Publications by authors named "Michael Peyrol"

38 Publications

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

High Risk of Sustained Ventricular Arrhythmia Recurrence After Acute Myocarditis.

J Clin Med 2020 Mar 20;9(3). Epub 2020 Mar 20.

Cardiology Department, Dijon Bourgogne University Hospital, 21000 Dijon, France.

Acute myocarditis is associated with cardiac arrhythmia in 25% of cases; a third of these arrhythmias are ventricular tachycardia (VT) or ventricular fibrillation (VF). The implantation of a cardiac defibrillator (ICD) following sustained ventricular arrhythmia remains controversial in these patients. We sought to assess the risk of major arrhythmic ventricular events (MAEs) over time in patients implanted with an ICD following sustained VT/VF in the acute phase of myocarditis compared to those implanted for VT/VF occurring on myocarditis sequelae. Our retrospective observational study included patients implanted with an ICD following VT/VF during acute myocarditis or VT/VF on myocarditis sequelae, from 2007 to 2017, in 15 French university hospitals. Over a median follow-up period of 3 years, MAE occurred in 11 (39%) patients of the acute myocarditis group and 24 (60%) patients of the myocarditis sequelae group. Kaplan-Meier MAE rate estimates at one and three years of follow-up were 19% and 45% in the acute group, and 43% and 64% in the sequelae group. Patients who experienced sustained ventricular arrhythmias during acute myocarditis had a very high risk of VT/VF recurrence during follow-up. These results show that the risk of MAE recurrence remains high after resolution of the acute episode.
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http://dx.doi.org/10.3390/jcm9030848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141537PMC
March 2020

High incidence of atrial fibrillation in patients treated with ibrutinib.

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

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

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

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

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

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

Dynamic iron status after acute heart failure.

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

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

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

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

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

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

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

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

Seasonal variations in cardiac implantable electronic device infections.

Heart Vessels 2019 May 10;34(5):824-831. Epub 2018 Nov 10.

APHM, Unit of Arrhythmias, Department of Cardiology, Aix-Marseille Univ, Hôpital Timone, Marseille, France.

Infections of cardiac implantable electronic devices (CIEDs) have increased over the past decade. However, the impact of the climate on CIED infections is unknown. To determine whether there is a seasonal variation in CIED infections. In this single-center observational study, retrospective analysis of prospectively collected data was performed. Timone Hospital in Marseille (south-east France) is a tertiary care institution and the regional reference center for management of CIED infections. All consecutive patients with CIED extractions for infectious reasons were included over a 12-year period. We noted the mean temperature (°C), precipitation (mm) and the incidence of CIED infections over this period. Among 612 patients [mean (standard deviation) age, 72.4 (13.0) years; 74.0% male], 238 had endocarditis alone (38.9%), 249 had pocket infection alone (40.7%), and 125 had both (20.4%). We found bacterial documentation in 428 patients (70.0%), commensal in 245 (40.0%). The incidence of CIED infections was positively associated with high temperature (regression coefficient = 0.075; P = 0.01) and precipitation (regression coefficient = 0.022; P < 0.01). Seasonal variation was specific of pocket infections, whether they were associated with endocarditis or not. Subgroups with infection seasonality were: women, elderly people (> 75 years), late CIED infection and skin commensal bacterial infections. We found a seasonal variation in pocket infections, whether associated with endocarditis or not. Infections were associated with elevated temperatures and precipitation. Therefore, specific prevention strategy should be discussed in high-risk patients.
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http://dx.doi.org/10.1007/s00380-018-1292-4DOI Listing
May 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

High-density mapping for catheter ablation of premature ventricular complexes originating from left ventricular papillary muscles: A case series.

Pacing Clin Electrophysiol 2018 09 7;41(9):1071-1077. Epub 2018 Aug 7.

Department of Cardiology, Assistance Publique - Hôpitaux de Marseille (APHM), Aix-Marseille University, Timone Hospital, France.

