Publications by authors named "Marc Laine"

78 Publications

Antithrombotic strategies in elderly patients with acute coronary syndrome.

Arch Cardiovasc Dis 2021 Mar 23;114(3):232-245. Epub 2021 Feb 23.

Mediterranean Association for research and studies in cardiology (MARS cardio), Centre for cardiovascular and nutrition research, AP-HM, Aix-Marseille University, INSERM 1263, INRA 1260, 13015 Marseille, France; Cardiology department, Hôpital Nord, 13015 Marseille, France; Mediterranean Association for research and studies in cardiology (MARS cardio), 13015 Marseille, France.

Elderly patients represent a growing proportion of the acute coronary syndrome population in Western countries. However, their frequent atypical symptoms at presentation often lead to delays in management and to misdiagnosis. Furthermore, their prognosis is poorer than that of younger patients because of physiological changes in platelet function, haemostasis and fibrinolysis, but also a higher proportion of comorbidities and frailty, both of which increase the risk of recurrent thrombotic and bleeding events. This complex situation, with ischaemic and haemorrhagic risk factors often being intertwined, may lead to confusion about the required treatment strategy, sometimes resulting in inadequate management or even to therapeutic nihilism. It is therefore critical to provide a comprehensive overview of our understanding of the pathophysiological processes underlying acute coronary syndrome in elderly patients, and to summarise the results from the latest clinical trials to help decision making for these high-risk patients.
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http://dx.doi.org/10.1016/j.acvd.2020.12.002DOI Listing
March 2021

Impella CP Implantation during Cardiopulmonary Resuscitation for Cardiac Arrest: A Multicenter Experience.

J Clin Med 2021 Jan 18;10(2). Epub 2021 Jan 18.

Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix-Marseille University, 13015 Marseille, France.

Background: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown.

Methods: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival.

Results: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min ( = 0.035 and = 0.008, respectively).

Conclusions: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.
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http://dx.doi.org/10.3390/jcm10020339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831079PMC
January 2021

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

On-Ticagrelor Platelet Reactivity and Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

Thromb Haemost 2020 Dec 1. Epub 2020 Dec 1.

Intensive care Unit, Department of Cardiology, Assistance publique des hopitaux de Marseille, Hôpital Nord, Aix Marseille University, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Marseille, France.

Background:  A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting.

Objectives:  We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI.

Methods:  We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization.

Results:  We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE ( = 0.12 and  = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR).

Conclusion:  On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.
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http://dx.doi.org/10.1055/a-1326-5110DOI Listing
December 2020

Acute Coronary Syndrome in the Era of SARS-CoV-2 Infection: A Registry of the French Group of Acute Cardiac Care.

CJC Open 2021 Mar 11;3(3):311-317. Epub 2020 Nov 11.

Univ Paris Est Créteil, INSERM, IMRB, Créteil, France.

Background: In this study, we aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection who were referred for acute coronary syndrome (ACS) during the peak of the pandemic in France.

Methods: We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south, and north of France), all performing primary percutaneous coronary intervention.

Results: The study included 237 patients (67 ± 14 years old; 69% male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2-associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen > 6 L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%;  = 0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs 6.6%; < 0.001). The presence of significant coronary artery disease and culprit artery occlusion in SARS-CoV-2 patients respectively, was 92% and 69.4% for those with STEMI, and 50% and 15.5% for those with NSTEMI. Percutaneous coronary intervention was performed in the same percentage of STEMI (84.6%) and NSTEMI (84.8%) patients, regardless of SARS-CoV-2 infection, but no-reflow (19.2% vs 3.3%; < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared with noninfected patients (26.9% vs 6.2%; < 0.001).

Conclusions: In this registry, ACS in SARS-CoV-2 patients presented with high a percentage of cardiac arrest on admission, high incidence of no-reflow, and high in-hospital mortality.
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http://dx.doi.org/10.1016/j.cjco.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657607PMC
March 2021

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

Anakinra for severe forms of COVID-19.

Lancet Rheumatol 2020 Oct 7;2(10):e586. Epub 2020 Aug 7.

