Antithrombotic treatment of atrial fibrillation: new insights.

The incidence and prevalence of atrial fibrillation are quickly increasing, mainly due to the ageing of the population. Atrial fibrillation is, to date, a problem of public health. Atrial fibrillation is associated to a five-fold risk of stroke, which may be identified by score risks, such as CHADS(2) score. The classical antithrombotic treatment of atrial fibrillation is based on vitamin K antagonists. Trials made in the 90's have clearly shown that vitamin K antagonists were able to decrease stroke risk by about 60%. New oral anticoagulants are now available on the market to treat patients with atrial fibrillation. These drugs are dabigatran which has demonstrated an interest in the RE-LY trial. Two doses may be prescribed, 110 mg bid and 150 mg bid. Anti Xa have also demonstrated an interest : rivaroxaban in the ROCKET AF trial and apixaban in the AVERROES (versus aspirin) and ARISTOTLE trials. In the future these drugs will have a major place in the armamentarium used to treat patients with atrial fibrillation. In all these trials a decrease in intra cranial haemorrhages has been demonstrated. In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.

Whole body [(18) F]fluorodeoxyglucose positron emission tomography imaging for the diagnosis of pacemaker or implantable cardioverter defibrillator infection: a preliminary prospective study.

We studied the potential use of [(18) F]fluorodeoxyglucose ((18) F-FDG) whole body positron emission tomography (PET)-computed tomography for the diagnosis of device infection and extension of infection. Twenty-one patients with suspected device infection were prospectively included and compared with 14 controls free of infection. (18) F-FDG uptake on the box and on the leads was visually and quantitatively interpreted (using the maximal standard uptake value). The final diagnosis was obtained either from bacteriological data after device culture (n = 11) or by a 6-month follow-up according to modified Duke's criteria (n = 10). Ten patients finally showed infection on bacteriological study (n = 8) or during follow-up (n = 2). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 80%, 100%, 100% and 84.6% on patient-based analysis (presence or absence of infection). They were 100%, 100%, 100% and 100% for boxes, but only 60%, 100%, 100% and 73% for leads. Quantitative analysis could be useful for boxes but not for leads, for which the presence of a mild hot spot was the best criterion of infection. The four false negatives on leads received antibiotics for longer than the six true positives (20 ± 7.2 vs. 3.2 ± 2.3 days, p <0.01). Although the study was not designed for this purpose, management could have been modified by PET results in six of 21 patients. (18) F-FDG PET imaging may be useful for the diagnosis of device infection, and could impact on clinical management. Interpretation of negative cases should be performed with caution if patients have received antibiotics.

[Management of atrial fibrillation, what to know on old and new antiarrhythmics]. / Prise en charge de la fibrillation atriale, ce qu'il faut savoir sur les anciens et les nouveaux anti-arythmiques.

The management of atrial fibrillation, despite the development of ablative techniques, is mainly a pharmacological issue. For the last 25 years, no new oral antiarrhythmic drug has been launched in France. Class I antiarrhythmic drugs are efficient and safe if they are prescribed taking into account their contra-indications, but their therapeutic index is narrow. Class III antiarrhythmic drugs have limits, mainly due to the repolarization prolongation they induce and the risk of torsades de pointes. The mode of action of new antiarrhythmic drugs are based on an IKur blocking approach or on a multichannel blockade approach like that of dronedarone which is the only antiarrhythmic drug, to date, to have demonstrated an interest in terms of morbi-mortality in atrial fibrillation.

[Perspectives in cardiology: evidence of efficacy in atrial fibrillation and hopes in acute coronary syndrome]. / Perspectives en cardiologie : une efficacité démontrée dans la fibrillation atriale, des espoirs dans le syndrome coronaire aigu.

New antithrombotic drugs, antithrombin or anti Xa, will probably be very useful in cardiology. Two directions are interesting: in one hand atrial fibrillation, in which the unmet need concern drugs as effective as vitamine K antagonists but easier to use. On the other hand, in acute coronary syndrome the situation is different, there are many antithrombotic drugs available but there is still a place for innovative drugs which could provide a gain in terms of efficacy, but the hemorrhagic risk must remain acceptable. In atrial fibrillation, the RELY trial, performed in 18,113 patients has demonstrated, as compared to warfarin, a non inferiority of dabigatran at the dose of 110 mg BID and a superiority of dabigatran at 150 mg BID with a reduction of 34% of the primary endpoint, i.e.stroke and systemic embolism.

[Management of atrial fibrillation in France: the observational FACTUEL study]. / Fibrillation atriale, description de la prise en charge par les cardiologues, étude observationnelle. Résultats de l'étude Factuel.

