Heterogeneous changes in electrophysiologic properties in the paroxysmal and chronically fibrillating human atrium

INTRODUCTION: The regional changes in atrial electrophysiologic properties related to atrial fibrillation (AF) in patients with paroxysmal AF (PAF) and chronic AF (CAF) remain unclear. The purpose of this study was to investigate the regional changes in atrial electrophysiology in patients with AF. METHODS AND RESULTS: We evaluated the atrial electrophysiology at different sites (high right atrium, low right atrium [LRA], and distal coronary sinus [DCS]) in 11 patients with CAF, 8 patients with PAF, and 10 controls. Patients with CAF had significantly prolonged interatrial conduction and corrected sinus node recovery time, and shortened atrial effective refractory period (ERP) with loss of rate-related adaptation in the DCS, but had paradoxic prolongation of atrial ERP in the LRA, as compared with patients with PAF and the controls. As a result, the spatial distribution of atrial ERP that was observed in the controls and in patients with PAF was reversed in patients with CAF, without an increase in the dispersion of atrial refractoriness. Patients with PAF showed intermediate changes in atrial conduction times and atrial refractoriness as compared with patients with CAF and controls. CONCLUSION: There was a regional heterogeneity on the changes of atrial electrophysiology in different parts of the atrium, and the "normal" spatial distribution of atrial refractoriness was reversed in patients with CAF. The electrophysiologic changes observed in patients with PAF appear to behave as if in transition from the control state to CAF, suggesting progressive changes in atrial electrophysiologic properties.     

Spatial dispersion of action potential duration restitution kinetics is associated with induction of ventricular tachycardia/fibrillation in humans

INTRODUCTION: Action potential duration restitution (APDR) plays a role in initiation and maintenance of ventricular tachycardia (VT)/ventricular fibrillation (VF). We hypothesized that the steeply sloped APDR and its spatial heterogeneity contribute to VT/VF inducibility in patients with ventricular arrhythmia. METHOD AND RESULTS: After programmed ventricular stimulation (PVS) for evaluation of clinically documented VT, patients (n = 20, 15 male, age 52.5 +/- 9.5 years) were divided into two groups: inducible sustained VT/VF (IVT, n = 10) and noninducible VT/VF (NVT, n = 10). Data were compared with the corresponding results obtained from normal controls (C, n = 10). Right ventricular (RV) monophasic action potential duration at 90% repolarization (APD90) and ventricular effective refractory period (VERP) in the right ventricular apex (RVA) and right ventricular outflow tract (RVOT) were determined. APDR was acquired by scanning diastole with premature ventricular beats during a pacing cycle length of 600 msec (S1-S2) in all patients and by rapid pacing at the cycle lengths that induced APD alternans in three patients. Maximal slopes (Smax) of the APDR curves and DeltaAPD90 (APD90 at S2 400 ms - APD90 at the shortest S2) were measured. VERP and APD90 at each RV site did not differ among the three groups. Smax obtained by S1-S2 (1.6 +/- 0.6) did not differ from Smax obtained by rapid pacing (1.2 +/- 0.7), with a significant correlation noted between these values (r = 0.92, P < 0.01). The IVT group had a higher spatial dispersion of Smax (Smax at RVOT - Smax at RVA) compared to the C group (P < 0.05), with no difference between the NVT group and the IVT or C groups. The IVT group had a higher spatial dispersion of DeltaAPD90 compared to the NVT and C groups (P < 0.01, respectively). Smax at the RVOT (2.7 +/- 1.9) was steeper than that at the RVA (1.9 +/- 1.2, P < 0.05). Inducibility of sustained VT/VF was greater at the RVOT (83.3%) than at the RVA (50.0%, P < 0.05). CONCLUSION: In patients with ventricular arrhythmia, VT/VF is highly inducible under conditions of greater spatial dispersion of ventricular refractoriness and APDR.     

