Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap

Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of excitable gap and pattern of resetting in atrial flutter for determining reentry circuit location

Clinical and experimental data show that type I atrial flutter is due to a reentry mechanism with an excitable gap. To define the location of the reentry circuit of atrial flutter, width of excitable gap, poststimulation cycle and pattern of reset after premature stimulus were analyzed in 18 patients during atrial flutter at multiple atrial sites (high, lateral, posterior and septal right atrium, and coronary sinus). The pattern of reset was defined as flat or increasing whether the return cycle remained unchanged or prolonged with increasing prematurity. Shorter values of the excitable gap were found at the coronary sinus (33 +/- 8 ms) and high right atrium (30 +/- 10 ms) than at the posterior (43 +/- 9 ms) or septal right atrium (45 +/- 11 ms). Intermediate values (36 +/- 8 ms) were measured at the lateral right atrium. Poststimulation cycle, corrected for atrial flutter cycle length, was shorter in the posterior (6 +/- 7 ms) and septal right atrium (5 +/- 7 ms) than in the coronary sinus (35 +/- 9 ms), and the high (23 +/- 10 ms) and lateral right atrium (15 +/- 9 ms). A flat pattern of resetting occurred more frequently at the septal (18 of 18 patients) and posterior right atrium (15 of 18) than at the lateral (8 of 18) and high right atrium (2 of 17), and was never observed at the coronary sinus. Atrial flutter was successfully terminated by overdrive atrial pacing in 15 of 18 patients, and termination was more easily obtained from the septal and posterior right atrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacologic conversion and suppression of experimental canine atrial flutter: differing effects of d-sotalol, quinidine, and lidocaine and significance of changes in refractoriness and conduction

The electrophysiologic determinants of conversion and the prevention of atrial flutter are poorly defined. This issue was therefore investigated by evaluating the effects of the new class III antiarrhythmic drug d-sotalol and the class I antiarrhythmic drugs quinidine and lidocaine. Atrial flutter was reproducibly induced in the open-chest anesthetized dog with intercaval crush and rapid atrial pacing. In this preparation, intravenous d-sotalol restored sinus rhythm in 14 of 15 (93%) dogs, whereas quinidine converted nine of 15 (60%) and lidocaine two of 10 (20%). d-Sotalol prevented reinduction in eight (53%), whereas quinidine was effective in four (27%) and lidocaine in none (0%). In the atria, d-sotalol induced significant increases in effective refractory period (+32%; p less than .01), functional refractory period (+30%; p less than .01), conduction time at an atrial paced cycle length of 150 msec (+9%; p less than .05), and atrial flutter cycle length (+8%; p less than .01). Quinidine increased effective refractory period (+40%; p less than .01), functional refractory period (+27%; p less than .01), conduction time at sinus cycle length (+13%; p less than .01), conduction time at an atrial paced cycle length of 150 msec (+18%; p less than .01), and atrial flutter cycle length (+31%; p less than .01). Lidocaine decreased functional refractory period (-6%; p less than .05) while lengthening the atrial flutter cycle length (+13%; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic determinants of recurrent atrial flutter after successful termination by overdrive pacing

The potential ability of electrophysiologic abnormalities to predict recurrence of atrial flutter was evaluated. Twenty-five patients with chronic atrial flutter resistant to combined digitalis and quinidine therapy were studied electrophysiologically after restoration of sinus rhythm by overdrive pacing or by eventual direct current cardioversion. Recurrence of atrial flutter was observed in 12 patients during a mean follow-up period of 17 months (range 3 to 50). Electrophysiologic testing included programmed high right atrial stimulation at a paced drive cycle length of 600 ms and incremental pacing up to 200-ms paced intervals. When coupling intervals of 90% of the drive cycle length were compared to coupling intervals of 48% of the drive cycle length, the increase in S1A1 interval, defined as the interval between the stimulus artifact and the atrial activation near the atrioventricular junction, was greater in patients with subsequent recurrence of atrial flutter (47 +/- 11 vs 21 +/- 18 ms). Stepwise logistic regression analysis identified the S1A1 increase to be the sole independent predictor of recurrence (p = 0.0082) while previous episodes of atrial flutter or the presence of organic heart disease were identified as dependent variables. Reclassification showed a 91% sensitivity and a 92% specificity. Correct classification was achieved in 92% of patients. The initiation of atrial dysrhythmia had no predictive value. The assessment of the S1A1 interval by programmed atrial stimulation appears helpful in delineating the patient risk of recurrent atrial flutter after termination by overdrive pacing.     

