Irene Savelieva

2012 focused update of the ESC Guidelines for the management of atrial fibrillation

ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American–Australian–African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association ANDROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d. for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid (ASA) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospective, randomized, double-blind, Active-controlled, superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die (twice daily) b.p.m. : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled)-Vascular disease, Age 65–74, Sex category (female) CHADS2 : Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke (doubled) CI : confidence interval CRAFT : Controlled Randomized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : Randomized Double blind trIal to evaluate efficacy and safety of drOnedarone (400 mg b.i.d.) vs . amiodaroNe (600 mg q.d. for 28 daYS, then 200 mg qd thereafter) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v. : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d. : omni die (every day) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy PCI : percutaneous coronary intervention PREVAIL : Prospective Randomized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : Randomized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d. : ter in die (three times daily) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on …

Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention.

Atrial fibrillation (AF) is associated with significant morbidity and mortality. It is also a progressive disease secondary to continuous structural remodelling of the atria due to AF itself, to changes associated with ageing, and to deterioration of underlying heart disease. Current management aims at preventing the recurrence of AF and its consequences (secondary prevention) and includes risk assessment and prevention of stroke, ventricular rate control, and rhythm control therapies including antiarrhythmic drugs and catheter or surgical ablation. The concept of primary prevention of AF with interventions targeting the development of substrate and modifying risk factors for AF has emerged as a result of recent experiments that suggested novel targets for mechanism-based therapies. Upstream therapy refers to the use of non-antiarrhythmic drugs that modify the atrial substrate- or target-specific mechanisms of AF to prevent the occurrence or recurrence of the arrhythmia. Such agents include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, n-3 (ω-3) polyunsaturated fatty acids, and possibly corticosteroids. Animal experiments have compellingly demonstrated the protective effect of these agents against electrical and structural atrial remodelling in association with AF. The key targets of upstream therapy are structural changes in the atria, such as fibrosis, hypertrophy, inflammation, and oxidative stress, but direct and indirect effects on atrial ion channels, gap junctions, and calcium handling are also applied. Although there have been no formal randomized controlled studies (RCTs) in the primary prevention setting, retrospective analyses and reports from the studies in which AF was a pre-specified secondary endpoint have shown a sustained reduction in new-onset AF with ACEIs and ARBs in patients with significant underlying heart disease (e.g. left ventricular dysfunction and hypertrophy), and in the incidence of AF after cardiac surgery in patients treated with statins. In the secondary prevention setting, the results with upstream therapies are significantly less encouraging. Although the results of hypothesis-generating small clinical studies or retrospective analyses in selected patient categories have been positive, larger prospective RCTs have yielded controversial, mostly negative, results. Notably, the controversy exists on whether upstream therapy may impact mortality and major non-fatal cardiovascular events in patients with AF. This has been addressed in retrospective analyses and large prospective RCTs, but the results remain inconclusive pending further reports. This review provides a contemporary evidence-based insight into the role of upstream therapies in primary (Part I) and secondary (Part II) prevention of AF.

EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.

Christian Torp Pedersen (EHRA Chairperson, Denmark), G. Neal Kay (HRS Chairperson, USA), Jonathan Kalman (APHRS Chairperson, Australia), Martin Borggrefe (Germany), Paolo Della-Bella (Italy), Timm Dickfeld (USA), Paul Dorian (Canada), Heikki Huikuri (Finland), Youg-Hoon Kim (Korea), Bradley Knight (USA), Francis Marchlinski (USA), David Ross (Australia), Frédéric Sacher (France), John Sapp (Canada), Kalyanam Shivkumar (USA), Kyoko Soejima (Japan), Hiroshi Tada (Japan), Mark E. Alexander (USA), John K. Triedman (USA), Takumi Yamada (USA), and Paulus Kirchhof (Germany)

Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS).