Monophasic action potentials of the right atrium in patients with paroxysmal atrial fibrillation

To investigate the mechanism of atrial fibrillation (AF), monophasic action potentials (MAPs) from the atrial myocardium were studied in 7 patients with paroxysmal AF (PAF) and in 7 control individuals. The MAPs were recorded using a contact catheter during sinus rhythm and continuous pacing at the high right atrium (HRA) with pacing cycle lengths of 600, 500 and 400 ms. MAPs were obtained from 6 sites in each participant. The MAPD90 was measured from onset to 90% of MAP repolarization. Average, maximal and minimal MAPD90 (avMAPD90, maxMAPD90 and minMAPD90) were obtained from all participants. The dispersion of MAPD90 (dispMAPD90) was defined as the difference between maxMAPD90 and minMAPD90. The width of each atrial potential (WAP) and the wavelength index (WLI=MAPD90/WAP) were determined. Average, maximal and minimal WLI (avWLI, maxWLI and minWLI) were obtained from all participants. The avMAPD90 and maxMAPD90 did not significantly differ between the 2 groups. The minMAPD90 in the PAF group was significantly smaller than that in the control group at HRA pacing with cycle lengths of 500 and 400 ms (210+/-18ms vs 245+/-14 ms, p<0.05; 207+/-23 ms vs 238+/-20 ms, p<0.05; respectively). The dispMAPD90 was significantly longer in the PAF group than in the control group during sinus and HRA pacing. The WAP value did not differ between the 2 groups. The minWLI in the PAF group was significantly smaller than that in the control group at HRA pacing with cycle lengths of 500 and 400 ms (3.3+/-0.5 vs 3.8+/-0.3, p<0.05; 3.2+/-0.4 vs 3.7+/-0.3, p<0.02). A shortened and widened dispersion of atrial refractoriness may play an important role in the genesis of AF. Furthermore, smaller wavelengths may form in the atrium of patients with PAF.     

The repolarization-excitability relationship in the human right atrium is unaffected by cycle length, recording site and prior arrhythmias.

OBJECTIVES: The goal of this study was to determine the relationship between repolarization and excitability in the human atrium under various conditions. BACKGROUND: Action potential duration (APD) measurements from monophasic action potential (MAP) recordings provide a surrogate for measuring the effective refractory period (ERP) in human ventricle. The relationship between repolarization and refractoriness in human atrium and the effect of prior atrial fibrillation/flutter on the ERP/APD correlation are unknown. METHODS: Seven patients with sinus rhythm and 15 patients after conversion of atrial flutter or fibrillation were evaluated. Monophasic action potentials were recorded at multiple right atrial sites and during different basic cycle lengths from 300 to 700 ms, while ERPs were determined by extrastimulus technique using the MAP recording-pacing combination catheter. RESULTS: There was a close correlation between ERP and APD at 70% repolarization (APD70, r = 0.97; p < 0.001) and 90% repolarization (APD90, r = 0.98; p < 0.001), respectively. Refractoriness occurred at a repolarization level of 72 +/- 8%. The ERP/APD70 and ERP/APD90 ratios averaged 1.06 +/- 0.10 and 0.86 +/- 0.08, respectively. These ratios were nearly constant over the entire range of basic cycle lengths, between different sites in individual patients and between different patients. Patients cardioverted from atrial fibrillation or flutter exhibited no significant differences in the ERP/APD relationship compared with patients with sinus rhythm. CONCLUSIONS: Effective refractory period and APD are closely related in the human right atrium. Using the MAP recording technique, atrial ERPs can be assessed by measurement of APDs. Effective refractory period is most closely reflected by APD70. Thus, MAP recordings allow investigation of the local activation and repolarization time course beat by beat, visualizing the excitable gap.     