Department of Cardiology, Assistance Publique des Hôpitaux de Marseille, Hôpital Nord, Marseille 13015, France.

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http://dx.doi.org/10.1016/S2665-9913(20)30272-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413647PMC
October 2020

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Am Heart J 2020 07 30;225:19-26. Epub 2020 Apr 30.

Aix-Marseille Univ, Intensive cardiac care unit, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.
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http://dx.doi.org/10.1016/j.ahj.2020.04.013DOI Listing
July 2020

Optimal Timing of Intervention in NSTE-ACS Without Pre-Treatment: The EARLY Randomized Trial.

JACC Cardiovasc Interv 2020 04;13(8):907-917

Aix-Marseille Université, Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Mediterranean Association for Research and Studies in Cardiology, Marseille, France; Centre for CardioVascular and Nutrition Research, INSERM 1263, INRA 1260, Marseille, France. Electronic address:

Objectives: The aim of this study was to compare a delayed and a very early invasive strategy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) without pre-treatment.

Background: The optimal delay of the invasive strategy in patients with NSTE-ACS remains debated and has never been investigated in patients not pre-treated with P2Y-adenosine diphosphate receptor antagonists.

Methods: A prospective, open-label, randomized controlled trial was conducted. Altogether, 741 patients presenting with intermediate- or high-risk NSTE-ACS intended for an invasive strategy were included. The modified intention-to-treat analysis was composed of 709 patients after 32 withdrew consent. Patients were randomized 1:1 to the delayed invasive group (DG) (n = 363) with coronary angiography (CA) performed 12 to 72 h after randomization or the very early invasive group (EG) (n = 346) with CA within 2 h. No pre-treatment with a loading dose of a P2Y-adenosine diphosphate receptor antagonist was allowed before CA. The primary endpoint was the composite of cardiovascular death and recurrent ischemic events at 1 month, as determined by a blinded adjudication committee.

Results: Most patients had high-risk NSTE-ACS in both groups (93% in the EG vs. 92.5% in the DG). The median time between randomization and CA was 0 h (interquartile range [IQR]: 0 to 1 h) in the EG group and 18 h (IQR: 11 to 23 h) in the DG. The primary endpoint rate was significantly lower in the EG (4.4% vs. 21.3% in the DG; hazard ratio: 0.20; 95% confidence interval: 0.11 to 0.34; p < 0.001), driven by a reduction in recurrent ischemic events (19.8% vs. 2.9%; p < 0.001). No difference was observed for cardiovascular death.

Conclusions: Without pre-treatment, a very early invasive strategy was associated with a significant reduction in ischemic events at the time of percutaneous coronary intervention in patients with intermediate- and high-risk NSTE-ACS. (Early or Delayed Revascularization for Intermediate and High-Risk Non ST-Elevation Acute Coronary Syndromes; NCT02750579).
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http://dx.doi.org/10.1016/j.jcin.2020.01.231DOI Listing
April 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 prevalence of mutations in perilipin 1 in patients with precocious acute coronary syndrome.

Atherosclerosis 2020 01 12;293:86-91. Epub 2019 Dec 12.

MARS Cardio, Mediterranean Association for Research and Studies in Cardiology, Intensive Care Unit, Hospital Nord, Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France. Electronic address:

Background And Aims: Genetic partial lipodystrophies are rare heterogeneous disorders characterized by abnormalities of fat distribution and associated metabolic complications including a predisposition for atherosclerotic cardiovascular disease. We hypothesized that the milder forms of these diseases might be underdiagnosed and might result in early acute coronary syndrome (ACS) as the first sign of the pathology.

Methods: We performed targeted sequencing on a panel of 8 genes involved in genetic lipodystrophy for 62 patients with premature ACS, and selected heterozygous missense variations with low frequency. To confirm those results, we analyzed a second independent group of 60 additional patients through Sanger sequencing, and compared to a control group of 120 healthy patients.

