Publications by authors named "Mélanie Gaubert"

19 Publications

  • Page 1 of 1

Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice.

Int J Mol Sci 2020 Jun 6;21(11). Epub 2020 Jun 6.

Department of Cardiology, Aix-Marseille University, Hôpital Nord, 13015 Marseille, France.

Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.
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http://dx.doi.org/10.3390/ijms21114066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312288PMC
June 2020

Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis.

J Immunother Cancer 2020 12;8(2)

University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France

Background: Myocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST.

Methods: This case-control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca's criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not.

Results: A total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005).

Conclusion: The need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.
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http://dx.doi.org/10.1136/jitc-2020-001887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725077PMC
December 2020

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

J Clin Med 2020 Oct 22;9(11). Epub 2020 Oct 22.

Cardiology Department, APHM, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Centre for CardioVascular and Nutrition Research (C2VN), Aix-Marseille Univ, INSERM 1263, INRA 1260, Hopital Nord, 13015 Marseille, France.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895-2277) vs. 2622 (2264-2993) dynes-s·cm·m ( = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88-2.18) vs. 1.78 (1.65-1.96) L·min·m ( = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.
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http://dx.doi.org/10.3390/jcm9113384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690259PMC
October 2020

Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases.

Int J Mol Sci 2020 Jul 27;21(15). Epub 2020 Jul 27.

C2VN, INSERM, INRA, Aix-Marseille University, F-13015 Marseille, France.

Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates the cardiovascular system via four specific G-protein-coupled receptors named AR, AR, AR, and AR. Among them, A subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.
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http://dx.doi.org/10.3390/ijms21155321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432452PMC
July 2020

Homocysteine concentration and adenosine A receptor production by peripheral blood mononuclear cells in coronary artery disease patients.

J Cell Mol Med 2020 08 29;24(16):8942-8949. Epub 2020 Jun 29.

C2VN, INSERM, INRA, Aix Marseille University, Marseille, France.

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A receptors (A R). We addressed in CAD patients the relationship between HCy and A R production, and in cellulo the effect of HCy on A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A R production as well as on basal and stimulated cAMP production following A R activation by an agonist-like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7-45] vs 8 [5-12] µM, P < 0.001). A R production was lower in patients vs controls (1.1[0.62-1.6] vs 1.53[0.7-1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A R production (r = -0.43; P < 0.0001), with decreased A R production above 25 µM HCy. In cellulo, HCy inhibited A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A R production in CAD patients, as well as with A R and cAMP production in cellulo. The decrease in A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.
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http://dx.doi.org/10.1111/jcmm.15527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417719PMC
August 2020

Trials of mechanical circulatory support with percutaneous axial flow pumps in cardiogenic shock complicating acute myocardial infarction: Mission impossible?

Arch Cardiovasc Dis 2020 Jun - Jul;113(6-7):448-460. Epub 2020 Apr 11.

PhyMedExp, CNRS, Cardiology Department, université de Montpellier, Inserm, CHU de Montpellier, 34295 Montpellier, France.

Cardiogenic shock is a complex clinical entity associated with very high mortality and intensive resource utilization. Despite the widespread use of timely reperfusion and appropriate pharmacotherapy, the survival rate remains at around 50%. Recently, percutaneous axial flow pumps have been integrated into the therapeutic spectrum of cardiogenic shock management. However, most of the literature supporting their use stems from observational studies. To date, attempts to perform randomized controlled trials with percutaneous axial flow pumps have failed. This underlines the challenge of performing a well-conducted randomized controlled trial that provides the highest level of evidence. Such a trial is warranted, because percutaneous axial flow pumps are costly, and are associated with serious complications. The major pitfalls of previous studies were lack of standardized cardiogenic shock definitions according to clinical severity, inappropriate patient and device selection, lack of standardized trial endpoints and high rates of crossovers; these issues must be carefully considered and evaluated. In light of recent trial failures, we aim to summarize the challenges associated with performing randomized controlled trials of percutaneous axial flow pumps in patients experiencing acute myocardial infarction complicated by cardiogenic shock, and to suggest potential means of overcoming them.
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http://dx.doi.org/10.1016/j.acvd.2020.02.001DOI Listing
September 2020

Etiology and Prognosis of Cardiogenic Shock in a Secondary Center without Surgical Back-Up.