Since the advent of the non-vitamin K antagonist oral anticoagulant (NOAC) agents, which act as direct thrombin inhibitors or inhibitors of Factor Xa, clinicians are provided with valuable alternatives to vitamin K antagonists (VKAs). At the same time, electrophysiologists frequently perform more invasive procedures, increasingly involving the left chambers of the heart. Thus, they are constantly faced with the dilemma of balancing the risk for thromboembolic events and bleeding complications. These changes in the rapidly evolving field mandate an update of the European Heart Rhythm Association (EHRA) 2008 consensus document on this topic.1 The present document covers the antithrombotic management during different ablation procedures, implantation or exchange of cardiac implantable electronical devices (CIEDs), as well as the management of peri-interventional bleeding complications. The document is not a formal guideline and due to the lack of prospective randomized controlled trials (RCTs) for many of the clinical situations encountered, the recommendations are often ‘expert opinion’. The document strives to be practical for which reason we subdivided it in the three main topics: ablation procedure, CIED implantation or generator change, and issues of peri-interventional bleeding complications on concurrent antiplatelet therapy. For quick reference, every subchapter is followed by a short section on consensus recommendations. Many RCTs are ongoing in this field and it is hoped that this document will help to prompt further well-designed studies. ### Ablation of atrial fibrillation, left atrial arrhythmias and right sided atrial flutter In patients with symptomatic paroxysmal or even persistent atrial fibrillation (AF), catheter ablation is indicated when antiarrhythmic drugs have failed in controlling recurrences or even as a first-line therapy in selected patients.2–4 Patients with AF have an increased risk of thromboembolic events, which varies according to the presence of several risk factors.5,6 Apart from their intrinsic thromboembolic risks, ablation in these patients increases thromboembolic risk due to the introduction and manipulation …

Primary and secondary prevention of atrial fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical relevance

Atrial fibrillation (AF) is an increasingly common arrhythmia that now stands at epidemic proportion, with more than 2.3 million people affected in the USA and over 4.5 million people affected in Western Europe. AF is an expression of underlying heart disease and is increasingly associated with hypertension, congestive heart failure, and ischemic heart disease. It is also a progressive disease secondary to continuous structural remodeling of the atria, which relates to AF itself, to changes associated with aging and to progression of the underlying heart disease. Traditionally, AF has been addressed only after it has already presented with pharmacological and nonpharmacological therapies designed for rhythm or rate control (secondary prevention). Although secondary prevention is the most feasible approach at present, the concept of primary prevention of AF with therapies aimed at preventing the development of substrate and correcting the risk factors for AF has emerged as a strategy, which is likely to produce a larger effect in the general population. Recent experiments provided new insights into AF pathophysiology, which generated background for new mechanism-based therapies. Agents targeting inflammation, oxidative injury, atrial myocyte metabolism, extracellular matrix remodeling, and fibrosis have theoretical advantages as novel therapeutic strategies. In this respect, drugs that are not traditionally antiarrhythmic such as angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, statins, and omega-3 polyunsaturated fatty acids have shown an antiarrhythmic potential in addition to any treatment effect on the underlying disease. These agents are thought to have an advantage of targeting both the occurrence and progression of the substrate for AF, thus, providing primary and secondary prevention of the arrhythmia. Although first experimental and hypothesis-generating small clinical studies or retrospective analyses have been encouraging, several larger, properly designed, prospective trials have not confirmed earlier observations. This review provides a contemporary evidence-based insight into the possible preventative and reverse remodeling role of statins and polyunsaturated fatty acids in AF.

Practical Considerations for Using Novel Oral Anticoagulants in Patients With Atrial Fibrillation

Novel oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, represent new options for preventing stroke in patients with atrial fibrillation, as shown by the results from large, randomized phase III trials. Because of their greater specificity, rapid onset of action, and predictable pharmacokinetics, the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) address several limitations of warfarin or other vitamin K antagonists in day‐to‐day clinical practice. However, a range of practical questions relating to the novel oral anticoagulants has emerged, including topics such as patient selection, treatment of patients with renal impairment, risk of myocardial infarction, drug interactions, switching between anticoagulants, and management of bleeding, in addition to use of these agents in patients requiring antiplatelet drug treatment or undergoing cardioversion or percutaneous interventions (eg, ablation). In this review, practical aspects of the use of novel oral anticoagulants in patients with atrial fibrillation are discussed, with reference to available data and guidance from prescribing information.

Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study

BACKGROUND Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF. OBJECTIVE The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent. METHODS This prospective, multicenter, randomized, double-blind, placebo-control parallel group phase II dose-ranging trial randomized patients with persistent AF (7 days to 6 months) 2 hours after successful electrical cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients were monitored daily by transtelephonic ECG. The primary end-point was the time to first AF recurrence. RESULTS Of 241 patients randomized, 238 took at least 1 drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500 mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF recurrence in the combined 500-mg and 750-mg groups was of borderline significance compared to the placebo group (P = .053) and significant compared to 375-mg group (P = .035). CONCLUSION No dose of ranolazine significantly prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined reduced AF recurrences, suggesting a possible role for this agent in the treatment of AF.

