Joint Position Paper of the Working Group of Pacing and Electrophysiology of the French Society of Cardiology (SFC) and the Société française d'imagerie cardiaque et vasculaire diagnostique et interventionnelle (SFICV) on magnetic resonance imaging in patients with cardiac electronic implantable devices.

Magnetic resonance imaging (MRI) has become the reference imaging for the management of a large number of diseases. The number of MR examinations increases every year, simultaneously with the number of patients receiving a cardiac electronic implantable device (CEID). A CEID was considered an absolute contraindication for MRI for years. The progressive replacement of conventional pacemakers and defibrillators by MR-conditional CEIDs and recent data on the safety of MRI in patients with "MR-nonconditional" CEIDs have progressively increased the demand for MRI in patients with a CEID. However, some risks are associated with MRI in CEID carriers, even with "MR-conditional" devices because these devices are not "MR-safe". A specific programing of the device in "MR-mode" and monitoring patients during MRI remain mandatory for all patients with a CEID. A standardized patient workflow based on an institutional protocol should be established in each institution performing such examinations. This joint position paper of the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Société française d'imagerie cardiaque et vasculaire diagnostique et interventionnelle (SFICV) describes the effect and risks associated with MRI in CEID carriers. We propose recommendations for patient workflow and monitoring and CEID programming in MR-conditional, "MR-conditional nonguaranteed" and MR-nonconditional devices.

Arrhythmogenic response to isoproterenol testing vs. exercise testing in arrhythmogenic right ventricular cardiomyopathy patients.

Aims: To compare the arrhythmic response to isoproterenol and exercise testing in newly diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results: We studied isoproterenol [continuous infusion (45 µg/min) for 3 min] and exercise testing (workload increased by 30 W every 3 min) performed in consecutive newly diagnosed ARVC patients. Both tests were evaluated with regard to the incidence of (i) polymorphic premature ventricular contractions (PVCs) and couplet(s) or (ii) sustained or non-sustained ventricular tachycardia (VT) with left bundle branch block [excluding right ventricular outflow tract VT]; and compared to a control group referred for the evaluation of PVCs without structural heart disease. Thirty-seven ARVC patients (63.5% male, age 38 ± 16 years) were included. The maximal sinus rhythm heart rate achieved during isoproterenol testing was significantly lower compared to exercise testing (149 ± 17 bpm vs. 166 ± 19 bpm, P < 0.0001). However, the incidence of polymorphic ventricular arrhythmias was much higher during isoproterenol testing compared to exercise testing [33/37 (89.2%) vs. 16/37 (43.2%), P < 0.0001]. Interestingly, isoproterenol testing was arrhythmogenic in all 15 patients in whom baseline PVCs were reduced or suppressed during exercise testing. During both isoproterenol and exercise testing, control group presented a low incidence of ventricular arrhythmias compared to ARVC patients (8.1% vs. 89.2%, P < 0.0001 and 2.7% vs. 43.2%, P < 0.0001, respectively). Conclusions: The incidence of polymorphic ventricular arrhythmias is significantly higher during isoproterenol compared to exercise testing in newly diagnosed ARVC patients, suggesting its potential utility for the diagnosis.

VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome.

BACKGROUND: Despite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known. OBJECTIVE: To study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS. METHODS: ECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months. RESULTS: Thirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025). CONCLUSIONS: Type 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.

Telemetric assessment of referred vaginal hyperalgesia and the effect of indomethacin in a rat model of endometriosis.

Symptoms of endometriosis (ENDO), among others, include pelvic/abdominal and muscle pain. Non-steroidal anti-inflammatory agents are first-line treatment for this pain. Similar to women, rats with surgically induced ENDO, but not its surgical control, exhibit vaginal hyperalgesia, which in rats is evidenced by a decreased threshold for the visceromotor response (VMR) induced by vaginal distention. Here we assess the VMR in rats with implanted probes that telemetrically transmit EMG activity from the abdominal muscle. The feasibility and sensitivity of this technique for monitoring the VMR threshold across the estrous cycle and the influence of Indomethacin on ENDO-induced vaginal hyperalgesia were evaluated. VMR thresholds in response to vaginal distention with an infusion pump were measured in different estrous stages. Indomethacin (5 or 10 mg/kg i.p. or s.c.) was injected in proestrus rats and 40-60 min later the VMR threshold was measured. The VMR threshold varied across the estrous cycle only in ENDO rats, being lowest in proestrus. Indomethacin increased this threshold in proestrus ENDO rats. These results show that telemetric assessment of the VMR is a sensitive tool, suitable for long-term studies in conscious rats. The results with this technique also suggest that ENDO-associated vaginal hyperalgesia involves COX activity, the feature that also underlies inflammatory pains.

Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

Inter-laboratory exercise on steroid estrogens in aqueous samples.

An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: "Xenobiotics in Urban Water Cycle". The objective was to evaluate the performance of testing laboratories determining "Endocrine Disrupting Compounds" (EDC) in various aqueous matrices. As the main task three steroid estrogens: 17alpha-ethinylestradiol, 17beta-estradiol and estrone were determined in four spiked aqueous matrices: tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS. Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones.

Development of a common priority list of pharmaceuticals relevant for the water cycle.

Pharmaceutically active compounds (PhACs), including prescription drugs, over-the-counter medications, drugs used in hospitals and veterinary drugs, have been found throughout the water cycle. A desk study was initiated by the Global Water Research Coalition to consolidate a uniform selection of such compounds in order to judge risks of PhACs for the water cycle. By identifying major existing prioritization efforts and evaluating the criteria they use, this study yields a representative and qualitative profile ('umbrella view') of priority pharmaceuticals based on an extensive set of criteria. This can then be used for further studies on analytical methods, occurrence, treatability and potential risks associated with exposure to PhACs in water supply, identifying compounds most likely to be encountered and that may have significant impact on human health. For practical reasons, the present study excludes veterinary drugs. The pragmatic approach adopted provides an efficient tool to manage risks related to pharmaceuticals and provides assistance for selecting compounds for future studies.

[Catheter ablation for atrial fibrillation]. / Ablation par radiofréquence de la fibrillation atriale.

The mainstay of treatment for atrial fibrillation (AF) remains pharmacological, however, catheter ablation, since an early attempt in 1994 has undergone many evolutions up to the present day whereby it has taken an increasing place in the management of this arrhythmia. In paroxysmal AF, the most recent studies report a success rate of more than 80% at 1 year of follow-up after a single procedure (free of symptoms without antiarrhythmic drugs). In persistent AF the technique continues to evolve with a success rates between 70% and 95% even if several long and complex procedures are often needed, which are not without risk, to achieve these results. With constant improvement in this field catheter ablation has become a valuable tool in the management strategy of AF.

The expression of the testis-specific Dyrk4 kinase is highly restricted to step 8 spermatids but is not required for male fertility in mice.

Members of the dual specificity tyrosine phosphorylated and regulated kinase family (Dyrk) were shown to have a highly testis-abundant or testis-restricted expression pattern. Furthermore, for some members of the family an involvement in gene expression regulation by phosphorylating transcription factors has been shown. Since little is known about the complex regulation of germ cell differentiation in spermatogenesis, we analysed the possible involvement of Dyrk kinases in this process. ISH experiments showed specific distribution of Dyrk kinases mainly in postmeiotic germ cell. We identified Dyrk4 as a testis-specific kinase with a very restricted expression to stage VIII postmeiotic spermatids. In vitro and in vivo experiments proved the enzymatic activity and suggested the cytoplasmatic localisation of Dyrk4. Finally, analysis of a Dyrk4 deficient mouse line showed that Dyrk4 is dispensable for male fertility, hence suggesting a functional redundancy of some Dyrk isoforms during spermiogenesis.

[Identification of candidates for multisite pacing: results and presumed mechanisms of action after five years experience]. / Identification des patients candidats a la stimulation multisite. Résultats et mécanismes d'action supposés a l'issue d'une expérience monocentrique de 5 ans.

Biventricular resynchronisation is an additional therapeutic option in the management of refractory heart failure, with a functional and haemodynamic benefit as well as an improved morbidity and mortality. However, the rate of non-responsive patients has prompted a re-think about the presumed mechanisms of action for this procedure. This study aims to identify candidates more successfully. Based on five years experience in this centre, our work confirmed a medium and long term clinical benefit with multisite pacing. Nevertheless, there was evidence of a relative discordance between the functional benefit and the haemodynamic impact in terms of ejection fraction achieved with resynchronisation. While QRS narrowing appears to be a predictive factor for a successful procedure, the ECG alone is not sufficient to select 'unsynchronised' candidates. Statistical analysis reveals that before implantation the independent predictive factors to identify non-responsive patients include the presence of a complication of myocardial infarction and a low grade mitral leak. The limits of the ECG suggest a more mechanical than electrical approach to understanding the mechanisms of action for resynchronisation. Its effectiveness in cases of right bundle branch block confirm the hypothesis of left intra-ventricular conduction defects, not apparent on the surface ECG but accessible through new imaging techniques. Based on the hypothesis of delayed movement of the ventricular walls, the principle of resynchronisation aims to restore homogenous contraction. Echocardiography allows observation of electromechanical delay and opens new perspectives in the future for selecting patients for pacing. Ar

Competitive and hindering effects of natural organic matter on the adsorption of MTBE onto activated carbons and zeolites.

