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.

Implementation of a classification strategy of Raman data collected in different clinical conditions: application to the diagnosis of chronic lymphocytic leukemia.

The literature is rich in proof of concept studies demonstrating the potential of Raman spectroscopy for disease diagnosis. However, few studies are conducted in a clinical context to demonstrate its applicability in current clinical practice and workflow. Indeed, this translational research remains far from the patient's bedside for several reasons. First, samples are often cultured cell lines. Second, they are prepared on non-standard substrates for clinical routine. Third, a unique supervised classification model is usually constructed using inadequate cross-validation strategy. Finally, the implemented models maximize classification accuracy without taking into account the clinician's needs. In this paper, we address these issues through a diagnosis problem in real clinical conditions, i.e., the diagnosis of chronic lymphocytic leukemia from fresh unstained blood smears spread on glass slides. From Raman data acquired in different experimental conditions, a repeated double cross-validation strategy was combined with different cross-validation approaches, a consensus label strategy and adaptive thresholds able to adapt to the clinician's needs. Combined with validation at the patient level, classification results were improved compared to traditional strategies.

Conformation changes in human hair keratin observed using confocal Raman spectroscopy after active ingredient application.

OBJECTIVE: In hair care cosmetic products' evaluation, one commonly used method is to evaluate the hair appearance as a gold standard in order to determine the effect of an active ingredient on the final state of the hair via visual appreciation. Although other techniques have been proposed for a direct analysis of the hair fibres, they give only surface or structural information, without any accurate molecular information. A different approach based on confocal Raman spectroscopy has been proposed for tracking in situ the molecular change in the keratin directly in the human hair fibres. It presents a high molecular specificity to detect chemical interactions between molecules and can provide molecular information at various depths at the cortex and cuticle levels. METHODS: To evaluate the potential of confocal Raman spectroscopy in testing the efficiency of cosmetic ingredients on keratin structure, we undertook a pilot study on the effectiveness of a smoothing shampoo on natural human hair, by analysing α-helix and ß-sheet spectral markers in the Amide I band and spectral markers specific to the cystin sulfur content. RESULTS: We confirmed that an active proved to be effective on a gold standard decreases α-helix keratin conformation and promotes ß-sheet keratin conformation in the hair fibres. We also showed that treatment with the effective active decreases the intensity of covalent disulfide (S-S at 510 cm-1 ) cross-linking bands of cysteine. These data confirm that the effective active also acts on the tertiary structure of keratin. CONCLUSION: From these experiments, we concluded that the effective active has a smoothing effect on the human hair fibres by acting on α-helix and ß-sheet keratin conformation and on the tertiary structure of keratin. Based on these results, confocal Raman spectroscopy can be considered a powerful technique for investigating the influence of hair cosmetic ingredients on keratin structure in human hair fibres. Moreover, this analytical technique has the advantage of being non-destructive and label free; in addition, it does not require sample extraction or purification and it can be applied routinely in cosmetic laboratories.

OBJECTIF: Dans l'évaluation des produits cosmétiques pour le soin des cheveux, une méthode communément utilisée consiste à évaluer l'aspect des cheveux afin de déterminer l'effet d'un principe actif sur l'état final des cheveux via l'appréciation visuelle. Bien que d'autres techniques ont été proposées pour une analyse directe de la fibre capillaire, elles ne donnent que des informations de surface ou de structure, sans aucune information moléculaire précise. Une approche différente par la spectroscopie confocale Raman a été proposée pour le suivi in situ du changement moléculaire de la kératine directement dans les fibres de cheveux humains. Il présente une grande spécificité moléculaire, détecter les interactions chimiques entre les molécules et peut fournir des informations moléculaires à différents niveaux de profondeur du cortex et de la cuticule. MÉTHODES: Afin d'évaluer le potentiel de la spectroscopie Raman confocale pour tester l'efficacité des ingrédients cosmétiques sur la structure de la kératine, nous avons entrepris une étude pilote sur l'efficacité d'un shampooing lissant sur cheveux naturels, en analysant les marqueurs spectraux de l'hélice α et du feuillet ß dans la bande Amide I et les marqueurs spectraux spécifiques au contenu en sulfure-cystine. RÉSULTATS: Nous avons confirmé qu'un actif s'avérant efficace sur un gold standard diminue la conformation de la kératine en hélice α et favorise la conformation de la kératine en feuillet ß dans les fibres des cheveux. Nous avons également montré que le traitement avec l'actif efficace diminue l'intensité des bandes de cystéine réticulant sous forme de ponts disulfures covalents (S - S à 510 cm-1). Ces données confirment que l'actif efficace agit également sur la structure tertiaire de la kératine. CONCLUSION: À partir de ces expériences, nous avons conclu que l'actif efficace a un effet lissant sur les fibres du cheveu humain en agissant sur la conformation hélice α et feuillet ß de la kératine et sur la structure tertiaire de la kératine. Sur la base de ces résultats, la spectroscopie confocale Raman peut être considérée comme une technique puissante pour étudier l'influence des ingrédients cosmétiques sur la structure de la kératine dans les fibres de cheveux. De plus, cette technique analytique a l'avantage d'être non destructive et ne nécessite pas de marquage; de plus, elle ne nécessite pas d'extraction ou de purification des échantillons et peut être appliquée en routine dans les laboratoires de cosmétiques.

Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy.

BACKGROUND: Topical delivery of molecules into the human skin is one of the main issues in dermatology and cosmetology. Several techniques were developed to study molecules penetration into the human skin. Although widely accepted, the conventional methods such as Franz diffusion cells are unable to provide the accurate localization of actives in the skin layers. A different approach based on Raman spectroscopy has been proposed to follow-up the permeation of actives. It presents a high molecular specificity to distinguish exogenous molecules from skin constituents. METHODS: Raman micro-imaging was applied to monitor the skin penetration of hyaluronic acids (HA) of different molecular weights. The first step, was the spectral characterization of these HA. After, we have determined spectral features of HA by which they can be detected in the skin. In the second part, transverse skin sections were realized and spectral images were recorded. RESULTS: Our results show a difference of skin permeation of the three HA. Indeed, HA with low molecular weight (20-300 kDa) passes through the stratum corneum in contrast of the impermeability of high molecular weight HA (1000-1400 kDa). CONCLUSION: Raman spectroscopy represents an analytical, non-destructive, and dynamic method to evaluate the permeation of actives in the skin layers.

Contribution of Raman spectroscopy in nephrology: a candidate technique to detect hydroxyethyl starch of third generation in osmotic renal lesions.

BACKGROUND AND OBJECTIVES: HydroxyEthyl Starch (HES) has been one of the most commonly used colloid volume expanders in intensive care units for over 50 years. The first and second generation HES, with a high molecular weight (≥200 kD) and a high degree of substitution (≥0.5), has been associated with both renal dysfunction and osmotic nephrosis-like lesions in histological studies. Recently, third generation HES (130 kD/<0.5) has also been shown to impair renal function in critically ill adult patients although tubular accumulation of HES has never been proven in the human kidney. Our objective was to demonstrate the potential of Raman micro-imaging to bring out the presence of third generation-HES in the kidney of patients having received the volume expander. DESIGN: Four biopsies presenting osmotic nephrosis-like lesions originated from HES-administrated patients with impaired renal function were compared with HES-negative biopsies (n = 10) by Raman microspectroscopy. RESULTS: The first step was dedicated to the identification of a specific vibration of HES permitting the detection of the cellular and tissue accumulation of the product. This specific vibration at 480 cm(-1) is assigned to a collective mode of the macromolecule; it is located in a spectral region with a limited contribution from biological materials. Based on this finding, HES distribution within tissue sections was investigated using Raman micro-imaging. Determination of HES positive pixels permitted us to clearly distinguish positive cases from HES-free biopsies (proportions of positive pixels from the total number of pixels: 23.48% ± 28 vs. 0.87% ± 1.2; p = 0.004). CONCLUSIONS: This study shows that Raman spectroscopy is a candidate technique to detect HES in kidney tissue samples currently manipulated in nephrology departments. In addition, on the clinical aspect, our approach suggests that renal impairment related to third generation HES administration is associated with osmotic nephrosis-like lesions and HES accumulation in the kidney.