Atrial gradient as a potential predictor of atrial fibrillation

OBJECTIVES: We tested the utility and comparability of the atrial gradient and atrial ERP as early markers of electrical remodeling and a propensity to atrial fibrillation (AF). BACKGROUND: Pacing at physiologic rates from the left atrium alters the atrial gradient and is associated with atrial tachyarrhythmias. At these physiologic rates, there is no change in the atrial effective refractory period (ERP). METHODS: Sixty-one chronically instrumented mongrel dogs in complete heart block were paced from the left or right atrium at 400 to 900 bpm for 46 +/- 3 days. Dogs were monitored weekly and electrophysiologic studies conducted to determine changes in the atrial gradient, ERP, and rhythm. RESULTS: Rapid atrial pacing was associated with concordant decreases in atrial gradient, ERP, and occurrence of AF. Incidence of AF increased with increasing pacing rate. Although there ultimately was an equal incidence of AF with left atrial and right atrial pacing, the onset of AF occurred earlier with left atrial pacing. As expected, ERP decreased in both atria. Animals with long control ERP did not fibrillate. CONCLUSIONS: Rapid pacing induces changes in atrial gradient, which can be used as a noninvasive marker of electrical remodeling. AF is accompanied by decreases in atrial gradient and ERP, and the incidence is highest in dogs with short control ERP.     

Wave similarity mapping shows the spatiotemporal distribution of fibrillatory wave complexity in the human right atrium during paroxysmal and chronic atrial fibrillation

INTRODUCTION: The complexity of waveforms during atrial fibrillation may reflect critical activation patterns for the arrhythmia perpetuation. In this study, we introduce a novel concept of map, based on the analysis of the wave morphology, which gives a direct evidence in the human right atrium on the spatiotemporal distribution of fibrillatory wave complexity in paroxysmal (PAF) and chronic (CAF) atrial fibrillation. METHODS AND RESULTS: Electrograms were recorded from a 64-electrode catheter in the right atrium of 15 patients during PAF (n = 8) and CAF (n = 7). Wave similarity maps were constructed by calculating the degree of morphological similarity of activation waves (S) at each atrial site and by following its temporal evolution. During PAF the spatiotemporal distribution of the waveforms was highly consistent across the subjects and was determined by the anatomic location. Wave similarity maps showed the existence of an extended area with low similarity index, which covered the low posteroseptal atrium (S = 0.28 +/- 0.09) and the septal region (S = 0.22 +/- 0.04), and the presence of a large tongue with high similarity index, which penetrated the lateral wall (S = 0.55 +/- 0.08) starting from the high anterolateral atrium (S = 0.54 +/- 0.06). A completely different spatiotemporal pattern was seen during CAF. No distinct regions with different similarity indexes were recognized, but a uniformly distributed low similarity index (S = 0.27 +/- 0.07) was found. The spatial pattern was highly stable in time with fluctuations of S < 0.04. CONCLUSION: Quantification of the spatiotemporal distribution of fibrillatory wave complexity is feasible in humans by wave similarity mapping. Anatomic anchoring of waveforms during PAF and pattern destruction during CAF was determined.     

Bigeminy pacing: a new protocol to unmask atrial vulnerability

INTRODUCTION: One of the most exciting developments in our understanding of atrial fibrillation (AF) mechanisms has been the recognition that "AF begets AF" in a process termed atrial remodeling. Little information is available about the events that mediate short-term remodeling. In a bigeminy atrial pacing protocol that produces a continuous extrasystole-postextrasystole cycle length, we sought to evaluate the electrophysiologic consequences of irregular atrial pacing. METHODS AND RESULTS: This study included 22 consecutive patients with documented paroxysmal AF and 10 control subjects. After evaluating the effective refractory period (ERP) and functional refractory period (FRP), bigeminy atrial pacing was performed for 5 minutes. The S1-S2 coupling interval during bigeminy pacing was programmed to a mean value of 275 +/- 45 msec, i.e., 45 msec longer than the basic ERP measured at 100 beats/min. During bigeminy pacing, AF that lasted longer than 1 minute occurred in 12 AF patients and in none of the control subjects (group I). Short salvos of AF occurred in 5 patients and 3 controls (group II). No arrhythmia occurred in 5 patients and 7 controls (group III). Sensitivity, specificity, and negative and positive predictive values of sustained AF induced by bigeminy pacing were 54%, 100%, 50%, and 100%, respectively. No differences were observed between different pacing rates during bigeminy, the premature coupling interval S1-S2, or the conduction parameters S2-A2 and A2. Group I had the shortest basic ERP (222 +/- 38 msec) and group III the longest ERP (242 +/- 21 msec, P < 0.05); group II was intermediate. Atrial ERPs and FRPs measured immediately after termination of 5 minutes of bigeminy pacing were shorter than during baseline. The degree of shortening was similar in AF patients and in controls. The locoregional conduction delay A2 did not change after the bigeminy protocol. CONCLUSION: This study demonstrates that atrial bigeminy pacing highly increases atrial vulnerability. This protocol appears interesting because its sensitivity and specificity are higher than those of the conventional extrastimulation test. This makes it attractive for routine diagnosis of undocumented paroxysmal AF. Because it may induce atrial arrhythmias independently of the classic mechanisms of wavelength shortening, this study emphasizes the need for new modalities in the prevention of atrial arrhythmias.     

