Ibutilide with magnesium for conversion of atrial fibrillation or flutter in rheumatic heart disease patients: Ibutilide with magnesium for chemical cardioversion of atrial fibrillation or flutter.

BACKGROUND: Data on adjunctive use of magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm is lacking. AIM: We aimed to study the efficacy of adjunctive supplementation of intravenous magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm and to define a definite level of serum magnesium which leads to significant increase in rates of such conversion. METHODS AND RESULTS: This was a prospective study including 33 Rheumatic heart disease patients (13 males and 20 females) with mean age of 49.27 ± 11.4 years and persistent AF or AFl. All patients received intravenous magnesium to raise serum magnesium level in range of 4 mg/dl to 4.5 mg/dl prior to administration of Ibutilide. 25 out of 33 (76%) patients converted to sinus rhythm. Upon univariate analysis, presence of background beta blocker therapy, serum potassium and magnesium at time of Ibutilide injection were found to have significant relation with conversion to sinus rhythm. Upon multivariate analysis serum magnesium level at the time of Ibutilide injection was found to have significant contribution on post injection rhythm reversal (p-value = 0.006). The level of magnesium at 3.8 mg/dl was found to have maximum sensitivity of 96% and specificity of 62.5% for conversion to sinus rhythm by ibutilide with magnesium (p-value< 0.05). CONCLUSIONS: Ibutilide is highly effective in cardioversion of persistent rheumatic atrial fibrillation/flutter patients. Raising Serum Magnesium levels above 3.8 mg/dl significantly improves efficacy of ibutilide.

Improving Appropriate Dosing of Intravenous dilTIAZem in Patients With Atrial Fibrillation or Flutter With Rapid Ventricular Response in the Emergency Department.

INTRODUCTION: Atrial fibrillation and atrial flutter are common supraventricular arrhythmias in patients who present to the emergency department. Under the American Heart Association guidelines, dilTIAZem is the calcium channel blocker frequently used by many practitioners for rate control. Currently, institution-specific data have identified that many patients receiving dilTIAZem for atrial fibrillation or atrial flutter are given initial doses that exceed the recommended dose by more than 10%, resulting in hypotension in some patients. METHODS: ED personnel were surveyed to determine their current knowledge of appropriate intravenous dilTIAZem dosing and methods of prescribing intravenous dilTIAZem to determine the causes of higher dosing. Based on the baseline data, an intervention of adding a text alert when withdrawing dilTIAZem from the automated medication dispensing cabinet was implemented. RESULTS: Following the intervention, 29 patients received intravenous dilTIAZem for rate control of atrial fibrillation or flutter with rapid ventricular response. For the primary outcome, the incidence of high-dose dilTIAZem decreased by 19% (P = 0.03). There was no change in the secondary outcome of a reduction in hypotension (P = 0.3). DISCUSSION: The interventions of education and medication alerts resulted in a significant increase in the percentage of patients receiving appropriate doses of dilTIAZem and a nonsignificant decrease in the incidence of hypotension. This process-oriented intervention resulted in an improvement in appropriate dilTIAZem doses at our site. Rate control was not statistically significantly different between the 2 groups. Long-term sustainability of this intervention requires further study.

Incidence of left atrial abnormalities under treatment with dabigatran, rivaroxaban, and vitamin K antagonists.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown. METHODS: We studied 306 patients with AF (94 %) and AFL (6 %) undergoing transesophageal echocardiography. Patients received VKAs (n = 138), dabigatran (n = 68), or rivaroxaban (n = 100) for at least 3 weeks prior to investigation. Time in therapeutic range was 67 % for VKA. Mean CHADS2 score and CHA2DS2-VASc score were 1.3 and 2.5, respectively. Left atrial abnormality was defined as either dense SEC, low LAAV <20 cm/s, or thrombus. RESULTS: Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA. CONCLUSION: With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. AIMS: To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. METHODS: Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. RESULT: Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). CONCLUSION: DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF.

[Antithrombotic therapy in patients with atrial flutter before planned cardioversion].

