Advances in Antiarrhythmic Drug Therapy: Chronic Maintenance of Normal Sinus Rhythm Using Anti-arrhythmic Drugs in Patients with Atrial Fibrillation and Atrial Flutter.

POSTER PRESENTATIONS

Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter

Despite advances in catheter ablation techniques and device-based therapies for cardiac arrhythmias, antiarrhythmic drugs remain essential components of any comprehensive therapeutic strategy. Antiarrhythmic drug therapy, however, has been limited by both incomplete efficacy and a substantial potential for cardiac and extracardiac toxicity. As a result, only a few new antiarrhythmic agents have successfully completed clinical development programs and reached routine clinical usage over the past 20 years. Antiarrhythmic drugs may be indicated for ventricular tachycardia, sudden death prevention, or specific types of supraventricular arrhythmia. Implantable cardioverter-defibrillator (ICD) therapy has evolved as the primary treatment for most life-threatening ventricular arrhythmias, and antiarrhythmic drugs for these rhythms are currently mostly used either as acute interventions or as adjuncts to chronic ICD therapy. Although numerous trials have evaluated the effect of antiarrhythmic drugs to decrease ICD shocks or therapies, such data have yet to provide the sole basis for approval for any new agent. At the same time, drug therapy for atrial arrhythmias is often limited by the drug’s simultaneous effects on the ventricles, which has led to efforts to identify ionic channel targets specific to or preferentially located in the atria. The sustained outward K+ current (IKur, encoded by the Kv 1.5 subunit), the acetylcholine-activated outward K+ current (IKAch), and both peak and late atrial Na+ currents have therefore become potential targets for antiarrhythmic drug developers.1–4 Another approach has been to seek agents that synergistically affect multiple channels simultaneously, resulting in a net beneficial effect while minimizing toxicity. Other nontraditional targets for drug therapy that do not directly involve ion channels have also emerged as our understanding of the mechanisms of arrhythmias has improved. As a result, several new compounds are now at or near completion of phase 3 clinical trials, and other promising …

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

Objective The purpose of this study was to compare the outcome after biatrial ablation or left atrial ablation in patients with atrial fibrillation(AF) associated with mitral valve diseases.Methods All 109 patients who received biatrial ablation (n =61) or left atrial ablation (n =48) of atrial fibrillation combined with mitral valve surgery from January 2008 to December 2012 were analyzed for outcome differences.The etiology of mitral valve disease was rheumatic(n =81) and degenerative(n =28).Age at operation ranged from 39 to 62 years.AF duration ranged from 7 months to 13 years.Clinical manifestations of atrial fibrillation were persistent in 34 patiens and long-standing persistent in 75 patients.Results All patients successfully underwent radiofrequency modified maze procedure and mitral valve surgery.The biatrial ablation group had longer cardiopulmonary bypass time and crossclamp time.But there was no significant difference in mechanical ventilation,hospital length of stay and major postoperative complications or other postoperative outcome variables between biatrial ablation and lefi atrial ablation groups.There was 1 early death in left arial ablation group.At postoperative moment,the elimination rate of atrial fibril lation were 100％ (sinus rhythm in 94 and junctional rhythm in 15).At discharge,maintenance of normal sinus rhythm was 93.4％ in biatrial group and 80.9％ in left atrial group (P =0.046).Cumulative maintenance of normal sinus rhythm without atrial fibrillation recurrence at 3 years postoperatively was (89.0 ± 4.4) ％ in biatrial group and (75.6 ± 7.3) ％ in left atrial group,P =0.096.But the incidence of atrial flutter at 1 year postoperatively in left atrial group(10.6％) was significantly higher than the biatrial group (0),P =0.032.Conclusion Compared with left atrial ablation,biatrial ablation was more effective in restoration and maintenance of sinus rhythm without increasing the risk of postoperative complications.In addition,biatrial ablation was more effective in preventing the occurrence of postoperative atrial flutter. Key words: Atrial fibrillation ; Mitral valve ; Catheter ablation

