Prednisone prevents inducible atrial flutter in the canine sterile pericarditis model

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model.
Methods: Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON). EP testing was performed daily using epicardial electrodes placed at initial surgery. High-resolution (404 sites) epicardial mapping was performed during the terminal study. Baseline and daily CRP levels were obtained in all dogs.
Results: Sustained AFL was absent in PRED (0%) versus CON dogs (91%; P < 0.001); AF induced in the early postoperative course in PRED dogs was of very short CL (mean 66 ms). Tissue inflammation was significantly attenuated in PRED dogs. Thresholds were lower in PRED versus CON dogs, significantly so on postoperative day (POD) 3. There was a trend toward lower ERPs in the PRED group at all CLs. CRP levels were markedly reduced in PRED versus CON dogs (peak CRP 78 ± 7 mg/L vs 231 ± 21 mg/L, P < 0.001), and returned to baseline in PRED dogs by POD 4, correlating with a virtual absence of sustained arrhythmia. During open chest mapping studies on POD 4, PRED dogs showed only nonsustained AF/AFL.
Conclusions: Prednisone eliminated postoperative AFL, affected all EP parameters studied, and attenuated the inflammatory response associated with pericarditis.     

Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment.

AIMS: To investigate the rate of transformation of atrial fibrillation to atrial flutter in patients taking antiarrhythmic drugs for the prophylaxis of atrial fibrillation, we retrospectively analysed data from 305 consecutive patients with paroxysmal atrial fibrillation (155 male; mean age 63 +/- 11 years) treated with ventricular rate controlling drugs, antiarrhythmic drugs, or without drugs. METHODS AND RESULTS: At a mean follow-up of 9 months (range 1-24) all patients experienced recurrence of arrhythmia: 48 (14.6%, Group A) suffered Type 1 atrial flutter, and 257 (85.4%, Group B) atrial fibrillation. The relative rate of recurrence of atrial flutter vs atrial fibrillation was similar in patients without treatment or with ventricular rate controlling drugs (from 6.8% to 14.6%, P=ns). However, recurrence was higher (25%) in patients administered antiarrhythmic drug therapy. The relative risk in these patients was 3.02 times greater, compared with patients without treatment, or treated with rate controlling drugs (P<0.001). There were no differences between groups concerning the baseline clinical characteristics and the clinical consequences of the recurrence; patients with atrial flutter had a lower rate of conversion to sinus rhythm (42% vs 64%) and a higher rate of hospital admission (69% vs 36%) compared with those with atrial fibrillation. Six patients (8.5%) experienced 1:1 atrioventricular conduction during atrial flutter with a ventricular rate of 240-280 beats x min(-1). CONCLUSION: Our data suggest that the use of antiarrhythmic drugs for the prophylaxis of atrial fibrillation is associated with a threefold increase in the probability of Type 1 atrial flutter recurrence, as opposed to atrial fibrillation, which may have important clinical consequences, but which did not in our study.     

Antiarrhythmic effects of JTV-519, a novel cardioprotective drug,on atrial fibrillation/flutter in a canine sterile pericarditis model

Effect of JTV-519 on AF. INTRODUCTION: A new cardioprotective drug, JTV-519, blocks Na+ current and inwardly rectifying K+ current and inhibits Ca2+ current. However, its role in atrial electrophysiology is unknown. We investigated the antiarrhythmic effects of JTV-519 on atrial fibrillation/flutter in the canine sterile pericarditis model. METHODS AND RESULTS: In nine dogs with sterile pericarditis, 38 episodes of sustained (>30 sec) atrial fibrillation (8 dogs) and 24 episodes of sustained atrial flutter (7 dogs) were induced by rapid atrial pacing. When atrial fibrillation or atrial flutter was sustained >15 minutes, it was cardioverted and reinduced. The inducibility of atrial fibrillation/flutter, the atrial effective refractory period, and the intra-atrial conduction time were compared before and after the continuous infusion of JTV-519 (0.03 mg/kg/min). JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). In contrast, atrial flutter was still inducible in 4 dogs after JTV-519 (from 2.7 +/- 2.5 to 1.6 +/- 2.1, P = NS). JTV-519 significantly prolonged effective refractory period (from 123 +/- 18 to 143 +/- 14 msec, from 127 +/- 18 to 151 +/- 12 msec, and from 132 +/- 13 to 159 +/- 9 msec at basic cycle lengths of 200, 300, and 400 msec, respectively, P < 0.01), but it did not affect the intra-atrial conduction time (from 47 +/- 11 msec to 48 +/- 11 msec, P = NS). CONCLUSION: JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.     

