0328: Assessment of radiation exposure during cardiac device implantation: lessons learned from a multicenter registry

BackgroundFew data exist about radiation exposure during implantation of cardiac electrical device. No dose reference levels (DRLs) were reported.Purpose to define DRLs and to analyze factors related to an increased radiation dose delivered to patients and medical staff.Methods the Raypace study is a multicenter, prospective observational registry. Using a national database, patient demographic, procedural and radiation data were collected. Fluoroscopy time (FT) and dose-area product (DAP) were registered. Physician/staff exposure was measured using 2 real-time personal dosimeters, one worn under the lead apron and the other one worn outside the apron. Statistical analysis used log-transformation of DAP, FT and DAP/FT ratio.ResultsA total of 657 procedures from 9 institutions were reviewed. Pacemaker (PM) and cardioverter-defibrillator (ICD) implantation was performed in 481 and 176 patients, respectively. A cardiac resynchronization device was implanted in 153 patients. Fluoroscopy time was similar for PM and ICD implantations. Median fluoroscopy time was 836, 117 and 101 second and median DAP was 1410, 150 and 129 cGy.cm2 for biventricular, dual chamber and ventricular device implantation, respectively. LAO projection, in addition to AP projection, was used in 47% of the procedures. Five centers out of 9 used collimation. The median Hp (10) effective dose measured outside the lead apron was 4.6 µSv and 0.1 µSv under the lead apron.Regarding CRT implant procedures, four systems out of 6 were responsible for an increased exposure (p<0.001). DRLs were 2600, 338 and 332 cGy.cm2 for biventricular, dual chamber and ventricular device implantation, respectively.ConclusionsDAP reduction was improved with the use of latest generators but needed customized settings. Biventricular device implantation was responsible for the highest radiation exposure. However, radiation exposure during those procedures have decreased as compared to previously reported values

Effect of monovalency on anti-contactin-1 IgG4

Altres ajuts: Agence Nationale pour le Développement de la Recherche en Santé ; Association Française contre les Myopathies ; ArgenxAutoimmune nodopathies (AN) have been diagnosed in a subset of patients fulfilling criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who display no or poor response to intravenous immunoglobulins. Biomarkers of AN are autoantibodies, mainly IgG4, directed against the ternary paranodal complex composed by neurofascin-155, contactin-1 (CNTN1), and Contactin-associated-protein-1 (CASPR1) or against the nodal isoforms of neurofascin. IgG4 can undergo a Fab-arm exchange (FAE) which results in functionally monovalent antibody. This phenomenon differentially affects the pathogenicity of IgG4 depending on the target of autoantibodies. Here, we have evaluated this issue by examining the impact of valency on anti-CNTN1 IgG4 which induces paranodal destruction through a function blocking activity. Sera were obtained from 20 patients with AN associated with anti-CNTN1 antibodies. The proportion of monospecific/bispecific anti-CNTN1 antibodies was estimated in each patient by ELISA by examining the ability of serum antibodies to cross-link untagged CNTN1 with biotinylated CNTN1. To determine the impact of monovalency, anti-CNTN1 IgG4 were enzymatically digested into monovalent Fab and tested in vitro on cell aggregation assay. Also, intraneural injections were performed to determine whether monovalent Fab and native IgG4 may penetrate paranode, and antibody infiltration was monitored 1- and 3-days post injection. We found that the percentage of monospecific antibodies were lower than 5% in 14 out of 20 patients (70%), suggesting that IgG4 have undergone extensive FAE in situ. The levels of monospecific antibodies correlated with the titers of anti-CNTN1 antibodies. However, no correlation was found with clinical severity, and patients with low or high percentage of monospecific antibodies similarly showed a severe phenotype. Native anti-CNTN1 IgG4 were shown to inhibit the interaction between cells expressing CNTN1/CASPR1 and cells expressing neurofascin-155 using an in vitro aggregation assay. Similarly, monovalent Fab significantly inhibited the interaction between CNTN1/CASPR1 and neurofascin-155. Intraneural injections of Fab and native anti-CNTN1 IgG4 indicated that both mono- and bivalent anti-CNTN1 IgG4 potently penetrated the paranodal regions and completely invaded this region by day 3. Altogether, these data indicate anti-CNTN1 IgG4 are mostly bispecific in patients, and that functionally monovalent anti-CNTN1 antibodies have the pathogenic potency to alter paranode

IgG4 Valency Modulates the Pathogenicity of Anti-Neurofascin-155 IgG4 in Autoimmune Nodopathy

