Publications by authors named "Laurent Bonello"

197 Publications

Pump flow setting and assessment of unloading in clinical practice.

Eur Heart J Suppl 2021 Mar 27;23(Suppl A):A23-A26. Epub 2021 Mar 27.

Department of Anesthesia and Intensive Care, IRCCS ISMETT, UPMC Italy, Via Ernesto Tricomi, 5, 90127 Palermo, Italy.

The rationale for mechanical circulatory support (MCS) in cardiogenic shock is to restore cardiac output in selected patients when critically low or in case of refractory cardiac arrest. Furthermore, an MCS device that moves blood from either the left atrium or the left ventricle to the systemic circulation will potentially unload the ventricle. These devices are used alone or in combination with venoarterial extracorporeal membrane oxygenation (VA-ECMO). If a left-sided Impella device is used, it should be run at the highest possible performance level during treatment while avoiding suction events. When combined with VA-ECMO, the Impella device should be run at a lower performance level, ensuring sufficient left ventricular emptying but avoiding suction. Continuous monitoring is pivotal and patients managed outside the catheterization laboratory should be monitored with an arterial line, a central venous catheter, frequent use of pulmonary artery catheters and regular imaging by transthoracic echocardiogram.
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http://dx.doi.org/10.1093/eurheartj/suab004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005883PMC
March 2021

Cardioprotective shock management: monitoring and supportive therapies.

Eur Heart J Suppl 2021 Mar 27;23(Suppl A):A3-A9. Epub 2021 Mar 27.

Intensive Care Unit, University Hospital Basel, University of Basel, Petersgraben 5, 4031 Basel, Switzerland.

Cardiogenic shock is a highly lethal syndrome, leading to rapid death or secondary multiorgan damage, but current shock therapies, including mechanical support devices, also have a significant side effect profile. The overarching goal of shock therapy is ensuring long-term survival with good quality of life. This implies averting death, modifying the disease course by promoting heart recovery and avoiding additional cardiac damage, protecting other organs, and circumventing complications. Monitoring and supportive therapies are subordinate to these goals. Rather than merely following preconceived notions, the rapid evolution in mechanical support technology requires iterative and critical review of the benefits of current procedures, protocols and drugs in view of their overall contribution to the therapeutic goals. This article discusses various monitoring and supportive pharmaceutical modalities typically used in patients with cardiogenic shock requiring mechanical support.
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http://dx.doi.org/10.1093/eurheartj/suab001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005889PMC
March 2021

IMPELLA or Extracorporeal Membrane Oxygenation for Left Ventricular Dominant Refractory Cardiogenic Shock.

J Clin Med 2021 Feb 14;10(4). Epub 2021 Feb 14.

Cardiac Intensive Care Unit, Heart and Lung Institute, CHU Lille, 59000 Lille, France.

Mechanical circulatory support (MCS) devices are effective tools in managing refractory cardiogenic shock (CS). Data comparing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and IMPELLA are however scarce. We aimed to assess outcomes of patients implanted with these two devices and eligible to both systems. From 2004 to 2020, we retrospectively analyzed 128 patients who underwent VA-ECMO or IMPELLA in our institution for refractory left ventricle (LV) dominant CS. All patients were eligible to both systems: 97 patients were first implanted with VA-ECMO and 31 with IMPELLA. The primary endpoint was 30-day all-cause death. VA-ECMO patients were younger (52 vs. 59.4, = 0.006) and had a higher lactate level at baseline than those in the IMPELLA group (6.84 vs. 3.03 mmol/L, < 0.001). Duration of MCS was similar between groups (9.4 days vs. 6 days in the VA-ECMO and IMPELLA groups respectively, = 0.077). In unadjusted analysis, no significant difference was observed between groups in 30-day mortality: 43.3% vs. 58.1% in the VA-ECMO and IMPELLA groups, respectively ( = 0.152). After adjustment, VA-ECMO was associated with a significant reduction in 30-day mortality (HR = 0.25, = 0.004). A higher rate of MCS escalation was observed in the IMPELLA group: 32.3% vs. 10.3% ( = 0.003). In patients eligible to either VA-ECMO or IMPELLA for LV dominant refractory CS, VA-ECMO was associated with improved survival rate and a lower need for escalation.
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http://dx.doi.org/10.3390/jcm10040759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918655PMC
February 2021

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

Early Evaluation of Patients on Axial Flow Pump Support for Refractory Cardiogenic Shock is Associated with Left Ventricular Recovery.