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.     

Frequency and implications of resetting and entrainment with right atrial stimulation in atrial flutter.

Thirty-three patients (24 with typical and 9 with atypical flutter-wave morphology) were studied to evaluate the incidence and implications of resetting and entrainment of atrial flutter with right atrial stimulation. Resetting with single extrastimulus was present in 23 cases (group A) and absent in 10 (group B). Most cases of reset flutter were typical (20 of 23). Fixed fusion indicative of entrainment was observed in all 29 cases with pacing trains. Groups A and B did not differ significantly in flutter cycle length (230 +/- 20 vs 223 +/- 19 ms), atrial functional refractory period (165 +/- 18 vs 167 +/- 22 ms) or longest paced cycle length producing entrainment (213 +/- 19 vs 210 +/- 19 ms). In contrast, the return cycle after the longest paced cycle length producing entrainment was significantly shorter in group A (228 +/- 27 vs 284 +/- 56 ms; p = 0.001). The return cycle in group A was virtually identical to the flutter cycle length, whereas in group B it was greater (p = 0.002 compared with group A). Resetting was more frequent in typical than atypical flutter (20 of 24 vs 3 of 9; p = 0.01). Both typical and atypical flutter can be transiently entrained by right atrial pacing. Lack of resetting and longer return cycle, suggesting a longer conduction time between the reentrant circuit and the stimulation site, were mostly observed in atypical flutter. The data suggest a different location for both types of flutter, and may have implications for ablation techniques. A more cautious approach, with more extensive mapping, appears appropriate for ablation attempts of atypical flutter.     

Mechanisms of termination of reentrant atrial arrhythmias by class I and class III antiarrhythmic agents

We studied atrial flutter due to circus movement in chronically instrumented conscious dogs to identify the mechanism by which class I and class III antiarrhythmic drugs terminate reentrant excitation. We used a crossover experimental design administering five class I agents and one class III agent, by intravenous bolus followed by intravenous infusion. The class I agents other than lidocaine were almost uniformly effective in terminating the arrhythmia (disopyramide in six of seven dogs, propafenone in six of six, flecainide in seven of seven, and SC-40230 in seven of seven). Termination was preceded by a marked increase in cycle length (ranging from +78% with propafenone to +55% with disopyramide), but with the exception of disopyramide, class I agents did not significantly shorten the excitable gap. With disopyramide the gap decreased from 49 +/- 3% to 28 +/- 3% of the cycle length. With no class I agent did the wavelength of effective refractoriness increase to approach the cycle length of the arrhythmia. Lidocaine, used as a negative control, terminated the reentry in one dog with modest prolongation of the cycle length. Terminations with class I agents correlated with depression of conduction rather than prolongation of refractoriness. In contrast with class I agents, D-sotalol prolonged the cycle length minimally (+10%) and terminated the arrhythmia in six of seven dogs. It decreased the excitable gap from 42 +/- 4% to 26 +/- 6% of the cycle, but it still did not cause the wavelength of effective refractoriness to equal the cycle length. Terminations by D-sotalol seemed to result from either failure of the lateral boundaries of the circus path or reflection within the path.     

Circus movement atrial flutter in the canine sterile pericarditis model. Differential effects of procainamide on the components of the reentrant pathway