Guías de práctica clínica para el manejo de la fibrilación auricular

Responsabilidad: Las Guias de Practica Clinica recogen la opinion de la ESC y se han elaborado tras una consideracion minuciosa de las evidencias disponibles en el momento en que fueron escritas. Se anima a los profesionales de la sanidad a que las tengan en plena consideracion cuando ejerzan su juicio clinico. No obstante, las Guias de Practica Clinica no deben invalidar la responsabilidad individual de los profesionales de la salud a la hora de tomar decisiones adecuadas a las circunstancias individuales de cada paciente, consultando con el propio paciente y, cuando sea necesario y pertinente, con su tutor o representante legal. Tambien es responsabilidad del profesional de la salud verificar las normas y los reglamentos que se aplican a los farmacos o dispositivos en el momento de la prescripcion. El contenido de las Guias de Practica Clinica de la Sociedad Europea de Cardiologia (ESC) ha sido publicado para uso exclusivamente personal y educacional. No esta autorizado su uso comercial. No se autoriza la traduccion o reproduccion en ningun formato de las Guias de la ESC ni de ninguna de sus partes sin un permiso escrito de la ESC. El permiso puede obtenerse enviando una solicitud por escrito a Oxford University Press, la empresa editorial de European Heart Journal y representante autorizada de la ESC para gestionar estos permisos.

Pharmacological cardioversion of atrial fibrillation with vernakalant: evidence in support of the ESC Guidelines

Pharmacological rhythm control (often including electrical or pharmacological cardioversion) is an integral part of therapy for atrial fibrillation (AF) worldwide. Antiarrhythmic drug strategies would be preferred in many patients provided effective and safe antiarrhythmic agents are available. Also, pharmacological cardioversion could be the preferred option if the limitations of currently available drugs, such as restriction to patients without structural heart disease (flecainide and propafenone), risk of torsade de pointes (ibutilide), and slow onset of action (amiodarone), were overcome. The intravenous formulation of vernakalant (Brinavess, Cardiome) has been approved for pharmacological cardioversion of recent-onset AF (≤7 days) and early (≤3 days) post-operative AF in the European Union, Iceland, and Norway. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and has minimal effects in the ventricles and thus, is thought to have a low proarrhythmic potential. Vernakalant is administered as a 10 min infusion of 3 mg/kg, and if AF persists after 15 min, an additional dose of 2 mg/kg can be given. The efficacy and safety of the drug has been extensively investigated in randomized controlled trials against placebo and an active comparator (amiodarone). The placebo-extracted efficacy of vernakalant is ∼47%. A significant advantage is a rapid effect, with the median to conversion ranging between 8 and 14 min, with the majority of patients (75-82%) converting after the first dose. Vernakalant retained its efficacy in subgroups of patients with associated cardiovascular disease such as hypertension and ischaemic heart disease, but its benefit may be lower and risk of adverse effects is higher in patients with heart failure. In the post-market reports, cardioversion rates with vernakalant are 65-70%. This review focuses on the role of vernakalant in pharmacological cardioversion for AF.

European Heart Rhythm Association/Heart Failure Association joint consensus document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society

Arrhythmias confer a substantial risk of mortality and morbidity in patients with heart failure (HF), and this represents a major healthcare burden worldwide. There are at least 15 million patients with HF in Europe alone.1 The overall prevalence of HF ranges between 2 and 3%, but increases sharply after 75 years of age, reaching 10–20% among those in the eighth decade of life.1 Heart failure hospitalizations are increasing, and many of these may be related to cardiac arrhythmias. Indeed, episodes of decompensation may be related to arrhythmias, such as atrial fibrillation (AF). Atrial fibrillation per se contributes to an increased risk of mortality and morbidity from stroke and thromboembolism, and silent AF is common among patients with HF, not infrequently leading to a first presentation of AF with an ischaemic stroke.2 New developments in stroke prevention offer additional challenges in the HF patient. Sudden cardiac death (SCD) is also a major cause of mortality among HF patients and is commonly related to cardiac arrhythmias, particularly ventricular arrhythmias (VAs).3 In addition, associated co-morbidities, such as renal impairment, may influence cardiac arrhythmias, their complications, associated treatments, and prognostic implications.4 New developments in cardiac monitoring, cardiac resynchronization therapy (CRT), and other implantable devices have been introduced. These allow better detection and treatment of cardiac arrhythmias in HF, opening more opportunities for improvements in management. To address the management of arrhythmias in HF, a Task Force was convened by the European Heart Rhythm Association (EHRA) and the Heart Failure Association (HFA), endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS), with the remit to comprehensively review the published evidence available, to publish a joint consensus document on …