Publications by authors named "Frederic Franceschi"

46 Publications

Smartwatch Electrocardiogram and Artificial Intelligence for Assessing Cardiac-Rhythm Safety of Drug Therapy in the COVID-19 Pandemic. The QT-logs study.

Int J Cardiol 2021 05 29;331:333-339. Epub 2021 Jan 29.

Institut Cardiovasculaire Paris-Sud, Hôpital Privé Jacques Cartier, Ramsay, Massy, France.

Background: QTc interval monitoring, for the prevention of drug-induced arrhythmias is necessary, especially in the context of coronavirus disease 2019 (COVID-19). For the provision of widespread use, surrogates for 12‑lead ECG QTc assessment may be useful. This prospective observational study compared QTc duration assessed by artificial intelligence (AI-QTc) (Cardiologs®, Paris, France) on smartwatch single‑lead electrocardiograms (SW-ECGs) with those measured on 12‑lead ECGs, in patients with early stage COVID-19 treated with a hydroxychloroquine-azithromycin regimen.

Methods: Consecutive patients with COVID-19 who needed hydroxychloroquine-azithromycin therapy, received a smartwatch (Withings Move ECG®, Withings, France). At baseline, day-6 and day-10, a 12‑lead ECG was recorded, and a SW-ECG was transmitted thereafter. Throughout the drug regimen, a SW-ECG was transmitted every morning at rest. Agreement between manual QTc measurement on a 12‑lead ECG and AI-QTc on the corresponding SW-ECG was assessed by the Bland-Altman method.

Results: 85 patients (30 men, mean age 38.3 ± 12.2 years) were included in the study. Fair agreement between manual and AI-QTc values was observed, particularly at day-10, where the delay between the 12‑lead ECG and the SW-ECG was the shortest (-2.6 ± 64.7 min): 407 ± 26 ms on the 12‑lead ECG vs 407 ± 22 ms on SW-ECG, bias -1 ms, limits of agreement -46 ms to +45 ms; the difference between the two measures was <50 ms in 98.2% of patients.

Conclusion: In real-world epidemic conditions, AI-QTc duration measured by SW-ECG is in fair agreement with manual measurements on 12‑lead ECGs. Following further validation, AI-assisted SW-ECGs may be suitable for QTc interval monitoring.

Registration: ClinicalTrial.govNCT04371744.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845555PMC
May 2021

Percutaneous catheter ablation of malignant, recurrent ventricular arrhythmia in a 10-month-old toddler.

HeartRhythm Case Rep 2019 Jun 2;5(6):299-303. Epub 2019 Mar 2.

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

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http://dx.doi.org/10.1016/j.hrcr.2019.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587056PMC
June 2019

Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion.

Purinergic Signal 2019 03 7;15(1):45-52. Epub 2018 Dec 7.

Department of Cardiology, Timone University Hospital, 13005, Marseille, France.

The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of endogenous adenosine plasma level (APL) at the onset of AF and during ablation procedure. Ninety-one patients (68 with paroxysmal AF: 40 males, 66 ± 16 years; 23 with persistent AF: 14 males, 69 ± 11 years) and 18 controls were included. Among paroxysmal patients: i) medical therapy alone was performed in 45 cases and ablation procedure in 23. AF was spontaneously resolutive in 6 cases; ii) 23 underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the left atrium; 17 were spontaneously in sinus rhythm while 6 were in sinus rhythm after direct current cardioversion. Among persistent patients: i) in 17 patients, blood samples were collected in a brachial vein before and after direct current cardioversion; ii) in 6 patients, blood samples were collected simultaneously in a brachial vein and in left atrium before and after cardioversion during ablation procedure. CV-APL was higher in patients with persistent AF vs patients with paroxysmal AF (median [range]: 0.9[0.6-1.1] vs 0.7[0.4-1.1] μM; p < 0.001). In patients with paroxysmal AF, LA-APL increased during the AF episode (0.95[0.85-1.4] vs 2.7[1.5-7] μM; p = 0.03) and normalized in sinus rhythm after DCCV. In patients with persistent AF, LA-APL was higher than CV-APL (1.2[0.7-1.8] vs 0.9[0.6-1.1] μM; p < 0.001), and both normalized in sinus rhythm (CV-APL: 0.8[0.6-1.1] vs 0.75[0.4-1] μM; p = 0.03), (LA-APL: 1.95[1.3-3] vs 1[0.5-1.15] μM; p = 0.03). The occurrence of AF is associated with a strong increase of APL in the atrium. The cause of this increase needs further investigations.
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http://dx.doi.org/10.1007/s11302-018-9636-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439011PMC
March 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

