Intra-atrial Conduction Research Articles

Pacing-Induced Chronic Atrial Fibrillation Impairs Sinus Node Function in Dogs

We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

Atrioventricular conduction during adenosine-induced hypotension in dogs anaesthetized with sevoflurane

We have studied the effects of adenosine-induced hypotension on A-H interval (atrioventricular (AV) nodal conduction time during sinus rhythm), St-H interval (intra-atrial plus AV nodal conduction time during atrial pacing), H-V interval (His-Purkinje conduction time) and H-S interval (total ventricular conduction time) by His-bundle electrocardiography in addition to surface electrocardiogram during both sinus rhythm and atrial pacing in nine dogs anaesthetized with 1 MAC of sevoflurane. Stepwise increases in infusion rates of adenosine to 0.1, 0.3, 0.5 and 1.0 mg kg-1 min-1 produced a dose-related decrease in mean arterial pressure from 91 (6) to 38 (2) mm Hg. Adenosine significantly increased the A-H interval at infusion rates of 0.5 mg kg-1 min-1 and above, and the St-H interval at 1.0 mg kg-1 min-1. The H-V and H-S intervals remained unchanged. Heart rate decreased significantly only at 1.0 mg kg-1 min-1 with a significant increase in the PR interval. Adenosine-induced hypotension did not have deleterious effects on AV conduction times and the surface electrocardiogram in dogs anaesthetized with 1 MAC of sevoflurane. This may indicate that the effects of adenosine on AV conduction were small and therefore are unlikely to be a contraindication to the use of adenosine for inducing hypotension in patients with initially normal conduction during sevoflurane anaesthesia.

Site-dependent intra-atrial conduction delay. Relationship to initiation of atrial fibrillation.

Atrial dysrhythmia patients have exaggerated intra-atrial conduction delays and prolonged relative refractoriness in response to atrial premature depolarizations (APDs). Furthermore, atrial fibrillation (AF) is more readily inducible by APDs from the high right atrium (HRA) than the coronary sinus (CS). In this study, we postulated that site-specific intra-atrial conduction delays can explain why AF is initiated more from the HRA than from the CS. We examined 17 patients (age, 49 +/- 22 years) without a history of atrial flutter, AF, or structural heart disease. Programmed stimulation was carried out from the HRA and distal CS, and bipolar recordings were made at the HRA, His bundle, posterior triangle of Koch, and CS. More prolongations in conduction and relative refractoriness in all intra-atrial sites were observed during HRA than CS APDs. AF was induced in 8 patients after HRA and not CS stimulation. During HRA stimulation, patients with AF inducibility exhibited significant prolongation of conduction to the posterior triangle of Koch and marked broadening of the posterior triangle of Koch electrogram compared with CS stimulation. In patients without AF inducibility, the posterior triangle of Koch electrogram width was the same during HRA and CS stimulation. The existence of site-dependent intra-atrial conduction delays and site-dependent dispersion of refractoriness appears to be a common property of the atrial myocardium and does not necessarily forecast AF inducibility. However, the presence of nonuniform anisotropic characteristics of the posterior triangle of Koch may be critical for AF induction.

Unravelling the electrical mysteries of atrial fibrillation.

Animal experiments have confirmed that a short but variable excitable gap is present during induced atrial fibrillation. The existence of this gap allows atrial fibrillation to be locally captured by rapid pacing. An area of up to 4 cm in diameter can be activated by uniform wave fronts propagating away from the site of stimulation, although the size of this area may be limited by intra-atrial conduction block or by collision with fibrillation waves. Rapid pacing can accelerate atrial fibrillation by inducing local re-entry circuits with a cycle length shorter than the pacing interval. During pacing-induced atrial fibrillation in patients undergoing surgery for Wolff-Parkinson-White syndrome, three types of atrial activation have been identified, which vary in their degree of complexity and in the length of their fibrillation intervals. It appears that the spectrum of varying cycle lengths during atrial fibrillation might be explained by a mixture of different sorts of atrial re-entry patterns, comprising purely functional intra-atrial re-entry, random re-entry, anatomical re-entry, and nodal re-entry.

