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Papers by Lionel Leroux

Research paper thumbnail of b-adrenergic relaxation in pulmonary arteries: preservation of the endothelial nitric oxide-dependent b2 component in pulmonary hypertension

Aims b-adrenoceptor (b-AR)-mediated relaxation was characterized in pulmonary arteries from normo... more Aims b-adrenoceptor (b-AR)-mediated relaxation was characterized in pulmonary arteries from normoxic and hypoxic (as model of pulmonary hypertension) mice. The endothelial NO synthase (eNOS) pathway was especially investigated because of its potential vasculoprotective effects. Methods Pulmonary arteries from control or hypoxic (0.5 atm for 21 days) wild-type or eNOS 2/2 mice were used for pharmacological characterization of b-AR-mediated relaxation in myograph, and for immunohistochemistry using anti-b-AR antibodies. Results In pulmonary arteries from normoxic mice, isoproterenol (b-AR agonist) and procaterol (selective b 2 -AR agonist) elicited relaxation, while cyanopindolol and CL316243 (b 3 -AR agonists) were ineffective. The effect of isoproterenol was antagonized by CGP20712A and ICI118551 (b 1 -or b 2 -AR antagonists, respectively) and also partially inhibited by N v -nitro-L-arginine methylester (L-NAME, a NOS inhibitor), endothelium denudation, or eNOS gene deletion. Relaxation to procaterol was abolished by L-NAME or endothelium removal. In eNOS 2/2 mice, procaterol-induced relaxation was decreased but was insensitive to L-NAME, this residual effect involving other endothelium-dependent relaxant factors as compensatory mechanisms. Immunostaining for b 2 -AR was observed in the endothelial layer, but not the medial layer of pulmonary arteries. Pulmonary arteries from hypoxic mice exhibited decreased endothelial NO-dependent relaxation to acetylcholine. However, in these arteries, relaxation to procaterol was either unaffected (extralobar segments) or even increased (intralobar segments) and was still abolished by L-NAME or endothelium removal. Conclusion b 1 -and b 2 -AR, but not b 3 -AR, mediate relaxation of mice pulmonary arteries. The b 2 -AR component is dependent on eNOS activity and is preserved following chronic hypoxia. These data highlight the role of the b 2 -AR as a pharmacological target to induce/restore endothelial NO-dependent protective effects in pulmonary circulation.

Research paper thumbnail of Lethal aorto-right ventricle defect post transcatheter aortic valve implantation in a patient with radiation-induced porcelain aorta: notes of caution

Canadian Journal of Cardiology, 2015

A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery ... more A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery because of porcelain aorta. We successfully implanted an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA), but the patient was readmitted 3 weeks later for heart failure with a continuous murmur on auscultation. Echocardiography showed a small defect between the aorta and the infundibulum of the right ventricle, which was also confirmed with aortography and computed tomography. Medical therapy was optimized; however, he died unexpectedly a few weeks later. We concluded that irradiated tissues are particularly fragile and require specific attention during transcatheter aortic valve implantation. Furthermore, this case suggests that a more aggressive closure should have been applied.

Research paper thumbnail of Evaluation des facteurs de risque cardiovasculaire après pontages aorto-coronariens : intérêt d'une stratégie agressive avec mise en place d'un suivi systématique

Background: Coronary artery by-pass graft surgery is the treatment of choice for patient with mut... more Background: Coronary artery by-pass graft surgery is the treatment of choice for patient with mutivessel disease. This is a palliative therapy in which risk factors must be controlled to prevent ischemic heart disease resurgence and ischemic heart failure. The goal of our study was to evaluate prematurely the outcome of cardiovascular risk factors after CABG, and to adjust an aggressive

Research paper thumbnail of 0050: Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: experience from Bordeaux

Archives of Cardiovascular Diseases Supplements, 2015

Research paper thumbnail of CV18 Apport de l’IRM cardiaque dans le diagnostic de la cardiomyopathie apicale transitoire ou Tako Tsubo

Journal de Radiologie, 2006

Research paper thumbnail of Apport de l’IRM dans le diagnostic de la cardiomyopathie apicale transitoire (Tako-Tsubo)

Journal de Radiologie, 2006

Research paper thumbnail of Apport de l’IRM dans le diagnostic de la cardiomyopathie apicale transitoire (Tako-Tsubo)

Journal de Radiologie, 2006

Research paper thumbnail of Percutaneous mitral commissurotomy during pregnancy: With or without pelvic lead apron use?