Purpose: Ablation of premature ventricular complexes (PVCs) originating from left-sided papillary muscles is challenging. We tested a new approach by performing high-density mapping of PVC.

Methods And Results: We used a 20-pole deflectable spiral catheter during ablation procedures in four consecutive patients. Three presented with mitral valve prolapse, one with dilated cardiomyopathy. PVC burden was 24 ± 13%. The procedures lasted 182 ± 55.4 minutes, including 10 ± 3.2 minutes of radiofrequency. In all patients, mapping evidenced internal primary activation relative to the left ventricle shell (mean distance 21.3 ± 5.1 mm). Endocavitary prematurity was -38.3 ± 4.8 ms. Primary ablation success was achieved for all patients.

Conclusions: High-density mapping of the papillary muscles in the left ventricle using a spiral catheter may be feasible. We identified the PVC foci away from the left ventricular shell. This consolidates the assumption for the origin of these ectopic beats at the junction between the chordae tendineae and the papillary muscles.
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http://dx.doi.org/10.1111/pace.13417DOI Listing
September 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

Prevalence and characteristics of coronary artery disease in heart failure with preserved and mid-range ejection fractions: A systematic angiography approach.

Arch Cardiovasc Dis 2018 Feb 12;111(2):109-118. Epub 2017 Oct 12.

Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, hôpital Nord, Aix-Marseille University, AP-HM, chemin des Bourrely, 13015 Marseille, France; Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), 13015 Marseille, France. Electronic address:

Background: Guidelines recommend careful screening and treatment of coronary artery disease (CAD) in heart failure with preserved or mid-range ejection fraction (HFpEF/HFmEF).

Aim: We aimed to determine the prevalence and characteristics of CAD using a prospective systematic coronary angiography approach.

Methods: A systematic coronary angiography protocol was applied in consecutive patients admitted for HFpEF/HFmEF during a 6-month period in a single centre. History of CAD and results of angiography, including revascularization, were reported.

Results: Of the 164 patients with HFpEF/HFmEF who were included, an angiography assessment was applied in 108 (66%) (median age: 79 years [interquartile range: 70-85 years]; 54% were women). In our analysis, 64% (95% confidence interval [CI] 55-73%) of patients had a significant coronary stenosis corresponding to a global CAD prevalence of 80% (95% CI 73-88%). The prevalence of CAD was similar for HFpEF and HFmEF. The left main coronary artery presented a significant stenosis in 6.5% of cases and 39% of patients had a two- or three-vessel disease. The rate of significant coronary stenosis was non-significantly higher in patients with a history of CAD. Patients with HFpEF/HFmEF with and without CAD did not differ in clinically meaningful ways, in terms of symptoms or laboratory and echocardiography results. This strategy led to complete revascularization in 36% of patients with significant stenosis and in 23% of all patients with HFpEF/HFmEF.

Conclusions: Our study differs from others in that we used a systematic angiography approach. The results suggest a much higher prevalence of CAD in HFpEF/HFmEF than previously reported and should encourage clinicians to aggressively identify this co-morbidity.
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http://dx.doi.org/10.1016/j.acvd.2017.05.006DOI Listing
February 2018

Ventricular Arrhythmia Occurrence and Compliance in Patients Treated With the Wearable Cardioverter Defibrillator Following Percutaneous Coronary Intervention.

Heart Lung Circ 2018 Aug 25;27(8):984-988. Epub 2017 Sep 25.

Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (AP-HM), Department of Cardiology, Nord Hospital, France; Mediterranean Academic Association for Research and Studies in Cardiology (MARS Cardio), France. Electronic address:

Background: The wearable cardioverter defibrillator (WCD) is a life-saving therapy in patients with high risk of arrhythmic death. We aimed to evaluate ventricular arrhythmia (VA) occurrence rate and compliance with the WCD during the first 90 days following myocardial revascularisation with percutaneous coronary intervention (PCI) in patients with left ventricular ejection fraction (LVEF) <30%.