To evaluate the mechanisms of action of procainamide on the components of the reentrant pathway, drug-induced changes in activation patterns, effective refractory periods (ERPs), and stimulation thresholds were analyzed in nine dogs with sterile pericarditis and sustained atrial flutter. Activation maps were based on 127 close bipolar recordings from a special "jacket" electrode. From the control map, 22 +/- 2 sites covering the slow zone and the normal zone of the reentrant circuit were selected to measure ERPs and thresholds. The excitable gap was estimated from the longest ERP during pacing at the tachycardia cycle length. During atrial flutter, epicardial activation proceeded as a single wave around an arc of functional conduction block in the proximity of the atrioventricular (AV) ring or around a combined functional/anatomic obstacle, with the arc being contiguous with one of the venae cavae. An area of slow conduction, which accounted for 53 +/- 15% of the revolution time within 35 +/- 15% of the total length of the reentrant pathway, was bordered by the arc of block and the AV ring or a caval vein and the AV ring, respectively. Procainamide (5-10 mg/kg i.v.) prolonged the cycle length of atrial flutter from 144 +/- 17 to 190 +/- 24 msec (p less than 0.05) and then terminated the arrhythmia in all studies. The increase in cycle length was due to an increase in conduction time in the slow zone by 37 +/- 11 msec (86 +/- 17% of the total cycle length increase). During the last reentrant beat, conduction failed in the slow zone, with the arc of block joining the AV ring. At termination, procainamide had prolonged conduction time, stimulation threshold, and ERP in the normal zone by 11 +/- 18%, 40 +/- 80%, and 5 +/- 15%, respectively, compared with 51 +/- 16%, 86 +/- 93%, and 14 +/- 21%, respectively, in the slow zone (p less than 0.05 for all three parameters). The duration of the excitable gap did not change significantly. We conclude that procainamide preferentially affected the slow zone of single loop reentrant circuits. The drug terminated circus movement atrial flutter without abolishing the excitable gap, and its effect on conduction seemed the major determinant of the antiarrhythmic action.     

Activation patterns in experimental canine atrial flutter produced by right atrial crush injury.

OBJECTIVES. This study was designed to localize and characterize the atrial flutter reentrant circuit and the electrophysiologic effects of right atrial crush injury in a new canine model. BACKGROUND. In previous studies sustained atrial flutter was induced in the canine heart by rapid atrial pacing after a linear crush injury was placed in the right atrial free wall. METHODS. Eight dogs (group 1) with three electrode plaques on the right and left atria and Bachmann's bundle and seven dogs (group 2) with a single high density electrode plaque on the right atrium were studied with use of a 64-channel computerized mapping system. RESULTS. At baseline, during sinus rhythm and right and left atrial pacing, activation spread uniformly without areas of slow conduction. Crush injury produced marked conduction delay or complete block during sinus rhythm, increasing the mean difference in activation times across the injury compared with control values (group 1, 31 +/- 4 vs. 14 +/- 5 ms, p less than 0.01; group 2, 28 +/- 10 vs. 7 +/- 2 ms, p less than 0.01). Rapid atrial pacing (S1S1 200 ms) above and below the crush injury revealed a line of complete block across which adjacent electrodes recorded markedly different activation times (33 +/- 5 and 38 +/- 12 ms difference, respectively) and around which activation wave fronts proceeded, colliding opposite the stimulating electrodes. The mean atrial flutter cycle length of 11 episodes induced in group 1 and 14 episodes in group 2 was 157 +/- 16 and 140 +/- 16 ms, respectively (p = NS). Activation mapping revealed a reentrant circuit in the right atrium around the crush injury in all episodes. Although the reentrant circuit did not contain a discrete area of slow conduction, activation time below was longer than that above the crush injury (92 +/- 14 vs. 66 +/- 8 ms and 82 +/- 12 vs. 59 +/- 9 ms in groups 1 and 2, respectively, p less than 0.01 for both). Rapid atrial pacing or premature stimuli produced progressive conduction delay and unidirectional block between the crush injury and the tricuspid anulus, inducing atrial flutter directly in 9 of 25 episodes. In 16 episodes, atrial flutter developed after transient induction of atrial fibrillation. CONCLUSIONS. 1) Atrial flutter in this model is due to reentry in the right atrium; 2) the crush injury functions as an anatomic obstacle around which reentry may occur; and 3) the reentrant circuit does not contain a discrete area of slow conduction but, rather, generally slower conduction below the crush injury.     