Electrophysiologic characteristics of human atrial muscle in paroxysmal atrial fibrillation

There are several limitations in clinical electrophysiologic studies of PAF, mainly related to its mechanism, which is not an ordered reentry but a random reentry of multiple independent wavelets within the atrium. Recent investigations based on the recordings of local AAEs during sinus rhythm and their characteristic distribution within the right atrium of patients with PAF provide us with new information on the electrophysiologic properties of the diseased atrium. Moreover, several abnormal responses have been elicited by premature atrial stimulation, including repetitive atrial firing, fragmented atrial activity, and intraatrial conduction delay. Although these responses do not show the localization and characteristics of reentry circuits, they are found to be closely related to the development and maintenance of atrial fibrillation in predisposed patients. These indicators of atrial vulnerability and their corresponding zones, which are defined as the difference between the longest coupling interval eliciting the abnormal responses and the atrial effective refractory period, are useful parameters indicative of predisposition to atrial fibrillation. Electrophysiologic studies in patients with PAF have led to essential understanding of the underlying clinical pathophysiologic process of atrial fibrillation and would further contribute to future development of more suitable treatments.

Atrial natriuretic peptide and cardiac electrophysiology: autonomic and direct effects.

Atrial natriuretic peptide (ANP) has varied effects on cardiac electrophysiologic parameters including heart rate, intraatrial conduction time, and refractory period. ANP's vagoexcitatory and sympathoinhibitory actions as well as its direct actions on cardiac ion currents may be responsible for some of these effects. This review discusses the role of ANP in cardiac electrophysiology, its interactions with the autonomic nervous system and baroreceptor reflex, and its effects on cardiac ion currents.

Electrophysiologic abnormalities of cardiac function in progressive systemic sclerosis

The heart has been generally recognized as a target organ in progressive systemic sclerosis. Noninvasive studies have assessed the incidence and prognostic importance of cardiac arrhythmias in these patients. However, detailed exploration of the function of impulse formation and the conduction system of the heart in these patients has never been reported. Therefore, invasive electrophysiologic studies were performed in 30 patients with systemic sclerosis, all of whom had neither obvious cardiac involvement nor cardiac arrhythmias, and in 32 subjects with no evidence of heart disease, who served as a control group. Corrected sinus node recovery time in patients with systemic sclerosis was significantly longer ( P < .001) than in the control group, as was the HV interval ( P < .05). Of the 30 patients with systemic sclerosis, 10 had an HV interval of 60 ms or longer. In four patients with systemic sclerosis, the recorded AH interval exceeded 125 ms. The intra-atrial conduction time tended to increase to a significant degree ( P < .05) in patients with systemic sclerosis. The interatrial conduction time was much longer ( P < .001), and the maximal conduction delay to the atrioventricular junction and to the distal coronary sinus was much greater in the patients with systemic sclerosis than in the control group ( P < .001 for both). Supraventricular tachyarrhythmias were induced in 15 patients with systemic sclerosis versus 3 control group subjects ( P < .001). With respect to corrected sinus node recovery time, AH and HV intervals, atrial vulnerability, and ventricular tachycardia, 3 of the 30 patients with systemic sclerosis had abnormal findings in one of these parameters and 14 had abnormalities in more than one. These results suggest that a broad spectrum of electrophysiologic abnormalities is present in patients with systemic sclerosis, which can be revealed only by invasive studies. Furthermore, this study provides additional support for the hypothesis that diffuse myocardial involvement is characteristic of scleroderma patients, since a number of these patients showed more than one electrophysiologic defect.

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.

Electrophysiological basis for antiarrhythmic efficacy, positive inotropy and low proarrhythmic potential of (—)‐caryachine