Methods: From September 2015 to November 2016, clinical characteristics, WCD recordings and compliance data of the aforementioned subset of patients were prospectively collected.

Results: Twenty-four patients (men=20, 80%) were included in this analysis. Mean age was 56±10 years and mean LVEF at enrolment was 26.6±4.3%. During a mean wearing period of 3.0±1.3 months, two episodes of VA occurred in two patients (8.3%): one successfully treated with WCD shock and one with spontaneous termination. The mean and median daily use of the WCD was 21.5hours and 23.5hours a day, respectively. Eighteen patients (75%) wore the WCD more than 22hours a day.

Conclusions: The rate of VA, during the WCD period use after myocardial revascularisation with PCI, was high in our study. Otherwise it underlined that patient compliance is critical during the WCD period use. Remote monitoring and patient education are keys to achieve good compliance.
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http://dx.doi.org/10.1016/j.hlc.2017.08.022DOI Listing
August 2018

Wearable cardioverter defibrillator: Bridge or alternative to implantation?

World J Cardiol 2017 Jun;9(6):531-538

Jeremie Barraud, Jennifer Cautela, Morgane Orabona, Johan Pinto, Olivier Missenard, Marc Laine, Franck Thuny, Franck Paganelli, Laurent Bonello, Michael Peyrol, Department of Cardiology, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Nord Hospital, 13015 Marseille, France.

The implantable cardioverter-defibrillator (ICD) is effective to prevent sudden cardiac death (SCD) in selected patients with heart disease known to be at high risk for ventricular arrhythmia. Nevertheless, this invasive and definitive therapy is not indicated in patients with potentially transient or reversible causes of sudden death, or in patients with temporary contra-indication for ICD placement. The wearable cardioverter defibrillator (WCD) is increasingly used for SCD prevention both in patients awaiting ICD implantation or with an estimated high risk of ventricular arrhythmia though to be transient. We conducted a review of current clinical uses and benefits of the WCD, and described its technical aspects, limitations and perspectives.
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http://dx.doi.org/10.4330/wjc.v9.i6.531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491470PMC
June 2017

Controlled sedation with midazolam and analgesia with nalbuphine to alleviate pain in patients undergoing subcutaneous implantable cardioverter defibrillator implantation.

J Interv Card Electrophysiol 2017 Aug 23;49(2):191-196. Epub 2017 May 23.

Aix-Marseille University, Marseille, France.

Purpose: Subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to transvenous ICD to prevent sudden cardiac death. Subcutaneous ICD implantation frequently requires general anesthesia because of procedure nociceptive steps during creation of a large device pocket and lead tunneling. This study aims to determine if a strategy of operator-guided controlled sedation with midazolam and analgesia with nalbuphine is effective in alleviating pain during S-ICD implantation.

Methods: This prospective study included consecutive patients undergoing S-ICD implantation under controlled sedation with midazolam and combined analgesia with nalbuphine. The Critical-Care Pain Observation Tool (CPOT), a behavioral pain scale, was used for pain assessment during S-ICD placement and the Numeric Rate Scale (NRS) was used for evaluation of pain recollection after patient recovery. CPOT score of 3 or above and NRS score of 4 or above are considered to be associated with significant pain.

Results: Sixteen patients were included in this study: Ten men (62.5%) and six women with a mean age of 54 ± 11 years. Indication for S-ICD implantation was primary prevention in 11 patients (68.8%). Mean dose of administrated midazolam and nalbuphine was 0.11 ± 0.03 and 0.27 ± 0.05 mg/kg, respectively. Mean CPOT during the whole procedure was 1.4 ± 1.6. No patient presented procedural pain recollection as all 16 patients had NRS score less than 4. No serious adverse event related to sedation occurred during S-ICD implantation.