International journal of cardiology, Jan 9, 2015

Research paper thumbnail of Percutaneous mitral commissurotomy during pregnancy: With or without pelvic lead apron use?

International journal of cardiology, Jan 9, 2015

Research paper thumbnail of Gene therapy for chronic peripheral arterial disease: what role for the vascular surgeon?

Annals of vascular surgery, 2004

The incidence of peripheral arterial disease is rising and despite advances in clinical managemen... more The incidence of peripheral arterial disease is rising and despite advances in clinical management, many problems remain unsolved. Better knowledge of the mechanisms and consequences associated with chronic muscle ischemia has opened the way for development of new treatment strategies, including therapeutic angiogenesis. Therapeutic angiogenesis is a promising technique based on experimental studies showing that growth factors or genes able to increase capillary density can be used to reduce the impact of muscle ischemia and increase blood flow to ischemic tissue. Enthusiasm for this technique has prompted numerous clinical trials with encouraging results, but data are still inconclusive. Optimal indications for gene therapy must be defined and further experimental progress is needed to respond to ethical issues. Therapeutic angiogenesis should be viewed as an adjunct to rather than as a competitor of current surgical revascularization techniques.

Research paper thumbnail of The Use of Impella 2.5 in Severe Refractory Cardiogenic Shock Complicating an Acute Myocardial Infarction

Journal of Interventional Cardiology, 2015

Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complic... more Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. Background: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. Methods: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. Results: In this analysis, patients were relatively young with a mean age of 57.9 AE 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 AE 5.3 mmol/L to 2.41 AE 2.1 mmo/L, (P ¼ 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 AE 10% vs. 27 AE 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. Conclusion: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome. (J Interven Cardiol 2015;28:41-50) ST-segment elevation myocardial infarction. 1 In AMI, CS results from the loss of myocardium contractility, leading to a failure to maintain an adequate systemic perfusion. In this pathophysiologic context, patient in profound CS may not respond to increasing dose of inotropes and intra-aortic balloon pump (IABP) and, thus, requires the use of more powerful mechanical circulatory support devices to save their lives. At our institution, mechanical hemodynamic support plays a central role in the management of AMI complicated by CS. While IABP is used as the first-line

Research paper thumbnail of The Use of Impella 2.5 in Severe Refractory Cardiogenic Shock Complicating an Acute Myocardial Infarction

Journal of Interventional Cardiology, 2015

Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complic... more Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. Background: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. Methods: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. Results: In this analysis, patients were relatively young with a mean age of 57.9 AE 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 AE 5.3 mmol/L to 2.41 AE 2.1 mmo/L, (P ¼ 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 AE 10% vs. 27 AE 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. Conclusion: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome. (J Interven Cardiol 2015;28:41-50) ST-segment elevation myocardial infarction. 1 In AMI, CS results from the loss of myocardium contractility, leading to a failure to maintain an adequate systemic perfusion. In this pathophysiologic context, patient in profound CS may not respond to increasing dose of inotropes and intra-aortic balloon pump (IABP) and, thus, requires the use of more powerful mechanical circulatory support devices to save their lives. At our institution, mechanical hemodynamic support plays a central role in the management of AMI complicated by CS. While IABP is used as the first-line

Research paper thumbnail of Caseous Necrosis of Mitral Annulus: A Rare Cause of Stroke

Case Reports in Cardiology, 2013

The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ven... more The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ventricle, revealed by stroke. Cerebral MRI, showing multiples lacunes, evocates a cardioembolic mechanism. Transthoracic and transesophageal echocardiography demonstrate a large hyperechogenic mass fixed to the posterior mitral valve and annulus while thoracic tomography revealed a fully calcified lesion, at the mitral annulus, evocative of caseus necrosis. Medical therapy was preferred (anticoagulation), because of her age and the decaying nature of surgery.