静脉地尔硫治疗快速房颤、房扑的疗效分析

为检验静脉地尔硫艹卓控制房颤、房扑心室率的有效性和安全性，对４７例快速房颤、房扑患者一次静脉注射０．２５ｍｇ／ｋｇ地尔硫艹卓后以５ｍｇ／ｈ～１０ｍｇ／ｈ微泵维持，平均起效时间５．２±２．７ｍｉｎ，总有效率９３．６％，心功能较用药前明显改善（Ｐ＜０．０５），对血压无明显影响，副作用发生率为１０．６％，均不严重。结果提示地尔硫艹卓是一种能迅速、安全、有效控制房颤、房扑患者心室率的药物     

Simultaneous occurrence of atrial fibrillation and atrial flutter

INTRODUCTION: Early reports suggested that some patients with "atrial fibrillation/flutter" might have atrial fibrillation in one atrium and atrial flutter in the other. However, more recent conceptions of atrial fibrillation/flutter postulate that the pattern is due to a relatively organized (type I) form of atrial fibrillation. We report the occurrence and ECG manifestations of simultaneous atrial fibrillation and flutter in patients undergoing attempted catheter ablation of atrial flutter. METHODS AND RESULTS: In patients undergoing radiofrequency ablation for atrial flutter, an attempt was made to entrain atrial flutter by pacing in the right atrium. The arrhythmias observed occurred following attempts at entrainment, or spontaneously in one case. Twelve transient episodes of simultaneous atrial fibrillation and flutter were observed in five patients. The atrial fibrillation was localized to all or a portion of one atrium, during which the other atrium maintained atrial flutter. In each case, the surface 12-lead ECG reflected the right atrial activation pattern. No patients had interatrial or intra-atrial conduction block during sinus rhythm, suggesting functional intra-atrial block as a mechanism for simultaneous atrial fibrillation/flutter. CONCLUSION: In certain patients, the occurrence of transient, simultaneous atrial fibrillation and flutter is possible. In contrast to prior studies in which it was suggested that left atrial or septal activation determines P wave morphology, the results of the present study show that P wave morphology is determined by right atrial activation. Functional interatrial block appears to be a likely mechanism for this phenomenon.     

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results

Vanoxerine, A New Cardiac Multichannel Blocker. Background: Vanoxerine is a promising, new, investigational antiarrhythmic drug. The purpose of this study was to test the hypothesis that oral dosing of vanoxerine would first terminate induced atrial flutter (AFL) and atrial fibrillation (AF), and then prevent their reinduction. Methods: In 5 dogs with sterile pericarditis, on the fourth day after creating the pericarditis, we performed electrophysiologic (EP) studies at baseline, measuring atrial excitability, refractoriness (AERP), and conduction time (CT) when pacing from the right atrial appendage, Bachmann's bundle (BB), and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms. Then, after induction of AFL or AF, all dogs received hourly oral doses of vanoxerine: 90 mg, followed by 180 mg and 270 mg. Blood was obtained to determine plasma vanoxerine concentrations at baseline, every 30 minutes, when neither AFL nor AF were inducible, and, finally, 1 hour after the 270 mg dose. Then we repeated the baseline EP studies. Results: Four dogs had inducible, sustained AFL, and 1 dog only had induced, nonsustained AF. In 4 AFL episodes, oral vanoxerine terminated the AFL and then rendered it noninducible after an average of 111 minutes (range 75–180 minutes) after the first dose was administered. The mean vanoxerine plasma level at the point of noninducibility was 84 ng/mL, with a narrow range of 76–99 ng/mL. In the dog with induced, nonsustained AF, it was no longer inducible at a drug level of 75 ng/mL. Vanoxerine did not significantly (1) prolong the AERP except at BB, and then only at the faster pacing CLs; (2) change atrial excitability thresholds; (3) prolong atrial conduction time, the PR interval, the QRS complex or the QT interval. Conclusions: Orally administered vanoxerine effectively terminated AFL and rendered it noninducible. It also suppressed inducibility of nonsustained AF. These effects occurred at consistent plasma drug levels. Vanoxerine's insignificant or minimal effects on measured electrophysiologic parameters are consistent with little proarrhythmic risk. (J Cardiovasc Electrophysiol, Vol. pp. 1‐8)     