INTRODUCTION: atrium flutter and fibrillation are the heart rhythm disorders that increase the risk of life-dangerous complications, e.g. cardioembolic stroke, pulmonary embolism. Recommendations for managing patients with atrial fibrillation - atrial flutter, with paroxysm duration over 48 hours, demand anticoagulant therapy. Oral anticoagulants, which are the antagonists of K vitamin (Varpharin) and the new oral anticoagulants (Rivaroxaban), are used during the per-manipulative procedure of patients with atrial flutter before restoring the sinus rhythm with transesophageal cardiac pacing. AIM: the present investigation aims to compare efficiency and safety of Varpharin and Rivaaroxaban in treatment patients with atrial flutter before planned cardioversion with transesophageal heart pacing. MATERIALS AND METHODS: Varpharin (control group) - in doses equivalent for reaching the target МНВ - or Rivaroxaban (research group), 20 mg., were prescribed to 42 patients with coronary heart disease, concomitant arterial hypertension, and non-valvular paroxysm of atrial flutter with more than 48-hour duration, divided into two groups. There was held the general clinical, echocardioscopy examination. Thrombotic Risk Factor Assessment was made according to the CHA2DS2-VASc scale, Hemorrhagic Risk Factor Assessment was performed according to the HAS-BLED scale, and clinical symptoms assessment was made according to the EHRA scale. The heart rhythm was restored with the transesophageal heart pacing. RESULTS: the per-manipulative procedure of the patients of research group (21 days were suggested according to the guidelines) shortened, unlike the patients of control group (the period of target МНВ selection had made 30,76±0,62days), the reduction of the symptoms severity by EHRA was considered in dynamics. According to the results of transesophageal heart pacing, the heart rhythm of 15 research group patients restored, and 6 research group patients had atrial fibrillation. Among the patients of the control group, 6 had their heart rhythm restored, as 10 patients had the atrial fibrillation. CONCLUSIONS: the use of Rivaroxaban during the per-manipulative procedure before planned cardioversion with transesophageal heart pacing causes shortening of the permanipulative period, reduces the risk of development of symptoms of heart failure, helps to restore the heart rhythm of the patients with atrium flutter.

Termination of Atrial Flutter and Fibrillation by K201's Metabolite M-II: Studies in the Canine Sterile Pericarditis Model.

INTRODUCTION: K201, a 1,4-benzodiazepine derivative, acts on multiple cardiac ion channels and the ryanodine receptor. We tested whether administration of M-II, the main metabolite of K201, would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model. METHODS: In 6 dogs, electrophysiologic studies were performed at baseline and after drug administration, measuring atrial effective refractory period (AERP), and conduction time from 3 sites during pacing at cycle lengths (400, 300, and 200 milliseconds) on postoperative days 1-4. In 12 induced episodes of sustained AF/AFL (2/10, respectively), M-II was administered intravenously to test efficacy. Five of the AFL episodes were studied in the open chest state during simultaneous multisite atrial mapping. RESULTS: M-II terminated 2/2 AF and 8/10 AFL episodes, prolonged AERP (P < 0.05), significantly increased atrial pacing capture thresholds but did not significantly change atrial conduction time. AFL CL prolongation was largely explained by prolonged conduction in an area of slow conduction in the reentrant circuit. AFL terminated with block in the area of slow conduction. CONCLUSIONS: M-II was very effective in terminating AFL/AF in the canine sterile pericarditis model. AFL terminated due to block in the area of slow conduction of the reentrant circuit.

Is the acetylcholine-regulated inwardly rectifying potassium current a viable antiarrhythmic target? Translational discrepancies of AZD2927 and A7071 in dogs and humans.