An Oscillating Mass Attached to a Pacemaker Lead: Thrombus or Vegetation? A Fishing Story.

JACC Clin Electrophysiol 2017 Aug 29;3(8):915-916. Epub 2017 Mar 29.

Department of Cardiology, AP-HM, La Timone Hospital, Marseille, France; URMITE, Aix-Marseille Université UM 63, CNRS 7278, IRD 198, INSERM 1095, IHU, Marseille, France.

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http://dx.doi.org/10.1016/j.jacep.2016.12.028DOI Listing
August 2017

Extensive Endothelialization or Thrombus Related to New-Generation Left Atrial Appendage Occluders.

JACC Clin Electrophysiol 2017 Jul 29;3(7):787-788. Epub 2017 Mar 29.

Department of Cardiology, La Timone Hospital, Marseille, France; UMR MD2, Aix-Marseille University, Marseille, France.

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http://dx.doi.org/10.1016/j.jacep.2016.12.021DOI Listing
July 2017

Device-Related Thrombosis After Percutaneous Left Atrial Appendage Occlusion for Atrial Fibrillation.

J Am Coll Cardiol 2018 04;71(14):1528-1536

Grenoble University Hospital, Grenoble, France.

Background: Transcatheter left atrial appendage (LAA) occlusion is an alternative strategy for stroke prevention in patients with atrial fibrillation (AF).

Objectives: This study sought to determine the incidence, predictors, and prognosis of thrombus formation on devices in patients with AF who were treated with LAA closure.

Methods: The study retrospectively analyzed data from patients treated with 2 LAA closure devices seen in 8 centers in France from February 2012 to January 2017.

Results: A total of 469 consecutive patients with AF underwent LAA closure (272 Watchman devices [Atritech, Boston Scientific, Natick, Massachusetts] and 197 Amplatzer devices [St. Jude Medical, Minneapolis, Minnesota]). Mean follow-up was 13 ± 13 months, during which 339 (72.3%) patients underwent LAA imaging at least once. There were 98 major adverse events (26 thrombi on devices, 19 ischemic strokes, 2 transient ischemic attacks, 18 major hemorrhages, 33 deaths) recorded in 89 patients. The incidence of device-related thrombus in patients with LAA imaging was 7.2% per year. Older age (hazard ratio [HR]: 1.07 per 1-year increase; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.02) and history of stroke (HR: 3.68; 95% CI: 1.17 to 11.62; p = 0.03) were predictors of thrombus formation on the devices, whereas dual antiplatelet therapy (HR: 0.10; 95% CI: 0.01 to 0.76; p = 0.03) and oral anticoagulation at discharge (HR: 0.26; 95% CI: 0.09 to 0.77; p = 0.02) were protective factors. Thrombus on the device (HR: 4.39; 95% CI: 1.05 to 18.43; p = 0.04) and vascular disease (HR: 5.03; 95% CI: 1.39 to 18.23; p = 0.01) were independent predictors of ischemic strokes and transient ischemic attacks during follow-up.

Conclusions: Thrombus formation on the device is not uncommon in patients with AF who are treated by LAA closure. Such events are strongly associated with a higher risk of ischemic stroke during follow-up. (REgistry on Real-Life EXperience With Left Atrial Appendage Occlusion [RELEXAO]; NCT03279406).
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http://dx.doi.org/10.1016/j.jacc.2018.01.076DOI Listing
April 2018

Theophylline as an adjunct to control malignant ventricular arrhythmia associated with early repolarization.