Equilibrium and kinetic adsorption of methyl tert-butyl ether (MTBE) onto three coal-based activated carbons, one coconut-based activated carbon, and two zeolites are elucidated in this study. Natural organic matter (NOM) and MTBE competed for the adsorption of activated carbons to different extents. The ideal adsorbed solution theory (IAST) combined with the equivalent background compound (EBC) model can adequately describe the NOM competition and predict the isotherms of MTBE onto the activated carbons. No competitive adsorption was observed for one of the zeolites, mordenite, due to the molecular effect. Besides, the aperture size, and the SiO2/Al2O3 ratio of the zeolite may also play an important role in the adsorption of MTBE from the aqueous phase. The surface diffusion model accurately simulated the transport of MTBE within the adsorbents employed in different water matrices. For all the activated carbons tested, the surface diffusivity of MTBE in natural water was nearly equal to that in deionized water, indicating that no apparently hindering effect occurs. A much slower adsorption kinetic of mordenite in natural water was observed since the opening apertures on mordenite may be appreciably hindered and blocked by NOM.

[Characterization of premature ventricular contraction initiating ventricular fibrillation]. / Caractéristiques morphologiques des extrasystoles ventriculaires initiatrices des fibrillations ventriculaires.

UNLABELLED: The aim of this study is to characterize the electrocardiographic features of premature ventricular contractions (PVC) from different anatomical region that trigger ventricular fibrillation (VF). METHODS AND RESULTS: 36 consecutives patients (20 males, 42+/-14 yrs) undergoing VF ablation from 7 centres were studied (22 with idiopathic VF, 4 associated with a long QT syndrome, 3 with Brugada syndrome, 4 with ischaemic cardiomyopathy and 3 associated with other substrate). Mapping of these PVC showed 2 different origins, which were then confirmed by ablation: right ventricular outflow tract (RVOT) (22%) and peripheral Purkinje network (81%). One patient had PVC from both origins (Brugada). RVOT PVC were frequent but had triggered only 5+/-5 episodes of VF for 26+/-33 months. Purkinje PVC were more likely to be present during electrical storm with 18+/-28 episodes of VF for 33+/-45 months. Right Purkinje PVC have a left bundle branch block with superior axis morphology whereas left Purkinje ones have a right bundle branch block. The axis of activation showed variation from inferior to superior depending on the area of origin from the Purkinje network and the exit site to the myocardium. However Purkinje PVC were characterized by short QRS duration (126+/-18 vs 145+/-13ms for RVOT PVC; p=0.05). In addition the coupling interval was significantly shorter compared to RVOT PVC (292+/-45 vs 358+/-37ms respectively; p=0.005). CONCLUSION: PVC initiating VF demonstrate specific electrocardiographic features that facilitate determination of their origin. Ablation of these typical PVC is feasible in order to reduce ICD shock.

Thioarsenates in sulfidic waters.

It has long been recognized that the formation of soluble arsenic sulfur complexes plays a key role for the mobility and toxicity of arsenic in sulfate-reducing environments. Knowledge of the exact arsenic species is essential to understand the behavior of arsenic in sulfidic aquifers and to develop remediation strategies. In the past, monomeric and trimeric thioarsenites were assumed to be the existing species in sulfidic systems. In this study, thioarsenates were identified by IC-ICP/MS in arsenite- and sulfide-containing solutions as well as in a reduced groundwater from a contaminated site. The unexpected finding of an oxidation of As(lll) to As(V) in thioarsenates in strongly reducing systems can be explained by the high affinity between As(Ill) and sulfur. In sulfide-containing solutions without oxidant, As(lll) therefore undergoes disproportionation to thioarsenates (As(V)) and elemental arsenic. It has previously been supposed that mobility as well as toxicity of arsenic increases if the redox state decreases. For sulfidic waters, the opposite is probably the case. Thus, the formation of thioarsenates could be used in connection with remediation strategies. Thioarsenates are highly sensitive to oxygen and pH. This is important for analytical procedures. A loss of soluble arsenic as well as a conversion to arsenite and arsenate may occur if water samples containing thioarsenates are analyzed with conventional methods.

Echocardiographic advances in atrial fibrillation and supraventricular arrhythmias.

