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Background and Purpose: Measurement of QT intervals during atrial flutter (AFL) is relevant to monitor the safety of drug delivery. Our aim is to compare QT and QTc intervals in AFL patients before and after catheter ablation in order to validate QT measurement during AFL., Methods: 25 patients suffering from AFL underwent catheter ablation; 9 were in sinus rhythm and 16 were in AFL at the time of the procedure. Holter ECGs were continuously recorded before, during and after the procedure. In AFL signals, flutter waves were subtracted using a previously-validated deconvolution-based method. Fridericia's QTc was computed before and after ablation after hysteresis reduction., Results: Comparing QTc values obtained before and after ablation showed that (1) the intervention did not significantly affect QTc, and (2) the QTc during AFL was concordant with the QTc value in sinus rhythm., Conclusion: QTc can be reliably measured in patients with AFL using flutter wave subtraction and hysteresis reduction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Background and Objective: Recurrence of atrial flutter (AFl) on antiarrhythmic drugs is frequently observed. To determine the reasons for drug inefficacy, the electrophysiological parameters of AFl were studied in eight patients without drug, six patients on sotalol (Sot), eight patients on amiodarone (Amio) and four patients on propafenone (PPF) who presented to the electrophysiology laboratory for conversion of AFl by rapid atrial pacing., Methods: A quadripolar electrode catheter was positioned in the right atrium in the pathway of the AFl circuit. The duration and composition of the excitable gap (EG) were determined by premature stimuli during AFl., Results: The EG in AFl recurring on Sot (80 +/- 25 ms), Amio (78 +/- 13 ms) and PPF (83 +/- 26 ms) was not significantly different from that without drug (88 +/- 14 ms). Furthermore, a fully excitable portion of the EG was present whether with or without drug., Conclusions: AFl recurrence on Amio, PPF or Sot is associated with the continued presence of an EG and fully excitable portion. These findings explain the persistent viability of the AFl circuit despite drug therapy in these patients.

Previous studies on atrial flutter (AF) presumed that resetting was due to the prematurity effect (PE) in which the stimulated antegrade wavefront travels in the tail of the AF preexisting wavefront. We studied the collision effect (CE) between the AF and the stimulated retrograde wavefronts, its contribution to resetting, and its relationship to AF termination and how they are affected by the Class IC agent propafenone (PPF). A canine model of AF was created using a Y-shaped lesion in the right atrium in 14 dogs (33 +/- 3 kg). Five atrial bipolar electrodes were positioned around the tricuspid valve. In a subsequent set of 11 dogs, we used 16 bipolar electrodes for recording. AF was induced by burst pacing. Single and multiple stimuli were applied to measure conduction time and reset-response curves (RRCs). This was repeated after the administration of PPF (1 mg/kg loading dose for 10 minutes, followed by 1.8 mg/kg/per hour infusion). Three distinct mechanisms were found to contribute to the RRC: the PE, the CE, and heterogeneity. PPF stabilized the RRC, increased significantly the cycle length (CL), the duration of the effective refractory period, as well as the duration of the excitable gap. However, PPF did not alter the duration of the fully excitable portion. We studied 36 annihilations without and 48 with PPF. Transient fibrillation was found in 75% of the episodes without, compared to 22% with PPF. Other types of termination such as conduction block, CL oscillations, and reversal of activation were found for 25% of the episodes without and 78% with PPF. In many cases, conduction block and CL oscillations were associated with a failure of propagation of the stimulated antegrade wavefront in the region of collision. Termination by reversal of activation suggests that propagation was two dimensional and could not be represented by a one dimensional movement. The average coupling interval (in percent of CL), that induced fibrillation was not significantly different from that at which conduction block occurred. This suggests that transient fibrillation is associated with a weak CE rather than with rapid pacing. The CE is amplified by multiple stimuli and PPF. The incidence of transient fibrillation in AF annihilation diminishes with PPF as the CE becomes more important. This suggests that the evaluation of PE and CE in AF may be an indication of the risk of atrial fibrillation.