Atrial electrophysiologic abnormalities in patients with Wolff-Parkinson-White syndrome but without paroxysmal atrial fibrillation

BACKGROUND: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. HYPOTHESIS: The purpose of this study was to analyze the atrial electrophysiologic abnormalities and vulnerability to develop atrial fibrillation (AF) in patients with WPW syndrome but with no previous history of PAF. METHODS: We investigated atrial electrophysiologic abnormalities and vulnerability to AF in patients with WPW syndrome but without PAF. An electrophysiologic study was performed in 28 patients with WPW syndrome, 23 with atrioventricular nodal reentrant tachycardia (AVNRT) and 25 with other arrhythmias (control), all of whom had no history of PAF. The following atrial excitability parameters were assessed: effective refractory period (ERP), spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (%MAF; A2/A1 x 100), wavelength index (WLI; ERP/A2), and inducibility of AF. RESULTS: The ERP tended to be shorter in patients with WPW syndrome and in those with AVNRT than in the control group. The %MAF increased (154 +/- 33 vs. 137 +/- 23%, p < 0.05) and WLI decreased (2.7 +/- 0.8 vs. 3.4 +/- 1.0, p < 0.05) significantly in patients with WPW syndrome compared with the control group; however, these parameters in patients with AVNRT showed intermediate values. Atrial fibrillation was more inducible in patients with WPW syndrome (4/28 [14.3%]) than in those with AVNRT (4.3% [1/23]) and the control group (0/25 [0%]). With respect to patients with WPW syndrome and with and without inducible AF, the %MAF increased (195 +/- 23 vs. 148 +/- 30%, p < 0.01) and the WLI decreased (2.2 +/- 0.3 vs. 2.9 +/- 0.9, p < 0.05) in subjects with inducible AF. CONCLUSIONS: Atrial electrophysiologic abnormalities, especially atrial conduction delays, are more prominent in patients with WPW syndrome, even if they had no previous history of PAF. These abnormalities may play an important role in determining the vulnerability to AF.     

Electrophysiologic characteristics of paroxysmal and chronic atrial fibrillation in human right atrium

OBJECTIVES: The aim of the study was to analyze the electrophysiologic characteristics of paroxysmal (PAF) and chronic (CAF) atrial fibrillation (AF) in the human right atrium (RA). BACKGROUND: Differences that exist between PAF and CAF and the mechanisms of self-sustenance of these arrhythmias are incompletely understood. METHODS: A total of 53 patients with PAF (25 patients, mean age 59 +/- 6.1 years, 3 women) and CAF (28 patients, mean age 59 +/- 13 years, 7 women) underwent multisite mapping of the RA during ongoing AF using a 64-electrode basket catheter. Quantitative evaluation and three-dimensional activation patterns were performed using a computerized system. RESULTS: Patients with PAF, as compared with patients with CAF, had significantly longer AF cycle length, shorter time intervals with type III AF throughout the RA and a smaller number of endocardial breakthroughs (mean 51 +/- 19 vs. 104 +/- 40, p < 0.001). The majority of endocardial breakthrough points (88% in PAF patients and 98% in CAF patients) were located in the septal region and coincided anatomically with major interatrial connection routes. Coexistence of re-entrant and apparently focal activation determined maintenance of AF in the RA in PAF, whereas random re-entry was documented more frequently in patients with CAF. In patients with CAF, the duration of arrhythmia (in years) correlated strongly with the percentage of time during which type III AF was observed in the lateral wall of the RA (r = 0.71). CONCLUSIONS: Clinical PAF and CAF, as recorded in the RA, have, at least quantitatively, distinct electrophysiologic features and different mechanisms of maintenance.     

