Reliable pace termination of postoperative atrial fibrillation in the canine sterile pericarditis model: Implications for atypical atrial flutter.

BACKGROUND: We have identified a reentrant circuit in the pulmonary vein region, which drives the atria, producing fibrillatory conduction, as one mechanism of postoperative atrial fibrillation (POAF) in the canine sterile pericarditis model. OBJECTIVE: In this model, we tested the hypothesis that overdrive pacing from a site at or near such a reentrant circuit would interrupt it and thereby terminate POAF. METHODS: We studied 11 sterile pericarditis dogs on postoperative days 1-4. Atrial electrograms (AEGs) were recorded during POAF, overdrive pacing, and pace termination from 3 sites simultaneously: Bachmann's bundle, posterior left atrium, and right atrial appendage. When recorded AEGs demonstrated regular activation, pace termination was attempted at that site by delivering a drive train starting with 4 consecutive beats at a cycle length (CL) of 2-5 ms shorter than that of the intrinsic CL. RESULTS: Sixteen episodes of sustained POAF (>5 minutes) diagnosed by electrocardiogram were induced. During all episodes of POAF, AEGs recorded from the left atrium exhibited regular activation, ie, constant AEG morphology and CL. When capture of the reentrant circuit by overdrive pacing occurred (mean 13 ± 5, range 5-23 beats), all 16 POAF episodes were successfully terminated. In all termination episodes, at the end of pacing but prior to the return of sinus rhythm, there was disorganized atrial activation in the previously organized sites (mean 2 seconds, range 0.1-8 seconds). However, these beats did not sustain POAF in the absence of a reentrant circuit ("driver"). CONCLUSION: Overdrive pacing from a site demonstrating regular activation during sustained POAF terminated the POAF by interrupting the reentrant circuit.

Confirmation of novel noninvasive high-density electrocardiographic mapping with electrophysiology study: implications for therapy.

BACKGROUND: Twelve lead ECGs have limited value in precisely identifying atrial and ventricular activation during arrhythmias, including accessory atrioventricular conduction activation. The aim of this study was to report a single center's clinical experience validating a novel, noninvasive, whole heart, beat-by-beat, 3-dimensional mapping technology with invasive electrophysiological studies, including ablation, where applicable. METHODS AND RESULTS: Using an electrocardiographic mapping (ECM) system in 27 patients, 3-dimensional epicardial activation maps were generated from >250 body surface ECGs using heart-torso geometry obtained from computed tomographic images. ECM activation maps were compared with clinical diagnoses, and confirmed with standard invasive electrophysiological studies mapping. (1) In 6 cases of Wolff-Parkinson-White syndrome, ECM accurately identified the ventricular insertion site of an accessory atrioventricular connection. (2) In 10 patients with premature ventricular complexes, ECM accurately identified their ventricular site of origin in 8 patients. In 2 of 10 patients transient premature ventricular complex suppression was observed during ablation at the site predicted by ECM as the earliest. (3) In 10 cases of atrial tachycardia/atrial flutter, ECM accurately identified the chamber of origin in all 10, and distinguished isthmus from nonisthmus dependent atrial flutter. (4) In 1 patient with sustained exercise induced ventricular tachycardia, ECM accurately identified the focal origin in the left ventricular outflow tract. CONCLUSIONS: ECM successfully provided valid activation sequence maps obtained noninvasively in a variety of rhythm disorders that correlated well with invasive electrophysiological studies.

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.

New antiarrhythmic drugs for prevention of atrial fibrillation.

