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined.
Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test.
Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.
American Journal of Respiratory and Critical Care Medicine 03/2008; 177(5):536-43. · 11.08 Impact Factor
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Olivier Morel,
Patrick Ohlmann,
Eric Epailly,
Babe Bakouboula,
Fatiha Zobairi, Laurence Jesel,
Nicolas Meyer,
Marie-Pierre Chenard,
Jean-Marie Freyssinet,
Pierre Bareiss,
Jean-Philippe Mazzucotelli,
Florence Toti
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ABSTRACT: Circulating procoagulant microparticles are reliable markers of vascular damage. The microparticle phenotypes provide additional information reflecting the nature of cell injury. This study assessed procoagulant microparticle levels and phenotypes in the diagnosis of acute allograft rejection after heart transplantation.
Microparticles were prospectively investigated in the venous blood of 64 heart transplant patients, 23 with allograft rejection mainly of low score, and 41 without a rejection episode. Plasma concentrations of cytokines, cytoadhesins, and platelet activation markers were determined.
By univariate analysis, the mean time elapsed from heart transplant, cold ischemia time, E-selectin-, Fas- and tissue factor-bearing microparticles were associated with allograft rejection. By multivariate analysis, E-selectin-microparticle levels appeared independently associated with allograft rejection, even when other significant variables were included in the model (odds ratio, 9.8; 95% confidence interval, 1.36-71.4; p = 0.023).
The pattern of procoagulant microparticles released during acute allograft rejection suggests endothelial cell activation and Fas-mediated apoptosis. E-selectin-bearing microparticles appeared as an independent marker of acute allograft rejection that was still informative after adjustment for graft characteristics.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2008; 27(1):38-45. · 3.54 Impact Factor
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Thrombosis and Haemostasis 11/2007; 98(4):896-9. · 5.04 Impact Factor
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Vincent Probst,
Isabelle Denjoy,
Paola G Meregalli,
Jean-Christophe Amirault,
Fréderic Sacher,
Jacques Mansourati,
Dominique Babuty,
Elisabeth Villain,
Jacques Victor,
Jean-Jacques Schott,
Jean-Marc Lupoglazoff,
Philippe Mabo,
Christian Veltmann, Laurence Jesel,
Philippe Chevalier,
Sally-Ann B Clur,
Michel Haissaguerre,
Christian Wolpert,
Hervé Le Marec,
Arthur A M Wilde
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ABSTRACT: Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and augmented risk of sudden cardiac death. Little is known about the clinical presentation and prognosis of this disease in children.
Thirty children affected by Brugada syndrome who were <16 years of age (mean, 8+/-4 years) were included. All patients displayed a type I ECG pattern before or after drug provocation challenge. Diagnosis of Brugada syndrome was made under the following circumstances: aborted sudden death (n=1), syncope of unexplained origin (n=10), symptomatic supraventricular tachycardia (n=1), suspicious ECG (n=1), and family screening for Brugada syndrome (n=17). Syncope was precipitated by fever in 5 cases. Ten of 11 symptomatic patients displayed a spontaneous type I ECG. An implantable cardioverter-defibrillator was implanted in 5 children; 4 children were treated with hydroquinidine; and 1 child received a pacemaker because of symptomatic sick sinus syndrome. During a mean follow-up of 37+/-23 months, 1 child experienced sudden cardiac death, and 2 children received an appropriate implantable cardioverter-defibrillator shock; all of them were symptomatic and had manifested a type I ECG spontaneously. One child had a cardioverter-defibrillator infection that required explantation of the defibrillator.
In the largest population of children affected by Brugada syndrome described to date, fever represented the most important precipitating factor for arrhythmic events, and as in the adult population, the risk of arrhythmic events was higher in previously symptomatic patients and in those displaying a spontaneous type I ECG.
Circulation 04/2007; 115(15):2042-8. · 14.74 Impact Factor