Effects of N-acetylprocainamide on experimental atrial flutter and atrial electrophysiologic properties in conscious dogs with sterile pericarditis: comparison with the effects of quinidine

N-acetylprocainamide (NAPA) is said to have class III antiarrhythmic drug properties. The effects of NAPA (25 mg/kg intravenously) on sustained, stable, reentrant atrial flutter induced in 12 conscious dogs using a sterile pericarditis model were studied and compared with the effects of quinidine (5 mg/kg intravenously) given on a different day in 10 of the same 12 dogs. The effects of these drugs on atrial excitability, the atrial effective refractory period and intraatrial conduction time measured during rapid atrial pacing performed during sinus rhythm were also compared. The mean NAPA and quinidine serum levels were 17.7 and 7.1 micrograms/ml, respectively. Both NAPA and quinidine immediately prolonged the atrial flutter cycle length in all dogs, from 118 +/- 15 to 141 +/- 18 ms and from 119 +/- 17 to 153 +/- 21 ms, respectively (both p less than 0.001), and then terminated atrial flutter in 11 of the 12 NAPA studies and in 6 of the 10 quinidine studies. Neither drug affected atrial excitability. Both NAPA and quinidine increased the atrial effective refractory period significantly, from 138 +/- 17 to 168 +/- 20 ms (p less than 0.001) and from 136 +/- 14 to 148 +/- 16 ms (p less than 0.01), respectively. NAPA did not change intraatrial conduction time measured during atrial pacing at 150 beats/min, but during atrial pacing at 300 beats/min, it prolonged it from 51 +/- 9 to 54 +/- 10 ms (p less than 0.05), and at 400 beats/min, from 52 +/- 10 to 64 +/- 13 ms (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective blockade of retrograde fast pathway by intravenous disopyramide in paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways.

Electrophysiological effects of 2 to 2.5 mg/kg iv disopyramide were studied in 10 patients with dual nodal pathways who used a slow pathway for anterograde and a fast pathway for retrograde conduction during paroxysmal supraventricular tachycardia (mean cycle length 308.5 +/- 37 ms; range 260-370 ms). Disopyramide terminated the tachycardia in six cases by production of ventriculoatrial block in five and by sinus overdrive in one. In the remaining four patients cycle length of the paroxysmal supraventricular tachycardia increased significantly from 270 +/- 8 ms to 377.5 +/- 28 ms. In all 10 patients disopyramide depressed retrograde fast pathway conduction manifest by an increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 296.5 +/- 25 ms to 358 +/- 60 ms, and increase in retrograde fast pathway effective refractory period from less than or equal to 246 +/- 34 ms to 325 +/- 36 ms; the drug abolished ventriculoatrial conduction in two cases. Anterograde slow pathway and fast pathway conduction properties were unchanged after disopyramide (atrial paced cycle length producing AH block 292 +/- 30 to 306.5 +/- 30 ms; effective refractory period of anterograde fast pathway less than or equal to 274 +/- 56 to 284 +/- 44 ms, before and after the drug, respectively) suggesting that anterograde conduction was not crucial either for sustainment or for failure to initiate paroxysmal supraventricular tachycardia after the drug. Paroxysmal supraventricular tachycardia could not be reinduced in six cases after disopyramide. In the other four the ventricular paced cycle lengths producing ventriculoatrial block (318 +/- 41 ms) and effective refractory period of retrograde fast pathway (320 +/- 28 ms) were shorter than the cycle length of reinduced paroxysmal supraventricular tachycardia (367.5 +/- 35 ms) allowing perpetuation of the tachycardia. We conclude that disopyramide breaks atrioventricular nodal re-entrant tachycardia by specific blockade of the retrograde fast pathway though the effect on anterograde atrioventricular nodal conduction is variable.     

Selective blockade of retrograde fast pathway by intravenous disopyramide in paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways

Electrophysiological effects of 2 to 2.5 mg/kg iv disopyramide were studied in 10 patients with dual nodal pathways who used a slow pathway for anterograde and a fast pathway for retrograde conduction during paroxysmal supraventricular tachycardia (mean cycle length 308.5 +/- 37 ms; range 260-370 ms). Disopyramide terminated the tachycardia in six cases by production of ventriculoatrial block in five and by sinus overdrive in one. In the remaining four patients cycle length of the paroxysmal supraventricular tachycardia increased significantly from 270 +/- 8 ms to 377.5 +/- 28 ms. In all 10 patients disopyramide depressed retrograde fast pathway conduction manifest by an increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 296.5 +/- 25 ms to 358 +/- 60 ms, and increase in retrograde fast pathway effective refractory period from less than or equal to 246 +/- 34 ms to 325 +/- 36 ms; the drug abolished ventriculoatrial conduction in two cases. Anterograde slow pathway and fast pathway conduction properties were unchanged after disopyramide (atrial paced cycle length producing AH block 292 +/- 30 to 306.5 +/- 30 ms; effective refractory period of anterograde fast pathway less than or equal to 274 +/- 56 to 284 +/- 44 ms, before and after the drug, respectively) suggesting that anterograde conduction was not crucial either for sustainment or for failure to initiate paroxysmal supraventricular tachycardia after the drug. Paroxysmal supraventricular tachycardia could not be reinduced in six cases after disopyramide. In the other four the ventricular paced cycle lengths producing ventriculoatrial block (318 +/- 41 ms) and effective refractory period of retrograde fast pathway (320 +/- 28 ms) were shorter than the cycle length of reinduced paroxysmal supraventricular tachycardia (367.5 +/- 35 ms) allowing perpetuation of the tachycardia. We conclude that disopyramide breaks atrioventricular nodal re-entrant tachycardia by specific blockade of the retrograde fast pathway though the effect on anterograde atrioventricular nodal conduction is variable.     

The effects of class IA antiarrhythmic drug on the common type of atrial flutter in combination with pacing therapy

In 11 patients with common type of atrial flutter (common AF), rapid atrial pacing from the high right atrium was performed before and/or after class Ia antiarrhythmic drug administration, confirming transient entrainment by decreasing the pacing cycle length by 10 ms. In 10 patients before the drug administration, common AF was not interrupted although the pacing cycle length was decreased to 200 ms in 5 patients, accelerated atrial flutter or atrial fibrillation was induced in 4 patients, and common AF was converted into sinus rhythm in only 1 patient. After the drug administration common AF was converted into sinus rhythm in 5 out of 6 patients. The class Ia antiarrhythmic drug prolonged the common AF cycle length (255 +/- 12 ms vs. 298 +/- 37 ms, p less than 0.005) and widened the entrainment zone (64 +/- 7 ms vs. 90 +/- 20 ms, p less than 0.05). The widening of the entrainment zone and the prolongation of the common AF cycle length facilitate the successful conversion of common AF at a longer pacing cycle length, which would not precipitate atrial fibrillation or accelerated atrial flutter. The combination therapy of rapid atrial pacing and the class Ia antiarrhythmic drug is thought to be useful in the therapy of common AF.     

Combined amiodarone and silymarin treatment,but not amiodarone alone,prevents sustained atrial flutter in dogs

Amiodarone/Silymarin Treatment for Sustained Atrial Flutter. INTRODUCTION: Because amiodarone generates free radicals that may mediate amiodarone's toxicity, simultaneous therapy with an antioxidant might be beneficial if the antioxidant did not impair amiodarone's antiarrhythmic action. We tested whether simultaneous administration of a flavonoid antioxidant, silymarin, altered the electrophysiologic (EP) actions of amiodarone in 62 open chest dogs with electrically induced atrial flutter created by a Y-shaped right atrial incision. METHODS AND RESULTS: Fifteen dogs received oral amiodarone (600 mg/day); 15 dogs received amiodarone (600 mg/day) and silymarin (70 mg bid); and 8 dogs received silymarin (70 mg bid) alone. All dosing was for 8 weeks; 24 control dogs received no drugs prior to induction of atrial flutter. Atrial flutter was induced by rapid right atrial pacing, and EP measurements were made before (presurgical) and after (postsurgical) creation of a Y-shaped right atrial incision. There was no difference in the frequency of induction of atrial flutter lasting >30 minutes among amiodarone-treated (8/15 [53%]), silymarin-treated (4/6 [67%]), and control (15/21 [71%]) groups, whereas the frequency of induction in the amiodarone+silymarin dogs (2/15 [13%]) was significantly reduced (P = 0.008) compared with the other three groups. Both amiodarone and amiodarone+silymarin treatment prolonged the presurgical and postsurgical right atrial effective refractory period (P = 0.012) compared with control; however, there was no significant difference in either parameter between the amiodarone+silymarin-treated and amiodarone-treated groups. The increase in atrial flutter mean cycle length (postsurgical minus presurgical) was significantly (P = 0.005) less in the amiodarone+silymarin-treated and control dogs compared with the amiodarone-treated dogs (16 +/- 11 msec for amiodarone+silymarin; 24 +/- 8 msec for control; and 42 +/- 14 msec for amiodarone treatment). Amiodarone+silymarin treatment resulted in a longer postsurgical right atrial refractory period (155 +/- 13 msec) than atrial flutter mean cycle length (154 +/- 19 msec), consistent with reduction and/or elimination of the excitable gap. Silymarin alone did not exert significant EP or antiarrhythmic action. CONCLUSION: Amiodarone exerted no preventative antiarrhythmic action in this atrial flutter model, probably because it could not reduce the excitable gap of atrial flutter. However, an antioxidant, silymarin, without a direct antiarrhythmic action, when administered together with amiodarone, potentiated amiodarone's antiarrhythmic actions and prevented sustained atrial flutter by reduction and/or elimination of the excitable gap.     