Cardiol Res Pract 2019 9;2019:3869603. Epub 2019 Dec 9.

USIC et Centre Hémodynamique, Institut Cœur Poumon, Centre Hospitalier Régional et Universitaire de Lille, Faculté de Médecine de l'Université de Lille, INSERM UMR1011, Lille F-59000, France.

Background: Cardiogenic shock (CS) remains a major challenge in contemporary cardiology. Data regarding CS etiologies and their prognosis are limited and mainly derived from tertiary referral centers.

Aims: To investigate the current etiologies of cardiogenic shock and their associated short- and long-term outcomes in a secondary center without surgical back-up.

Methods: We performed an observational prospective monocenter study. All patients admitted for a first episode of CS related to left ventricular dysfunction were enrolled. The definition of CS was consistent with the European Society of Cardiology guidelines. Patients were followed for 6 months. Etiologies were analyzed, and survival rates derived from Kaplan-Meier estimates were compared with the log-rank test.

Results: Between January 2015 and January 2016, 152 patients were included. The first most common cause of CS was acute decompensation of chronic heart failure (CHF). Acute coronary syndromes (ACS) were the second most common cause of CS (35.4%). At one month, the all-cause mortality rate was 39.5% and was similar between ACS and CHF (43% vs 35%, respectively; =0.7). In a landmark analysis between 1 and 6 months, we observed a significantly higher mortality in patients with CHF than in patients with ACS (18% vs. 0%; =0.01).

Conclusions: In the present registry, acute decompensation of chronic heart failure was the most common cause of CS, while ACS complicated by CS was the second most common cause. Of importance, acute decompensation of CHF was associated with a significantly worse outcome than ACS in the long term.
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http://dx.doi.org/10.1155/2019/3869603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925788PMC
December 2019

High incidence of atrial fibrillation in patients treated with ibrutinib.

Open Heart 2019;6(1):e001049. Epub 2019 May 8.

Department of Cardiology, Unit of Heart Failure and Valvular Heart Diseases, Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Hôpital Nord, Aix-Marseille I University, Marseille, France.

Objective: Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.

Methods: A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.

Results: 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.

Conclusions: This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.
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http://dx.doi.org/10.1136/openhrt-2019-001049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519413PMC
May 2019

Dynamic iron status after acute heart failure.

Arch Cardiovasc Dis 2019 Jun - Jul;112(6-7):410-419. Epub 2019 Apr 18.

Heart Failure and Valvular Heart Disease Unit, Mediterranean University Cardio-Oncology (MEDI-CO) Centre, Department of Cardiology, Aix-Marseille University, hôpital Nord, AP-HM, chemin des Bourrely, 13015 Marseille, France; Inserm 1263, INRA, centre de recherche cardiovasculaire et nutrition (C2VN), Aix-Marseille University, 13385 Marseille, France. Electronic address:

Background: Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment.

Aim: To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF.

Methods: Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines.

Results: The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67-83%), 61% (95% CI: 52-70%), and 70% (95% CI: 61-79%) (P=0.008). Changes in prevalence were significant between admission and discharge (P=0.0018). Despite a similar ID prevalence at admission and 1 month (P=0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ=0.30; P=0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month.

Conclusions: Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients.
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http://dx.doi.org/10.1016/j.acvd.2019.02.002DOI Listing
December 2019

The hidden side of oral thrombin inhibitors.

Int J Cardiol 2019 01 6;274:186-187. Epub 2018 Sep 6.

Aix-Marseille University, APHM, Cardiology Department, Hospital Nord, Marseille, France.

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http://dx.doi.org/10.1016/j.ijcard.2018.09.001DOI Listing
January 2019

Doppler echocardiography for assessment of systemic vascular resistances in cardiogenic shock patients.