Results: In the first cohort, only PLIN1 exhibited variants in more than 1 patient. In PLIN1, 3 different variants were found in 6 patients. We then analyzed PLIN1 sequence in the second cohort with premature ACS and found 2 other patients. Altogether, 8 patients were carriers of 4 different mutations in PLIN1. The variant frequencies in the total cohort of 122 patients were compared to frequencies observed in a local control cohort and in 2 different public databases showing a significant difference between patient vs control group frequencies for two mutations out of 4 (c.245C > T p = 10; c.839G > A p = 0.014).

Discussion: This is the first study that identifies a high frequency of potential pathogenic mutations in PLIN1 related to early onset ACS. These findings could contribute to the prevention and care of precocious ACS in families carrying those mutations.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.12.002DOI Listing
January 2020

Letter by Delmas et al Regarding Article, "Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock: Matched-Pair IABP-SHOCK II Trial 30-Day Mortality Analysis".

Circulation 2019 09 9;140(11):e555-e556. Epub 2019 Sep 9.

Aix-Marseille University, APHM, Mediterranean Association for Research and Studies in Cardiology, Centre for CardioVascular and Nutrition Research, INSERM 1263, INRA 1260, Hopital Nord, Cardiology Department, Marseille, France (M.L., L.B.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041272DOI Listing
September 2019

Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

J Thromb Haemost 2019 12 27;17(12):2188-2195. Epub 2019 Jul 27.

Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix-Marseille University, Marseille, France.

Background: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.

Objectives: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).

Methods: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.

Results: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.

Conclusion: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.
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http://dx.doi.org/10.1111/jth.14592DOI Listing
December 2019

Is there still a role for the intra-aortic balloon pump in the management of cardiogenic shock following acute coronary syndrome?

Arch Cardiovasc Dis 2019 Dec 24;112(12):792-798. Epub 2019 Jun 24.

Aix-Marseille Université, AP-HM, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Centre for CardioVascular and Nutrition research (C2VN), Inserm 1263, INRA 1260, Cardiology Department, Hôpital Nord, 13000 Marseille, France.

The intra-aortic balloon pump has been widely used in the management of cardiogenic shock. Reducing cardiac afterload and myocardial oxygen consumption, and improving coronary blood flow, this safe and simple mechanical circulatory support has been considered the cornerstone of cardiogenic shock management for decades. However, because it failed to provide any clinical benefit in recent randomized trials, the latest guidelines discourage its routine use in this clinical setting. Moreover, new percutaneous circulatory supports providing greater haemodynamic improvement have recently been developed. Thus, intra-aortic balloon pump use has declined considerably in this clinical setting. However, the device does retain a minor role in cardiogenic shock management - mainly in the setting of mechanical complication of acute coronary syndrome, and for left ventricular unloading in patients treated with extracorporeal life support.
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http://dx.doi.org/10.1016/j.acvd.2019.04.009DOI Listing
December 2019

Letter by Laine et al Regarding Article, "Antithrombotic Agents: New Directions in Antithrombotic Therapy".

Circ Res 2019 06 6;124(12):e117-e118. Epub 2019 Jun 6.

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

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http://dx.doi.org/10.1161/CIRCRESAHA.119.315213DOI Listing
June 2019

An Unusual Acute Coronary Syndrome Due to a Septic Embolism: A Case Presentation and Review of Revascularization Strategies.

J Invasive Cardiol 2019 Jun;31(6):E148-E153

Hôpital Universitaire Nord, Chemin des Bourrely, 13015 Marseille France.

Treatment of acute coronary syndromes secondary to septic coronary valvular embolism in endocarditis patients remains unclear. Several revascularization strategies have been described, including thromboaspiration, stent implantation, balloon angioplasty, and surgical intervention. We herein present an illustration of an atypical case of an acute coronary syndrome related to a coronary bifurcation occlusion due to a septic embolism in a patient presenting with infective endocarditis. We also summarized previous similar cases and their management.
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June 2019

Response to the letter to the editor: anticoagulant activity of bivalirudin.

Expert Opin Pharmacother 2019 08 15;20(11):1415. Epub 2019 May 15.

a Department of Cardiology, Intensive care unit , Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord , Marseille , France.

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http://dx.doi.org/10.1080/14656566.2019.1616427DOI Listing
August 2019

Letter by Bonello et al Regarding Article, "Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: VERDICT Randomized Controlled Trial".

