Fragmented Atrial Activity Zone Research Articles

Effects of flecainide on the electrophysiological properties of atrial vulnerability in humans.

The aims of this study were to evaluate the changes in the electrophysiological characteristics of the right atrium after the administration of flecainide and to clarify whether flecainide has a selective effect on human atrial tissue. Electrophysiological measurements were made in 38 patients, before and after intravenous administration of flecainide (2 mg/kg per 10 min). The effective refractory period of the right atrium (ERP-A), maximum conduction delay (Max.CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were studied in the patients who were divided into 2 groups based on whether repetitive atrial firing (RAF) was induced in the baseline study. Flecainide significantly prolonged the ERP-A (202+/-22 to 238+/-33 ms, p<0.001) and shortened Max.CD (77+/-17 to 63+/-32 ms, p<0.05) in the patients with RAF, but not in those without RAF in the baseline study. After flecainide administration, there were significant reductions in the RAFZ (43+/-22 to 13+/-19 ms, p<0.0001), FAAZ (51+/-22 to 28+/-26 ms, p<0.001) and CDZ (70+/-21 to 48+/-30 ms, p<0.01) in the patients with RAF. However, atrial fibrillation (AF) was induced by stimulation after flecainide in 2 patients without RAF in the baseline study. There was a significant negative correlation between the ERP-A in the baseline study and the change in the ERP-A upon flecainide administration (r=0.45, p<0.01). Flecainide may preferentially activate the substrate for AF and RAF, but that action is mainly based on the electrophysiological characteristics found in the baseline study.

Clinical significance of the atrial fibrillation threshold in patients with paroxysmal atrial fibrillation.

AF threshold and the other electrophysiological parameters were measured to quantify atrial vulnerability in patients with paroxysmal atrial fibrillation (PAF, n = 47), and those without AF (non-PAF, n = 25). Stimulations were delivered at the right atrial appendage with a basic cycle length of 500 ms. The PAF group had a significantly larger percentage of maximum atrial fragmentation (%MAF, non-PAF: mean +/- SD = 149 +/- 19%, PAF: 166 +/- 26%, P = 0.009), fragmented atrial activity zone (FAZ, non-PAF: median 0 ms, interquartile range 0-20 ms, PAF: 20 ms, 10-40 ms, P = 0.008). Atrial fibrillation threshold (AF threshold, non-PAF: median 11 mA, interquartile range 6-21 mA, PAF: 5 mA, 3-6 mA, P < 0.001) was smaller in the PAF group than in the non-PAF group. Sensitivity, specificity, and positive predictive value of electrophysiological parameters were as follows, respectively: %MAF (cut off at 150%, 78%, 52%, 76%), FAZ (cut off at 20 ms, 47%, 84%, 85%), AF threshold (cut off at 10 mA, 94%, 60%, 81%). There were no statistically significant differences between the non-PAF and PAF groups in the other parameters (effective refractory period, interatrial conduction time, maximum conduction delay, conduction delay zone, repetitive atrial firing zone, wavelength index), that were not specific for PAF. In conclusion, the AF threshold could be a useful indicator to evaluate atrial vulnerability in patients with AF.

Abnormalities of electrocardiographic P wave morphology and their relation to electrophysiological parameters of the atrium in patients with sick sinus syndrome.

