Oral Anticoagulant Use Around the Time of Atrial Fibrillation Ablation: A Review of the Current Evidence of Individual Oral Anticoagulant Use for Periprocedural Atrial Fibrillation Ablation Thromboembolic Prophylaxis

Atrial fibrillation is the most common arrhythmia and ablation is becoming more prevalent as a treatment option. Appropriate treatment of atrial fibrillation mandates thromboembolic prophylaxis, and atrial fibrillation ablation periprocedural management of oral anticoagulation is paramount because of the unique susceptibility for thromboembolism that exists for a patient undergoing ablation. Uninterrupted warfarin therapy is the current standard approach for periprocedural atrial fibrillation anticoagulation. Novel oral anticoagulants, including direct thrombin and factor Xa inhibitors, are being used more frequently for thromboembolic prophylaxis in atrial fibrillation patients, but the best strategy for using novel oral anticoagulants in periprocedural anticoagulation is unknown. Optimal periprocedural anticoagulation management strategies with oral anticoagulants, limitations of using novel oral anticoagulants, and future directions in this field are discussed.     

Predictive Value of Thromboembolic Risk Scores Before an Atrial Fibrillation Ablation Procedure

Risk Scores for Atrial Fibrillation Ablation Introduction: It is not clear whether transesophageal echocardiography (TEE) should be performed prior to a planned atrial fibrillation (AF) ablation in all patients. Methods and Results: The objectives of this study were to determine in 681 consecutive patients: (i) the relationship between the CHADS2 and CHA2DS2‐VASc scores, the presence of a thrombogenic milieu and left atrial (LA) volume; (ii) the need for TEE in patients with low and intermediate thromboembolic risk assessed; and (iii) the predictive accuracy of the these 2 scores for the presence of thrombi in the LA/LAA (LA appendage) before a planned AF ablation. The prevalence of thrombi was 1%. All patients with thrombi had LA dilatation, a CHADS2 score ≥1 and a CHA2DS2‐VASc score ≥2. CHADS2 or CHA2DS2‐VASc scores <2 had an almost maximal negative predictive capability of excluding the presence of a thrombus (99.8% and 100%, respectively; 95% CI: 99–100). A CHADS2 score ≥2 had a sensitivity and specificity of 86% (95% CI: 42–100) and 82% (95% CI: 79–85), respectively, to predict the presence of a thrombus in the LA/LAA, while a CHA2DS2‐VASc score ≥2 had a sensitivity and specificity of 100% (95% CI: 59–100) and 67% (95% CI: 63–70). The area under the curve for CHADS2 and CHA2DS2‐VASc scores ≥2 was 0.928 (95% CI: 0.906–0.946) and 0.933 (95% CI: 0.912–0.951), respectively. Conclusion: Not all patients undergoing planned endocardial pulmonary vein isolation need preprocedural TEE. Both scores <2 had an almost maximal negative predictive capability of excluding the presence of a thrombus in the LA/LAA. (J Cardiovasc Electrophysiol, Vol. 24, pp. 139‐145, February 2013)     

阵发性心房颤动P波最大时间及P波离散度的相关分析

目的 探讨P波最大时间（Pmax）和P波离散度（Pd）与阵发性心房颤动的关系.方法 测定72例阵发性心房颤动患者的Pd值、Pmax值、心房颤动时间和左心房内径（LAD）,并作相关性分析.结果 Pd≥40ms者心房颤动时间显著大于Pd〈40ms者（P〈0.05）;Pmaxt〉110ms者LAD大于Pmax〈110ms者（P〈0.05）.Pmax与心房颤动时间、LAD和年龄相关（P〈0.01或0.05）,Pd与心房颤动时间相关（P〈0.05）,Pmax与Pd之间存在相关性.结论 在预测心房颤动中,Pd特异性较高,Pmax敏感性较高,Pd与Pmax结合可提高阳性预测值.     