Comparison of atrial overdrive pacing with and without extrastimuli for termination of atrial flutter.

Atrial overdrive pacing has been successfully used to terminate atrial flutter. This study compared the efficacy of atrial extrastimuli following a rapid pacing train to overdrive pacing without atrial extrastimuli for the termination of atrial flutter. Patients were randomized to treatments of short or long burst atrial overdrive pacing or atrial overdrive pacing followed by atrial extrastimuli in a crossover study design. A total of 22 patients (73%) had successful conversion of atrial flutter to sinus rhythm. The success rates in patients exposed to each therapy, including crossover therapies, were 62% with the atrial extrastimuli method, 8% with the short burst pacing method, and 8% with the long burst pacing method (p less than 0.001). Transient atrial fibrillation developed in 15 patients and in 9 of these this arrhythmia preceded conversion to sinus rhythm. Sustained atrial fibrillation was induced in 3 additional patients but never with the atrial extrastimuli method. In conclusion, the method of delivering atrial extrastimuli after a rapid pacing train is highly efficacious for the termination of atrial flutter. Furthermore, this method is more effective than atrial overdrive pacing methods delivered at the same pacing cycle length. These observations have important implications for the programming of antitachycardia pacemakers.     

Usefulness of invasive and non-invasive electrophysiologic studies in the selection of antiarrhythmic drugs for the patients with paroxysmal supraventricular tachyarrhythmia

A comparison of the effects of several antiarrhythmic agents was made in a study of 70 patients - 15 with manifest Wolff-Parkinson-White (WPW) syndrome, 17 with concealed WPW syndrome, 18 with AV nodal re-entrant tachycardia, 14 with paroxysmal atrial fibrillation and 6 with paroxysmal atrial flutter - employing intracardiac stimulation and esophageal pacing. For the termination of paroxysmal supraventricular tachycardia, intravenous administration of verapamil or aprindine was more effective than that of disopyramide or procainamide. In AV nodal re-entrant tachycardia, verapamil was the most effective for termination. In the manifest WPW syndrome, disopyramide or aprindine was indicated especially for patients with the accessory pathways of the short antegrade refractory period, because these drugs lengthened the refractory period of the accessory pathways. For the purpose of converting atrial fibrillation or flutter to the sinus rhythm, type IA drugs such as disopyramide were indicated. However, verapamil was effective for slowing down the ventricular rate in atrial fibrillation or flutter except in cases of manifest WPW syndrome. A 6-month follow-up study showed that oral administration of verapamil was also useful for putting a stop to the attacks in 24 out of 32 patients with paroxysmal supraventricular tachycardia, while oral disopyramide prevented the recurrence of atrial fibrillation in only 4 of 10 patients.     