1. (-)-Caryachine, isolated from the plant (Cryptocarya chinensis), increased the contractility of atrial and right ventricular strips and significantly suppressed the reperfusion arrhythmias in adult rabbit heart (ED50 = 1.27 microM). 2. Data obtained by the whole-cell voltage clamp technique has shown that (-)-caryachine causes a negative shift of the steady-state Na channel inactivation and a slower rate of recovery from inactivation. The maximal Na current amplitude decreased to 67 +/- 7%, 29 +/- 8% and 12 +/- 5% after 0.5, 1.5 and 4.5 microM (-)-caryachine, respectively. 3. This agent also had effects on the time- and voltage-dependent K currents. (-)-Caryachine markedly suppressed the 4-AP-sensitive transient outward current (I10). However, it produced very little voltage-dependent shift in inactivation. After 0.5, 1.5 and 4.5 microM of the compound, the respective value of I10 elicited at +60 mV was 80 +/- 7%, 45 +/- 8% and 15 +/- 3%. At higher concentrations, the inward rectifier K current (IK1) was also inhibited but to a much smaller extent. Its slope conductance after 0.5, 1.5 and 4.5 microM (-)-caryachine was reduced to 71 +/- 9%, 51 +/- 12% and 42 +/- 11%, respectively. The outward hump of inward rectification was not changed. 4. In contrast, the L-type Ca current was not significantly changed by (-)-caryachine. 5. Electrophysiological studies in perfused whole heart preparations revealed that (-)-caryachine increased the intra-atrial conduction interval and also prolonged the atrial refractory period. No proarrhythmic effects were induced during the infusion of this compound (up to 13.5 microM). 6. We conclude that (-)-caryachine predominantly blocks the Na and I10 currents. These changes alter the electrophysiological properties of the heart and terminate the induced ventricular arrhythmias. The relatively selective I10 inhibition, safety margin of Ik1 suppression and lack of effect on Ica-L will provide an opportunity to develop an effective antiarrhythmic agent with positive inotropy as well as low proarrhythmic potential.

Signal-averaged P wave in patients with wolff-parkinson-white syndrome after successful radiofrequency catheter ablation

We attempted to establish a relation between the atrial conduction time assessed by the signal-averaged P wave electrocardiogram and episodes of paroxysmal atrial fibrillation in patients with the Wolff-Parkinson-White syndrome. The incidence of paroxysmal atrial fibrillation is higher in patients with the Wolff-Parkinson-White syndrome than in normal persons. However, the role of intraatrial conduction delay in precipitating the disorganization of atrial rhythm is not completely understood. The total duration of the signal-averaged P wave and the P wave in standard lead II was evaluated after successful radiofrequency catheter ablation in 28 patients with the Wolff-Parkinson-White syndrome. The data obtained from 17 patients (61%) with a documented history of prior paroxysmal atrial fibrillation (group I) were compared with those obtained from 11 patients (39%) without a history of atrial fibrillation (group 2). Both groups were further compared with a normal control population. The mean +/- SD signal-averaged P wave duration in group 1 was 141.94 +/- 9.47 ms (range 130.0 to 171.0). Fourteen patients (82%) in this group showed a P wave duration > 135.0 ms. In group 2, the signal-averaged P wave duration was 126.64 +/- 8.72 ms (range 111.0 to 136.0). Only one patient in this group (9%) showed a P wave duration > 135.0 ms (p < 0.000, group 1 vs. group 2). The signal-averaged P wave duration in the control group was 124.46 +/- 4.49 ms (range 115.0 to 129.5; p < 0.000, group 1 vs. the control group; p < 0.454, group 2 vs. the control group). The P wave duration in lead II was 92.06 +/- 8.85 ms in group 1 and 92.27 +/- 7.86 ms in group 2 (p < 0.949). Using a cutoff value of < 135.0 ms for a normal signal-averaged P wave duration, the method had a sensitivity and specificity and positive and negative predictive values of 82%, 91%, 93% and 77%, respectively, for identifying patients with clinical paroxysmal atrial fibrillation. In the current study, the signal-averaged P wave showed a prolonged intraatrial conduction time in patients with the Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation. These patients can be differentiated from those with the pre-excitation syndrome without clinical atrial fibrillation as well as from normal subjects. The prolonged intraatrial conduction time may serve as an atrial substratum for development and maintenance of the fibrillatory state.

Atrial electromechanical sequence in normal subjects and patients with DDD pacemakers.