Research paper thumbnail of Caseous Necrosis of Mitral Annulus: A Rare Cause of Stroke

Case Reports in Cardiology, 2013

The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ven... more The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ventricle, revealed by stroke. Cerebral MRI, showing multiples lacunes, evocates a cardioembolic mechanism. Transthoracic and transesophageal echocardiography demonstrate a large hyperechogenic mass fixed to the posterior mitral valve and annulus while thoracic tomography revealed a fully calcified lesion, at the mitral annulus, evocative of caseus necrosis. Medical therapy was preferred (anticoagulation), because of her age and the decaying nature of surgery.

Research paper thumbnail of Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled ... more Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled pathway, is expressed in the heart and vessels during mouse embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular cells and angiogenesis. We assessed the hypothesis that FrzA could control the healing process after myocardial infarction (MI). Methods and Results—We demonstrated an upregulation of sFRP-1 and distinct

Research paper thumbnail of Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled ... more Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled pathway, is expressed in the heart and vessels during mouse embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular cells and angiogenesis. We assessed the hypothesis that FrzA could control the healing process after myocardial infarction (MI). Methods and Results—We demonstrated an upregulation of sFRP-1 and distinct

Research paper thumbnail of How should I treat a cardiac arrest during transcatheter aortic valve implantation?

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 2014

Research paper thumbnail of Delayed immunologic thrombocytopenia induced by abciximab

Thrombosis and Haemostasis, 2004

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percu... more Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.

Research paper thumbnail of Delayed immunologic thrombocytopenia induced by abciximab

Thrombosis and Haemostasis, 2004

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percu... more Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.

Research paper thumbnail of Secreted Frizzled-Related Protein-1 Enhances Mesenchymal Stem Cell Function in Angiogenesis and Contributes to Neovessel Maturation

Stem Cells, 2008

Mesenchymal stem cell (MSC) transplantation offers a great angiogenic opportunity in vascular reg... more Mesenchymal stem cell (MSC) transplantation offers a great angiogenic opportunity in vascular regenerative medicine. The canonical Wnt/beta-catenin signaling pathway has been demonstrated to play an essential role in stem cell fate. Recently, genetic studies have implicated the Wnt/Frizzled (Fz) molecular pathway, namely Wnt7B and Fz4, in blood growth regulation. Here, we investigated whether MSC could be required in shaping a functional vasculature and whether secreted Frizzled-related protein-1 (sFRP1), a modulator of the Wnt/Fz pathway, could modify MSC capacities, endowing MSC to increase vessel maturation. In the engraftment model, we show that murine bone marrow-derived MSC induced a beneficial vascular effect through a direct cellular contribution to vascular cells. MSC quickly organized into primitive immature vessel tubes connected to host circulation; this organization preceded host endothelial cell (EC) and smooth muscle cell (SMC) recruitment to later form mature neovessel. MSC sustained neovessel organization and maturation. We report here that sFRP1 forced expression enhanced MSC surrounding neovessel, which was correlated with an increase in vessel maturation and functionality. In vitro, sFRP1 strongly increased platelet-derived growth factor-BB (PDGF-BB) expression in MSC and enhanced beta-catenin-dependent cell-cell contacts between MSC themselves and EC or SMC. In vivo, sFRP1 increased their functional integration around neovessels and vessel maturation through a glycogen synthase kinase 3 beta (GSK3beta)-dependent pathway. sFRP1-overexpressing MSC compared with control MSC were well elongated and in a closer contact with the vascular wall, conditions required to achieve an organized mature vessel wall. We propose that genetically modifying MSC to overexpress sFRP1 may be potentially effective in promoting therapeutic angiogenesis/arteriogenesis processes. Disclosure of potential conflicts of interest is found at the end of this article.