Conclusions: This study suggests that operator-guided controlled sedation with midazolam and analgesia with nalbuphine is effective to alleviate procedural pain in patients undergoing S-ICD implantation and may constitute an alternative to general anesthesia.
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http://dx.doi.org/10.1007/s10840-017-0255-5DOI Listing
August 2017

Practices in management of cancer treatment-related cardiovascular toxicity: A cardio-oncology survey.

Int J Cardiol 2017 Aug 21;241:387-392. Epub 2017 Mar 21.

Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (AP-HM), Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, France; Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), France; Groupe Méditerranéen de Cardio-Oncologie (gMEDICO), France; Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (AP-HM), Oncosaftey Network of the Early Phases Cancer Trials Center (CLIP(2)), France. Electronic address:

Background: Cardiovascular toxicity has become a challenging issue during cancer therapy. Nonetheless, there is a lack of consensual guidelines for their management. We aimed to determine the current practices of oncologists regarding cardiovascular toxicity related to anthracyclines, trastuzumab and angiogenic inhibitors and to gather their opinions on the development of cardio-oncology programs.

Methods: A cross-sectional declarative study was submitted to French oncologists in the form of an individual, structured questionnaire.

Results: A total of 303 oncologists responded to the survey. Ninety-nine percent of oncologists prescribed cardiotoxic therapies, including anthracyclines (83%), trastuzumab (51%) and other angiogenic inhibitors (64%). The method adopted for managing cardiovascular toxicity was based on guidelines from expert oncology societies for only 35% of oncologists. None was aware of recommendations from expert cardiology societies. Prescription of pre-, peri- and post-therapy cardiovascular assessment was inconsistent and significantly less frequent for all classes of angiogenic inhibitors than for anthracyclines and trastuzumab (P<0.0001). Relative to pre-therapy assessment, post-therapy assessment was prescribed significantly less often for all cancer therapies (P<0.0001). Attitudes regarding the onset of left ventricular dysfunction were much more inconsistent when angiogenic inhibitors were involved. Additionally, the management of hypertension and QT prolongation was also inconsistent. Finally, 88% of oncologists supported projects of cardio-oncology programs development.

Conclusions: Practices of oncologists are disparate in the field of cardiovascular toxicity. This finding underlines the complexity of managing many different situations and the need for distribution of formal guidelines from oncology and cardiology expert societies. The development of personalized cardio-oncology programs seems essential.
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http://dx.doi.org/10.1016/j.ijcard.2017.02.154DOI Listing
August 2017

For Whom the Bell Tolls.

JACC Clin Electrophysiol 2017 01 16;3(1):84. Epub 2017 Jan 16.

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http://dx.doi.org/10.1016/j.jacep.2016.09.018DOI Listing
January 2017

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Int J Cardiol 2016 Dec 17;224:366-375. Epub 2016 Sep 17.

Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (AP-HM), Mediterranean university Cardio-Oncology center (MEDI-CO center), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, France; Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (AP-HM), Oncosafety Network of the Early Phases Cancer Trials Center (CLIP(2)), France; Groupe Méditerranéen de Cardio-Oncologie (gMEDICO), France; Mediterranean Academic association for Research and Studies in Cardiology (MARS Cardio), France. Electronic address:

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.
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http://dx.doi.org/10.1016/j.ijcard.2016.09.046DOI Listing
December 2016

Prehospital and in-hospital course of care for patients with acute heart failure: Features and impact on prognosis in "real life".

Arch Cardiovasc Dis 2017 Feb 29;110(2):72-81. Epub 2016 Sep 29.

Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (AP-HM), Unit of Heart Failure and Valvular Heart Disease, Department of Cardiology, Nord Hospital, 13915 Marseille cedex 20, France; Mediterranean Academic association for Research and Studies in Cardiology (MARS Cardio), Marseille, France. Electronic address:

Background: Acute heart failure (AHF) is a life-threatening medical emergency for which no new effective therapies have emerged in recent decades. No previous study has exhaustively described the entire course of care of AHF patients from first medical contact to hospital discharge or assessed its impact on prognosis.