Pacing Clin Electrophysiol 2018 05 7;41(5):444-446. Epub 2017 Dec 7.

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

Early repolarization (ER) has been associated with an increased risk of sudden cardiac arrest. Interestingly, ventricular arrhythmias seem to be triggered by parasympathetic stimulation. In the present case report, we describe complete control of highly frequent malignant ventricular arrhythmias after adding theophylline to ineffective oral hydroquinidine and high-rate pacing in a patient suffering from malignant ER. We hypothesize that the theophylline-mediated enhanced beta-adrenergic stimulation could reduce the transmural myocardial voltage discrepancy by increasing the inward I current.
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http://dx.doi.org/10.1111/pace.13240DOI Listing
May 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

Right ventricular and tricuspid valve function in patients chronically implanted with leadless pacemakers.

Europace 2018 05;20(5):823-828

Service de Cardiologie et Maladies Vasculaires, Hôpital de la Timone, 268 Rue Saint-Pierre, F-13385 Marseille Cedex, France.

Aims: Leadless cardiac pacing has recently been proposed as alternative to conventional right ventricular (RV) pacing. With this approach, devices are directly screwed or fixed with tines in the RV wall, but the possible consequences on RV and tricuspid valve (TV) structure and function remain unknown. We thus conducted a study to evaluate this potential impact in chronically implanted patients.

Methods And Results: Repeated echocardiographic studies were performed prior to implantation, at discharge, and 2 months thereafter on all consecutive patients implanted with a leadless pacemaker at our centre between October 2014 and end-December 2015. Whenever possible, patients were evaluated in non-paced rhythm. Anatomical and functional parameters of RV, TV, and left cardiac structures were assessed. Overall, 23 patients (12 females, aged 85.2 ± 6.3 years) were included, with 14 implanted using Nanostim™ (Saint Jude Medical) and 9 with Micra™ (Medtronic). Indications for pacing were paroxysmal atrio-ventricular block in 12 patients, intermittent sinus bradycardia in 5, unexplained syncope in 3, and atrial fibrillation with slow ventricular rate in the remaining 3. The pacing percentage was 34 ± 42% at the last visit. Most devices were implanted in the septo-apical or mid-septal region. There were no significant changes in echocardiographic parameters observed. One patient developed significantly increased TV regurgitation, without abnormal leaflet motion or TV annulus size changes, suggesting it to be due to RV pressure changes.

Conclusion: In patients chronically implanted with leadless pacemakers, there were no significant changes in heart structure and function observed, especially concerning the RV and TV.
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http://dx.doi.org/10.1093/europace/eux101DOI Listing
May 2018

Comparison of epicardial vs. endocardial reimplantation in pacemaker-dependent patients with device infection.

Europace 2018 04;20(4):e42-e50

Service de Cardiologie-Rythmologie, CHU Timone, 264 Rue Saint-Pierre, 13385 Marseille, France.

Aims: Reimplantation of cardiac implantable electronic devices (CIEDs) after extraction due to device infection is a major issue in pacemaker-dependent patients. We compared in-hospital and long-term outcomes with two techniques: epicardial reimplantation (EPI) before CIED extraction and temporary pacing (TP) with a view to delayed endocardial reimplantation.

Methods And Results: Two cohorts of consecutive pacemaker-dependent patients who underwent transvenous lead extraction at our tertiary centre were included in this retrospective cohort study. According to successive policies, either the EPI or the TP approach was used. In-hospital complications occurred at similar rates in the EPI (n = 59) and TP (n = 52) cohorts (37.3% vs. 32.7%, respectively; P = 0.61). Thirteen (25.0%) patients in the TP cohort eventually were reimplanted epicardially, mainly because of infection of the temporary lead. Finally, 65 patients were discharged with an epicardial device and 37 with an endocardial device. Median follow-up was 41.7 (interquartile range 34.1-51.5) months. No difference was observed in long-term mortality according to the reimplantation strategy, but use of TP was associated with a reduced risk of late endocarditis and device reintervention (hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.09-0.069, P = 0.01), whereas epicardial device reimplantation was associated with an increased risk (HR 3.62, 95% CI 1.07-12.21, P = 0.04).