Research paper thumbnail of b-adrenergic relaxation in pulmonary arteries: preservation of the endothelial nitric oxide-dependent b2 component in pulmonary hypertension

Aims b-adrenoceptor (b-AR)-mediated relaxation was characterized in pulmonary arteries from normo... more Aims b-adrenoceptor (b-AR)-mediated relaxation was characterized in pulmonary arteries from normoxic and hypoxic (as model of pulmonary hypertension) mice. The endothelial NO synthase (eNOS) pathway was especially investigated because of its potential vasculoprotective effects. Methods Pulmonary arteries from control or hypoxic (0.5 atm for 21 days) wild-type or eNOS 2/2 mice were used for pharmacological characterization of b-AR-mediated relaxation in myograph, and for immunohistochemistry using anti-b-AR antibodies. Results In pulmonary arteries from normoxic mice, isoproterenol (b-AR agonist) and procaterol (selective b 2 -AR agonist) elicited relaxation, while cyanopindolol and CL316243 (b 3 -AR agonists) were ineffective. The effect of isoproterenol was antagonized by CGP20712A and ICI118551 (b 1 -or b 2 -AR antagonists, respectively) and also partially inhibited by N v -nitro-L-arginine methylester (L-NAME, a NOS inhibitor), endothelium denudation, or eNOS gene deletion. Relaxation to procaterol was abolished by L-NAME or endothelium removal. In eNOS 2/2 mice, procaterol-induced relaxation was decreased but was insensitive to L-NAME, this residual effect involving other endothelium-dependent relaxant factors as compensatory mechanisms. Immunostaining for b 2 -AR was observed in the endothelial layer, but not the medial layer of pulmonary arteries. Pulmonary arteries from hypoxic mice exhibited decreased endothelial NO-dependent relaxation to acetylcholine. However, in these arteries, relaxation to procaterol was either unaffected (extralobar segments) or even increased (intralobar segments) and was still abolished by L-NAME or endothelium removal. Conclusion b 1 -and b 2 -AR, but not b 3 -AR, mediate relaxation of mice pulmonary arteries. The b 2 -AR component is dependent on eNOS activity and is preserved following chronic hypoxia. These data highlight the role of the b 2 -AR as a pharmacological target to induce/restore endothelial NO-dependent protective effects in pulmonary circulation.

Research paper thumbnail of Lethal aorto-right ventricle defect post transcatheter aortic valve implantation in a patient with radiation-induced porcelain aorta: notes of caution

Canadian Journal of Cardiology, 2015

A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery ... more A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery because of porcelain aorta. We successfully implanted an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA), but the patient was readmitted 3 weeks later for heart failure with a continuous murmur on auscultation. Echocardiography showed a small defect between the aorta and the infundibulum of the right ventricle, which was also confirmed with aortography and computed tomography. Medical therapy was optimized; however, he died unexpectedly a few weeks later. We concluded that irradiated tissues are particularly fragile and require specific attention during transcatheter aortic valve implantation. Furthermore, this case suggests that a more aggressive closure should have been applied.

Research paper thumbnail of Evaluation des facteurs de risque cardiovasculaire après pontages aorto-coronariens : intérêt d'une stratégie agressive avec mise en place d'un suivi systématique

Background: Coronary artery by-pass graft surgery is the treatment of choice for patient with mut... more Background: Coronary artery by-pass graft surgery is the treatment of choice for patient with mutivessel disease. This is a palliative therapy in which risk factors must be controlled to prevent ischemic heart disease resurgence and ischemic heart failure. The goal of our study was to evaluate prematurely the outcome of cardiovascular risk factors after CABG, and to adjust an aggressive

Research paper thumbnail of 0050: Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: experience from Bordeaux

Archives of Cardiovascular Diseases Supplements, 2015

Research paper thumbnail of CV18 Apport de l’IRM cardiaque dans le diagnostic de la cardiomyopathie apicale transitoire ou Tako Tsubo

Journal de Radiologie, 2006

Research paper thumbnail of Apport de l’IRM dans le diagnostic de la cardiomyopathie apicale transitoire (Tako-Tsubo)

Journal de Radiologie, 2006

Research paper thumbnail of Apport de l’IRM dans le diagnostic de la cardiomyopathie apicale transitoire (Tako-Tsubo)

Journal de Radiologie, 2006

Research paper thumbnail of Percutaneous mitral commissurotomy during pregnancy: With or without pelvic lead apron use?