We examined the incidence of long P wave duration in lead II and increased P terminal force in lead V1 (PTFV1), and their relationship to electrophysiological findings of atrial muscle in 34 patients with sick sinus syndrome (SSS). Patients were divided into three groups: Group I, consisting of 20 patients with various cardiac arrhythmias other than SSS and paroxysmal atrial fibrillation (PAF) who served as controls; Group II, consisting of 18 patients with SSS but without PAF; and Group III consisted of 16 patients with SSS and PAF. P wave duration was significantly longer in Group III (122 +/- 11 ms, mean +/- SD, P < 0.0001) and Group II (111 +/- 15 ms, P < 0.002) than in Group I (98 +/- 10 ms). PTFV1 was greater in Group III (0.052 +/- 0.025 ms) than in Group I (0.028 +/- 0.011 ms, P < 0.05). P wave duration and PTFV1 had significantly and/or borderline correlations with longest duration of right atrial electrograms (r = 0.84, P < 0.0001 and 0.47, P < 0.02, respectively), maximal number of fragmented deflections of atrial electrograms (r = 0.69, P < 0.0001 and r = 0.51, P < 0.02, respectively), repetitive atrial firing zone (RAFZ) (r = 0.81, P < 0.0001 and 0.48, P < 0.05, respectively) and fragmented atrial activity zone (FAAZ)(r = 0.53, P < 0.01 and r = 0.45, P = 0.06, respectively). We concluded that long P wave duration and increased PTFV1 are electrocardiographic indicators for coexistence of electrophysiological abnormalities in the atria in SSS without recognizable heart disease.

Repetitive Atrial Firing and Fragmented Atrial Activity Elicited by Extrastimuli in the Sick Sinus Syndrome With and Without Abnormal Atrial Electrograms

Endocardial catheter mapping of the right atrium during sinus rhythm and programmed atrial stimulation were performed in 50 patients with sick sinus syndrome to investigate the relationship between abnormal atrial electrograms recorded during sinus rhythm and some determinants of the atrial vulnerability such as repetitive atrial firing and fragmented atrial activity elicited by single extrastimulus. The patients were divided into 2 groups on the basis of the presence (Group I) or absence (Group II) of abnormal atrial electrograms recorded during sinus rhythm. In Group I (N = 32), repetitive atrial firing was induced in 23 (72%) patients, and in Group II (N = 18) in 6 (33%) patients; p less than 0.01. The repetitive atrial firing zone was 41 +/- 37 ms in Group I and 12 +/- 18 ms in Group II; p less than 0.001. Fragmented atrial activity was induced in 30 (94%) patients from Group I, and in 8 (44%) patients from Group II; p less than 0.0001. The fragmented atrial activity zone was 47 +/- 42 ms in Group I and 14 +/- 19 ms in Group II; p less than 0.0001. The atrial electrogram width at the premature beat (A2; p < 0.02) and the maximum A2/A1 ratio (p < 0.002) were 178 +/- 53 ms and 196% +/- 40%, respectively in Group I, and 141 +/- 36 ms and 159% +/- 30%, respectively in Group II. Atrial fibrillation was induced in 13 (41%) patients from Group I, and in 1 (6%) patient from Group II (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological effects of a new class III antiarrhythmic agent (E-4031) on the conduction and refractoriness of the in vivo human atrium.

The aim was to test the efficacy of a new class III drug, E-4031, on human atrial muscle in vivo. Electrophysiological measurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 microgram.kg-1.min-1) which followed an initial dose of 9 micrograms.kg-1 x 5 min-1. Extrastimuli at 500 ms were delivered from the right atrial appendage, high lateral right atrium, and low lateral right atrium. The effective refractory period, repetitive atrial firing zone, and fragmented atrial activity zone were assessed at three sites in the right atrium. The conduction delay zone from the stimulus artefact to the distal electrode pair at the coronary sinus was also measured. E-4031 caused a significant increase in overall right atrial effective refractory period from 210(SD 29) to 232(26) ms (p < 0.001, n = 30 sites). There were significant decreases in the incidence of repetitive atrial firing (67% to 37%: p < 0.005), in the repetitive atrial firing zone [23(20) to 11(22) ms: p < 0.01], and in the fragmented atrial activity zone [15(22) to 3(8) ms: p < 0.005], but no significant change in the conduction delay zone. However, E-4031 significantly prolonged the longest coupling interval that elicited conduction delay, from 249(31) ms to 267(28) ms (p < 0.01). E-4031 had no effect on the conduction time except at coupling intervals close to the atrial effective refractory period. These results suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.