Prevention of Vascular Events in Patients with Atrial Fibrillation:

Atrial fibrillation (AF) is a common arrhythmia that is associated with an increased risk for vascular events, particularly stroke. Two different therapies have been extensively evaluated for prevention of vascular events in AF: oral anticoagulation (such as warfarin), and aspirin. Placebo-controlled trials of warfarin have been performed and summarized in a meta-analysis. There is clear evidence of a benefit, with a relative risk reduction in stroke of 67% and in total vascular events of 42%. Aspirin also has been studied and is effective, but with a more modest benefit (relative risk reduction of 22%). Several studies have compared warfarin and aspirin, and showed a clear benefit in favor of warfarin for reduction of vascular events and stroke. Compared to aspirin, the risk of major hemorrhage with oral anticoagulation is increased by 70% to 100%. Current practice guidelines recommend oral anticoagulation therapy for high-risk patients with AF, unless there is an increased risk for bleeding. Nonetheless, oral anticoagulation therapy with drugs such as warfarin is difficult for both patients and physicians because of the increased risk for bleeding and the need for ongoing monitoring of coagulation status. Many patients do not receive anticoagulation therapy despite its proven benefits. (J Cardiovasc Electrophysiol, Vol. 14, pp. S52-S55, September 2003, Suppl.)     

AFFIRM and RACE Trials: Implications for the Management of Atrial Fibrillation

The Atrial Fibrillation (AF) Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study (RACE) Trials evaluated strategies of rate control or rhythm control in atrial fibrillation. AFFIRM enrolled patients with recent onset AF, and at entry over half of all patients were in sinus rhythm. At any point in the trial, the achieved difference in cardiac rhythm was likely only about 30%. In RACE all patients were entered in AF, and at the end of the study, sinus rhythm was present in 10% vs 39%. The strategy of rate control was non-inferior to the rhythm control strategy in both trials, and permits consideration of rate control as primary therapy. However, the actual differences in rhythm were relatively small, and do not allow the conclusion that maintenance of sinus rhythm is inferior to non-maintenance.Current guidelines recommend that patients with paroxysmal AF receive warfarin if they have risk factors for stroke. This is supported by data from AFFIRM. Most strokes in AFFIRM occurred either during subtherapeutic INR, or after cessation of warfarin. Since more patients in the rhythm control arm of AFFIRM discontinued warfarin, it is possible that asymptomatic recurrences of paroxysmal AF fostered clot development and embolization. We cannot answer from the data available whether or not it is safe to discontinue anticoagulation if all episodes of AF are suppressed.Among the reasons that AF is associated with increased mortality may be that it encourages development of congestive heart failure or progressive left ventricular dysfunction. Congestive heart failure occurrence was monitored in both trials, and occurred at a rate of 2-5% without significant differences between rate and rhythm arms. In patients with heart failure at entry, a mortality trend in AFFIRM favored the rhythm control arm. The issue of survivorship and rhythm control in AF in congestive heart failure is undergoing further testing.     

Azimilide for Atrial Fibrillation: Clinical Trial Results and Implications

Azimilide dihydrochloride (or azimilide) is a class III antiarrhythmic drug currently under investigation that has been tested in atrial fibrillation in four randomized, placebo-controlled clinical trials to assess efficacy and dose range. These investigational trials showed that doses of azimilide 100 and 125 mg once daily prolonged the time to symptomatic arrhythmia recurrence in patients with a history of symptomatic atrial fibrillation, atrial flutter or both. Doses of 75 mg or less were not useful in this indication. Safety of azimilide has been examined in several different types of studies. In a large randomized clinical trial of post-infarct patients, azimilide neither increased nor decreased mortality risk. In patients with supraventricular arrhythmias, the most common adverse effects reported by patients on azimilide were approximately equal in frequency with those on placebo: headache, asthenia, infection, diarrhea and dizziness. Infrequent cases of torsade de pointes and severe neutropenia were reported in patients taking azimilide. Azimilide is an investigational antiarrhythmic drug that has shown efficacy in patients with atrial fibrillation.     

P波离散度预测阵发性心房颤动的研究

目的观察阵发性心房颤动（PAF）病人的体表心电图P波离散度（Pd）、最大P波时限（Pmax）的变化.研究Pd与Pmax对PAF的预测价值.方法观察和测量80例PAF病人（观察组）的Pd和Pmax.并与70名健康者（对照组）对照分析.结果 PAF组与对照组比较,Pd与Pmax均有统计学意义（P＜0.001）.结论 Pd是一种新的预测PAF的体表心电图指标.     