International journal of cardiology, Jan 9, 2015

Research paper thumbnail of Percutaneous mitral commissurotomy during pregnancy: With or without pelvic lead apron use?

International journal of cardiology, Jan 9, 2015

Research paper thumbnail of Gene therapy for chronic peripheral arterial disease: what role for the vascular surgeon?

Annals of vascular surgery, 2004

The incidence of peripheral arterial disease is rising and despite advances in clinical managemen... more The incidence of peripheral arterial disease is rising and despite advances in clinical management, many problems remain unsolved. Better knowledge of the mechanisms and consequences associated with chronic muscle ischemia has opened the way for development of new treatment strategies, including therapeutic angiogenesis. Therapeutic angiogenesis is a promising technique based on experimental studies showing that growth factors or genes able to increase capillary density can be used to reduce the impact of muscle ischemia and increase blood flow to ischemic tissue. Enthusiasm for this technique has prompted numerous clinical trials with encouraging results, but data are still inconclusive. Optimal indications for gene therapy must be defined and further experimental progress is needed to respond to ethical issues. Therapeutic angiogenesis should be viewed as an adjunct to rather than as a competitor of current surgical revascularization techniques.

Research paper thumbnail of The Use of Impella 2.5 in Severe Refractory Cardiogenic Shock Complicating an Acute Myocardial Infarction

Journal of Interventional Cardiology, 2015

Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complic... more Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. Background: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. Methods: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. Results: In this analysis, patients were relatively young with a mean age of 57.9 AE 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 AE 5.3 mmol/L to 2.41 AE 2.1 mmo/L, (P ¼ 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 AE 10% vs. 27 AE 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. Conclusion: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome. (J Interven Cardiol 2015;28:41-50) ST-segment elevation myocardial infarction. 1 In AMI, CS results from the loss of myocardium contractility, leading to a failure to maintain an adequate systemic perfusion. In this pathophysiologic context, patient in profound CS may not respond to increasing dose of inotropes and intra-aortic balloon pump (IABP) and, thus, requires the use of more powerful mechanical circulatory support devices to save their lives. At our institution, mechanical hemodynamic support plays a central role in the management of AMI complicated by CS. While IABP is used as the first-line

Research paper thumbnail of The Use of Impella 2.5 in Severe Refractory Cardiogenic Shock Complicating an Acute Myocardial Infarction

Journal of Interventional Cardiology, 2015

Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complic... more Objectives: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. Background: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. Methods: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. Results: In this analysis, patients were relatively young with a mean age of 57.9 AE 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 AE 5.3 mmol/L to 2.41 AE 2.1 mmo/L, (P ¼ 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 AE 10% vs. 27 AE 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. Conclusion: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome. (J Interven Cardiol 2015;28:41-50) ST-segment elevation myocardial infarction. 1 In AMI, CS results from the loss of myocardium contractility, leading to a failure to maintain an adequate systemic perfusion. In this pathophysiologic context, patient in profound CS may not respond to increasing dose of inotropes and intra-aortic balloon pump (IABP) and, thus, requires the use of more powerful mechanical circulatory support devices to save their lives. At our institution, mechanical hemodynamic support plays a central role in the management of AMI complicated by CS. While IABP is used as the first-line

Research paper thumbnail of Caseous Necrosis of Mitral Annulus: A Rare Cause of Stroke

Case Reports in Cardiology, 2013

The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ven... more The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ventricle, revealed by stroke. Cerebral MRI, showing multiples lacunes, evocates a cardioembolic mechanism. Transthoracic and transesophageal echocardiography demonstrate a large hyperechogenic mass fixed to the posterior mitral valve and annulus while thoracic tomography revealed a fully calcified lesion, at the mitral annulus, evocative of caseus necrosis. Medical therapy was preferred (anticoagulation), because of her age and the decaying nature of surgery.