Circulation 2019 05;139(20):e959-e960

Aix-Marseille Université, MARS Cardio, Mediterraneen Association for Research and Studies in Cardiology, INSERM UMR-S 1076, Vascular Research Center of Marseille, France (G.L.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037810DOI Listing
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

Bivalirudin during percutaneous coronary intervention in acute coronary syndromes.

Expert Opin Pharmacother 2019 02 4;20(3):295-304. Epub 2018 Dec 4.

a Department of Cardiology , Intensive care unit, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord , Marseille , France.

Introduction: Anticoagulant therapy is critical to prevent ischemic recurrences and complications in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Unfractionated heparin (UFH), an injectable anticoagulant has several limitations: lack of predictability of its biological efficacy, platelets activation, heparin-induced thrombopenia and bleedings. Bivalirudin, a synthetic direct thrombin inhibitor has biological properties that promised better clinical outcome in ACS patients undergoing PCI.

Areas Covered: The present review aimed to summarize two decades of randomized clinical trials that compared bivalirudin to UFH in ACS patients treated with PCI. Early trials highlighted a reduction of bleedings with bivalirudin compared to UFH in combination with glycoprotein inhibitors (GPI). Recent studies questioned this reduction given that GPI are less and less used during PCI. Further, trials raised concerns about the risk of stent thrombosis in patients treated with bivalirudin. In light of this data, bivalirudin has been downgraded in international guidelines and appears as a second line anticoagulant agent after UFH.

Expert Opinion: The highly questioned reduction of bleedings under bivalirudin and the potential risk of stent thrombosis are unwarranted. Based on clinical trials, UFH has no equivalent in terms of anticoagulation in ACS patients undergoing PCI.
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http://dx.doi.org/10.1080/14656566.2018.1551361DOI Listing
February 2019

OCT Analysis of Very Early Strut Coverage of the Synergy Stent in Non-ST Segment Elevation Acute Coronary Syndrome Patients.

J Invasive Cardiol 2019 01 11;31(1):10-14. Epub 2018 Nov 11.

Service de Cardiologie, Hôpital Nord Chemin des Bourrely, 13015, Marseille, France.

Objectives: Early endothelialization of drug-eluting stent (DES) is a major challenge to reduce the risk of stent thrombosis and the duration of dual-antiplatelet therapy (DAPT) in high bleeding-risk patients. The aim of the present study is to evaluate very early strut coverage with optical coherence tomography (OCT) of the Synergy stent (Boston Scientific) at 1 month in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients.

Methods: This substudy of the EARLY trial prospectively included NSTE-ACS patients treated with the Synergy DES. OCT analysis of the Synergy stent was performed during a staged PCI of additional lesions at 1 month. The primary endpoint was the percentage of covered struts assessed with OCT at 1 month.

Results: Twenty-four patients were included, with a mean stent length of 35.9 ± 10.1 mm per patient. The rate of covered struts was 78.5% out of 3839 struts analyzed. Nineteen patients (79.2%) had at least 70% of their struts covered. The average neointimal thickness was 0.0508 ± 0.016 mm.

Conclusions: In NSTE-ACS patients undergoing culprit percutaneous coronary intervention with the Synergy stent, the rate of covered struts at 1 month was 78.5%. This rapid coverage is in line with the results of clinical trials demonstrating the safety of short-duration DAPT in selected patients who are at high bleeding risk and treated with new-generation DES options.
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January 2019

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

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

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

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

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

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

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

Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

Thromb Haemost 2018 Oct 20;118(10):1839-1846. Epub 2018 Sep 20.

Department of Public Health (BIOSTIC), Aix-Marseille University, Hôpital de la Timone, Marseille, France.

Background:  The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown.

Objective:  We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS.

Methods:  We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings.

Results:  We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies ( = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79-0.99;  = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95-1.27;  = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77-0.93;  < 0.001), including a reduction in mortality (pHR = 0.82) (95% CI: 0.7-0.96;  = 0.016).

Conclusion:  Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.
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http://dx.doi.org/10.1055/s-0038-1669426DOI Listing
October 2018

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

Specific Pharmacological Profile of A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease.