AIMS: We aimed at examining the acetylcholine-dependent inward-rectifier current (IKAch) as a target for the management of atrial fibrillation (AF). METHODS AND RESULTS: The investigative agents AZD2927 and A7071 concentration-dependently blocked IKACh in vitro with minimal off-target activity. In anaesthetized dogs (n = 17) subjected to 8 weeks of rapid atrial pacing (RAP), the left atrial effective refractory period (LAERP) was maximally increased by 50 ± 7.4 and 50 ± 4.8 ms following infusion of AZD2927 and A7071. Ventricular refractoriness and the QT interval were unaltered. During sustained AF, both drugs significantly reduced AF frequency and effectively restored sinus rhythm. AZD2927 successfully restored sinus rhythm at 10/10 conversion attempts and A7071 at 14/14 attempts, whereas saline converted 4/17 episodes only (P<0.001 vs. AZD2927 and A7071). In atrial flutter patients (n = 18) undergoing an invasive investigation, AZD2927 did not change LAERP, the paced QT interval, or ventricular refractoriness when compared with placebo. To address the discrepancy on LAERP by IKACh blockade in man and dog and the hypothesis that atrial electrical remodelling is a prerequisite for IKACh blockade being efficient, six dogs were studied after 8 weeks of RAP followed by sinus rhythm for 4 weeks to reverse electrical remodelling. In these dogs, both AZD2927 and A7071 were as effective in increasing LAERP as in the dogs studied immediately after the 8-week RAP period. CONCLUSION: Based on the present series of experiments, an important role of IKACh in human atrial electrophysiology, as well as its potential as a viable target for effective management of AF, may be questioned.

Rate-dependent and site-specific conduction block at the posterior right atrium and drug effects evaluated using a noncontact mapping system in patients with typical atrial flutter.

INTRODUCTION: Conduction block in the posterior right atrium (RA) plays an important role in perpetuating atrial flutter (AFL). Although conduction blocks have functional properties, it is not clear how the block line changes with the pacing rate, pacing site, and administration of antiarrhythmic drugs. METHODS AND RESULTS: Forty patients with typical AFL were enrolled. Pacing (110, 170, 230 ppm) from the coronary sinus ostium (CSo) and low lateral RA was performed. After 1 mg/kg pilsicainide (pure sodium channel blockade) administration, the pacing protocol was repeated. Conduction block was assessed based on a color-coded isopotential map and 20 points of virtual unipolar electrograms in the posterior RA using noncontact mapping. Block line proportion was defined as the percentage of length of the block line between the superior and inferior vena cava. The pacing rate-dependent extension of the block proportion was significant during pacing from both sides (pacing from the CSo: 59 ± 17% at 110 ppm, 69 ± 16% at 230 ppm, P < 0.05; pacing from the low lateral RA: 43 ± 19% at 110 ppm, 55 ± 22% at 230 ppm, P < 0.05). The block line was significantly longer during CSo pacing than during low lateral RA pacing at each rate (all P < 0.05). After pilsicainide administration, the block line extended further. CONCLUSION: In addition to pacing rate-dependent and site-dependent changes in the block line, pilsicainide further extended the block line length. This phenomenon explains the clinical observation that counterclockwise AFL occurs more frequently than clockwise AFL, and the mechanism of class IC AFL.

Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. METHODS: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. CONCLUSIONS: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

Arrhythmias (IV). Clinical approach to atrial tachycardia and atrial flutter from an understanding of the mechanisms. Electrophysiology based on anatomy.

In 2009, 2343 catheter ablation procedures were performed in Spain for focal atrial tachycardia or atrial flutter (typical and atypical), with a yearly growth rate of 8%, indicating the clinical importance of these arrhythmias. The classic categorization of atrial tachycardia and atrial flutter based on rate and morphological criteria has become almost irrelevant at a time when clinical electrophysiology may lead to curative intervention based on a definition of the mechanism, making it necessary to bring laboratory experience closer to clinical practice. In this review we outline our present understanding of atrial tachycardia mechanisms, both focal and macroreentrant, and attempt to establish the conceptual links with classic concepts that may help the clinician to make a differential diagnosis and establish therapeutic indications, including that of an electrophysiologic study. Some of the concepts may seem complex, but we thought it important to provide an overview of the electrophysiological methods that may eventually lead to the description of the anatomic bases of the arrhythmias; currently, these are easier to understand thanks to the virtual anatomic casts built using computerized navigation systems.