J Clin Med 2020 Dec 21;9(12). Epub 2020 Dec 21.

Intensive Cardiac Care Unit, Department of Cardiology, Rangueil University Hospital, 31059 Toulouse, France.

We investigated prognostic factors associated with refractory left ventricle (LV) failure leading to LV assist device (LVAD), heart transplant or death in patients on an axial flow pump support for cardiogenic shock (CS). Sixty-two CS patients with an Impella CP or 5.0 implant were retrospectively enrolled, and clinical, biological, echocardiographic, coronarographic and management data were collected. They were compared according to the 30-day outcome. Patients were mainly male ( = 55, 89%), 58 ± 11 years old and most had no history of heart failure or coronary artery disease (70%). The main etiology of CS was acute coronary syndrome ( = 57, 92%). They presented with severe LV failure (LV ejection fraction (LVEF) 22 ± 9%), organ malperfusion (lactate 3.1 ± 2.1 mmol/L), and frequent use of inotropes, vasopressors, and mechanical ventilation (59, 66 and 30%, respectively). At 24 h, non-recovery was associated with higher total bilirubin (odds ratios (OR) 1.07 (1.00-1.14); = 0.039), lower LVEF (OR 0.89 (0.81-0.96); = 0.006) and the number of administrated amines (OR 4.31 (1.30-14.30); = 0.016). Early evaluation in patients with CS with an axial flow pump implant may enable the identification of factors associated with an unlikely recovery and would call for early screening for LVAD or heart transplant.
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http://dx.doi.org/10.3390/jcm9124130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767477PMC
December 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

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

Utility and safety of coronary angiography in patients with acute infective endocarditis who required surgery.

J Thorac Cardiovasc Surg 2020 Oct 7. Epub 2020 Oct 7.

USIC et Centre Hémodynamique, Institut Coeur Poumon, Centre Hospitalier Universitaire de Lille, Lille, France; Faculté de Médecine de l'Université de Lille, Lille, France; INSERM UMR 1011, Institut Pasteur de Lille, Lille, France; FACT (French Alliance for Cardiovascular Trials), Paris, France. Electronic address:

Objectives: To assess the benefit/risk ratio to perform a coronary angiography (CA) before surgery for infective endocarditis (IE).

Methods: We conducted a single-center prospective registry including 272 patients with acute IE intended for surgery and compared patients who underwent a preoperative CA (n = 160) with those who did not (n = 112). A meta-analysis of 3 observational studies was also conducted and included 551 patients: 342 who underwent a CA and 209 who did not.

Results: In our registry, combined bypass surgery (CABG) was performed in 17% of the patients with preoperative CA. At 2 years, the rate of the primary composite end point (all-cause death, new systemic embolism, stroke, new hemodialysis) was similar in the CA (38%) and no-CA (37%) groups. In-hospital and 2-year individual end points were all similar between groups. There were only 2 episodes of systemic embolism after CA and only one possibly related to a vegetation dislodgement. In the meta-analysis, combined CABG was performed in 18% of the patients with preoperative CA. All-cause death was similar in both groups: odds ratio, 0.98 [0.62-1.53], P = .92. Only 5 cases of systemic embolism possibly related to a vegetation dislodgement were reported. New hemodialysis was numerically more frequent in the CA group: odds ratio, 1.68 [0.79-3.58] (18% vs 14%, P = .18).