Eur Heart J Acute Cardiovasc Care 2020 Mar 20;9(2):102-107. Epub 2018 Aug 20.

Intensive Care Unit, Aix-Marseille University, France.

Objective: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock.

Methods: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment.

Results: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m/cm and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m/cm. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution (=0.86, 95% confidence interval (CI) 0.74, 0.93; <0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was -111.95 dynes.s.m/cm (95% CI -230.06, 6.16). Limits of agreement were -785.86, 561.96.

Conclusions: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.
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http://dx.doi.org/10.1177/2048872618795514DOI Listing
March 2020

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

Crit Care Med 2018 09;46(9):e874-e880

Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.

Objectives: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock.

Design: Prospective observational study.

Setting: Monocentric, Hopital Nord, Marseille, France.

Subjects: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16).

Interventions: None.

Measurements And Main Results: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005).

Conclusions: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.
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http://dx.doi.org/10.1097/CCM.0000000000003252DOI Listing
September 2018

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

Purinergic Signal 2018 06 6;14(2):191-199. Epub 2018 Apr 6.

Department of Cardiology, Hopital Nord, Marseille, France.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.
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http://dx.doi.org/10.1007/s11302-018-9604-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940631PMC
June 2018

Outcomes and costs associated with two different lead-extraction approaches: a single-centre study.

Europace 2017 Oct;19(10):1710-1716

Service de Cardiologie-Rythmologie, CHU la Timone, Marseille 13385, France.

Aims: We sought to compare outcomes and costs of a stepwise approach to transvenous lead extraction (TLE) involving laser-assisted sheaths or mechanical polypropylene sheaths, with/without crossover.

Methods And Results: We prospectively included patients who underwent TLE (between August 2013 and December 2014) as part of a stepwise approach involving simple traction, lead snaring, and sheath-assisted dissection; all of these patients underwent a first-line polypropylene-sheath-extraction approach (Group A). The comparison group (Group B) was consecutive patients who had undergone TLE before August 2013, during which laser-assisted sheath extraction was the first-line approach. The number of patients in Group B was adjusted to match the number who eventually needed sheaths in Group A. Procedural data, outcomes, and costs were compared between groups (comparison of approaches) and in patients who needed sheath-assisted extraction (comparison of techniques). Overall, 521 leads were extracted (131 patients in Group A, 104 in Group B). Radiological and clinical success rates were similar; crossover from polypropylene to laser sheaths was needed in 10 patients in Group A (vs. none in Group B). Radiological (P< 0.001) and clinical (P= 0.01) success rates were higher and were achieved with a lower radiation exposure (P= 0.03) with laser sheaths in patients (60 in each group) who needed sheath-assisted extraction. Complication rates were similar in both groups (P= 0.66) but two deaths occurred in Group B. The laser approach had higher material cost (P= 0.002).

Conclusions: Although laser-assisted TLE was more effective than polypropylene sheath-assisted TLE, the latter was associated with fewer complications and was more cost-effective.
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http://dx.doi.org/10.1093/europace/euw254DOI Listing
October 2017

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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http://dx.doi.org/10.1016/j.acvd.2016.04.001DOI Listing
January 2017

Comparison of Ticagrelor Versus Prasugrel to Prevent Periprocedural Myonecrosis in Acute Coronary Syndromes.

Am J Cardiol 2015 Aug 9;116(3):339-43. Epub 2015 May 9.