[Relation between cavo-tricuspid isthmus anatomy studied by transesophageal echocardiography and the immediate outcome of radiofrequency ablation of common atrial flutter]. / Relation entre l'anatomie de l'isthme cavo-tricuspide étudiée par échocardiographie trans-oesophagienne et les résultats immédiats de l'ablation par radiofréquence du flutter auriculaire commun.

Radiofrequency ablation is the only curative treatment of common atrial flutter. The aim of the treatment is to create a line of bidirectional block at the level of the cavo-tricuspid isthmus. This objective can be achieved in the vast majority of the patients. However, it may difficult or even not possible to create an isthmus block. The anatomy of the right atrium is subject to important variations, especially at the isthmus level. We therefore tested the hypothesis that these anatomic variations might influence the immediate outcome of cavo-tricuspid isthmus ablation. The anatomy of cavo-tricuspid isthmus was studied by trans-oesophageal echocardiography. The shape of the isthmus (concave or not), the presence of diverticula and the degree of development of the Eustachian ridge were analysed. From these data, the cavo-tricuspid anatomy was classified as simple or complex. The immediate outcome of radiofrequency ablation was reviewed in 94 patients (mean age of 63 years) according to the anatomy, simple or complex. When the anatomy was classified as simple, the success rate of radiofrequency ablation was 95.6%; when the anatomy was complex, the success rate was 76.9% (overall success rate for the entire population equal to 90.4%). The length of the cavo-tricuspid isthmus did not influence the outcome of radiofrequency ablation. In summary, it appears that the anatomy of cavo-tricuspid isthmus seems to play a role in the immediate outcome of radiofrequency ablation of cavo-tricuspid isthmus.

Histopathological characterization of primary cutaneous melanoma using infrared microimaging: a proof-of-concept study.

BACKGROUND: The diagnosis of malignant melanoma is based upon the histological evaluation of the lesion. As such, the morphological interpretation relies on the expertise of a dermatopathologist. Infrared microimaging is emerging as a new powerful tool to investigate tissue biochemistry. Infrared spectra probe the biochemical constitution of the sample and are real tissue-specific spectroscopic fingerprints. OBJECTIVES: To assess the potential of infrared microimaging to aid in the analysis of tissue sections from primary cutaneous melanomas. METHODS: Ten samples of melanoma sections from the main histological subtypes were investigated using infrared microimaging combined with multivariate statistical analyses. RESULTS: This methodology yielded highly contrasted colour-coded images that permitted to highlight tissue architecture without any staining. It was possible to discriminate tumour areas from normal epidermis automatically, and intratumoral heterogeneity as revealed by our approach was correlated with the aggressiveness of the tumour. CONCLUSIONS: This proof-of-concept study shows that infrared microimaging could help in the diagnosis of primary cutaneous melanoma.

[Atrial fibrillation and heart failure: a dangerous criminal conspiracy]. / Fibrillation atriale et insuffisance cardiaque: une redoutable association de malfaiteurs.

Atrial fibrillation (AF) and heart failure (HF) often coexist. Both associated with an altered prognosis, their coexistence is associated with a higher mortality. This dangerous criminal conspiracy is explained by common risk factors but also by a strong causative relationship. AF can be the cause of HF, especially by leading to a tachycardia-induced cardiomyopathy, either isolated or associated to an underlying heart disease. HF is a common cause of AF. It remains to be determined whether AF is an independent mortality risk factor or a simple marker of advanced HF, perhaps because available therapeutic tools are not enough successful to prevent AF.

[Case report and review about radiofrequency catheter ablation in a patient with dilated cardiomyopathy and an implantable cardioverter defibrillator]. / Prise en charge d'une tachycardie ventriculaire récidivante sur cardiopathie non ischémique chez un patient implanté d'un défibrillateur.

The benefit of implantable cardioverter defibrillators (ICD) on total mortality has been demonstrated in primary prevention for heart failure patients, in whom they improve clinical outcomes. However, some of these patients present incessant ventricular tachycardia and receive appropriated shocks and antitachycardia therapy. Radiofrequency catheter ablation is an efficacious method to prevent the occurrence of stable ventricular tachy-arrythmia. We present here, the case of a patient with dilated cardiomyopathy implanted with an ICD in secondary prevention (ventricular tachycardia [VT]). The ICD delivered multiple appropriated shocks for monomorphic VT. A radiofrequency catheter ablation was successfully performed and the patient receives no further shock for the whole 18 months follow-up.