Conclusion: We observed similar in-hospital outcomes in our EPI and TP cohorts. Twenty-five percent of the patients initially paced by a TP strategy finally needed an epicardial device, mainly because of infection of their TP lead. Use of TP resulted in lower rates of late endocarditis and device reintervention.
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http://dx.doi.org/10.1093/europace/eux111DOI Listing
April 2018

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

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

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

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

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

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

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

Spare Adenosine A2a Receptors Are Associated With Positive Exercise Stress Test In Coronary Artery Disease.

Mol Med 2016 Oct 19;22:530-536. Epub 2016 Jul 19.

UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.

During exercise, cardiac oxygen-consumption increases and the resulting low oxygen level in myocardium triggers coronary vasodilation. This response to hypoxia is controlled notably by the vasodilator adenosine and its A receptor (AR). According to the "spare receptor" pharmacological model, a strong AR-mediated response can occur in the context of a large number of receptors remaining unoccupied, activation of only a weak fraction of AR (evaluated using K) resulting in maximal cAMP production (evaluated using EC), and hence in maximal coronary vasodilation. In coronary artery disease (CAD), myocardial ischemia limits adaptation to exercise, which is commonly detected using the exercise stress test (EST). We hypothesized that spare AR are present in CAD patients to correct ischemia. Seventeen patients with angiographically-documented CAD and 17 control subjects were studied. We addressed adenosine-plasma concentration and AR-expression at the mononuclear cell-surface, which reflects cardiovascular expression. The presence of spare AR was tested using an innovative pharmacological approach based on a homemade monoclonal antibody with agonist properties. EST was positive in 82% of patients, and in none of the controls. Adenosine plasma-concentration increased by 60% at peak exercise in patients only (p<0.01). Most patients (65%), and none of the controls, had spare AR (identified when EC/K≤0.1) and a low AR-expression (mean: -37% vs controls; p<0.01). All patients with spare AR had a positive EST whereas the subjects without spare AR had a negative EST (p<0.05). Spare AR are therefore associated with positive EST in CAD patients and their detection may be used as a diagnostic marker.
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http://dx.doi.org/10.2119/molmed.2016.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082304PMC
October 2016

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

Ischaemia-modified albumin during experimental apnoea.

Can J Physiol Pharmacol 2015 Jun 6;93(6):421-6. Epub 2015 Feb 6.

UMR MD2, Aix Marseille Université and Institut de Recherche Biomédicale des Armées, Faculty de Medicine Nord, boulevard Pierre Dramard 13015 Marseille, France., Université de Toulon et du Var, avenue de l'Université, B.P. 20132-83957 La Garde Cedex, France.

Ischaemia-modified albumin (IMA) is a marker of the release of reactive oxygen species (ROS) during hypoxaemia. In elite divers, breath-hold induces ROS production. Our aim was to evaluate the kinetics of IMA serum levels during apnea. Twenty breath-hold divers were instructed to perform a submaximal static breath-hold. Twenty non-diver subjects served as controls. Blood samples were collected at rest, every minute, at the end of breath-hold, and 10 min after recovery. The IMA level increased after 1 min of breath-hold (p < 0.003) and remained high until recovery. Divers were separated into 2 groups: subjects who held their breath for less than 4 min (G-4) and those who held it for more than 4 min (G+4). After 3 min of apnoea, the increase of IMA was higher in the G-4 group than in the G+4 group (p < 0.008). However, at the end of apnoea, the IMA level did not differ between groups. If IMA level was globally correlated with the apnoea duration, it is interesting to note that the higher IMA level was not found in the best divers. Similarly, if arterial blood oxygen saturation (SpO2) was globally inversely correlated with apnoea duration, the lowest SpO2 at the end of breath-hold was not found in the divers that performed the best apnoea. We concluded that these divers save their oxygen. The IMA level provides a useful measure of resistance to hypoxaemia.
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http://dx.doi.org/10.1139/cjpp-2014-0538DOI Listing
June 2015

Electromyographic monitoring for prevention of phrenic nerve palsy in second-generation cryoballoon procedures.