Analysis of the Surface Electrocardiogram for Monitoring and Predicting Antiarrhythmic Drug Effects in Atrial Fibrillation

Specific antiarrhythmic therapy with class I and III drugs for atrial fibrillation (AF) conversion and prevention of its recurrence is frequently utilized in clinical practice. Besides being only moderate effective, the utilization of antiarrhythmic drugs may be associated with serious side effects. In the clinical setting it is difficult to directly evaluate the effects of antiarrhythmic drugs on the individual patient’s atrial electrophysiology, thereby predicting their efficacy in restoring and maintaining sinus rhythm. Analysis of the surface electrocardiogram in terms of P-wave signal averaged ECG during sinus rhythm and spectral characterization of fibrillatory waves during AF for evaluation of atrial antiarrhythmic drug effects is a new field of investigation. Both techniques provide reproducible parameters for characterizing atrial electrical abnormalities and seem to contain prognostic information regarding antiarrhythmic drug efficacy. Further research is needed which elucidates the most challenging clinical questions in AF management whom to place on antiarrhythmic drug treatment and what antiarrhythmic drug to prescribe. Analysis of the surface ECG might have the potential to answer these questions.     

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals.
Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (∼9 μM plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29–50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24–34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71–109) ms to 98 (86–121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811–1220) seconds to 621 (549–761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7–20.5) Hz to 7.6 (2.9–8.8) Hz (P = 0.02, n = 6).
Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation.     

Pilot Study: Noninvasive Monitoring of Oral Flecainide's Effects on Atrial Electrophysiology during Persistent Human Atrial Fibrillation Using the Surface Electrocardiogram

Background: The relation between flecainide's plasma level and its influence on human atrial electrophysiology during acute and maintenance therapy of atrial fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma levels and atrial fibrillatory rate obtained from the surface ECG during initiation and early maintenance of oral flecainide in patients with persistent lone AF and assessed their relationship. Methods and Results: In 10 patients (5 males, mean age 63 ± 14 years, left atrial diameter 46 ± 3 mm) with persistent lone AF, flecainide was administered as a single oral bolus (day 1) followed by 200–400 mg/day (days 2–5). The initial 300 mg flecainide bolus resulted in therapeutic plasma levels in all patients (range 288–629 ng/ml) with no side effects. Flecainide plasma levels increased on day 3 and remained stable thereafter. Day 5 plasma levels were lower (508 ± 135 vs 974 ± 276 ng/ml, P = 0.009) in patients with daily mean flecainide doses of 200 mg compared to patients with higher maintenance doses. Fibrillatory rate obtained from the surface electrocardiogram measuring 378 ± 17 fpm at baseline was reduced to 270 ± 18 fpm (P < 0.001) after the flecainide bolus but remained stable thereafter. Fibrillatory rate reduction was independent of flecainide plasma levels or clinical variables. Conclusion: A 300 mg oral flecainide bolus is associated with electrophysiologic effects that are not increased during early maintenance therapy in persistent human lone AF. In contrast to drug plasma levels, serial analysis of fibrillatory rate allows monitoring of individual drug effects on atrial electrophysiology.     

Evaluation of Left Atrial Appendage Functions According to Different Etiologies of Atrial Fibrillation with a Tissue Doppler Imaging Technique by Using Transesophageal Echocardiography

Background: Atrial fibrillation (AF) occurs due to various etiologies that carry different risks for thromboembolism. However, the effect of different etiologies on left atrial appendage (LAA) function has not been investigated. This study aimed to examine the LAA function in AF that occurred under various etiologies and to compare the findings with a novel tissue Doppler imaging (TDI) technique by using transesophageal echocardiography (TEE). Methods: LAA function was assessed in 84 patients with permanent AF according to various etiologies [mitral stenosis in 20 (24%), hypertension in 44 (52%), and hyperthyroidism in 20 (24%) patients] and in 23 controls with sinus rhythm. LAA area change, PW-Doppler and tissue velocities of LAA were measured. The presence of SEC or thrombus and their relation to LAA function was evaluated. Results: LAA velocities were lowest in mitral stenosis and highest in hyperthyroidism. Moderate–severe LAA SEC was detected in 61 and thrombi in 23 patients. Factors associated with the severity of SEC were the percentage of the LAA area change, PW-Doppler peak emptying velocity, and TDI septal wall downward velocity. The percent of the LAA area change and PW-Doppler peak emptying velocity were the significantly related factors for the presence of thrombi (OR = 0.84, 95% CI = 0.74–0.95, P = 0.005 and OR = 0.85, 95% CI = 0.74–0.98, P = 0.02, respectively). Conclusion: LAA function deteriorated most severely in mitral stenosis and least in hyperthyroidism. The LAA area change and PW-Doppler emptying velocity were important predictors for SEC or thrombi. Although TDI was not superior to classical methods, it provided complementary data to PW-Doppler velocities for predicting SEC and thrombi.