Risk of thromboembolism in acute atrial fibrillation or atrial flutter

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia, predominating in the elderly, with stroke as a potentially devastating complication. Prevention of the thromboembolic sequelae from AF remains a central focus of practicing clinicians. Although the risk of thromboembolism in chronic AF is well recognized, less is known about the potential risk of systemic embolism in acute AF. In addition, recent data support the notion of a group at considerable risk of embolism from atrial flutter, an arrhythmia typically believed to bestow little increased risk of thromboembolism. The mechanism of thrombus formation, embolization, and resolution in atrial arrhythmias is not well defined, particularly in that of acute AF or atrial flutter. The traditional concept proposes that atrial thrombus forms only after > 2 days of AF and embolizes by being dislodged from increases in shear forces. This widely accepted concept further holds that newly formed atrial thrombus, in the setting of AF, organizes over a span of 14 days. The results of studies based on observations from transesophageal echocardiography examinations have provided provocative insight into the temporal sequence of atrial thrombus formation, embolization, and resolution in AF or atrial flutter and have expanded the traditional concept of thromboembolism in these atrial dysrhythmias. Namely, left atrial thrombus may form before the onset of AF in the face of sinus rhythm. Conversion to sinus rhythm may increase the thrombogenic milieu of the left atrium. Importantly, atrial thrombus may form in the acute phase of AF. Last, thrombi may require > 14 days to become immobile or to resolve. Findings similar to those of acute AF have been reported in patients with atrial flutter and coexisting cardiac pathology. On the basis of these emerging insights fostered by the use of transesophageal echocardiography, it appears appropriate to consider anticoagulation in patients presenting with acute AF or atrial flutter with coexisting cardiac pathology predisposing to left atrial thrombus.     

Incidence of atrial fibrillation post-cavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence

Introduction: Atrial fibrillation and atrial flutter often coexist. The long-term occurrence of atrial fibrillation in patients presenting with atrial flutter alone is unknown. We report the long-term follow-up in patients who underwent cavotricuspid isthmus ablation for treatment of lone atrial flutter.
Methods and Results: Between January 1997 and June 2002, 632 patients underwent cavotricuspid isthmus ablation for the treatment of typical atrial flutter at the Cleveland Clinic Foundation. Three hundred sixty-three patients were included in this study and followed for a mean duration of 39 ± 11 months. The mean duration of atrial flutter symptoms was 12 ± 5 months. Mean left-atrial size and left-ventricular ejection fraction were 4.2 ± 0.8 cm and 47 ± 13%, respectively. After a mean follow-up time of 39 ± 11 months, 13% (48 of 363) of the patients remained in sinus rhythm. Five percent (18 of 363) of patients experienced recurrence of atrial flutter only. Sixty-eight percent (246 of 363) experienced the onset of atrial fibrillation and 14% (51 of 363) experienced recurrence of atrial flutter and the new onset of atrial fibrillation. Overall, 82% (297 of 363) of the patients experienced new onset of drug refractory atrial fibrillation. Left-atrial size was a predictor of atrial fibrillation recurrence post-atrial flutter ablation.
Conclusion: At long-term follow-up, approximately 82% of patients post-cavotricuspid isthmus ablation for atrial flutter developed drug refractory atrial fibrillation. This finding suggests that elimination of atrial flutter might delay, but does not prevent, atrial fibrillation. Evidence suggests both arrhythmias may share common triggers and such patients may derive a better long-term benefit from anatomical ablative treatment of atrial fibrillation as well.     