Aim: To fully describe the course of care and analyze its influence on outcomes in patients hospitalized with an AHF syndrome in an academic university center.

Methods: One hundred and nineteen adults with AHF from three public academic university hospitals were consecutively enrolled in a multicenter prospective observational cohort study. All of the emergency departments, intensive care units, coronary care units, cardiology wards and other medical wards participated in the study.

Results: The composite primary outcome (6-month rate of cardiovascular death, readmission for acute heart failure, acute coronary syndrome or stroke) occurred in 59% of patients. This rate was high and similar regardless of first medical contact, type of transport, first medical department of admission and number of medical departments involved in the course of care. A cardiologist was involved in management in 80% of cases. The global median hospital stay was shorter with cardiology vs non-cardiology management (7 days [interquartile range 4-11] vs 10 days [interquartile range 7-18]; P=0.003). History of hypertension (P=0.004), need for non-invasive ventilation (P=0.023) and Lee prognostic score (P=0.028) were independently associated with the primary outcome.

Conclusions: Morbimortality and readmissions were high regardless of the course of care in patients admitted for AHF in real life. The reduction in hospital stay when cardiologists were involved in management encourages the creation of "mobile AHF cardiology teams".
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http://dx.doi.org/10.1016/j.acvd.2016.05.004DOI Listing
February 2017

Pleiotropic effects of ticagrelor: Myth or reality?

Arch Cardiovasc Dis 2016 Aug-Sep;109(8-9):445-8. Epub 2016 Jun 21.

Aix Marseille University and Department of Cardiology, North Hospital, chemin des Bourrely, 13008 Marseille, France. Electronic address:

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

Vagal Reactions during Cryoballoon-Based Pulmonary Vein Isolation: A Clue for Autonomic Nervous System Modulation?

Biomed Res Int 2016 3;2016:7286074. Epub 2016 May 3.

APHM, Department of Cardiology, Timone University Hospital, 13385 Marseille Cedex 05, France.

Although paroxysmal atrial fibrillation (AF) is known to be initiated by rapid firing of pulmonary veins (PV) and non-PV triggers, the crucial role of cardiac autonomic nervous system (ANS) in the initiation and maintenance of AF has long been appreciated in both experimental and clinical studies. The cardiac intrinsic ANS is composed of ganglionated plexi (GPs), located close to the left atrium-pulmonary vein junctions and a vast network of interconnecting neurons. Ablation strategies aiming for complete PV isolation (PVI) remain the cornerstone of AF ablation procedures. However, several observational studies and few randomized studies have suggested that GP ablation, as an adjunctive strategy, might achieve better clinical outcomes in patients undergoing radiofrequency-based PVI for both paroxysmal and nonparoxysmal AF. In these patients, vagal reactions (VR) such as vagally mediated bradycardia or asystole are thought to reflect intrinsic cardiac ANS modulation and/or denervation. Vagal reactions occurring during cryoballoon- (CB-) based PVI have been previously reported; however, little is known on resulting ANS modulation and/or prevalence and significance of vagal reactions during PVI with the CB technique. We conducted a review of prevalence, putative mechanisms, and significance of VR during CB-based PVI.
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http://dx.doi.org/10.1155/2016/7286074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868893PMC
February 2017

Clinical presentation of inappropriate sinus tachycardia and differential diagnosis.

J Interv Card Electrophysiol 2016 Jun 2;46(1):33-41. Epub 2015 Sep 2.

Division of Cardiology, Centre Hospitalier Universitaire de Marseille, Hôpital Nord, Aix-Marseille Université, Marseille, France.