Effects of cytochalasin D on electrical restitution and the dynamics of ventricular fibrillation in isolated rabbit heart

Cytochalasin D in Rabbit Ventricle. INTRODUCTION: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. METHODS AND RESULTS: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 +/- 26 msec, 171 +/- 14 msec, and 177 +/- 14 msec) and steepened maximum slope of the APDR curve (1.1 +/- 0.2, 1.3 +/- 0.2, and 1.6 +/- 0.4 for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 +/- 0.6 Hz, 11.1 +/- 2.4 Hz, and 9.8 +/- 3.2 Hz for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 micromoles of cyto-D. CONCLUSION: Continuous perfusion of cyto-D at 5 or 10 micromoles prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.     

Increased sympathetic activity after atrioventricular junction ablation in patients with chronic atrial fibrillation

OBJECTIVES: The aim of this study was to determine the changes in sympathetic nerve activity (SNA) after atrioventricular junction (AVJ) ablation in patients with chronic atrial fibrillation (AF). BACKGROUND: Polymorphic ventricular tachycardia (PMVT) has been reported after AVJ ablation in patients paced at a rate of < or =70 beats/min. We hypothesized that AVJ ablation results in sympathetic neural changes that favor the occurrence of PMVT and that pacing at 90 beats/min attenuates these changes. METHODS: Sympathetic nerve activity, 90% monophasic cardiac action potential duration (APD90), right ventricular effective refractory period (ERP) and blood pressure measurements were obtained in 10 patients undergoing AVJ ablation. Sympathetic nerve activity was analyzed at baseline and during and after successful AVJ ablation for at least 10 min. Data were also collected after ablation at pacing rates of 60 and 90 beats/min. The APD90 and ERP were measured before and after AV block during pacing at 120 beats/min. RESULTS: Sympathetic nerve activity increased to 134 +/- 16% of the pre-ablation baseline value (p < 0.01) after successful AVJ ablation plus pacing at 60 beats/min and decreased to 74 +/- 8% of baseline (p < 0.05) with subsequent pacing at 90 beats/min. Both APD90 and ERP increased significantly. CONCLUSIONS: 1) Ablation of the AVJ followed by pacing at 60 beats/min is associated with an increase in SNA. 2) Pacing at 90 beats/min decreases SNA to or below the pre-ablation baseline value. 3) Cardiac APD and ERP increase after AVJ ablation. The increase in SNA, along with the prolongation in APD, may play a role in the pathogenesis of ventricular arrhythmias that occur after AVJ ablation.     

Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence

OBJECTIVE: To study the reversibility of atrial electrical remodeling and its relation with recurrence in post-conversion chronic atrial fibrillation (CAF) patients. METHODS: In 28 drug-free CAF patients (mean AF duration 41+/-39 months) electrically converted to sinus rhythm effective refractory period (ERP) at 500 ms, monophasic action potential at 90% of repolarization (MAPd90) at five cycle lengths (CL, 350, 400, 450, 500, 600 ms), and P wave duration were measured three times: within the interval 5-20 min post-conversion, 24 h and 1 month later. Fifteen subjects with no history of AF and normal atrial structure served as a control group. Patients were followed up for recurrence for 1 month; 12 relapsed. RESULTS: ERP changed from 205+/-20 to 243+/-31 to 241+/-24 ms (P<0. 001), attaining a level comparable to that of the controls (238+/-21 ms) within 24 h. MAPd90 significantly (P<0.001) increased (from 175+/-11 to 190+/-19 to 191+/-10 ms at CL 350 ms and 201+/-12 to 234+/-20 and 233+/-23 ms at CL 600 ms) also reaching control levels within 24 h. MAPd90 exhibited an abnormal adaptation to rate only in the first evaluation. P wave duration was prolonged (137+/-33 ms) and exhibited a slower course of shortening (130+/-32 to 123+/-27 ms, P<0.001), reaching control levels within 1 month. Patients with higher values of MAPd90 at CL 350 in the immediate post-conversion period were more likely to relapse (P<0.005). CONCLUSIONS: ERP and repolarization shortening as a result of CAF are reversed within 24 h after conversion, while P wave duration reduces more slowly. Post-conversion MAPd90 values contain prognostic information for recurrence.     

Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium.

OBJECTIVES: We sought to evaluate the effects of progressive shortening of the action potential duration (APD) on atrial wave front stability. BACKGROUND: The mechanisms of conversion from atrial flutter to atrial fibrillation (AF) are unclear. METHODS: Isolated canine right atria were perfused with 1 to 5 micromol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD(90) was measured during regular pacing (S(1)) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S(2)). RESULTS: At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD(90) from 124 +/- 15 ms to 72 +/- 9 ms (p < 0.01) with 1 to 2.5 micromol/l of ACh, S(2) pacing induced single, stable and stationary re-entrant wave fronts (307 +/- 277 cycles). They either anchored to pectinate muscles (5 tissues) or used pectinate muscles as part of the re-entry (4 tissues). When ACh was raised to 2.5 to 5 micromol/l, the APD(90) was further shortened to 40 +/- 12 ms (p < 0.01); S(2) pacing induced in vitro AF by two different mechanisms. In most episodes (n = 13), AF was characterized by rapid, nonstationary re-entry and multiple wave breaks. In three episodes with APD(90) <30 ms, AF was characterized by rapid, multiple, asynchronous, but stationary wave fronts. CONCLUSIONS: Progressive APD shortening modulates atrial wave front stability and converts atrial flutter to AF by two mechanisms: 1) detachment of stationary re-entry from the pectinate muscle and the generation of multiple wave breaks; and 2) formation of multiple, isolated, stationary wave fronts with different activation cycle lengths.     

Electrophysiologic characteristics of the atrium in sinus node dysfunction: atrial refractoriness and conduction

INTRODUCTION: Clinical electrophysiology (EP) has focused attention on the EP properties of atrial muscle in patients with atrial fibrillation (AF). Patients with sinus node dysfunction (SND) sometimes are included in these studies, but the characteristics of these patients with SND alone appear less well investigated. METHODS AND RESULTS: We reviewed EP data of 46 patients (mean age 70 +/- 8 years) with SND, who underwent EP study for evaluation of the atrial substrate. In 16 patients, a history of paroxysmal AF was documented, but not in the remaining 30 patients who had SND alone. We considered as control a group of 25 subjects (mean age 63 +/- 14 years), who were referred to our EP laboratory for unexplained syncope or AV conduction disturbances. Following pharmacologic washout and at a drive cycle of 600 msec, effective (ERP) and functional refractory periods (FRP), S1-A1 and S2-A2 latency, A1 and A2 width, latent vulnerability index (ERP/A2), and P wave duration on the surface ECG were measured. Intra-atrial conduction times were measured from the stimulus artifact by pacing the high right atrium (HRA), to the corresponding atriograms at the AV node (HRA-AVN), low lateral atrium (HRA-LLA), and low interatrial septum close to the coronary sinus ostium (HRA-CSO). Compared with the control group, SND patients did not show differences in ERP (238 +/- 26 msec vs 250 +/- 29 msec), FRP (274 +/- 25 msec vs 280 +/- 32 msec), S1-A1 (38 +/- 15 msec vs 33 +/- 11 msec) and S2-A2 latency (67 +/- 24 msec vs 63 +/- 25 msec), or HRA-AVN (81 +/- 24 msec vs 65 +/- 19 msec), HRA-LLA (36 +/- 30 msec vs 40 +/- 27 msec), and HRA-CSO (77 +/- 17 msec vs 80 +/- 15 msec) conduction times. In contrast, we observed strong differences in atriogram durations A1 (59 +/- 19 msec vs 39 +/- 13 msec; P < 0.001) and A2 (92 +/- 28 msec vs 57 +/- 18 msec; P < 0.001), as well as in the latent vulnerability index ERP/A2 (2.8 +/- 1.2 msec vs 4.8 +/- 1.7; P < 0.001). Also, the P wave was slightly longer (104 +/- 18 msec vs 94 +/- 45 msec; P < 0.05). No significant statistical difference in EP parameters was found between SND patients with or without documented AF. CONCLUSION: In patients with SND, atrial refractoriness appears similar to that of control subjects. The most important EP abnormality appears to be local conduction slowing disturbances, with prolonged basal and postextrastimuli atriograms, responsible for a lower vulnerability index. This could explain, at least in part, the tendency of patients with SND to develop AF during their natural history. Normality of atrial refractoriness, in contrast to atrial conduction disorders, might explain why atrial pacing shows a preventative effect on the development of AF and why antiarrhythmic drugs often are ineffective.     

Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation

OBJECTIVE: Although the incidence of atrial fibrillation (AF) increases with age, the cellular electrophysiological changes that render the atria of aged individuals more susceptible to AF remain poorly understood. We hypothesized that dispersion of atrial repolarization increases with aging, creating a substrate for initiation of AF. METHODS: Four groups of dogs were studied: adult and old dogs in normal sinus rhythm (SR) and adult and old dogs with chronic AF (CAF) induced by rapid atrial pacing. In each dog, action potentials (AP) were recorded with microelectrodes from isolated endocardial preparations of four regions of right atrium and three regions of left atrium. Two indices of AP duration (APD) heterogeneity were obtained in each dog by calculating standard deviation (SD) and the coefficient of variation (COV=[SD/mean] x 100%). RESULTS: In SR groups, APD averaged across all regions was significantly longer in old than in adult tissues. Both indices of APD heterogeneity were higher in old dogs in comparison to adult. At both ages, CAF was associated with significant APD shortening and a decrease in APD adaptation to rate. While CAF significantly increased both indices of APD heterogeneity in adult dogs, it significantly decreased them in old dogs. CONCLUSIONS: The increase of spatial variability in repolarization in old atria may contribute to the initiation of AF in the aged. CAF-induced APD shortening and a decrease in APD adaptation appear to be important for the maintenance of sustained AF in both adult and old atria. The CAF-induced increase in dispersion of repolarization may be important for AF stabilization in adults, while previously reported fibrosis and slowed conduction of premature beats may be important in the old for both AF initiation during SR and subsequent stabilization of AF.     

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

Aims Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post–repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. Methods In 12 patients with persistent AF (11 male, 58 ± 5 yrs, 27 ± 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Results Both drugs prolonged APD90 during AF (flecainide from 109 ± 7 ms to 137 ± 10 ms, sotalol from 108 ± 6 ms to 131 ± 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 ± 8 ms to 139 ± 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 ± 9 ms to 197 ± 28 ms, p < 0.05 vs. baseline and vs. sotalol). Conclusions Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.Drs. Kirchhof, Engelen and Breithardt are Members of the Kompetenznetz Vorhofflimmern     

心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

目的 研究在体犬左、右心房肌的电整复性即动作电位时程整复性(APDR),观察其与阵发性心房颤动(房颤)发生的潜在机制.方法 使用单相动作电位技术记录14只犬左、右心房复极达90%的动作电位时程(APD_(90)),并通过S_1S_2程序刺激,观察APDR变化,即每一个舒张间期与刺激后发生心房肌复极APD_(90)的关系,并观察房颤的诱发情况.结果 APD_(90)左心房为(157.4±43.5)ms明显小于右心房(170.9±37.9)ms,P<0.05.心房肌在S_1S_2递减程序刺激下,左心房与右心房具有不同斜率的APDR曲线,左心房的APDR曲线斜率1.3±0.4大于右心房0.9±0.3,P<0.05.进行心房快速起搏S_1S_2刺激时,14只犬中共诱发出18阵房颤,其中左心房刺激发作12阵,明显多于右心房6阵(P<0.05).结论 左、右心房间具有单相动作电位时程的异质性及APDR不均一的复极特性,是诱发折返、发生和维持房颤的基质之一.     

Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence

INTRODUCTION: Recurrence of atrial fibrillation (AF) may be related to AF-induced electrical remodeling characterized by shortening of the atrial action potential duration (APD) and loss of its rate adaptation. We investigated the effects of pretreatment with oral d,l-sotalol on rate-dependent changes in atrial monophasic action potential (MAP) duration after cardioversion of chronic AF with reference to the efficacy in preventing the arrhythmia recurrence. METHODS AND RESULTS: MAPs were recorded from the right atrium at six pacing cycle lengths (CLs) from 300 to 750 ms in 19 chronic AF patients after electrical cardioversion; 9 had been pretreated with oral d,l-sotalol (196 +/- 42 mg/day) for 7 days and 10 were untreated. MAP duration at 90% repolarization (MAPD90) in 11 control patients increased progressively with increases in CLs from 209 +/- 19 ms at CL = 300 ms to 264 +/- 28 ms at CL = 750 ms. In AF patients without sotalol, the CL-MAPD relation was shifted downward and flattened at longer CLs; MAPD90 values were 206 +/- 11 ms and 227 +/- 16 ms at CLs of 300 and 750 ms, respectively. MAPD90 values at CLs > or =500 ms in AF were significantly shorter than controls. In AF patients with sotalol, the normal CL-MAPD relation was preserved; MAPD90 increased from 226 +/- 19 ms to 282 +/- 46 ms in the CL range. AF recurred within 2 weeks after cardioversion in 14 of 24 patients pretreated with d,l-sotalol (216 +/- 51 mg/day) despite of continuation of sotalol treatment. CONCLUSION: Sotalol reverses AF-induced decrease in MAPD adaptation to rate in the atria of chronic AF patients, but this effect does not lead to prevention of AF recurrence.     

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.     

心脏起搏患者心房颤动和脑栓塞发生率的长期随访

为了解起搏患者心房颤动 (AF)和脑栓塞 (CE)的发生率及其影响因素 ,12 5例起搏患者术后每 6～ 12个月随访一次 ,随访时暴露自身心律并记录术后CE事件。 12 5例患者随访 5 .88± 0 .34(1.5～ 2 4.6 )年。术前AF总的发生率为 2 8% (35 / 12 5 ) ,术后为 40 % (5 0 / 12 5 ) ,其中术后新发生持续性AF(CAF) 15 % (18/ 12 0 )、阵发性AF(PAF) 5 .5 %(5 / 90 )。影响AF发生的因素 :①起搏方式 :VDD患者未见AF发生 ,AAI、VVI和DDD三种起搏方式间AF发生率无显著性差异。②术前存在PAF者 ,术后CAF发生率明显升高 ,达 2 6 .7% (8/ 30 )。③心律失常类型 :慢 快综合征患者术后CAF的发生率 30 .3% (10 / 33)显著高于缓慢性病窦综合征 6 .4% (3/ 47)和房室阻滞 11.1% (5 / 45 )患者 (P均<0 .0 5 )。④年龄 :6 0岁以上患者中CAF的发生率显著高于 6 0岁以下患者 (P <0 .0 5 )。术后CE发生率为 5 .6 % ,伴AF者显著高于不伴AF者 (P <0 .0 1) ,而未见起搏方式对其影响。结果提示 :在起搏随访时应重视对AF的检出及治疗 ,避免由此造成的起搏功能障碍、起搏并发症和CE ,并充分考虑基础心律失常类型、起搏方式和年龄可能产生的影响。