OBJECTIVES: To describe the management of patients with atrial fibrillation (AF) and to study consistency with guidelines on management of AF. PATIENTS AND METHODS: Observational study on a random sample of cardiologists from a French national database. Each cardiologist had to recruit the first five patients meeting inclusion criteria (patients diagnosed with AF between January 2004 and one month before inclusion and accepting the collection of their medical data). RESULTS: Between December 2006 and January 2207, 1789 patients aged 71 on average have been recruited by 481 cardiologists. Fifty-one percent were diagnosed with paroxysmal, 15% with persistent and 33% with permanent AF. Restoration of sinus rhythm was preferred in forms considered as paroxysmal or persistent forms whereas control of the ventricular rate was more frequent in AF considered as permanent. Overall, therapeutic guidelines are applied in practice, despite a frequent use of amiodarone in patients with no associated heart disease. Prevention of thromboembolism was observed in 88% of the patients. CONCLUSIONS: FACTUEL is the biggest observational study on AF ever conducted in France. The therapeutic strategies used by the cardiologists are consistent with the objectives of preventing thromboembolism and controlling heart rhythm and/or rate. In most cases, the treatment used is consistent with the therapeutic guidelines.

[New antithrombotic drugs]. / Enjeux du futur. Nouveaux médicaments antithrombotiques.

Many trials are ongoing in the field of thromboembolic event prevention in atrial fibrillation. These drugs are acting as antithrombin and antifactor Xa. The goal is to obtain drugs that could be as efficient as vitamine K antagonists but that could be more easily used, mainly by avoiding INR measurements.

[How to evaluate sudden cardiac death risk after myocardial infarction?]. / Comment évaluer le risque de mort subite dans les suites d'un infarctus du myocarde ?

Sudden cardiac death is the mode of death of more than half of coronary heart disease patients. Preventing sudden cardiac death involves prevention of ventricular arrhythmias occurrence as well as the treatment by an implantable cardioverter defibrillator. The evaluation of sudden cardiac death risk should consider the underlying cardiopathy, the associated coronary risk factors and all pharmacological treatment efficient to reduce ventricular remodeling and myocardial ischemia. Only significant low ejection fraction and positive ventricular testing in some cases are now considered are now considered by the current French recommendations for cardioverter defibrillator implantation in primary prevention. However, other noninvasive markers such as heart rate variability and T wave alternans are of interest in sudden cardiac death risk stratification after myocardial infarction.

[Flecainide acetate utilisation review among general practitioners and hospital or office-based cardiologists in France. Obepine: observational study of flecainide]. / Etude de l'usage de l'acétate de flécainide auprès des médecins généralistes et des cardiologues hospitaliers ou libéraux en France. OBEPINE: etude observationnelle des prescriptions de flécaïnide.

A pharmacoepidemiological cross-sectional observational study was performed among a representative sample of French general practitioners and cardiologists. The aim of this study was to describe the prescription modalities of flecainide acetate, an Ic class antiarrhythmic, and how these modalities match the marketing authorization and the current summary of product characteristics. A total of 941 physicians participated in the study, 496 GPs and 445 cardiologists, and 1116 patients treated with flecainide for more than one month were included. On average, the patients were 68.7-years-old and 54% of them were women. Most of the initial flecainide prescriptions came from cardiologists (96%) and the check-up included an electrocardiogram (98%), a Holter monitoring (56%) and/or an echocardiography (71%). The preferred indication was supraventricular rhythm disorders (95%) and mostly atrial fibrillation (63%). A small proportion of coronary patients (7%) and of patient suffering from cardiac insufficiency (4%) was found. Flecainide was prescribed with a median posology of 150 mg per day, mostly as LP form (64%). Overall, the indications specified in the summary of product characteristics were respected in 90% of the cases, the contraindications in 91% of the cases and the patient follow-up was appropriate in 99% of the cases. In conclusion, the study showed that the prescription's conditions of flecainide in France complied with the summary of product characteristics data for most of the prescribing physicians with a respect of the indications, contraindications and management recommendations in 84% of the cases.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

[Clinical evolution of patients following investigation of atrial vulnerability after a first cerebral ischaemic accident]. / Evolution clinique des patients ayant eu une recherche de vulnérabilité atriale après un premier accident ischémique cérébral.

Atrial vulnerability reflects the ability of the atrium to fibrillate. ISAV (Ischemic stroke and atrial vulnerability) is a French epidemiological registry whose main goal is to assess the evolution modalities of patients in whom an electrophysiological study of the atrium has been performed. A group of 269 patients with a history of non elucidated ischemic stroke and an electrophysiological study of the atrium performed in a mean delay of 3 months after the stroke has been included. Their mean age at the time of the stroke was 55 +/- 15.8 years. The electrophysiological study has measured the effective refractory period of the atrium, the locoregional right intra-atrial conduction time, the index of latent atrial vulnerability and assessed the inductibility. The mean delay between the date of the stroke and the date of the last news was 4.4 +/- 2.8 years. We observed 12 deaths and 11 patients presented during the follow up a spontaneous atrial arrhythmia and 17 a recurrence of stroke. If we consider the occurrence of the 28 combined events (atrial arrhythmia and/or stroke), it is not correlated with the presence of an atrial septal defect nor with the existence of an atrial vulnerability. On the contrary this occurrence is correlated with tobacco consumption and/or arterial hypertension; 82% of patients have these risk factors versus 54% of patients without events (p = 0.004). This association is not significant in patients younger than 55 years.