To assess the effect of right atrial appendage pacing on atrial electromechanical interrelations in patients with DDD pacemakers. Prospective study by M mode echocardiogram, Doppler echocardiogram, and apexcardiogram, along with electrocardiogram and phonocardiogram. Tertiary cardiac referral centre. 20 patients with DDD pacemakers and 20 age matched normal controls. Age, RR interval, atrial size, left ventricular size, and fractional shortening were similar in the two groups. Atrial electromechanical delay (the time from the onset of P wave or atrial pacing spike on ECG to the onset of atrial contraction on M mode echogram) was 68 (SD 7) ms at the lateral site of right atrium, 82 (9) ms at the central fibrous body, 93 (11) ms at the lateral site of left atrium in normals. In patients with DDD pacing, however, this delay increased to 85 (22) ms, 117 (23) ms, and 138 (25) ms respectively (all P < 0.01). Interatrial mechanical delay (the time from the onset of right atrial motion to the onset of the left) increased from 25 (6) ms in normal controls to 53 (18) ms in patients (P < 0.01). Intra-atrial mechanical dispersion (the time from the earliest to the latest onset of regional atrial motion around the atrioventricular ring) in the right atrium increased from 6 (2) ms in normals to 19 (2) ms in patients (P < 0.01), but it remained unchanged in the left atrium (6 (2) ms in normal controls v 7 (2) ms in patients, P > 0.05). Peak atrial shortening rate was not different between the two groups. Differences of atrial electromechanical activity between the two groups were also reflected on Doppler echocardiogram and apexcardiogram. Right atrial appendage pacing disturbs the normal coordinate sequence of right atrial mechanical activity and leads to a striking and variable increase in intra-atrial conduction time as well as in interatrial conduction time. Left atrial contraction remains synchronous although the timing of the start of its contraction was delayed. These values can be determined in individual patients to allow optimal setting of DDD pacemakers.

Linear ablation of the isthmus between the inferior vena cava and tricuspid annulus for the treatment of atrial flutter. A study in the canine atrial flutter model.

The isthmus between the inferior vena cava and the tricuspid annulus has been shown to be involved in the reentry circuit of common atrial flutter. The effects of radio-frequency catheter ablation of this isthmus were examined in the canine model of atrial flutter due to reentry around the tricuspid annulus. A model of atrial flutter was prepared in 11 of 14 dogs by creating intercaval and connected transverse lesions (Y-shaped lesion). Bipolar electrodes were attached at 24 atrial sites, and computer-assisted mapping was performed. Stable atrial flutter with a cycle length of 133 +/- 11 ms was repeatedly induced by rapid atrial pacing in all dogs, and atrial mapping revealed reentry around the tricuspid annulus including the isthmus. In 6 dogs, the isthmus was ligated during atrial flutter (mechanical ablation). In the other 5 dogs, a 7F large-tip electrode catheter was placed at the isthmus under a fluoroscopic control. Radiofrequency energy (25 W for 30 s) was delivered to three sequential sites from the tricuspid annulus to the inferior vena cava to ablate the isthmus linearly. Atrial flutter was terminated in all dogs after mechanical and radio-frequency ablation of the isthmus and was not induced again. Atrial pacing from the posterior left atrium during sinus rhythm demonstrated intra-atrial conduction block at the isthmus after ablation. Pathological examination of the isthmus showed transmural myocardial damage. Linear radiofrequency ablation of the isthmus can induce intra-atrial conduction block and is effective as a curative therapy for atrial flutter when the reentry circuit involves the isthmus.

Additive Cardiac Depression by Volatile Anesthetics in Isolated Hearts After Chronic Amiodarone Treatment

Some patients undergoing general anesthesia may be chronically receiving the antidysrhythmic drug amiodarone. The half-life of this drug is very long and it may not be advisable or possible to discontinue its administration prior to anesthesia. We examined depressant effects of three volatile anesthetics in hearts isolated from guinea pigs chronically treated with amiodarone. Hearts were isolated and perfused retrogradely through the aorta with oxygenated Krebs-Ringer solution at 37 degrees C at constant pressure. Variables measured in 26 hearts were heart rate (HR), atrioventricular, intraatrial, and intraventricular conduction times (AVCT, IACT, IVCT) during pacing at 240 bpm, coronary flow, and left ventricular pressure (LVP). Amiodarone (20 mg intraperitoneally) or placebo (Group 1) was given once daily for 1 (Group 2) or 4 (Group 3) wk. Cardiac tissue concentrations of amiodarone were similar (12.1 micrograms/g wet weight) in hearts in Groups 2 and 3 but serum levels were twice as high in hearts in Group 3 as in Group 2 (0.33 vs 0.17 microgram/mL). Before anesthetic exposure, all variables for hearts in Group 2 were not significantly different from those in Group 1. Significantly, for hearts in Group 3, compared to those in Group 1, HR was slower (-14%), conduction times were longer (IACT + 5 ms, IVCT + 4 ms, AVCT + 9 ms), coronary flow was higher (+23%), and LVP was lower (-12%). After control measurements, hearts were exposed to 0.5 and 1 minimum alveolar anesthetic concentration (MAC) halothane, enflurane, and isoflurane in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