The objectives of this study were: (1) to evaluate quantitatively the spatial resolution of pacemapping; and (2) to assess the predictive value and role of pacemapping for the catheter ablation of overt APs. Sixty-three unipolar leads were used instead of the standard 12-lead ECG to acquire more information and assess the intrinsic accuracy of pacemapping. Spatial resolution was evaluated in 19 patients for whom data were recorded during bipolar ventricular pacing near the AV ring using the three electrode pairs of a quadripolar ablation catheter with a 5-mm interelectrode spacing. The predictive value was assessed in 27 patients with overt APs who underwent RF ablation; their data were recorded during pacing at the site of successful ablation and at one or two sites where RF energy delivery was ineffective. Data from different beats were compared visually by using body surface potential maps and quantitatively by computing average correlation coefficients (r). Reproducibility was high for paced beats (r = 0.98 +/- 0.02). Displacements of 5 mm of the pacing site could be detected with a sensitivity of 90% and a specificity of 87%. Correlation between pacing at successful ablation sites and preexcited sinus rhythm was low (r = 0.79 +/- 0.11) and the ablation outcome could be predicted with a negative prediction accuracy of 87% and a positive prediction accuracy of 49%. Despite an excellent spatial resolution, pacemapping is of limited value for the identification of successful AP ablation sites, probably because APs can be interrupted at some distance from their ventricular insertion point.

The effects of increasing concentrations of procainamide on the composition of the excitable gap were determined in a canine model of atrial flutter. Using the model of a Y-shaped lesion in the right atrium, reentry around the tricuspid valve was induced by burst pacing in 10 open-chest chloralose-anesthetized dogs. Diastole was scanned with a single premature stimulus and the relationship between the coupling interval of the premature beat and the return cycle length (CL) determined a reset-response curve that described the excitable gap. This was repeated up to the maximum flutter CL while infusing procainamide (30 mg/kg) over 1 h. Procainamide progressively prolonged the flutter CL from 131 +/- 21 (+/-SD) to 188 +/- 46 ms (p < 0.01) and the effective refractory period from 96 +/- 19 to 149 +/- 47 ms (p < 0.01). At peak plasma levels of 77 +/- 33 mumol/L the drug terminated flutter only in two dogs. Neither the duration (35 +/- 10 to 39 +/- 13 ms) nor the composition of the excitable gap changed on drug. A fully excitable portion (7 +/- 3 ms or 20 +/- 11% of the excitable gap) persisted on procainamide (7 +/- 3 ms or 19 +/- 9% of the excitable gap). It was concluded that procainamide prolongs the atrial flutter CL and the effective refractory period but does not change either the duration or composition of the excitable gap even at plasma concentrations that significantly exceed those recommended in man.

Background: Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG., Methods and Results: Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post-myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57 +/- 10 years [mean +/- SD], left ventricular ejection fraction, 29 +/- 9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation were measured and analyzed according to location of the myocardial infarction. The global epicardial activation was characterized in all patients by a widespread initial breakthrough on the anterior right ventricle (16 +/- 8 milliseconds after QRS onset), which was followed by one or two other breakthroughs in 65% of patients. Subsequently, three characteristic epicardial patterns of the activation spread were found: (1) radial, from the right to the left ventricle, found in all patients with inferoposterior myocardial infarction; (2) counterclockwise rotation, in which posteroseptal crossing preceded the anteroseptal crossing, found in 38% of patients with anterior myocardial infarction; and (3) pincerlike encirclement, in which both septal crossings and/or breakthroughs occurred nearly simultaneously and merged at the left ventricular free wall (typical for apical involvement in anterior and combined myocardial infarction). The simultaneous presence of multiple major activation wave fronts typically found in patients with the pincerlike activation pattern was reflected on the surface ECG by multiphasic, notched QRS complexes. Activation delay was observed in 89% of patients, and terminal activation was topographically related to myocardial infarction in 94% of patients. Delayed activation exceeding the surface QRS was observed in 11% and 31% of cases on the endocardium and epicardium, respectively., Conclusions: These results offer a solid basis for a more precise interpretation of a wide range of electrophysiological data and provide a framework for future investigations of surface ECG reflections of endocardial and epicardial activation patterns recorded in patients with chronic myocardial infarction.

The effects of procainamide and propafenone on the composition of the excitable gap (EG) were studied in a canine model of atrial flutter (AFI) around the tricuspid valve. In 14 open-chest, chloralose-anesthetized dogs, a Y-shaped incision was made in the intercaval area extending to the right atrial appendage. Atrial effective refractory period (ERP) was measured at constant stimulation cycle lengths (CLs) (200 and 300 msec) at each of five recording sites around the tricuspid valve. The EG as defined by the reset-response curve was determined by introducing premature stimuli during AFI induced by burstpacing. Seven dogs each received procainamide or propafenone as a bolus followed by infusion. At constant plasma levels, both drugs increased ERP at constant paced CL and prolonged the reentry CL. In the absence of drug, reset-response curves were mixed, demonstrating an EG composed of both partially (increasing portion) and fully (flat portion) excitable tissue. Procainamide and propafenone shifted the curve upward and to the right and prolonged ERP during AFI, but did not change the duration of the EG. On procainamide, fully excitable tissue was preserved, but on propafenone, in some cases, the fully excitable part of the gap was reduced markedly or even eliminated. In conclusion, both drugs can prolong AFI CL by a direct effect on conduction velocity in fully excitable tissue. In addition, propafenone's effect on refractoriness can contribute significantly in some cases to slowing of AFI.