UMR MD2, Aix-Marseille Université, Marseille, France; Pole RUSH, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Guidelines recommend a ticagrelor loading dose (LD) before PCI or a prasugrel LD at the time of percutaneous coronary intervention (PCI) in intermediate and high-risk non-ST-elevation acute coronary syndrome (NSTE-ACS). However, achieving an optimal PR inhibition at the time of PCI is critical to prevent adverse events and depends on the timing of LD intake in relation to PCI. We aimed to compare the rate of myonecrosis related to PCI in patients with NSTE-ACS receiving ticagrelor pretreatment versus prasugrel at the time of intervention. We prospectively randomized 213 patients with NSTE-ACS to a 180 mg of ticagrelor LD given as soon as possible after admission and before PCI or to a 60 mg LD of prasugrel given at the time of PCI. The primary end point was the rate of periprocedural myonecrosis as defined by an increase of >5 times the ninety-ninth percentiles in troponin-negative patients or a 20% increase in troponin-positive patients. The 2 groups were similar regarding baseline characteristics including clinical setting (p = 0.2). Procedural characteristics were also identical including the number of treated vessels and stenting procedures. Patients in the prasugrel group more often required emergent PCI (p = 0.001). Patients in the ticagrelor group had less periprocedural myonecrosis compared with those in the prasugrel group (19.8% vs 38.3%; p = 0.03). The rate of major adverse cardiovascular events and Bleeding Academic Research Consortium ≥2 at 1-month follow-up was low and similar between the 2 groups. In conclusion, a ticagrelor LD as soon as possible before PCI is superior to prasugrel at the time of PCI to prevent periprocedural myonecrosis in NSTE-ACS.
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http://dx.doi.org/10.1016/j.amjcard.2015.04.050DOI Listing
August 2015

COMparison of Platelet reactivity following prAsugrel and ticagrelor loading dose in ST-Segment elevation myocardial infarctION patients: The COMPASSION study.

Platelets 2015 2;26(6):570-2. Epub 2014 Oct 2.

Service de Cardiologie, Centre Hospitalo-Universitaire Nord, Assistance-Publique Hôpitaux de Marseille , Chemin des Bourrely, Marseille , France .

Prasugrel and ticagrelor are potent P2Y12-ADP receptor antagonists which are superior to clopidogrel in acute coronary syndromes. To date no clinical trial directly compared these two drugs. Platelet reactivity correlates with ischemic and bleeding events in patients undergoing percutaneous coronary intervention. Recent pharmacological studies have observed a delayed onset of action of these two drugs in ST-segment elevation myocardial infarction (STEMI). We provide the first adequately powered pharmacological study comparing PR following ticagrelor and prasugrel loading dose (LD) in STEMI patients when the maximal biological effect is reached. In the present study, ticagrelor was associated with a lower rate of high on-treatment PR compared to prasugrel.
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http://dx.doi.org/10.3109/09537104.2014.959914DOI Listing
May 2016

Effect of ticagrelor-related dyspnea on compliance with therapy in acute coronary syndrome patients.

Int J Cardiol 2014 Apr 22;173(1):120-1. Epub 2014 Feb 22.

Département de Cardiologie Centre Hospitalo-Universitaire Nord, Aix-Marseille Univ., Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.02.028DOI Listing
April 2014

Assessing post-treatment platelet reactivity: a focus on patient selection and setting.

Expert Rev Cardiovasc Ther 2013 Nov 2;11(11):1557-66. Epub 2013 Sep 2.

Département de Cardiologie, Hôpital Universitaire Nord, Marseille, France.

Dual antiplatelet therapy is critical to inhibit platelet reactivity in order to prevent ischemic recurrences in stented patients. However, studies have observed a variable blockade of the P2Y12 adenosine diphosphate receptor between patients following clopidogrel intake. This interindividual variability in the biological response is not uncommon with clopidogrel (about 50%) and even prasugrel (20%). High on-treatment platelet reactivity (HTPR) is correlated with thrombotic events following percutaneous coronary intervention. Several studies suggested that tailoring of antiplatelet therapy based on platelet reactivity (PR) monitoring could safely reduce the rate of major adverse cardiovascular events in HTPR patients. In addition, low on-treatment PR was recently associated with bleeding events both in patients treated with prasugrel and clopidogrel. Of importance, bleedings are associated with a poor prognosis in stented patients. Overall, the potential of PR monitoring to individualize antiplatelet therapy might benefit stented patients by reducing both ischemic and bleeding risks. However, such strategies remain to be evaluated in adequately designed large-scale randomized clinical trials.
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http://dx.doi.org/10.1586/14779072.2013.820440DOI Listing
November 2013