943-15 Site-dependent Intra-atrial Conduction Delay: Relationship to Initiation of Atrial Flutter/Fibrillation

Atrial flutter/fibrillation (AF) are more readily inducible by atrial premature complexes (APCs) from the high right atrium (HRA) than from the coronary sinus (CS). Patients (pts) who have clinical AF have an exaggerated intraatrial conduction delay(IACD) and prolonged relative refractory period (RRP) in response to APCs delivered from the HRA. We therefore compared the response of APCs delivered from the HRA, posterior Triangle of Koch (SP), and CS to evaluate whether the propensity of HRA stimuli to induce AF is related to site-specific anisotropic conduction abnormalities. Programmed atrial stimulation at twice threshold was caried out in five pts from the HRA, SP, and CS. Recordings were made at the HRA, Sp, along the Tendon of Todaro (HBE catheter), and the CS. Pts were 3 women and 2 men, age 50 to 79, none of whom had clinical AF or organic heart disease. None had IACO during sinus rhythm. The RRP was defined as the range of intervals over which A1A2 was &gt;S1S2 at the stimulus site, and A1A2 at distance sites was &gt;A1A2 at stimulus sites. ΔCT denotes the maximum increase in conduction time at each site. Recording site ΔCT RRP Stimulation site HRA CS * SP HRA CS * CS * HRA 0 23 25 53 30 52 SP 65 24 0 82 30 32 HBEd 53 28 46 82 30 58 HBE2 52 28 33 78 28 58 HBE3 53 28 38 78 28 52 CSp 62 19 34 76 28 64 CS4 67 16 34 88 26 50 CS3 71 2 39 86 24 54 CS2 65 0 46 86 10 60 * p &lt; 0.03, Data are means (in msec) AF was induced in 2 pts from the HRA but not from other sites. Our results demonstrate the greatest degree of IACD and RRP was seen with HRA stimulation and the least with CS stimulation. SP stimulation resulted in intermediate results. The marked site-specific difference in IACD supports anisotropic impulse conduction in the atria, and may explain why AF is more often initiated from the HRA tha n the CS.

1025-100 Patients with WPW Syndrome and Paroxysmal Atrial Fibrillation Shows Prolonged Atrial Conduction Time by Signal-Averaged P-Wave Electrocardiogram

The purpose of this study was to establish a relationship between the atrial activation assessed by signal-averaged P wave ECG (SAPW) and episodes of paroxysmal atrial fibrillation (PAF) in patients (pts) with WPW syndrome (WPWS). fourteen pts with documented episodes of PAF, without underlying heart disease were selected (12 men: age = 35.2 ± 11.1 years) from a total of 70 consecutives pts successfully submitted to radiofrequency catheter ablation of accessory pathway (AP). All pts with anterograde conduction over the AP. left side AP in 9 pts and right side AP in 5 pts. The SAPW were recorded with the Corazonix Predictor II system from the X, Y, Z leads (40–250 Hz, least Square filter, final noise &lt; 0.3 μV). The total filter P wave duration (PWD) was obtained manually from the vector-magnitude in ms. Recordings were performed between 7 th and 14 th day after the ablation. No pts showed left atrial larger than 4.0 cm on the echocardiogram. The results were compared with a control group of 12 pts matched in age (5 men; age = 33.0 ± 10.2 years) without heart disease. Values were given as mean and 1SO and compared using non-paired Student t test (significance &lt; 0.05). Control Group In = 12): PWD ranged from 115.0 to 129.5 ms with a mean of 124.4 ± 4.4 ms. WPWS with PAF (n = 14): PWD ranged from 130.0 to 171.0 ms with a mean of 142.9 ± 1 0.1 ms (p &lt; 0.000). Eleven pts (78.5%) showed PWD &gt; 135.0 ms. There were no differences between PWD and AP location. Recurrent PAF after ablation was noted in 3 pts (21% – PWD: 171.0, 1505 and 139.0 ms for each patient). With a cutoff &lt; 135.0 ms for a normal PWD, the sensitivity was 78.5%, the specificity was 100%; the positive predictive value was 100% and the negative was 75% for SAPW to identify pts with WPWS and PAF. In the current study, pts with WPWS and PAF showed prolonged intra-atrial conduction time when compared with a control group. This may contribute to the development of PAF.