Effects of verapamil on electrophysiological properties in paroxysmal atrial fibrillation.

Verapamil is used to control ventricular response during atrial fibrillation (AF). Limited data is available on the effects of verapamil on atrial vulnerability in human AF. The effects of intravenous verapamil (0.15 mg/kg) on electrophysiological properties of the atrium were investigated in 12 patients with documented paroxysmal AF by electrophysiological studies. Sinus cycle length, sinus node recovery time, and the effective refractory period of the right atrium were not significantly affected by verapamil. The intraatrial conduction delay zone was significantly increased (33 +/- 20 msec before verapamil versus 50 +/- 22 msec after verapamil, P < 0.01), and the maximal intraatrial conduction delay was also significantly prolonged by verapamil, both to the His bundle region (30 +/- 12 msec before verapamil versus 42 +/- 15 msec after verapamil, P < 0.01) and to the coronary sinus (40 +/- 15 msec before verapamil versus 53 +/- 17 msec after verapamil, P < 0.01). The fragmented atrial activity zone was significantly increased (15 +/- 14 msec before verapamil versus 25 +/- 22 msec after verapamil, P < 0.02), and the percentile fragmented atrial activity was also significantly increased by verapamil (149 +/- 18 msec before verapamil versus 174 +/- 44 msec after verapamil, P < 0.05). The repetitive atrial firing zone remained unchanged. Sustained AF spontaneously occurred in only one patient after the administration of verapamil. Thus, verapamil may modulate the abnormal atrial electrophysiology in paroxysmal AF, and would favor production of atrial reentry.

Prolonged atrial activity due to delayed conduction in the atrium of patients with paroxysmal atrial fibrillation

We investigated the relationship between the duration of electrical atrial activity and intra-atrial conduction time to determine whether the prolonged atrial activity was due to delayed conduction in the human atrium. The study included 15 patients with paroxysmal atrial fibrillation (PAF) and 15 control patients. The duration of atrial electrical activity was measured by selecting a minimum electrographic amplitude of 50 microV. In patients with PAF, the duration of atrial activity was prolonged in proportion to the delay of interatrial conduction time from the high right atrium to the coronary sinus as the coupling interval of premature extrastimuli was decreased. Both the fragmented atrial activity zone and the interatrial conduction delay zone were wider in patients with PAF than in control patients. It is concluded that assessment of the duration of atrial activity with a minimum amplitude of 50 microV is useful in evaluating human atrial vulnerability since it reflects the atrial conduction delay in patients with PAF.

Electrophysiological properties in chronic lone atrial fibrillation.

Although the electrophysiological mechanisms underlying self-sustaining atrial fibrillation (AF) are unclear, recent studies suggest that one requirement for reentry, slow conduction, is frequently present in patients with AF. However, these observations limited to paroxysmal AF may not necessarily apply to chronic AF. Therefore, electrophysiological properties of the atrium and sinus nodal function in chronic lone AF were evaluated. Electrophysiological studies were performed after electrocardioversion in 12 patients with chronic lone AF. Atrial enlargement was absent in the patients with AF. Twelve patients without atrial arrhythmias served as the control group. The patients with AF had a higher incidence of sinus nodal dysfunction, a shorter atrial effective refractory period (215 +/- 19 msec versus 238 +/- 23 msec, p less than 0.02), and a longer P wave duration than control patients (115 +/- 16 msec versus 86 +/- 16 msec, p less than 0.01). The conduction delay zone was significantly greater in patients with AF (60 +/- 12 msec) than that in the control patients (8 +/- 13 msec, p less than 0.01), and the maximal conduction delay was also greater in the study patients than those in the control group, both to the His bundle region (31 +/- 12 msec versus 10 +/- 15 msec, p less than 0.01) and to the coronary sinus (41 +/- 15 msec versus 15 +/- 11 msec, p less than 0.01). The fragmented atrial activity zone was wider in the study group (23 +/- 25 msec) than in control subjects (1.7 +/- 4 msec, p less than 0.02). Repetitive atrial firing was observed in four patients with AF but it was not seen in the control group. These electrophysiological features, which are manifestations of the abnormal atrial electrophysiology, would favor production of atrial reentry in chronic lone AF.