Circ Arrhythm Electrophysiol 2015 Apr 4;8(2):303-7. Epub 2015 Mar 4.

From the APHM, Department of Cardiology, Timone University Hospital, Marseille, France (F.F., L.K., E.G., J.H., B.M., L.T., J.-C.D.) and UMR MD2, Aix, Marseille University (AMU), Marseille, France (F.F., J.-C.D.).

Background: Electromyography-guided phrenic nerve (PN) monitoring using a catheter positioned in a hepatic vein can aid in preventing phrenic nerve palsy (PNP) during cryoballoon ablation for atrial fibrillation. We wanted to evaluate the feasibility and efficacy of PN monitoring during procedures using second-generation cryoballoons.

Methods And Results: This study included 140 patients (43 women) in whom pulmonary vein isolation was performed using a second-generation cryoballoon. Electromyography-guided PN monitoring was performed by pacing the right PN at 60 per minute and recording diaphragmatic compound motor action potential (CMAP) via a quadripolar catheter positioned in a hepatic vein. If a 30% decrease in CMAP amplitude was observed, cryoapplication was discontinued with forced deflation to avoid a PNP. Monitoring was unfeasible in 8 of 140 patients (5.7%), PNP occurred in 1. Stable CMAP amplitudes were achieved before ablation in 132 of 140 patients (94.3%). In 18 of 132 patients (13.6%), a 30% decrease in CMAP amplitude occurred and cryoablation was discontinued. Each time, recovery of CMAP amplitude took <60 s. In 9 of 18 cases, a second cryoapplication in the same pulmonary vein was safely performed. We observed no PNP or complication related to electromyography-guided PN monitoring.

Conclusions: Electromyography-guided PN monitoring using a catheter positioned in a hepatic vein seems feasible and effective to prevent PNP during cryoballoon ablation using second-generation cryoballoon.
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http://dx.doi.org/10.1161/CIRCEP.115.002734DOI Listing
April 2015

Ablation of idiopathic ventricular tachycardia arising from posterior mitral annulus in an 11-month-old infant by transapical left ventricular access via median sternotomy.

Heart Rhythm 2015 Feb 29;12(2):430-2. Epub 2014 Oct 29.

APHM, Department of Cardiology, Timone University Hospital, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2014.10.030DOI Listing
February 2015

Novel electromyographic monitoring technique for prevention of right phrenic nerve palsy during cryoballoon ablation.

Circ Arrhythm Electrophysiol 2013 Dec 10;6(6):1109-14. Epub 2013 Oct 10.

Assistance Publique Hôpitaux de Marseille.

Background: Right phrenic nerve palsy (PNP) is the most frequent complication of cryoballoon ablation. Diaphragmatic electromyography can predict PNP with a comfortable safety margin. Our goal was to evaluate the feasibility, efficacy, and safety of electromyography-guided PN monitoring using a novel hepatic vein approach for prevention of PNP.

Methods And Results: This study includes 57 patients (47 males) indicated for cryoballoon ablation for treatment of atrial fibrillation. During right superior pulmonary vein ablation, the PN was paced at 60 beats per minute and diaphragmatic compound motor action potential (CMAP) amplitude was recorded via a quadripolar catheter positioned in a subdiaphragmatic hepatic vein. If a 30% drop in CMAP amplitude was observed, ablation was discontinued with forced deflation. Reliable recording of CMAP before ablation was feasible in 50 of 57 patients (88%). In 7 patients (12%), stable PN pacing could not be achieved. In 44 of 50 patients, CMAP amplitude remained constant during cryoapplication. The mean value of CMAP amplitude was 639.7±240.5 µV; mean variation was 13±4.3%. In 6 of 50 patients (12%) including 5 treated with a 23-mm cryoballoon and 1 with a 28-mm cryoballoon, the 30% reduction cutoff was reached and cryoablation was discontinued. Recovery of CMAP amplitude after discontinuing cryoablation took <60 seconds in all cases. No PNP or complication related to PN monitoring occurred.