Research paper thumbnail of Caseous Necrosis of Mitral Annulus: A Rare Cause of Stroke

Case Reports in Cardiology, 2013

The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ven... more The current report describes a rare case of a caseous necrosis presenting as a pseudotumor in ventricle, revealed by stroke. Cerebral MRI, showing multiples lacunes, evocates a cardioembolic mechanism. Transthoracic and transesophageal echocardiography demonstrate a large hyperechogenic mass fixed to the posterior mitral valve and annulus while thoracic tomography revealed a fully calcified lesion, at the mitral annulus, evocative of caseus necrosis. Medical therapy was preferred (anticoagulation), because of her age and the decaying nature of surgery.

Research paper thumbnail of Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled ... more Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled pathway, is expressed in the heart and vessels during mouse embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular cells and angiogenesis. We assessed the hypothesis that FrzA could control the healing process after myocardial infarction (MI). Methods and Results—We demonstrated an upregulation of sFRP-1 and distinct

Research paper thumbnail of Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA

Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled ... more Background—FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled pathway, is expressed in the heart and vessels during mouse embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular cells and angiogenesis. We assessed the hypothesis that FrzA could control the healing process after myocardial infarction (MI). Methods and Results—We demonstrated an upregulation of sFRP-1 and distinct

Research paper thumbnail of How should I treat a cardiac arrest during transcatheter aortic valve implantation?

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 2014

Research paper thumbnail of Delayed immunologic thrombocytopenia induced by abciximab

Thrombosis and Haemostasis, 2004

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percu... more Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.

Research paper thumbnail of Delayed immunologic thrombocytopenia induced by abciximab

Thrombosis and Haemostasis, 2004

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percu... more Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.

Research paper thumbnail of Secreted Frizzled-Related Protein-1 Enhances Mesenchymal Stem Cell Function in Angiogenesis and Contributes to Neovessel Maturation

Stem Cells, 2008

Mesenchymal stem cell (MSC) transplantation offers a great angiogenic opportunity in vascular reg... more Mesenchymal stem cell (MSC) transplantation offers a great angiogenic opportunity in vascular regenerative medicine. The canonical Wnt/beta-catenin signaling pathway has been demonstrated to play an essential role in stem cell fate. Recently, genetic studies have implicated the Wnt/Frizzled (Fz) molecular pathway, namely Wnt7B and Fz4, in blood growth regulation. Here, we investigated whether MSC could be required in shaping a functional vasculature and whether secreted Frizzled-related protein-1 (sFRP1), a modulator of the Wnt/Fz pathway, could modify MSC capacities, endowing MSC to increase vessel maturation. In the engraftment model, we show that murine bone marrow-derived MSC induced a beneficial vascular effect through a direct cellular contribution to vascular cells. MSC quickly organized into primitive immature vessel tubes connected to host circulation; this organization preceded host endothelial cell (EC) and smooth muscle cell (SMC) recruitment to later form mature neovessel. MSC sustained neovessel organization and maturation. We report here that sFRP1 forced expression enhanced MSC surrounding neovessel, which was correlated with an increase in vessel maturation and functionality. In vitro, sFRP1 strongly increased platelet-derived growth factor-BB (PDGF-BB) expression in MSC and enhanced beta-catenin-dependent cell-cell contacts between MSC themselves and EC or SMC. In vivo, sFRP1 increased their functional integration around neovessels and vessel maturation through a glycogen synthase kinase 3 beta (GSK3beta)-dependent pathway. sFRP1-overexpressing MSC compared with control MSC were well elongated and in a closer contact with the vascular wall, conditions required to achieve an organized mature vessel wall. We propose that genetically modifying MSC to overexpress sFRP1 may be potentially effective in promoting therapeutic angiogenesis/arteriogenesis processes. Disclosure of potential conflicts of interest is found at the end of this article.