Advances in echocardiography have paved the way for the development of intracardiac catheters with ultrasound transducers mounted on its tip. With this technology it has become possible for the interventional electrophysiologist to perform continuous echocardiographic examination during a procedure without the need for general anaesthesia or additional staff. Intracardiac echocardiography (ICE) allows the monitoring of catheter movement in real-time, assessment of catheter-tissue contact and potentially prevents and recognizes complications like thrombus formation and pericardial effusion. In addition recent technologies allow acquiring the full spectrum of Doppler-imaging permitting evaluation of haemodynamic data during the procedure. All these advances have made ICE an ideal tool for the interventional electrophysiologist, serving as a diagnostic and imaging tool during invasive electrophysiological procedures. This review will summarize currently available technology of ICE and its indications and applications in electrophysiological procedures.

[Mapping and ablation of malignant ventricular arrhythmias]. / Cartographie et ablation des arythmies ventriculaires malignes.

Endocavitary investigations showed that the ventricular extrasystoles originated in the common ventricular myocardium (pulmonary infundibulum) in only 9 cases whereas the majority arose from the Parkinje system either on the anterior wall of the right ventricle or in septal region of the left ventricle. The extrasystoles arising from the Parkinje system and pulmonary infundibulum differed in their duration and polymorphism (128 +/- 18 ms vs 145 +/- 13 ms, p = 0.05; 3.3 +/- 2.7 morphologies vs 1.1 +/- 0.4, p < 0.001, respectively). During the extrasystoles, the local Pukinje potential preceded the ventricular activation by variable intervals, some of which were very long, up to 150 ms. Seven applications of radiofrequency were delivered on average per patient on the most distal part of the Purkinje system leading to ablation of the specific activation. The clinical results were spectacular: 88% of patients had no further episodes of ventricular fibrillation as demonstrated by analysis of the defibrillator with an average follow-up period of more than 34 months.

[The place of ablation in the treatment of atrial fibrillation: where are we and where are we going?]. / Place de l'ablation dans le traitement de la fibrillation auriculaire: où en sommes-nous? où allons-nous?

Atrial fibrillation, the most common arrhythmia, is frequently disabling and drug resistant and is associated with significant complications, especially thromboembolic events. Non-pharmacological approaches including surgery and catheter-based ablation have been developed for the most symptomatic patients. These new treatment strategies have dramatically increased our knowledge of the pathophysiology of this arrhythmia but most importantly have demonstrated that atrial fibrillation is curable. Since 1994, 2 different concepts have been used, aiming to modify the substrate responsible for AF maintenance using linear lesions, or to ablate the triggers located from within the pulmonary veins (PV) in about 90% of cases. The vast majority of the laboratories in the world are now using approaches centred on isolation of the PV. These approaches are far from being perfect but good enough to be offered in routine practice to selected patients in experienced centres. The importance of PVs in the initiation of AF has been clearly demonstrated and they also have a possible role in the maintenance of AF. However, the existence of non venous foci or a prominent substrate for AF maintenance limits the success rate to about 70%. As a consequence, a combination of PV isolation and linear lesions is commonly used. This more complex procedure carries a significantly higher success rate however with an increased risk of tamponade. As a consequence, we need to identify which patients will require linear lesions in addition to PV isolation. At the present time, AF ablation is restricted to symptomatic patients who have failed at least 1-2 antiarrhythmic drugs but future technical improvements based on presently applied concepts are likely to widen the indications for ablation therapy of AF.

Mapping and ablation of ventricular fibrillation.

Sudden cardiac death frequently results from ventricular fibrillation (VF). While VF is frequently the eventual mode of death in patients with abnormal ventricular substrates, it has also been described in patients with structurally normally hearts. Until recently, the management of patients who have survived sudden cardiac death has focused on treating the consequences by implantation of a defibrillator. However, such therapy remains restricted in many countries, is associated with a prohibitive cost to the community, and may be a cause of significant morbidity in patients with frequent episodes or storms of arrhythmia. Evidence emerging from the study of fibrillation both in the atria and the ventricle suggests an important role for triggers arising from the Purkinje network or the right ventricular outflow tract in the initiation of VF. Initial experience in patients with idiopathic VF and even those with VF associated with abnormal repolarization syndromes (LQT or Brugada syndrome) or myocardial infarction suggests that long term suppression of recurrent VF may be feasible by the elimination of these triggers. With the development of new mapping and ablation technologies, and greater physician experience, catheter ablation of VF, with the ultimate aim of curing such patients at risks of sudden cardiac death, may not be an unrealistic goal in the future.