ORAL PRESENTATION

Four recent randomized controlled studies that compared rhythm control versus rate control therapy demonstrated that rate control therapy is an acceptable alternative to rhythm control therapy. The control of heart rate achievable with pharmacologic therapy is imperfect and, in many patients, difficult to obtain. Ablation and pacing therapy offers better control of heart rate than drug therapy. The aim of the PAF 2 trial was to evaluate the effect of antiarrhythmic drug therapy on long-term maintenance of normal sinus rhythm after ablation and pacing therapy and to evaluate the effect of maintenance of normal sinus rhythm on major clinical events, quality of life and cardiac performance and, therefore, to evaluate whether antiarrhythmic drug strategy yields any additional benefit to ablation and pacing therapy. In this multicenter randomized controlled trial, 68 patients with severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. Although patients in the antiarrhythmic drug arm had a reduction in the risk of developing chronic atrial fibrillation, there was no clinical benefit beyond that obtained with ablation and pacing alone. On the contrary, antiarrhythmic therapy was associated with more serious adverse clinical events, i.e. episodes of heart failure and hospitalization. This suggests that the control of ventricular rhythm by ablation and pacing has a greater beneficial effect on short-term clinical outcome than the preservation of atrial contraction. Therefore, the results of PAF2 study are consistent with the drug trials comparing rhythm and rate control.

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

Does atrial fibrillation ablation really reduce stroke rates?

Atrial fibrillation (AF) is common and highly variable in its clinical presentation and evolution. Iit causes substantial morbidity and mortality, including impaired quality of life, heart failure, systemic emboli, and stroke. An accurate diagnosis is important and should be distinguished from atrial flutter or other arrhythmias which involves the atrium. Management of patients with AF involves 3 objectives: rate control, rhythm control, and prevention of thromboembolism. A rate control strategy alone, without attempts at restoration or maintenance of sinus rhythm (SR), is reasonable in some patients with AF, especially those who are asymptomatic. In some circumstances, when the cause of AF is reversible, such as when AF occurs after cardiac surgery, no long-term therapy may be necessary. The CHADS2 scoring system can be used to risk stratify patients with nonvalvular AF to determine the need for warfarin. The risk of thromboembolism or stroke does not differ between pharmacological and electrical CV. Ablation of the AV conduction system and permanent pacing is an option for patients with rapid ventricular rates despite maximum medical therapy. However, there is growing concern about the negative effects of long-term RV pacing. Biventricular pacing may overcome many of the adverse hemodynamic effects associated with RV pacing. Pharmacological therapy to maintain SR should be considered in patients who have troublesome symptoms. Drugs should be used to decrease the frequency and duration of episodes, and to improve symptoms. AF recurrence while taking an antiarrhythmic drug is not indicative of treatment failure and does not necessitate a change in antiarrhythmic therapy. Antiarrhythmic drug choice is based on side effect profiles and the presence or absence of structural heart disease, heart failure, and hypertension. Catheter ablation for AF is currently considered a second-line therapy in highly symptomatic patients in whom one or more antiarrhythmic agents have failed. (J Karadiol Indones. 2010;31:187-95) Keywords: Atrial fibrillation, rate control, rhythm control, thromboembolisme, stroke, anticoagulation

Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Valentin Fuster), who responds to the information, sharing his reasoning with the reader (regular type). A discussion by the authors follows. A 61-year-old man presents with 2 weeks of exertional dyspnea. Pertinent medical history includes hypertension, nephrolithiasis, and internal hemorrhoids. He takes no medications and has no known drug allergies. His father died after a myocardial infarction at 57 years of age. He formerly smoked 1 pack of cigarettes daily for 15 years but ceased tobacco use 10 years before presentation. He ingests 2 glasses of alcohol weekly and denies illicit drug use. His caffeine intake is limited. He is an architect and is married, with healthy children. On physical examination, his temperature is 98.0°F, blood pressure is 130/85 mm Hg bilaterally, pulse is irregular at 130 beats per minute, and respiratory rate is 18 breaths per minute with an oxygen saturation of 97% while breathing room air. He is a slender white man in no distress. His jugular venous pressure is elevated at 14 cm H 2 O. There is no thyromegaly, and the carotid upstrokes are brisk, without bruits. Cardiovascular examination reveals a rapid and irregular heart rhythm with variation in the intensity of the first heart sound. The point of maximal impulse is not displaced. The remainder of the chest and abdominal examination is within normal limits. The extremities are warm and show mild pitting edema. Laboratory testing is significant for normal renal function and electrolytes, but a hemogram reveals a mild thrombocytopenia of 90 000 platelets/μL. ECG demonstrates atrial fibrillation (AF) with an average ventricular rate of 123 bpm ( Figure 1 ). Figure 1. The 12-lead ECG showing atrial fibrillation with a rapid ventricular rate. Dr Valentin Fuster : This is a …