[First experience of clinical use of new class III antiarrhythmic agent niferidil in patients with persistent atrial fibrillation and flutter].

The aim of the study was to evaluate the efficacy and safety of administered intravenously niferidil in doses 10, 20 and 30 mkg per kg in patients with persistent atrial fibrillation (AF) and flutter (AFL) for pharmacological cardioversion. The study included 30 patients (22 male) with persistent AF (n = 28) and AFL (n = 2) without structural heart diseases with median arrhythmia duration 6.1 +/- 4.8 months (2 weeks to 24 months). Niferidil was administered as 3 bolus injections (10 mkg per kg each) performed with the interval of 15 minutes. Antiarrhythmic efficacy of niferidil in dose of 10 mkg per kg was 60%, in dose of 20 mkg per kg it was 70%, and in dose of 30 mkg per kg reached 90% prespectively. The part of the patients, in whom QTc prolongation exceeded potentionally dangerous value of 500 mc, was 22.2% (6 of 27). None of the patients developed proarrhythmic side effect as torsade de pointes.

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.

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.

Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent.

Ibutilide is a class III antiarrhythmic agent indicated for cardioversion of atrial fibrillation and atrial flutter to sinus rhythm (SR). The most serious complication of ibutilide is torsades de pointes (TdP). Magnesium has been successfully used for the treatment of TdP, but its use as a prophylactic agent for this arrhythmia has not yet been established. The present study investigated whether high dose of magnesium would increase the safety and efficacy of ibutilide administration. A total of 476 patients with atrial fibrillation or atrial flutter who were candidates for conversion to SR were divided into 2 groups. Group A consisted of 229 patients who received ibutilide to convert atrial fibrillation or atrial flutter to SR. Group B consisted of 247 patients who received an intravenous infusion of 5 g of magnesium sulfate for 1 hour followed by the administration of ibutilide. Then, another 5 g of magnesium were infused for 2 additional hours. Of the patients in groups A and B, 154 (67.3%) and 189 (76.5%), respectively, were converted to SR (p = 0.033). Ventricular arrhythmias (sustained, nonsustained ventricular tachycardia, and TdP) occurred significantly more often in group A than in group B (7.4% vs 1.2%, respectively, p = 0.002). TdP developed in 8 patients (3.5%) in group A and in none (0%) in group B (p = 0.009). The administration of magnesium (despite the high doses used) was well tolerated. In conclusion, the administration of high doses of magnesium probably makes ibutilide a much safer agent, and magnesium increased the conversion efficacy of ibutilide.

[Next cardioversion or RF ablation in professional driver with recurrent typical atrial flutter and MAS syndromes]. / Nastepna elektrowersja czy ablacja RF podloza typowego trzepotania przedsionków u zawodowego kierowcy z napadami MAS.

We describe a 42-year-old professional driver with hypertension, obesity and recurrent episodes of highly symptomatic typical atrial flutter. Despite chronic sotalol treatment, 1:1 AV conduction with RBBB-morphology was observed. After excluding of thrombus in the heart chambers, the 'urgent' and successful RF ablation was performed.

In vivo cardiac electrophysiologic and antiarrhythmic effects of an isoquinoline IKur blocker, ISQ-1, in rat, dog, and nonhuman primate.