Further observations on entrainment of atrial flutter in the dog

To determine whether the first postpacing interval after entrainment was affected by recording and pacing sites, overdrive atrial pacing was undertaken in 13 episodes of atrial flutter with a mean flutter cycle length (FCL) of 140 +/- 8 msec induced in seven dogs. Atrial flutter was induced by means of an anatomic obstacle. Seven recording sites, four in the right atrium and three in the left atrium, and three pacing sites, two in the right atrium and one in the left atrium, were selected. After entrainment from the right atrium at pacing cycle lengths that were 94% of the FCL, the first postpacing interval was not significantly different from the intrinsic FCL at each recording site, but it tended to be shorter than the FCL at the recording sites near pacing sites. For entrainment from the left atrium, the first postpacing interval was longer than the FCL at recording sites in the left atrium (p less than 0.001), but it was not different from the FCL at recording sites in the right atrium. These results are due to differences in placement of recording and pacing electrodes relative to the reentrant circuit. Also we observed that activation sequences involving three appropriately selected recording sites were always identical when paced from two different pacing sites at a single constant pacing cycle length. This new phenomenon may best be explained by postulating reentry as the mechanism for atrial flutter.     

The effect of chronic atrial overdrive suppression pacing on the incidence of supraventricular tachyarrhythmias.

Chronic overdrive suppression pacing has been suggested as an effective adjunctive method for reducing the incidence of cardiac tachyarrhythmias. Documentation of effectiveness during prolonged monitoring is lacking, however. To assess more accurately the long-term utility of this treatment modality for medically refractory supraventricular tachyarrhythmias (SVTs), 10 patients with atrially implanted Intermedics Intertach pacemakers were randomly assigned to either a low or a high bradycardia (back-up) pacing rate. SVT counts were performed during matching follow-up periods both at the initial rate and after rate crossover. The primary antitachycardia modality of this pacemaker (P mod) provides burst pacing to terminate tachycardia episodes, and P mod counters were utilized to quantitate SVT episodes. Tachycardia termination algorithms were programmed to "no restart" and were not changed during the study. The P mod use counter, therefore, reflected the number of discrete episodes of SVTs. Pacemaker implantation diagnoses include atrial flutter, concealed bypass tract, AV nodal reentry, intraatrial reentry, and Wolff-Parkinson-White associated tachycardia. Patient age was 59 +/- 18 yrs. The average pacemaker back-up low rate was 45.7 +/- 4 versus a back-up high rate of 85.1 +/- 2 beats/min. Follow-up was for 57.4 days +/- 33 days at the low rate and 57.3 days +/- 34 days at the high rate (r = 0.99). There was no difference in SVT incidence with a P mod usage of 98.4 +/- 106 at the low rate and 100.8 +/- 94 at the high rate (p = NS). In this blinded, randomized cross-over trial, chronic atrial overdrive suppression pacing did not reduce the overall incidence of SVT episodes during prolonged monitoring.     

Characterization of return cycle responses predictive of successful pacing-mediated termination of ventricular tachycardia

Objectives. The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia.Background. Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied.Methods. Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared.Results. Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r²= 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit.Conclusions. The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms.     

Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume

The effects of passive upright tilting from 0 degrees to +60 degrees (n = 27), Valsalva maneuver (n = 16) and respiration (n = 10) on the rate of atrial flutter were studied in 27 patients. After tilting to +60 degrees, the atrial flutter cycle length shortened in all patients from 247.5 +/- 7 to 236.7 +/- 6.9 ms (range of shortening 1 to 21 ms, p less than 0.001). The Valsalva maneuver (strain of 40 mm Hg) shortened the flutter cycle length during the strain (phase 2) from 242.2 +/- 4.6 to 230.5 +/- 5 ms (range of shortening 2 to 19 ms, p less than 0.001). In 10 patients whose respiration was monitored, the flutter cycle length consistently prolonged during inspiration and shortened during expiration. Combined beta-adrenergic and muscarinic receptor blockade in six patients did not significantly alter the flutter cycle length at rest or the effects of the various maneuvers on the changes in flutter cycle length. This study revealed that the atrial flutter cycle length can be shortened by passive upright tilting, the strain phase of the Valsalva maneuver and expiration. Changes in flutter cycle length were independent of autonomic tone, implying that by decreasing cardiac volume, these maneuvers affect characteristics of the atrial flutter circuit, thereby producing dynamic changes in the rate of atrial flutter.