See Article by Diness et al There is an urgent unmet need for better treatment of atrial fibrillation (AF) given its strong impact on morbidity and mortality and the expected increase in AF prevalence with the aging of the population.1,2 Current AF management involves antithrombotic therapy to reduce the risk of stroke and normalization of the ventricular response rate (rate control) or restoration and maintenance of normal sinus rhythm (rhythm control).3,4 Although numerous clinical trials have established that both rate and rhythm control produce similar outcomes, rhythm control is often attempted to reduce AF symptoms.3,5 Antiarrhythmic drugs and catheter ablation are the most commonly used approaches for rhythm control therapy. Although ablation is generally more effective in maintaining normal sinus rhythm than antiarrhythmic drugs, it is associated with a significant risk for adverse events3,4 and is not an option for every AF patient, particularly in light of the high costs, the need of specialized skills, and the expected increase in AF prevalence. Moreover, a large fraction of the patients who undergo AF ablation receive additional subsequent treatment with antiarrhythmic drugs.3 Thus, antiarrhythmic drugs still have a major impact on AF management. However, currently available antiarrhythmic drugs have limited efficacy, particularly in longer-lasting forms of AF, and a substantial risk of adverse effects, including ventricular proarrhythmia, which are likely in large part because of their development in the absence of a detailed understanding of AF mechanisms.6,7 Pharmacological AF therapy generally targets the 2 main arrhythmogenic mechanisms: ectopic activity and reentry (Figure [A]).10 Ectopic activity is inhibited by reducing atrial excitability (eg, using class I …

The 2010 European Society of Cardiology Guidelines on the Management of Atrial Fibrillation: An Evolution or Revolution?

See Article by Srivatsa et al It is well known that atrial fibrillation (AF) is an independent risk factor for all-cause mortality and is also associated with an increased risk of stroke and heart failure.1,2 If these risks are indeed causal, then it would be logical that maintenance of sinus rhythm should improve mortality. Randomized trials have sought to compare rate and rhythm control strategies with the hypothesis that patients with AF would derive a mortality benefit from maintaining sinus rhythm, but most have failed to prove this hypothesis. Previous studies comparing a rate versus rhythm control strategy using antiarrhythmic drugs, such as AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management), RACE (Rate Control Versus Electrical Cardioversion), and STAF (Strategies of Treatment of Atrial Fibrillation)3–5 failed to show a reduction in stroke and mortality with a rhythm control strategy and at most demonstrated an improvement in symptoms and quality of life.6–8 Explanations for these results have included that the benefit of sinus rhythm may be offset by the harmful effects of antiarrhythmic drugs (particularly amiodarone); the percentage of patients maintaining sinus rhythm with medical rhythm control is low; and the relationship of AF and mortality may be associative and not causative. It should be noted, however, that a substudy of AFFIRM did demonstrate reduce mortality in those patients who actually maintained sinus rhythm regardless of their randomized strategy.9 In recent years, several randomized trials have shown that catheter ablation is superior to antiarrhythmic drugs to maintain sinus rhythm.10,11 If part of the benefit of sinus rhythm is being undermined by the toxicities of antiarrhythmics, then it would be logical to retest the hypothesis that rhythm control could benefit mortality through the use of ablation. The major limitation …

Cryoablation: Sooner or Later?