The cardiac electrophysiologic effects of ISQ-1, an isoquinolinone I(Kur) blocker, were characterized in vivo. In rat, ISQ-1 elicited maximal 33% to 36% increases in atrial and ventricular refractoriness at a plasma concentration of 11.5 microM. In African green monkey, ISQ-1 increased atrial refractory period (maximal 17% at plasma concentration up to 20 microM) with no effect on ventricular refractory period or ECG QTc. Likewise in dog, ISQ-1 increased atrial refractory period (maximal 16% at plasma concentration up to 2 microM) with no effect on ventricular refractory period or QTc. In contrast, studies with ibutilide in nonhuman primate and dog demonstrated concomitant increases in atrial and ventricular refractoriness and QTc. Additionally, in a dog model of atrial flutter, ISQ-1 terminated ongoing flutter at doses (2.5 +/- 0.5 mg/kg IV) that selectively prolonged atrial refractoriness (13% increase), whereas flutter termination with ibutilide occurred at doses that increased both atrial and ventricular refractoriness as well as QTc. Of note, the cardiac electrophysiologic profiles displayed by ISQ-1 in these species were similar to those reported previously by our lab with a structurally distinct I(Kur) blocker. Taken together, these results further support the inhibition of I(Kur) as an approach to terminate atrial arrhythmia.

Dofetilide: a new class III antiarrhythmic agent.

Dofetilide is a relatively new class III antiarrhythmic agent that selectively blocks the rapid component of the cardiac ion channel delayed rectifier current. This results in an increase in the action potential duration and effective refractory period of the myocyte, thereby terminating reentrant tachyarrhythmias and preventing their re-induction. Oral dofetilide is effective in the conversion of atrial fibrillation and flutter to sinus rhythm and in the maintenance of sinus rhythm after conversion. It is generally well tolerated but like other antiarrhythmic agents in its class, torsades de pointes may be induced as a consequence of therapy. This risk is minimized by dosage adjustment according to creatinine clearance and QT(c) interval, by selecting patients without known risk factors for torsades and by initiating treatment in a monitored hospital setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure, hence its importance as an alternative medication for the pharmacological conversion of atrial fibrillation and flutter, and maintenance of sinus rhythm after conversion in patients at high risk of sudden death.

Azd7009: a new antiarrhythmic drug with predominant effects on the atria effectively terminates and prevents reinduction of atrial fibrillation and flutter in the sterile pericarditis model.

INTRODUCTION: We tested the hypothesis that AZD7009 terminates induced atrial fibrillation (AF) and flutter (AFL) and prevents their reinduction, and that effects on refractoriness, conduction, and excitability are predominantly on the atria. METHODS AND RESULTS: Thirty-eight electrophysiologic studies were performed during AZD7009 infusion in 11 dogs with sterile pericarditis. The effects of AZD7009 on refractoriness, conduction, and capture threshold were studied and its antiarrhythmic efficacy tested. Simultaneous multisite biatrial mapping was performed in 7 dogs to assess arrhythmia termination. AZD7009 prolonged arrhythmia cycle length (CL) from 121 +/- 7.8 to 157 +/- 9.7 msec (P < 0.001) before terminating 23 of 23 AF/AFL episodes. Mapping demonstrated that AF/AFL CL prolonged and then terminated in area(s) of slow conduction in a reentrant circuit. Arrhythmia reinduction failed in 19 of 20 attempts. At 400-msec CL, atrial and ventricular refractoriness and QT interval increased 33%, 17% (P < 0.001 vs atrial refractoriness), and 9%, respectively. Atrial capture threshold increased in a CL-dependent manner: 1.8 +/- 0.3 to 2.2 +/- 0.3 mA (CL 400 msec); 2.1 +/- 0.3 to 2.8 +/- 0.5 mA (CL 300 msec), and 2.2 +/- 0.3 to 5.3 +/- 0.8 mA (CL 200 msec). Only minor nonsignificant changes occurred in the ventricles: 0.95 +/- 0.05 to 0.98 +/- 0.06 mA (CL 400 msec), and 1.14 +/- 0.12 to 1.16 +/- 0.13 mA (CL 333 msec). Atrial conduction time increased 8 +/- 1.4 msec (CL 400 msec), 8.3 +/- 1.5 msec (CL 300 msec), and 13.2 +/- 1.6 msec (CL 200 msec, all P < 0.001), but ventricular conduction time was unchanged. CONCLUSION: AZD7009 is highly efficacious in terminating AF/AFL and preventing reinduction in this model. It exhibits marked effects on atrial electrophysiology but has only modest effects on the ventricle.