Conclusions: In daily practice, two-thirds of the patients with acute IE who required surgery have a preoperative CA leading to a combined CABG in 18% of the patients. Our results suggest that to perform a preoperative CA in this context is not associated with improved prognosis.
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http://dx.doi.org/10.1016/j.jtcvs.2020.08.117DOI Listing
October 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

Reperfusion therapies in pulmonary embolism-state of the art and expert opinion: A position paper from the "Unité de Soins Intensifs de Cardiologie" group of the French Society of Cardiology.

Arch Cardiovasc Dis 2020 Nov 22;113(11):749-759. Epub 2020 Sep 22.

Intensive Care Unit, Department of Cardiology, Hôpital Nord, AP-HM, Aix-Marseille Université, 13015 Marseille; Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), 13000 Marseille, France; INSERM 1263, 1260, Centre for Cardiovascular and Nutrition Research (C2VN), INRA, 13385 Marseille, France. Electronic address:

Acute pulmonary embolism is a frequent cardiovascular emergency with an increasing incidence. The prognosis of patients with high-risk and intermediate-high-risk pulmonary embolism has not improved over the last decade. The current treatment strategies are mainly based on anticoagulation to prevent recurrence and reduce pulmonary vasculature obstruction. However, the slow rate of thrombus lysis under anticoagulation is unable to acutely decrease right ventricle overload and pulmonary vasculature resistance in patients with severe obstruction and right ventricle dysfunction. Therefore, patients with high-risk and intermediate-high-risk pulmonary embolism remain a therapeutic challenge. Reperfusion therapies may be discussed for these patients, and include systemic thrombolysis, catheter-directed therapies and surgical thrombectomy. High-risk patients require systemic thrombolysis, but may have contraindications as a result of the high risk of bleeding. In addition, intermediate-high-risk patients should not receive systemic thrombolysis, despite its high efficacy, because of prohibitive bleeding complications. Recently, percutaneous reperfusion techniques have been developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially higher safety than systemic thrombolysis. Some of these techniques improve key haemodynamic variables. Cardiac surgical techniques and venoarterial extracorporeal membrane oxygenation as temporary circulatory support may be useful in selected cases. The development of pulmonary embolism centres with multidisciplinary pulmonary embolism teams is mandatory to enable adequate use of reperfusion and improve outcomes. We aim to present the state of the art regarding reperfusion therapies in pulmonary embolism, but also to provide guidance on their indications and patient selection.
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http://dx.doi.org/10.1016/j.acvd.2020.06.002DOI Listing
November 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

Intra-aortic balloon pump: is the technique really outdated?

ESC Heart Fail 2020 06 19;7(3):1025-1030. Epub 2020 Apr 19.

Department of Cardiology, Montpellier University Hospital, 34295, Montpellier, Cedex 5, France.

Aims: Intra-aortic balloon pump (IABP) utilization was expected to be quickly abandoned following the IABP-shock trial and its class III, level B recommendation in the 2016 European Society of Cardiology (ESC) guidelines. The aim of this study was to evaluate the use of IABP compared with other mechanical support devices in a nationwide approach.

Methods And Results: We conducted a retrospective study based on the French national hospital discharge database. All patients undergoing assist device implantation by IABP, extracorporeal membrane oxygenation (ECMO), or IMPELLA® from 2014 to 2018 (2 years before/2 years after the 2016 guidelines) were included. The primary endpoint was the incidence of IABP implantation over the years. Secondary endpoints were incidence of total assist device, ECMO, and IMPELLA® implantations. From 2014 to 2018, a total of 18 940 patients benefited from mechanical support by IABP (n = 6657, 35.2%), ECMO (n = 11 881, 62.7%), or IMPELLA® (n = 402, 2.1%) in France. The incidence of total mechanical support implantations (ECMO and IABP) was constant over the years. IABP implantations decreased progressively from 1725 implantations in 2014 to 996 in 2018 (-42%). By contrast, ECMO implantations increased progressively from 1919 implantations in 2014 to 2763 implantations in 2018 (+44%). IMPELLA® implantations remained stable over the years from 63 (1.7%) implantations in 2014 to 83 (2.1%) in 2018.