Ibutilide: efficacy and safety in atrial fibrillation and atrial flutter in a general cardiology practice.

BACKGROUND: Published experience with ibutilide (IB) in randomized clinical trials reveals that conversion to sinus rhythm (SR) occurs in 31% of patients with atrial fibrillation (AF) and in 63% of patients with atrial flutter. HYPOTHESIS: The study was undertaken to test the efficacy and safety of IB in patients with AF and with atrial flutter and to compare them with those reported in previous studies. METHODS: In a general cardiology practice, 54 consecutive patients with AF or atrial flutter, no contraindication to IB, and a normal QTc interval, were treated with intravenous IB (0.4-2.0 mg). Duration of arrhythmia, left atrial (LA) size, ejection fraction (EF), time to conversion, QTc interval, and adverse drug events were determined. Patients were observed for a minimum of 6 h. Successful cardioversion was defined as arrhythmia termination within 6 h. RESULTS: Twenty-four of 34 (70.6%) patients with AF and 15 of 20 (75%) patients with atrial flutter converted to SR. Conversion of AF to SR was more likely to occur if duration of AF was approximately 96 h compared with > 96 h (81 vs. 17%, respectively; p = 0.006). The mean time to arrhythmia termination was 68.8 min. Left atrial size, determined by echocardiogram, was 44 +/- 13 mm in 43 patients. Patients with LA size approximately 45 mm had a conversion rate of 55% in both AF and flutter, compared with a conversion rate of 72% in patients with LA size < 45 mm. Ejection fraction was not a predictor of drug success. The QTc intervals were significantly prolonged after IB administration, with a mean change of 47.1 ms for successfully treated patients. Sustained polymorphic ventricular tachycardia occurred in one patient within 1 min of IB infusion, requiring electrical cardioversion to SR. This patient's serum electrolytes and QTc interval were normal prior to IB infusion; however, the QTc increased by 160 ms (from 387 to 547 ms) during drug infusion. No systemic or pulmonary emboli occurred. CONCLUSION: The efficacy of IB for conversion of AF to SR in this prospective observational study was considerably better than previously reported. Duration of AF remains an important predictor of conversion to SR. Complications are rare and without long-term adverse effects.     

阵发性房颤、房扑的心电散点图特征

目的观察阵发性房扑、房颤的心电散点图特征,并探讨其临床意义。方法选择20例阵发性房扑、房颤患者的24小时动态心电图,回顾分析其心电散点图。结果 20例阵发性房颤、房扑患者中,17例可以通过心电散点图区分出不同心律,占总例数85%;3例无法通过心电散点图区分出不同的心律,占总例数15%。结论阵发性房扑一般可以通过心电散点图迅速鉴别,阵发性房颤绝大多数病例可以通过心电散点图迅速鉴别,心电散点图有助于提高海量心电信息中阵发性房扑房颤的分析效率。此外,心电散点图可以获得更多的生理状态下整体动态的心电信息。     

Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study

BackgroundAtrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.HypothesisOutcomes with dronedarone may also be impacted by duration of AF/AFL history.MethodsIn this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long).ResultsOf 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo‐treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65‐0.96]) and intermediate (0.72 [0.56‐0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66‐1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug‐related safety issues were identified.ConclusionsPatients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.     

Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study.