Confocal Raman microspectroscopy on excised human skin: uncertainties in depth profiling and mathematical correction applied to dermatological drug permeation.

Confocal Raman microspectroscopy represents the advantage of giving structural and conformational information on samples without any destructive treatment. Recently, several studies were achieved to study the skin hydration, endogenous and exogenous molecules repartition in the skin using the confocal feature of this technique. Meanwhile, when working through a material boundary with a different refractive index, the main limitation remains the spatial precision, especially the distortion in the depth and the depth resolution. Recently, several authors described mathematical models to correct the depth and the resolution values. In this study, we combined theoretical approaches, proposed by different authors with experimental measurements to try to find out the most appropriate approach for correction. We then applied the corrections on in-depth profiles tracking the penetration of Metronidazole, a drug produced by Galderma for rosacea treatment, through excised human skin.

Changes in adsorption and permeability of mitoxantrone on plasma membrane of BCRP/MXR resistant cells.

A selective analysis of adsorbed mitoxantrone (MTX) was performed by surface-enhanced Raman scattering (SERS) at the range of cellular membrane. Disruption of the membrane fluidity was carried out to appraise changes in membrane adsorption of MTX and drug uptake in sensitive (HCT-116 S) and resistant BCRP/MXR (HCT-116 R) cells. Based on spectral MTX modifications, micro-SERS spectroscopy discriminated clearly drug adsorption phenomena on plasma membrane from drug in solution. A 3-fold higher SERS intensity of MTX for HCT-116 R was observed concluding to a higher drug adsorption on resistant membrane. The increase of membrane fluidity with benzyl alcohol (BA) or chloroform (CF) resulted in a 3-fold decrease of MTX adsorption on HCT-116 R, exclusively. BA and CF improved intracellular accumulation of MTX (e.g., 823 and 191 pmol MTX/10(6) HCT-116 R incubated with or without BA). At 4 degrees C, drug accumulation measurements showed a decrease of MTX permeability in resistant membrane (42 pmol MTX/10(6) cells), restored with fluidizers (e.g., 342 pmol MTX/10(6) cells with BA). Fluorescence confocal microscopy involved an exclusive MTX emission around the plasma membrane of resistant cells whereas fluidizers increased the intracellular uptake of MTX in both cell lines at the same time with less drug emission around the plasma membrane. Changes of the membrane structure of resistant cells should modify both drug adsorption and membrane permeation.

[The choice of pacing sites: should we change our practice?]. / Choix des sites de stimulation cardiaque: doit-on changer notre pratique?

For the past 45 years the sites used for elective pacing have been the apex of the right ventricle and the right atrium. Although the initial objective of pacing was the "simple" correction of a conduction disorder, a more recent evolution has been to achieve a favourable haemodynamic effect, considering left ventricular filling and synchronisation of ventricular contraction as essential. Demonstration of the benefit in terms of survival brought about by pacing in atrioventricular block has not required large trials. However, it is possible that this improvement in morbidity and mortality is in part offset by the altered haemodynamics due to pacing at the right ventricular apex. At the atrial level, the prevention of AF is the holy grail of atrial pacing, but is far from being attained, perhaps because the physiopathological bases are not clear and have not really been demonstrated, casting doubt on the final objective. The choice of pacing site is essential in this context, as much in the atrium as in the ventricle. The current problem regarding this choice is the same as for all medical treatment, where the risk/benefit ratio is evaluated: if the usual sites are potentially deleterious, is it possible to continue using them or is it necessary to change implantation practices, and what level of proof is needed?

[External electrical cardioversion of atrial arrhythmia: predictive criteria of success]. / Cardioversion électrique externe des troubles du rythme atriaux: critères prédictifs de succès.