Conclusions: Recording of diaphragmatic CMAP using a catheter positioned in a subdiaphragmatic hepatic vein seems feasible during cryoballoon ablation. Electromyography-guided PN monitoring seems safe and potentially helpful for prevention of PNP.
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http://dx.doi.org/10.1161/CIRCEP.113.000517DOI Listing
December 2013

Search for adenosine A2A spare receptors on peripheral human lymphocytes.

FEBS Open Bio 2013 17;3:1-5. Epub 2012 Nov 17.

Aix-Marseille Université, UMR MD2, Faculté de Médecine Nord, Marseille, France.

Some ligand-receptor couples involve spare receptors, which are apparent when a maximal response is achieved with only a small fraction of the receptor population occupied. This situation favours cross-reactions with low-affinity ligands, which may be detrimental for cell signaling. In the case of the adenosine A2A receptors (A2AR), which have an immunosuppressive effect on lymphocytes through cAMP production, the presence of spare A2AR remains to be established. We examined the situation using patients over-expressing lymphocyte A2AR and an agonist-like mAb to A2AR. We found that maximal mAb binding and functional response varied among the patients whereas the dissociation constant and half-maximal effective concentration had similar mean values (0.19 and 0.18 μM, respectively). Lymphocyte A2AR expression was correlated to plasma adenosine level and A2AR occupation but not to A2AR response. These results are consistent with a lack of a reserve of functional A2AR on human lymphocytes as a general rule and suggest that the amount and functional state of the expressed A2AR determine the maximal level of the lymphocyte response to adenosine.
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http://dx.doi.org/10.1016/j.fob.2012.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668538PMC
July 2013

Adenosine plasma level and A2A adenosine receptor expression: correlation with laboratory tests in patients with neurally mediated syncope.

Heart 2012 Jun;98(11):855-9

Department of Cardiology, CHU La Timone, 264, Rue Saint Pierre, 13005 Marseille, France.

Objectives: The purpose of this study was to investigate the hypothesis that responses to the ATP test and head-up tilt test (HUT) may be correlated with different purinergic profiles.

Design And Setting: The ATP and HUT identify distinct subsets of patients with neurally mediated syncope (NMS). Adenosine and its A(2A) receptors (A(2A)R) may be implicated in the pathophysiology of NMS in patients with positive HUT. Nothing is known about the purinergic profile of patients with positive ATP. PATIENTS AND MEASURES: This prospective study includes a consecutive series of patients with suspected NMS. All patients underwent both HUT and ATP. Before testing, samples were collected for measurement of baseline adenosine plasma level (APL) and expression.

Results: A total of 46 patients (25 men and 21 women) with a mean age of 57±18 years were enrolled. The HUT test was positive in 27 patients and the ATP test in 20. Both tests were positive in 9 and negative in 8. High APL was associated with high probability of positive HUT while low APL was associated with high probability of positive ATP. Expression of A(2A)R was lower in patients with positive ATP than in those with positive HUT.

Conclusion: These findings indicate that patients with NMS present different purinergic profiles and that responses to HUT and ATP are correlated with these profiles.
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http://dx.doi.org/10.1136/heartjnl-2011-301411DOI Listing
June 2012

Long-term outcomes following infection of cardiac implantable electronic devices: a prospective matched cohort study.

Heart 2012 May;98(9):724-31

Cardiology Department, CHU La Timone, Medical School of Marseilles, Marseilles, France.

Objective: To assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection.

Design: Two-group matched cohort study.

Setting: Tertiary-care institution.

Patients: Consecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device.

Interventions: In all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment.

Main Outcome Measures: All-cause mortality and predictors of long-term mortality.

Results: 197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12-70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034).

Conclusion: In patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.
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http://dx.doi.org/10.1136/heartjnl-2012-301627DOI Listing
May 2012