Supernormal atrial conduction and its relation to atrial vulnerability and atrial fibrillation in patients with sick sinus syndrome and paroxysmal atrial fibrillation

The purpose of this study was to evaluate prospectively the relationship between supernormal atrial conduction (SNC) and the atrial vulnerability to fibrillation in patients with sick sinus syndrome (SSS) and paroxysmal atrial fibrillation (PAF). Programmed atrial stimulation was performed in 32 age-matched control patients (group I), 26 with SSS but without tachyarrhythmias (group II), and 24 with both SSS and PAF (group III) to assess some determinants of atrial vulnerability, SNC, and atrial fibrillation inducibility. Supernormal atrial conduction was observed in 20 (63%) patients of group I, 12 (46%) patients of group II, and 5 (21%) patients of group III (group I vs group III; p < 0.002). The SNC zone was 46 ± 44 msec in group I, 36 ± 42 msec in group II, and 12 ± 24 msec in group III. (group I vs group III; p < 0.001). The absence of SNC showed a specificity of 89% and a positive predictive accuracy of 79% in predicting inducibility of atrial fibrillation. The sensitivity was 33% and the negative predictive accuracy was 52%. The SNC zone showed a significant inverse correlation with P wave duration ( r = −0.32; p < 0.003), intraatrial conduction time ( r = −0.28; p < 0.02), and maximum conduction delay ( r = −0.23; p < 0.05). The maximum decrease in conduction time during supernormal conduction showed a significant inverse correlation with P wave duration ( r = −0.27; p < 0.02), intraatrial conduction time ( r = −0.26; p < 0.02), and with the maximum conduction delay ( r = −0.27; p < 0.02). We conclude that the greater the atrial vulnerability and the greater the atrial conduction defects, the lower the occurrence of supernormal atrial conduction in the SSS. The absence of supernormal atrial conduction associated with atrial conduction defects may play an important role in the development of atrial fibrillation in patients with sick sinus syndrome and paroxysmal atrial fibrillation.

Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.

Moricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness. The effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra-atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the atrial threshold of excitability from a mean of 2.3 +/- 1.4 to 3.3 +/- 2.2 mA (P < .01) and prolonged intra-atrial conduction times (measured from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction. Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes in conduction in an area(s) of slow conduction are responsible for both cycle length prolongation and atrial flutter termination rather than the traditional wavelength concept of head-tail interaction.

Incidence and electrophysiologic characteristics of supernormal atrial conduction in humans

The incidence and electrophysiologic characteristics of supernormal atrial conduction (SNC) were examined by cardiac stimulation in 53 control subjects. Their ages ranged from 15 to 71 years (mean age, 50 ± 21 years) (mean ± SD). There were 27 women and 26 men in the study. Conduction of premature atrial responses from the sinus node to the atrioventricular node (intraatrial conduction time) was supernormal in 27 (51%) subjects and conduction to the left atrium (interatrial conduction time) was supernormal in 35 (66%) subjects (difference not significant). At coupling intervals ranging between 440 and 240 ms, the conduction time of the premature beats was as much as 25 ms shorter than that of the basic driven beats. The maximum decrease in interatrial conduction time during the period of SNC was 13 ± 5 ms and the maximum decrease in intraatrial conduction time was 9 ± 3 ms ( P < .001). The supernormal interatrial conduction zone was 71 ± 29 ms and the supernormal intraatrial conduction zone was 57 ± 25 ms ( P < .05). There was a significant positive correlation between the SNC zone and the maximum decrease in conduction time ( r = .82; P < .001). Supernormal atrial conduction was stable, reproducible, and remained constant in individual patients. Supernormal atrial conduction was found to be a relatively frequent phenomenon. There was a significantly greater SNC zone and maximum decrease in conduction time in interatrial conduction than in intraatrial conduction. Knowledge of the electrophysiologic characteristics and the incidence of SNC in control subjects should provide a better understanding of its role in the genesis of reentry when studied in patients with atrial flutter or paroxysmal atrial fibrillation.