Enhanced understanding of the mechanisms underlying atrial fibrillation (AF) and advent of catheter-based therapy for AF has altered the approach to patients with this most common arrhythmia. However, despite the success of aggressive procedural techniques, pharmacologic therapy remains the first-line and mainstay approach in the treatment of AF. This review of new antiarrhythmic drug (AAD) therapy for AF provides an in-depth overview of recently available classic and new investigational drugs being considered for AF treatment. Currently available AADs are associated with less than satisfactory efficacy in preventing AF and a significant side effect profile, including ventricular proarrhythmia. Recent investigations have focused on development of new AADs that, hopefully, will be more effective and safer even in patients with structural heart disease. These new AADs include selective multi-ion channel and atrial specific blockers and agents that target the underlying etiologies and substrate alterations that lead to AF. Included among the latter new category are agents that suppress activation of the renin-angiotensin-aldosterone system or inflammation, which represent novel targets for drug therapy for AF. Finally, new selective A1 adenosine receptor agonists may offer the possibility of more specific and successful ventricular rate control during AF. There is considerable hope and interest that improved understanding of AF mechanisms ultimately will result in more effective and less dangerous pharmacologic therapy becoming available in the future.

Electrocardiographic imaging (ECGI), a novel diagnostic modality used for mapping of focal left ventricular tachycardia in a young athlete.

We report the first clinical application of electrocardiographic imaging (ECGI), a new, noninvasive imaging modality for arrhythmias, in an athlete with focal ventricular tachycardia (VT) originating from a left ventricular (LV) diverticulum. A reconstructed map of the epicardial activation sequence during a single premature ventricular complex (PVC) of an identical QRS morphology to the clinical VT, generated from 224-electrode body surface ECGs and a chest CT (ECGI), localized the PVC to the site of the diverticulum. This correlated with subsequent maps obtained using standard techniques. We describe the first case that used ECGI to guide diagnosis and therapy of a clinical tachyarrhythmia.

Comparative effects of single- and linear triple-site rapid bipolar pacing on atrial activation in canine models.

Nonuniform conduction may cause block and/or delay, thereby providing a substrate for the onset and maintenance of reentrant atrial arrhythmias. We tested the hypothesis that linear triple-site, bipolar, rapid pacing (LTSBRP) of the right atrium generates more uniform wave-front propagation compared with single-site, bipolar, rapid pacing (SSBRP), thereby reducing and/or eliminating conduction block and delay that is otherwise present. Five dogs with pericarditis and three normal dogs were studied. Three plunge-wire electrode pairs were placed 5-7 mm apart in both perpendicular and parallel configurations at the superior aspect of the crista terminalis and were used to pace at 200- and 300-ms cycle lengths for < or =6 s. During pacing, 380 electrograms were recorded simultaneously from electrode arrays placed epicardially on the atria, which produced activation sequence maps for each pacing episode. Local conduction-velocity vectors were computed for each site during each episode. Histograms of absolute velocity vector angles from the x-axis (of the crista terminalis) were plotted to assess uniformity of wave-front propagation, and the magnitude of each vector was computed to assess the local speed. LTSBRP showed 1) more uniform linear activation wave fronts compared with SSBRP, 2) velocity vectors with a more uniform magnitude and direction compared with SSBRP, 3) a predominant absolute velocity vector angle vs. a scattered angle distribution with SSBRP, and 4) shorter right atrial activation time and faster mean epicardial speed than SSBRP for each pacing cycle length. LTSBRP created a more uniform wave-front propagation with less or no conduction block and/or delay compared with SSBRP.

Novel steerable telescoping catheter system for implantation of left ventricular pacing leads.

Advances in left ventricular transvenous lead delivery systems for biventricular pacing are leading to more refined techniques, shorter procedure times and higher implant success rates. Despite these advances, the inability to successfully cannulate the coronary sinus and deliver a lead to a distal location are still major causes of prolonged procedures times and implant failures. The pathophysiologic process of heart failure results in dilatation of the right atrium as well as other morphological changes in cardiac anatomy. Additionally, cannulation can be further complicated by congenital anomalous cardiac anatomy. This report describes the implant of a biventricular pacing system using a novel, steerable 7 French catheter system developed to aid in the cannulation of the coronary sinus ostium and its venous branches. The steerable catheter is used in conjunction with a 9 French braided sheath and guide-wire to create a telescoping system. The use of new tools and methods as described provides insight into available options for left ventricular transvenous lead implantation and dealing with difficult anatomy.

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.