J Am Heart Assoc 2018 04 13;7(8). Epub 2018 Apr 13.

UMR MD2, Aix-Marseille University, Marseille, France.

Background: The rapid and reliable exclusion of myocardial revascularization is a major unmet clinical need in patients with suspected coronary artery disease (CAD) and non-contributive electrocardiography and troponin. Non-invasive tests have high rates of false positives and negatives, and there is no biomarker to assess myocardial ischemia. The presence of spare adenosine A receptors (AR)-characterized by a high dissociation constant/half maximal effective concentration (K/EC) ratio-expressed on peripheral blood mononuclear cells (PBMC) has been associated with ischemia during exercise stress testing in patients with CAD. In this work, we investigated the diagnostic accuracy of spare AR versus fractional flow reserve (FFR) in patients with suspected CAD.

Methods And Results: Sixty patients with suspected CAD, but non-contributive electrocardiography and troponin, were consecutively enrolled in this prospective study. The binding (K), functional response (cyclic adenosine monophosphate [cAMP] production; EC) on PBMC AR were compared with FFR results. Patients were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13) or stenosis <20% (n=4); 21 with CAD and non-significant FFR (group 2); and 22 with CAD and significant FFR (group 3). Median K/EC was 6-fold higher in group 3 (4.20; interquartile range: 2.81-5.00) than group 2 (0.66; interquartile range: 0.47-1.25) and 7-fold higher than group 1 (0.60; interquartile range: 0.30-0.66).

Conclusions: In patients with suspected CAD and non-contributive electrocardiography and troponin, the absence of spare AR on PBMC may help to rule out myocardial ischemia.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.
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http://dx.doi.org/10.1161/JAHA.117.008290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015402PMC
April 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

To Have and Have Not: Intrinsic Platelet Hyperreactivity?

J Am Heart Assoc 2018 03 3;7(5). Epub 2018 Mar 3.

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

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http://dx.doi.org/10.1161/JAHA.118.008750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866346PMC
March 2018

Impact of the time-to-treatment concept on the outcome of acute heart failure: A pilot study.

Arch Cardiovasc Dis 2018 Apr 28;111(4):270-275. Epub 2018 Feb 28.

Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, Mediterranean Cardio-Oncology University Centre (MEDI-CO Centre), Aix-Marseille University, AP-HM, 13015 Marseille, France; Centre for CardioVascular and Nutrition research (C2VN), Inserm 1263, Inra 1260, Aix-Marseille University, 13385 Marseille, France. Electronic address:

Background: An optimal maximum time of 60minutes has been recommended in recent guidelines for the first evaluation and treatment of patients with acute heart failure (AHF); however, this has not been tested prospectively.

Aim: To analyze the impact of a time-to-treatment (TTT) strategy of <60minutes on the in-hospital outcome of patients with AHF.

Methods: During a single 1-month period, we consecutively enrolled all patients hospitalized with AHF in a prospective cohort. In this pilot study, TTT was defined as the time between the first medical contact to the onset of the first medical intervention. The primary outcome was a composite including in-hospital death or worsening AHF.

Results: Of the 74 patients included, 23 (31%) had a TTT of <60minutes. Although these patients were more likely to have a more severe episode of AHF, the primary outcome occurred only in patients with a TTT of ≥60minutes. The primary outcome was significantly associated with a TTT of ≥60minutes (P=0.036), low systolic blood pressure (P<0.01), rales more than halfway up the lung fields (P=0.02), infectious precipitating factor (P=0.04) and high serum concentrations of B-type natriuretic peptide (P<0.01) and urea (P=0.03). No significant differences were observed in the rate of treatment-induced acute renal insufficiency or in the long-term rates of death or rehospitalization for heart failure according to TTT.

Conclusions: This study suggests that the recently recommended TTT strategy of <60minutes in the setting of AHF might be associated with a better prognosis during hospitalization. Further large prospective works are needed to confirm these preliminary results, and to define more precisely which types of AHF could benefit from this strategy.
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http://dx.doi.org/10.1016/j.acvd.2017.11.005DOI Listing
April 2018