Conclusions: In this nationwide real-life study, despite a significant decline in IABP implantations over the years since the ESC guidelines, this device remained used in clinical practice with around 1000 implantations in 2018. The size of centres was not strictly correlated with this use, suggesting differential uses depending on the local background.
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http://dx.doi.org/10.1002/ehf2.12721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261556PMC
June 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

Trends in cardiogenic shock complicating acute myocardial infarction.

Eur J Heart Fail 2020 04 20;22(4):664-672. Epub 2020 Feb 20.

Faculty of Medicine, University Paris Descartes, Paris, France.

Aims: Few studies describe recent changes in the prevalence, management, and outcomes of cardiogenic shock (CS) patients complicating acute myocardial infarction (AMI) in the era of widespread use of invasive strategies. The aim of the present study was to analyse trends observed in CS complicating AMI over the past 10 years, focusing on the timing of CS occurrence (i.e. primary CS, CS on admission vs. secondary CS, CS developed subsequently during hospitalization).

Methods And Results: Three nationwide French registries conducted and designed to evaluate AMI management and outcomes in 'real-life' practice included consecutive AMI patients (n = 9951) admitted to intensive cardiovascular care units (ICCUs) over a 1-month period, 5 years apart. The prevalence of CS complicating AMI decreased from 2005 to 2015: 5.9%, mean age 74.1 ± 12.7 in 2005; 4.0%, mean age 73.9 ± 12.7 in 2010, 2.8%, mean age 71.1 ± 15.0 in 2015 (P < 0.001). It decreased for both primary (1.8% to 1.0%) and secondary CS (4.1% to 1.8%). The profile of CS patients also changed over time with more patients presenting out-of-hospital cardiac arrest. In both primary and secondary CS, the use of percutaneous coronary intervention increased markedly over time, as did the use of mechanical ventilation and cardiac assist devices. Over the 10-year period, in-hospital mortality remained unchanged for both primary CS (41.8% to 37.8%) or secondary CS (57.3% to 58.8%). However, 1-year mortality decreased in patients with primary CS (from 60% to 37.8%, P = 0.038), and remained unchanged in patients developing secondary CS (from 64.5% to 69.1%, P = 0.731).

Conclusion: Cardiogenic shock complicating AMI has become less frequent but, if present, CS, and particularly secondary CS, carries a very high mortality, which has not substantially improved over the past 10 years, in spite of the more frequent use of invasive strategies.
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http://dx.doi.org/10.1002/ejhf.1750DOI 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

Using an Impella device to reverse refractory cardiac arrest and enable efficient coronary revascularisation.

BMJ Case Rep 2019 Aug 10;12(8). Epub 2019 Aug 10.

Department of Cardiology, Intensive Care Unit, Assistance Publique - Hôpitaux de Marseille, Marseille, France.

We report the case of a 54-year-old man who suffered from refractory cardiac arrest secondary to acute myocardial infarction. As veno-arterial extracorporeal membrane oxygenation was unavailable, mechanical chest compression was performed and an Impella device was used that immediately delivered at 3.2 l/min flow to reach the optimal mean arterial pressure. Within 1 min, return of spontaneous circulation was achieved and a 40% left ventricular ejection fraction was measured on echography. Then, the right coronary artery could be revascularised. Despite 62 min low flow, the patient was discharged home on day 19 without neurological sequelae. During refractory cardiac arrest, the European Resuscitation Guidelines indicate that veno-arterial extracorporeal membrane oxygenation should be considered as rescue therapy. Other mechanical circulatory supports such as an Impella device (left ventricular assist device propelling blood in the ascending aorta) can be a promising treatment in select patients; however, insufficient data in humans are available.
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http://dx.doi.org/10.1136/bcr-2019-230654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700542PMC
August 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

Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y Receptor Inhibitor Treatment in Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2019 08 12;12(16):1521-1537. Epub 2019 Jun 12.

Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida. Electronic address:

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention.
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http://dx.doi.org/10.1016/j.jcin.2019.03.034DOI Listing
August 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