Inappropriate sinus tachycardia (IST) is a syndrome characterized by a sinus tachycardia not related to a medical condition, to a physiological response, or to medication or drugs and associated with symptoms, often invalidating and altering the quality of life of affected patients. It occurs predominantly in adolescents and young adults, and in the female sex. The diagnosis requires a complete work-up in order to exclude other causes of sinus tachycardia and one or several additional tests: 24-h ECG ambulatory recordings, echocardiogram, exercise testing, and autonomous nervous system assessment. It should be differentiated from the postural orthostatic tachycardia syndrome, with which it shares a number of symptoms, and other supraventricular tachycardias originating in the high right atrium. An electrophysiological study should be considered in selected cases in order to differentiate IST from other supraventricular tachycardias. The mechanism is still unclear, and possible etiologies may include intrinsic abnormality of the sinus node, autonomic dysfunction, hypersensitivity of the sinus node to catecholamines, blunted vagal system, or a combination of the above. The authors emphasize the wide spectrum of clinical presentations and the need to better define the IST and the criteria required to ascertain its diagnosis.
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http://dx.doi.org/10.1007/s10840-015-0051-zDOI Listing
June 2016

Simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation in patients with combined atrial fibrillation and typical atrial flutter.

J Electrocardiol 2015 Jul-Aug;48(4):729-33. Epub 2015 Mar 12.

Aix-Marseille Université, Marseille, France.

Pulmonary vein isolation (PVI) using cryoballoon (CB) technique and cavotricuspid isthmus (CTI) ablation using radiofrequency (RF) are established interventions for drug-resistant atrial fibrillation (AF) and typical atrial flutter (AFL). Twelve patients with a mean age of 62 ± 12 years underwent simultaneous delivery of RF energy at the CTI during CB applications at the PV ostia. Pulmonary vein isolation was achieved in all PVs and sustained bidirectional CTI conduction block obtained in all patients. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of the procedure duration or in prolonged radiation exposure when compared to CB-PVI alone. No interferences between both ablation energy systems were observed. These preliminary results suggest that combined paroxysmal AF and typical AFL can be successfully and safely ablated using hybrid energy sources with simultaneous CTI ablation using RF during CB applications at the PV ostia.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.03.013DOI Listing
March 2016

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

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

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

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

Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents.

Eur J Intern Med 2014 Jun 23;25(5):e63-5. Epub 2014 Feb 23.

Department of Cardiology, Centre Hospitalier Universitaire Nord, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2014.02.003DOI Listing
June 2014

A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity.

Int J Cardiol 2013 Oct 2;168(4):4244-8. Epub 2013 Aug 2.

Département de cardiologie, Hôpital universitaire nord, Aix-Marseille Univ., Marseille, France; INSERM UMRS 608, UFR de pharmacie, Marseille, France. Electronic address:

Background: Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR.

Methods: We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge.

Results: Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001).

Conclusion: In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.
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http://dx.doi.org/10.1016/j.ijcard.2013.07.147DOI Listing
October 2013

The safety of cardiac resynchronization therapy pacemaker implantation in octogenarians: a monocentric experience.

Int J Cardiol 2013 Oct 24;168(3):2969-70. Epub 2013 May 24.

Division of Cardiology, Hôpital Nord, Aix-Marseille Université, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.04.118DOI Listing
October 2013

Slow pathway elimination for atrioventricular nodal reentrant tachycardia with the 8-mm tip cryoablation catheter: an 18-month follow-up study.

J Interv Card Electrophysiol 2013 Jun 18;37(1):105-9. Epub 2012 Dec 18.

Division of Cardiology, Hôpital Nord, Aix-Marseille Université, Marseille, France.

Purpose: The 9-French 8-mm tip cryoablation catheter confers a high rate of acute slow pathway (SP) elimination and an acceptable short-term outcome in patients with atrioventricular nodal reentrant tachycardia (AVNRT). The aim of this study was to investigate the long-term outcome of patients treated with this electrode in this indication.

Methods: Eighty-two patients (female = 52) with a mean age of 54.9 ± 17.7 years underwent SP elimination for typical AVNRT with the 8-mm tip cryocatheter in our institution between November 2009 to June 2012. Clinical and procedural characteristics were prospectively collected.