Intra-atrial conduction delay and fragmented atrial activity in patients with paroxysmal atrial fibrillation.

To examine the electrophysiologic characteristics of paroxysmal atrial fibrillation (PAF), we studied intra-atrial conduction delay and fragmented atrial activity during premature stimulation of high right atrium in the following four groups: Group I (n = 25), patients without PAF and without sick sinus syndrome (SSS); Group II (n = 22), patients with PAF but without SSS; Group III (n = 10), patients without PAF and with SSS; Group IV (n = 6), patients with PAF and SSS. Intra-atrial conduction delay was the increase in the interval (from the stimuli to the coronary sinus electrogram) observed with early premature beats greater than or equal to 20 ms compared with that of basic rhythm. Fragmented atrial activity was defined as disorganized atrial activity greater than or equal to 150% of the duration of high atrial activity of basic beats recorded. The conduction delay zone (CDZ) and fragmented atrial activity zone (FAZ) were significantly wider in Groups II, III and IV than in Group I. There were no significant differences in either CDZs or FAZs among Groups II, III and IV. Thus, the widening of CDZs and/or FAZs are characteristic of PAF and SSS. CDZ and FAZ may be good indices of development of PAF in patients without SSS.

The effects of cycle length on the fragmented atrial activity zone in patients with sick sinus syndrome

To determine whether atrial pacing effectively decreases the fragmented atrial activity zone (FAZ) in patients with sick sinus syndrome (SSS), we compared FAZ at atrial pacing cycle lengths of 1000-1500 msec (CL1) with that of 750 msec (CL2) in 19 patients with SSS. The FAZ decreased in all patients except two when CL was reduced from CL1 to CL2. The mean decrease was 61.1 msec and was significant (P less than 0.001). Seven patients had frequent episodes of paroxysmal atrial fibrillation or flutter (AFF) prior to atrial pacemaker implantation. Chronic atrial pacing effectively prevented paroxysmal AFF in five of them. We concluded that the normalization of the slow atrial rate decreased FAZ in patients with SSS and may be helpful in preventing atrial tachyarrhythmia in some patients with SSS.

Relation between the widening of the fragmented atrial activity zone and atrial fibrillation

Fragmented electrical activity is often recorded by a local atrial electrogram in response to atrial extrastimuli. To assess the relation between fragmented activity and the spontaneous occurrence of atrial fibrillation or flutter (AFF), the fragmented activity zone was measured in 57 patients. The electrograms of the high right atrium, low right atrium and left atrium (through the coronary sinus) were recorded simultaneously during high right atrial stimulation. The fragmented activity zone was defined as the S 1–S 2 interval (S 1 = stimulus of a basic beat, S 2 = stimulus of a premature beat) during which a significant fragmented activity was recorded by a high right atrial electrogram after S 2. Fifteen patients had neither sinoatrial disease nor atrial arrhythmias (Group I, controls), 16 had sick sinus syndrome (SSS) with a history of paroxysmal AFF (Group II), 14 had SSS without a history of paroxysmal AFF (Group III), and 12 had idiopathic paroxysmal AFF (Group IV). The fragmented activity zone was significantly wider in Group II (112 ± 26 ms [mean ± standard deviation], p < 0.001), Group III (77 ± 38 ms, p < 0.001) and Group IV (86 ± 19 ms, p < 0.001) than in Group I (31 ± 25 ms). Patients in Group II had a wider fragmented activity zone than those in Group III (p < 0.01). Thus, the widening of the fragmented atrial activity zone is characteristic of AFF and may be a good index of a tendency to develop spontaneous AFF.