The efficacy of propafenone in preventing induction of ventricular tachycardia was evaluated in 25 consecutive patients (mean age 62 +/- 8 years) with remote myocardial infarction who underwent programmed electrical stimulation for ventricular arrhythmia using up to three extra-stimuli after basic drive at the right ventricular apex. In nine patients (Group A), propafenone prevented induction of sustained ventricular tachycardia (noninducible in four, nonsustained [less than 30 s] in five). In the other 16 patients (Group B), sustained ventricular tachycardia was still inducible; in 11 of the 16, the tachycardia configuration was unchanged but the cycle length was significantly longer (431 +/- 99 versus 284 +/- 44 ms, p less than 0.001). Propafenone did not significantly affect either sinus cycle length or AH and HV intervals. However, it prolonged QRS duration during sinus rhythm equally in both groups of patients. With ventricular pacing, propafenone also prolonged right ventricular effective and functional refractory periods and surface QRS duration. There was greater lengthening of the paced surface QRS duration when drug therapy was ineffective (for example, +35 +/- 12 ms in Group A versus +69 +/- 23 ms in Group B at a basic drive of 400 ms, p less than 0.01). Drug-induced prolongation of a paced QRS complex greater than 40 ms had a 94% positive predictive value for drug failure to prevent induction of ventricular tachycardia. Drug-induced percent prolongation of ventricular tachycardia cycle length in Group B did not correlate well with percent QRS prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)

Disopyramide phosphate is a new antiarrhythmic drug that has been shown to possess significant antiarrhythmic effects in animals and man. In the present investigation, the effects of 2, 5, and 10 mug/ml of disopyramide phosphate were studied on the electrophysiological properties of canine Purkinje fibers and ventricular muscle superfused in vitro. Transmembrane action potentials were recorded from Purkinje fibers in the region of maximum action potential duration (gate), from Purkinje fibers proximal and distal to the gate, and from ventricular muscle. Disopyramide phosphate produced a concentration-dependent decrease in the slope of phase 4 diastolic depolarization of spontaneously beating Purkinje fibers. In all electrically stimulated fibers, the drug decreased the amplitude and the maximum upstroke velocity of the action potential. This depression of phase 0 characteristics was accompanied by a decrease in conduction velocity. In Purkinje fibers located at the gate, a concentration-dependent parallel shift to the right and a depression of the maximum of the membrane responsiveness curve occurred. Effects on action potential duration were variable. Repolarization was altered so that action potentials with dissimilar durations recorded from sites proximal to, at, and distal to the gate became equal. The total action potential duration and the effective refractory period of gate Purkinje fibers were prolonged, but the change in action potential duration was always greater than the change in effective refractory period so that the ratio of the change in duration to the change in refractory period was always greater than one.

We studied the effect of lowering the extracellular potassium concentration ([K+]o) on the electrophysiological actions of disopyramide phosphate, a new antiarrhythmic drug. At low [K+]o, therapeutic concentrations of disopyramide phosphate caused significantly less depression of action potential amplitude and maximum upstroke velocity of both Purkinje fiber and ventricular muscle action potentials. The drug shifted the membrane responsiveness curve along the voltage axis to more negative membrane potentials regardless of [K+]o. However, a greater shift occurred when [K+]o was normal. Disopyramide phosphate prolonged both action potential duration and effective refractory period in all fibers but there was consistently greater prolongation of these parameters at low [K+]o. More importantly, disopyramide phosphate altered repolarization time course of action potentials in such a way that action potentials with dissimilar durations throughout the ventricular conducting system became more equal. The drug was less effective in decreasing this disparity in action potential durations throughout the ventricles in the presence of low [K+]o. These modifications of the electrophysiological actions of disopyramide by low [K+]o suggest that a therapeutic concentration of disopyramide might have less of an antiarrhythmic effect in the presence of hypokalemia.