AIMS: This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm. METHODS AND RESULTS: One hundred and fifty patients with atrial fibrillation or flutter (duration range 2 h-6 months) were given 15-min intravenous infusions of 8 microg. kg(-1)of dofetilide (n=48), 5 mg. kg(-1)of amiodarone (n=50), or placebo (n=52) and monitored continuously for 3 h. Sinus rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0.001, dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more effective in atrial flutter than in atrial fibrillation (cardioversion rates 75% and 22%, respectively;P=0.004). The mean time to conversion with dofetilide was 55+/-15 min. Dofetilide prolonged the QTc interval (+16% at 20 min). Amiodarone substantially decreased the ventricular rate in non-converters (-18 beats. min(-1)at 30 min). Two patients given dofetilide (4%) had non-sustained ventricular tachycardias, and four (8%) had torsade de pointes, in one case requiring electrical cardioversion. CONCLUSION: Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter. However, when infused intravenously at this dose and rate, dofetilide causes a significant incidence of torsade de pointes.     

Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone: A randomized, digoxin-controlled study

A 24 h intravenous dosing regimen of amiodarone was designedto reach a peak plasma concentration at 1 h and to maintainthe concentration above a certain level during the infusionperiod A randomized, open-label, digoxin-controlled study wasundertaken to observe the efficacy and safety of the dosingregimen of amiodarone in treating recent-onset, persistent,atrial fibrillation and flutter with ventricular rates above130 beats. min^–1. Fifty patients with a mean age of 70± 7 (SD) years were enrolled and randomly assigned toreceive either amiodarone intravenously (n=26) or digoxin (n=24).Amiodarone HCl was infused over 24 h according to the followingregimen: 5 mg. min^–1, 3 mg. min^–1, 1 mg. min^–1and 0.5 mg. min^–1 for 1, 3, 6 and 14 h, respectively,for a 70-kg subject. Digoxin (0.013 mg. kg^–1) was infusedin three divided doses, each dose 2 h apart and infused over30 min. The mean heart rates in the amiodarone group decreased significantlyfrom 157 ± 20 beats. min^–1 to 122 ± 25 beats.min^–1 after 1 h (P<005 vs baseline), and then decreasedfurther to stabilize at 96 ± 25 beats. min^–1 after6 h (P<0.05). The digoxin group had fewer dramatic alterationsin heart rates, compared to the amiodarone group, in the first8h (P<0.05, respectively). Maximum reduction was reachedonly after 8 h. The amiodarone infusion was prematurely abortedin two patients due to severe bradycardia and death after conversionin one patient and aggravation of heart failure in the other.Overall, 24 of 26 patients (92%) in the amiodarone group and17 of 24 (71%) in the digoxin group were restored to sinus rhythmwithin 24 h. The accumulated rates of conversion over 24 h weresignificantly different between the two groups (P=0.0048). Digoxin,while not as effective as amiodarone in the treatment of recent-onsetatrial fibrillation and flutter, appears to be safer. Therefore,we suggest the use of digoxin as the first line drug for thetype of patients that formed the basis of the current studyand reserve amiodarone for refractory cases or those in whomdigoxin is not suitable.     

非瓣膜病心房颤动或心房扑动患者应用不同起始剂量华法林对INR达标速度的影响

目的观察我国非瓣膜病心房颤动（NVAF）或心房扑动（AFL）患者应用不同起始剂量华法林时,国际标准化比值（INR）首次达标和稳定的时间及出血并发症的发生率等,以进一步了解中国人应用国产华法林的最佳起始剂量。方法人选84例,随机分入起始剂量3．125mg组（第1组）,起始5mg,2d后改为3．125mg组（第2组）和起始5mg治疗组（第3组）。于治疗第3、4、5、7、9天测定INR,根据INR调整华法林剂量,直到INR稳定于1．8～3．0,随访1个月。结果第3组比第1、2组提早达标并稳定,第1、2组差异无统计学意义。3组均无明显出血及血栓栓塞事件,INR增高发生率差异无统计学意义。结论对于中国NVAF或AFL患者,以5mg为初始剂量应用华法林能使INR安全、迅速、有效地达标并稳定。服药3次后即于第4天起测INR是安全的。