[AFFIRM: what we have learned ... and pending issues]. / AFFIRM: ce que nous avons appris ... et les questions en suspens.

During these last years, several therapeutic strategies trials have been performed in atrial fibrillation: the goal was to compare the rhythm control strategy (restoration and maintenance of sinus rhythm) to the rate control strategy (slowing of heart rate in atrial fibrillation). The most important of these different trials is the AFFIRM study. The main conclusion of this trial is that rate control can be chosen in first intention and not only in case of failure of the rhythm control strategy. These results can not be applied to 2 categories of patients: on one hand patients with heart failure and on the other hand young patients without cardiopathy in whom the strategy of rhythm control and sinus rhythm maintenance, mainly by class I antiarrhythmic drugs, remains the better choice.

[Long-term evaluation of endocavitary cryoablation of nodal reentry]. / Evaluation à long terme de la cryoablation endocavitaire dans le traitement des réentrées nodales.

Radiofrequency ablation is the reference treatment of refractory nodal reentry. Cryoablation has the advantage of having more modulable effects and minimises the risk of permanent atrioventricular block (AVB). Its immediate efficacy seems comparable to that of radiofrequency ablation but the long-term results are not well known. Endocavitary cryoablation of the slow pathway was undertaken in 26 patients (18 women) with an average age of 47.7 +/- 72.8 years with re-entrant nodal tachycardia refractory to medical therapy. The primary success rate was 92% (24 out of 26). On average, 2.6 +/- 2.2 (1 to 10) cryoablations at - 70 degrees C were delivered and were preceded by 6.4 +/- 4.5 (1 to 16) cryomappings to locate the site of the slow pathway. During cryomapping, 8 episodes of AVB were observed in 6 patients (6 second or third degree), all of which were revertible on rewarming. No cases of permanent AVB were observed. An oesophageal stimulation test of inducibility was performed on the 4th day in 21 patients, 16 of which were not reinducible. During follow-up of 355 +/- 194 days, 22 of the 26 patients (85%) had no recurrence of the arrhythmia. Two of the 24 primary successes had a recurrence, in addition to the two primary failures. Two of the four recurrences occurred in a non-sustained form which was less disabilitating for the patient and the recurrences were controlled in the 4 patients by antiarrhythmic therapy. These results suggest that cryoablation may be a reliable and effective long-term treatment of re-entrant nodal tachycardias. If confirmed in larger series in terms of efficacy and safety, cryoablation could become the treatment of choice of re-entrant nodal tachycardia.

[Automobile driving and implantable defibrillators]. / Conduite automobile et défibrillateur implantable.

The consequences of implanting an automatic cardioverter defibrillator (ICD) on vehicle driving in France are poorly known. This retrospective study examined the behaviour at the wheel of ICD recipients who were recommended to abstain from driving for 3 to 6 months after device implantation. The study population included 98 patients (mean age = 59.5 +/- 14.8 years) followed for a mean of 24. +/- 23.9 months, who underwent ICD implant for ventricular tachycardia (65% of patients ventricular fibrillation (15%), syncope (8%), as part of a research protocol of myocardial cell transplantation 6%, or for primary prevention (5%). The underlying heart disease was ischemic in 59% of patients dilated cardiomyopathy in 11%,hypertrophic cardiomyopathy in 8%, valvular in 6%. Brugada syndrome in 4%, right ventricular arrhythmogenic cardiomyopathy in 2%, and miscellaneous disorders in 9% of patients. Five patients died without post mortem interrogation of the ICD. Only 28% of drivers remembered, and 13% observed, the recommended driving limitations. However, 45% (the oldest) claimed to drive prudently. During follow-up, 47% of patients received an ICD shock. Their mean it ventricular ejection fraction was 34 +/- 14%, versus 43 +/- 18% in patients who received no ICD therapy (p = 0.015). Syncope occurred in 16% who received ICD shocks. Shocks were delivered during driving in 6 patients, without consequent accident. Despite their non-observance of recommended driving limitations. ICD recipients suffered few traffic accidents. Legislation in France should reproduce the guidelines issued by European professional societies and enacted by the British laws.

[New energy sources for ablative methods]. / Nouvelles sources d'énergie dans les méthodes ablatives.

Radiofrequency current is the reference energy source for endocavitary ablation of arrhythmias. It is particularly well adapted for the ablation of focal arrhythmogenic substrates such as accessory pathways or foyers of automatism. Technological advances have made the lesions larger but the extension of the indications of percutaneous ablation to more complex substrates such as atrial fibrillation have justified the evaluation of alternative energies. The production of linear transmural lesions or deeper lesions which respect the parietal myocardial architecture and endocardial structure are a challenge for these energies. The capacity of functional mapping specific to cryogenics has provided this energy source with a clinical application for ablation of high risk structures whereas other energies, despite the chronicity of their experimental evaluation, are still at the stage of preliminary clinical trials with the sophisticated catheters in special indications.