AIM: Supraventricular arrhythmia is a major public health problem because of its prevalence and clinical consequences. The first step of the treatment usually consists in restoring sinusal rhythm. The aim of this study is to evaluate results and predictive factors of success of electrical cardioversion. METHODS: We studied a series of 143 consecutive electric cardioversion preformed in 131 French patients. RESULTS: The rate of successful direct current cardioversion was 91.2%. Negative predictive factors are the height body mass index and the age of arrhythmia. Atrial flutter is a predictive factor of success. These results agree with published results. Our study highlights the interest of some nonantiarrhythmic drugs received by the patient during the period before the direct current cardioversion. Thus, a spironolactone treatment appears to be a new predictive factor of the success of electrical cardioversion (success in patients treated with spironolactone: 100% vs 89% without, P = 0.04). CONCLUSIONS: Our results agree with usual predictive factors of the success of cardioversion. Nevertheless, a new approach is that of the positive effect of spironolactone on cardioversion. A prospective randomized study is necessary to confirm this result.

[Electrophysiologic remodeling and drug treatment of atrial fibrillation]. / Remodelage électrophysiologique et traitement médicamenteux de la fibrillation atriale.

Since 1995, a number of studies have established and detailed the mechanisms of electrical and structural atrial remodeling induced by atrial fibrillation. Atrial remodeling involves many cellular components, from ionic channels to connexins. The determination of these mechanisms may help to define a new therapeutic targets of atrial fibrillation, a frequent arrhythmia that remains difficult to treat. Atrial remodeling prevention may lead to limit the evolution of the arrhythmia (early recurrences after reduction, AF secondary to atrial tachycardia, permanent AF, decrease in atrial contractility, sinus dysfunction). Except amiodarone, the usual antiarrhythmic drugs have no effect on atrial remodeling. Calcium channel inhibitors prevent early remodeling but have no effect on prolonged remodeling. Digoxin increases remodeling. Angiotensin II receptor inhibitors have been shown to prevent early AF recurrence after reduction and are very promising in such a direction. Other methods such as the one of antioxidant therapy seem to be promising and could define soon a new antiarrhythmic therapeutic class, the antiremodeling drugs.

[Predictive criteria of early recurrence of atrial arrhythmia after reduction by electrical cardioversion]. / Critères prédictifs de récidive précoce d'un trouble du rythme atrial après réduction par choc électrique externe.

The management of atrial arrhythmias aims not only to restore sinus rhythm but also to maintain it. Ten to thirty per cent of patients have early recurrence of atrial arrhythmias, the treatment of which remains empiric. The aim of this study was to define factors predictive of early recurrence of atrial arrhythmias and the consequences on the length of hospital stay. A series of 131 patients who underwent reduction of atrial arrhythmias by electrical cardioversion was studied retrospectively. A recurrence within 24 hours was observed in 12.2% of the patients. These recurrences significantly increased the length of hospital stay (6.8+/-6.3 versus 3.6+/-3.8 days, p=0.005). This study confirms two previously reported results with respect to more long-term recurrences. In the "early recurrence" group, the duration of the atrial arrhythmia was longer (p=0.003) and there were fewer treatments with amiodarone (p=0.03). In addition, original results were obtained. In the "early recurrence" group, the patients were more often treated with furosemide (p=0.02), class Ic antiarrhythmics (p=0.007) or anaesthetised with thiopental (p=0.002) than patients without early recurrences. Experimental data explain these results. However, they require confirmation by a prospective randomised trial.

[Arrhythmic cardiomyopathy]. / Cardiomyopathie rythmique.

Arrhythmic cardiomyopathy (ACM) is a clinical entity which can be reproduced in experimental models and which corresponds to all myocardial changes induced by chronic tachycardia. It may affect the atria and/or ventricles and, in this case, occur with all types of arrhythmia. Arrhythmia complicating a cardiomyopathy is the differential diagnosis of ventricular ACM. Nevertheless, the potential deleterious haemodynamic changes of any chronic arrhythmia may aggravate pre-existing ventricular dysfunction and, therefore, should always be considered. The development of ACM is usually progressive and depends on the heart rate, but there may also be a myocardial predisposition in certain cases. ACM is an association of haemodynamic, electrophysiological, metabolic and histological changes. Regression, which is the rule, starts in the first days following control of the ventricular rhythm but continues clinically over several months. The physiopathological mechanisms of ACM are multiple and include essentially abnormal cellular calcium concentrations. The treatment is optimally the restoration and maintenance of sinus rhythm, or at least control of the ventricular rate. Because of its curative effects, selective radiofrequency ablation of the arrhythmogenic substrate is the treatment of choice when this is localised. In chronic atrial fibrillation, when sinus rhythm cannot be maintained, the control of the ventricular response at rest and on exercise depends on pharmacological treatment, and, when ineffective, on radiofrequency modification of atrioventricular conduction with optimisation of the pacing mode.