Relationship Between Atrial Conduction Defects and Fractionated Atrial Endocardial Electrograms in Patients with Sick Sinus Syndrome

The relationship between abnormal atrial electrograms (AAE) recorded during sinus rhythm by endocardial catheter mapping of the right atrium and the atrial conduction defects of sinus impulses or single atrial extrastimuli was investigated in 44 patients with sick sinus syndrome. The patients were divided into two groups on the basis of the presence (n = 29) or absence (n = 15) of AAE recorded during sinus rhythm. The P wave duration in the AAE (+) Group patients was 137 +/- 14 msec, and 125 +/- 15 msec in the AAE (-) Group; P < 0.02. The intraatrial conduction time of sinus impulses in the AAE (+) Group was 54 +/- 12 msec, and 39 +/- 9 msec in the AAE (-) Group; P < 0.001. The interatrial conduction time in the AAE (+) Group was 101 +/- 14 msec, and 78 +/- 16 msec in the AAE (-) Group; P < 0.001. In the AAE (+) Group, 11 (38%) patients had a sinus node recovery time > 4 seconds, whereas in the AAE (-) Group there was only one (6%) patient; P < 0.03. AAE showed a specificity of 93% and a positive predictive accuracy of 91% in predicting inducibility of atrial fibrillation. The sensitivity was 35% and the negative predictive accuracy was 42%. Sustained atrial fibrillation was induced in ten (35%) patients of the AAE (+) Group, and in one (7%) patient of the AAE (-) Group; P < 0.05. These data suggest that in patients with sick sinus syndrome who possess abnormal endocardial electrograms in sinus rhythm within the right atrium have: (1) a significantly longer P wave duration; (2) a significantly longer intraatrial and interatrial conduction time of sinus impulses; and (3) a significantly greater sinus node dysfunction and higher incidence of induction of sustained atrial fibrillation. It is concluded that there are significantly greater atrial conduction defects in patients with sick sinus syndrome who possess AAE within the right atrium during sinus rhythm.

Cardiac arrhythmias in Chagas' heart disease.

Chagas' disease is a chronic parasitosis affecting most Latin American countries. Its most important clinical manifestation is a late developing chronic myocarditis and, much less frequently, an early acute myocarditis. Chagasic myocardial damage is microfocal and disseminated throughout the heart. In most cases, the coexistence of areas of myocytic degeneration, inflammatory infiltration, and fibrosis suggests a permanent evolving process. Commonly, chronic chagasic myocarditis resembles a dilated cardiomyopathy, with characteristic ECG abnormalities (atrial and ventricular extrasystoles, intraventricular and/or AV conduction disturbances, and primary ST-T wave changes). Since myocardial damage is scattered throughout the heart, the ECG abnormalities (arrhythmias, conduction disturbances, and repolarization changes) are also representative of the widespread cardiac involvement. Thus, sick sinus syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial fibrillation or flutter are common findings in different stages of the disease. At the ventricular level, both conduction disturbances and arrhythmias are conspicuous expressions of the myocardial damage. Right bundle branch block alone or in combination with left anterior hemiblock are the most common conduction defects. Further compromise of the conduction system can lead to different degrees of AV block. Chagas' disease is the main cause of bundle branch block and AV block in endemic areas. In advanced cases of Chagas' heart disease, ventricular premature contractions are extremely frequent, multiform, and repetitive (couplets and runs of ventricular tachycardia), and show R on T phenomenon. These arrhythmias are usually aggravated by increased sympathetic tone, implying an enhanced risk of cardiac sudden death among chagasic patients, which is sometimes the first manifestation of the illness. Chronic chagasic myocarditis is the leading cause of cardiovascular death, mostly as a consequence of heart failure and sudden death, in areas where the disease is endemic.