Results: Acute procedural success defined as AVNRT non-inducibility at the end of the procedure was obtained in 81/82 patients (98.7 %). Mean procedure duration and fluoroscopy time were 74.4 ± 28.7 min (range, 35-160 min) and 8.7 ± 5.3 min (range, 2-26 min), respectively. Mean number of energy applications was 4.0 ± 2.4 (range, 2-15). No permanent atrioventricular block was observed. Transient atrioventricular block occurred in 12 patients (14.6 %). Traumatic fast pathway conduction block occurred in one patient before cryoenergy delivery. Using an intention-to-treat analysis, 78 patients (95.1 %) remained free of AVNRT recurrence during a mean follow-up of 17.8 ± 9.3 months.

Conclusions: This study confirmed that the 8-mm tip cryocatheter is both safe and highly effective for SP conduction elimination in patients with AVNRT and demonstrated a low recurrence rate during a long-term follow-up.
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http://dx.doi.org/10.1007/s10840-012-9768-0DOI Listing
June 2013

Clinical impact of genetically determined platelet reactivity.

J Cardiovasc Transl Res 2013 Jun 13;6(3):398-403. Epub 2012 Nov 13.

Département de Cardiologie, Centre Hospitalo-Universitaire Nord, Chemin des Bourrely, Marseille, France.

Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the rate of major adverse cardiac events following percutaneous coronary intervention. Clopidogrel is a prodrug which requires a two-step hepatic biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered clopidogrel metabolism is a major cause of high on-treatment platelet reactivity (HTPR), which translates into thrombotic events in stented patients. Studies demonstrated that HTPR could be overcome in poor metabolizers thanks to increased loading doses or maintenance doses of clopidogrel or with the use of more potent antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials with clinical endpoints remain necessary to determine the optimal antiplatelet therapy in patients carrying genetic polymorphism associated with HTPR and thrombotic events.
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http://dx.doi.org/10.1007/s12265-012-9421-4DOI Listing
June 2013

Reduction of procedure duration and radiation exposure with a dedicated inner lumen mapping catheter during pulmonary vein cryoablation.

Pacing Clin Electrophysiol 2013 Jan 18;36(1):24-30. Epub 2012 Oct 18.

Division of Cardiology, Hôpital Nord, Aix-Marseille Université, Marseille, France.

Background: The Achieve catheter (AC; Medtronic-CryoCath, Pointe-Claire, Canada) is a circular mapping catheter introduced through the lumen of the cryoballoon (CB) catheter which is safe and effective to both navigate the CB to the pulmonary veins (PV) and allow PV potential recording during PV cryoablation. The aim of this study was to evaluate the impact of the use of the AC on procedural outcomes.

Methods: Sixteen consecutive patients (14 men) underwent AC-guided PV isolation (PVI) for drug-refractory paroxysmal atrial fibrillation (AF; AC group). Clinical and procedural data of these patients were compared to those obtained from 16 consecutive patients who had undergone PVI for paroxysmal AF with the regular "single transseptal" approach (control group).

Results: Clinical characteristics of patients enrolled in both groups did not differ significantly. In the AC group, 64 PVs were targeted using a single 28-mm (n = 13) or 23-mm (n = 3) CB catheter with PVI achieved in 62 PVs (97%). In the control group, 66 PVs were targeted using a single 28-mm (n = 12) or 23-mm (n = 4) CB catheter with PVI achieved in 62 PVs (94%), (P = non-significant for CB size and PVI rate). Procedure duration and fluoroscopy time were significantly reduced in AC group compared to control group (96.6 ± 26 minutes vs 125.9 ± 25 minutes, P = 0.003 and 24.4 ± 10 minutes vs 32.6 ± 11 minutes, P = 0.04, respectively).

Conclusion: The use of the AC significantly reduced procedure duration and radiation exposure during PVI with the CB technique.
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http://dx.doi.org/10.1111/pace.12015DOI Listing
January 2013