Enoxaparin reduces brain edema, cerebral lesions, and improves motor and cognitive impairments induced by a traumatic brain injury in rats.

Traumatic brain injury (TBI) is often accompanied by secondary ischemia due, in part, to edema-induced blood vessel compression. Enoxaparin, a low-molecular weight heparin, which is efficacious in models of myocardial and brain ischemia was studied in lateral fluid percussion-induced TBI in rats. Enoxaparin was administered 2 h post-TBI at 0.5 mg/kg i.v. followed by 4 x 0.5, 4 x 1, or 4 x 2 mg/kg s.c. over 30 h. Brain edema was measured in the hippocampus, temporal cortex and parietal cortex. Edema was reduced by enoxaparin (0.5 + 4 x 0.5 mg/kg) in the hippocampus (-53%, p = 0.07) and the parietal cortex (-39%, ns). At 0.5 + 4 x 1 mg/kg edema was reduced in the hippocampus (-63%, p < 0.05) and the parietal cortex (-47%, p = 0.06). At 0.5 + 4 x 2 mg/kg, the reduction was more important in the hippocampus (-69%, p < 0.01) and in the parietal cortex (-50%, p < 0.05). No reduction was seen in the temporal cortex. The lesion size was reduced by enoxaparin at 0.5 + 4 x 1 mg/kg (-50%, p < 0.05), and at 0.5 + 4 x 2 mg/kg (-35%, ns). The neurological deficit evaluated with a 9-point scale was also improved with enoxaparin at 0.5 + 4 x 1 mg/kg 1 week post-TBI (p < 0.05). The cognitive impairment evaluated with a Lashley maze task was improved with enoxaparin (0.5 + 4 x 1 mg/kg) from 48 h (p < 0.05) to 2 weeks post-TBI (p < 0.01). Our results demonstrate for the first time that enoxaparin significantly reduces the brain contusion and edema, and improves the functional outcomes induced by a TBI. Therefore, enoxaparin could be a candidate drug to treat acute brain-injured patients.

[Electrophysiological remodeling induced by atrial fibrillation. An experimental curiosity or major factor in atrial fibrillation in man?]. / Remodelage électrophysiologique induit par la fibrillation atriale. Curiosité expérimentale ou déterminant majeur de la fibrillation atriale chez l'homme?

Atrial fibrillation usually progresses from a paroxysmal to a permanent arrhythmia, even in the absence of underlying cardiac disease. The treatment is more difficult when the arrhythmia is chronic. This progression may be explained by the aggravation of underlying cardiac disease with time. Another explanation is that the arrhythmia induces functional and structural changes of the atrial tissues (remodelling) which promote the perpetuation of the arrhythmia and which make treatment less effective. Although the electrophysiological changes predisposing to atrial fibrillation have been known for over 15 years, it was only in 1995 that experimental studies showed the presence of atrial electrophysiological remodelling induced by the arrhythmia. This process of long term adaptation of the atrial myocytes to the tachycardia comprises marked changes of the parameters which sustain the arrhythmia: changes in refractory period (decreased duration, inadaptation to the heart rate, increased dispersion), reduced conduction speed and sinus dysfunction. Atrial remodelling also affects the contractile function by the structural changes. The calcium currents play a major role in its development. This mechanism has not yet been completely defined in the clinical setting and its importance in sustaining the arrhythmia has not been clearly evaluated. Atrial fibrillation remains one of the most difficult arrhythmias to treat. A better understanding of cellular mechanisms of remodelling could open up new therapeutic approaches to limit the natural history of the arrhythmia with progression to chronicity and structural changes responsible for the degradation of atrial contractility.