Altres ajuts: Agence Nationale pour la Recherche; Association Française contre les Myopathies (23593).Background and Objective s : IgG4 autoantibodies to neurofascin-155 (Nfasc155) are associated with a subgroup of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), currently named autoimmune nodopathy. We previously demonstrated that those antibodies alter conduction along myelinated axons by inducing Nfasc155 depletion and paranode destruction. In blood, IgG4 have the potency to exchange their moiety with other unrelated IgG4 through a process called Fab-arm exchange (FAE). This process results in functionally monovalent antibodies and may affect the pathogenicity of autoantibodies. Here, we examined this issue and whether FAE is beneficial or detrimental for Nfasc155 autoimmune nodopathy. Methods : The bivalency and monospecificity of anti-Nfasc155 were examined by sandwich ELISA in 10 reactive patients, 10 unreactive CIDP patients, and 10 healthy controls. FAE was induced in vitro using reduced glutathione and unreactive IgG4, and the ratio of the : light chain was monitored. To determine the pathogenic potential of bivalent anti-Nfasc155 IgG4, autoantibodies derived from patients were enzymatically cleaved into monovalent Fab and bivalent F(ab')2 or swapped with unreactive IgG4 and then were injected in neonatal animals. Results : Monospecific bivalent IgG4 against Nfasc155 were detected in the serum of all reactive patients, indicating that a fraction of IgG4 have not undergone FAE in situ. These IgG4 were, nonetheless, capable of engaging into FAE with unreactive IgG4 in vitro, and this decreased the levels of monospecific antibodies and modulated the ratio of the : light chain. When injected in animals, monovalent anti-Nfasc155 Fab did not alter the formation of paranodes; by contrast, both native anti-Nfasc155 IgG4 and F(ab')2 fragments strongly impaired paranode formation. The promotion of FAE with unreactive IgG4 also strongly diminished the pathogenic potential of anti-Nfasc155 IgG4 in animals and decreased IgG4 clustering on Schwann cells. Discussion : Our findings demonstrate that monospecific and bivalent anti-Nfasc155 IgG4 are detected in patients and that those autoantibodies are the pathogenic ones. The transformation of anti-Nfasc155 IgG4 into monovalent Fab or functionally monovalent IgG4 through FAE strongly decreases paranodal alterations. Bivalency thus appears crucial for Nfasc155 clustering and paranode destruction

0107: Strategy of early detection and active management of supraventricular arrhythmia with remote monitoring: the randomized, multicenter SETAM trial

ObjectiveAtrial fibrillation (AF) is a common arrhythmia associated with increased risk of thromboembolic events or other complications. The French randomized, multicenter, SETAM trial assessed the impact of the home monitoring (HM) technology on detection and treatment of supra-ventricular arrhythmia (SVA).MethodsPatients (pts) implanted with a dual chamber pacemaker were enrolled in the study at hospital discharge if they had a sinusal rhythm at enrollment, no antiarrhythmic, anticoagulant or dual-antiplatelet therapy, and if they had a CHA2DS2-VASc score of 2 or more. The pts were randomly assigned to an active group (Act Gp), followed by Biotronik HM, or a control group (Cont Gp) without HM surveillance. The time from implantation to the first SVA-related intervention was compared between the 2 groups (primary endpoint).ResultsA total of 595 pts (mean age = 79±8 y.o, 63% male, mean CHA2DS2-VASc score = 3.7±1.2) were followed during 12.8±3.3Mo. The most prevalent co-morbidities were hypertension (82% pts), diabetes (29%) and vascular disease (24%). Implantation indications were atrio-ventricular blocks in 77% of pts, sinus node disease in 20% and others in 3%.The global SVA incidence was 25% (29% in the Act Gp vs 22% in the Cont Gp, p=ns).A therapy (drugs or ablation) was instituted for 49/291 pts (17%) in the Act Gp vs 43/304 pts (14%) in the Cont Gp (p=ns). The median time from implantation to the first therapy for SVA was 114 [44; 241] days in the Act Gp vs 224 [67; 366] days in the Cont Gp, representing a median gain of 110-days in SVA management (50% reduction, p=0.01). Over these 92 pts, 54 had AF (59%) and 38 had atrial flutter or tachyarrhythmia (41%). Anticoagulation was initiated in 80% of pts and antiarrhythmic drugs in 55%.ConclusionThe SETAM study demonstrated that HM allows earlier detection and treatment of SVA in pacemaker pts. The next step is to report how early detection of SVA with HM can possibly improve the patients clinical outcome

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study

Background: Undiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. Methods and results: In the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. Conclusions: We did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node

Implication du système NALP-1 dans le vitiligo non segmentaire (une étude immunohistochimique)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Resolved complete atrioventricular block and left ventricular severe dysfunction in patient with Wegener’s granulomatis after cyclophosphamide and corticosteroid treatment

Wegener&rsquo;s granulomatosis is a systemic granulomatous focus on small to medium sized vessels. It typically affects sinuses, lungs and kidneys due to necrotizing granulomatous vasculitis. Less commonly, cardiac involvement is reported up to 8%-44% of cases [1-3]. It often rises to supraventricular arrhythmia, left ventricular systolic dysfunction, pericarditis, myocarditis, and valvulitis [4,5]. Cardiac conducting tissue involvement is rare and associated with increased mortality. It was only reported in fourteen previous cases, some of them were reversible to medical treatment [6].&nbsp

The consensus Immunoscore in phase 3 clinical trials; potential impact on patient management decisions

The consensus Immunoscore has a prognostic value that has been confirmed in two randomized phase 3 clinical trials, and it provides a reliable estimate of the recurrence risk in colon cancer. The latest edition of the WHO classification of the Digestive System Tumors introduced for the first time the immune response as an essential and desirable diagnostic criteria for digestive cancers. Therefore, the immune response and Immunoscore evaluation within the tumor microenvironment is clinically relevant. In addition, the evaluation of the Immunoscore in stage III colon cancer patients from the IDEA France clinical trial evaluating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy demonstrated the predictive value of Immunoscore for treatment duration. Immunoscore predicted response to 6 months FOLFOX chemotherapy both in low- and high-risk Stage III patients. Low-risk patients (T1-3, N1) with High-Immunoscore had the 3-year DFS of 91.4% when treated with the 6-month FOLFOX, and only 80.8% with the 3-month regimen. The international validation of the prognostic value of the consensus Immunoscore together with its predictive value to guide treatment provides important information for the personalized management of colon cancer patients

Effect of monovalency on anti-contactin-1 IgG4

IntroductionAutoimmune nodopathies (AN) have been diagnosed in a subset of patients fulfilling criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who display no or poor response to intravenous immunoglobulins. Biomarkers of AN are autoantibodies, mainly IgG4, directed against the ternary paranodal complex composed by neurofascin-155, contactin-1 (CNTN1), and Contactin-associated-protein-1 (CASPR1) or against the nodal isoforms of neurofascin. IgG4 can undergo a Fab-arm exchange (FAE) which results in functionally monovalent antibody. This phenomenon differentially affects the pathogenicity of IgG4 depending on the target of autoantibodies. Here, we have evaluated this issue by examining the impact of valency on anti-CNTN1 IgG4 which induces paranodal destruction through a function blocking activity.MethodsSera were obtained from 20 patients with AN associated with anti-CNTN1 antibodies. The proportion of monospecific/bispecific anti-CNTN1 antibodies was estimated in each patient by ELISA by examining the ability of serum antibodies to cross-link untagged CNTN1 with biotinylated CNTN1. To determine the impact of monovalency, anti-CNTN1 IgG4 were enzymatically digested into monovalent Fab and tested in vitro on cell aggregation assay. Also, intraneural injections were performed to determine whether monovalent Fab and native IgG4 may penetrate paranode, and antibody infiltration was monitored 1- and 3-days post injection.Results and discussionWe found that the percentage of monospecific antibodies were lower than 5% in 14 out of 20 patients (70%), suggesting that IgG4 have undergone extensive FAE in situ. The levels of monospecific antibodies correlated with the titers of anti-CNTN1 antibodies. However, no correlation was found with clinical severity, and patients with low or high percentage of monospecific antibodies similarly showed a severe phenotype. Native anti-CNTN1 IgG4 were shown to inhibit the interaction between cells expressing CNTN1/CASPR1 and cells expressing neurofascin-155 using an in vitro aggregation assay. Similarly, monovalent Fab significantly inhibited the interaction between CNTN1/CASPR1 and neurofascin-155. Intraneural injections of Fab and native anti-CNTN1 IgG4 indicated that both mono- and bivalent anti-CNTN1 IgG4 potently penetrated the paranodal regions and completely invaded this region by day 3. Altogether, these data indicate anti-CNTN1 IgG4 are mostly bispecific in patients, and that functionally monovalent anti-CNTN1 antibodies have the pathogenic potency to alter paranode

“Neuro‐renal syndrome” related to anti‐contactin‐1 antibodies

International audienc