Characterization of right atrial substrate in patients with supraventricular tachyarrhythmias

Right atrial substrate of supraventricular tachyarrhythmias. BACKGROUND: Voltage mapping has been used to detect diseased myocardium. However, accurate determination of the local atrial voltage at the same site, and simultaneous recordings from multiple mapping sites were limited. The purpose of this study was to investigate the right atrial (RA) substrate properties in patients with supraventricular tachyarrhythmias (SVT). METHODS AND RESULTS: Forty patients (aged 55+/-20 years) undergoing noncontact mapping and ablation of SVT constituted the study population. There were eight patients with atrioventricular node reentrant tachycardia (AVNRT), eight patients with focal atrial tachycardia (AT), 14 patients with atrial flutter (AFL), and 10 patients with atrial fibrillation (AF). The mean peak negative voltage (PNV) was analyzed in virtual unipolar electrograms, which were obtained from 256 equally distributed RA endocardial sites during sinus rhythm (SR), atrial pacing, and tachycardia. The mean PNV of global RA during SR (-1.34+/-0.22 vs. -0.90+/-0.40 vs. -1.00+/-0.36 vs. -0.85+/-0.35 mV, P=0.04), atrial pacing at cycle lengths of 500 ms (-1.30+/-0.29 vs. -0.70+/-0.35 vs. -0.76+/-0.25 vs. -0.64+/-0.26 mV, P=0.02), and 300 ms (-1.54+/-0.47 vs. -0.94+/-0.21 vs. -0.75+/-0.27 vs. -0.57+/-0.22 mV, P<0.01) were significantly greater in patients with AVNRT compared to AT, AFL, and AF. Furthermore, the mean PNV decreased during atrial pacing with shorter pacing cycle length was demonstrated only in patients with AFL and AF. CONCLUSION: Negative unipolar voltage analysis of global RA showed different RA substrate characteristics during various SVT. The substrate property of activation and cycle length-dependent voltage reduction may be related to the development of AFL and AF.     

Long-term changes in sequence of atrial activation and refractory periods: no evidence for "atrial memory".

OBJECTIVES: The purpose of this study was to test whether the spatial distribution of the atrial refractory period (AERP) and the vulnerability to atrial fibrillation (AF) are altered by long-term changes in the sequence of atrial activation. BACKGROUND: The spatial distribution of the AERP plays an important role in AF. Changes in the activation sequence have been postulated to modulate atrial repolarization ("atrial memory"). METHODS: Six goats were chronically instrumented with epicardial atrial electrodes to determine activation time and AERP at 11 different areas of the right (RA) and left (LA) atrium and the Bachmann bundle. Activation time and AERP were measured during sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the number of atrial sites where single premature stimuli induced AF paroxysms >1 second. RESULTS: During sinus rhythm (106 +/- 4 bpm), AERP was longest at the Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms, P < .001). In five of six goats, an inverse correlation between local activation time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The increase in atrial rate during RA and LA pacing caused an overall shortening of AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long-term RA and LA pacing did not significantly change AERP at any of the 11 atrial regions and had no significant effect on AF inducibility. CONCLUSIONS: During sinus rhythm, an inverse relationship exists between the sequence of atrial activation and the local refractory period. However, long-term changes in the sequence of atrial activation do not alter the spatial distribution of AERP or the inducibility of AF.     

Differences in organization between acute and chronic atrial fibrillation in dogs

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.     

Right ventricular pacing to assess transisthmus conduction in patients undergoing isthmus-dependent atrial flutter ablation: a new useful technique?

BACKGROUND: Successful radiofrequency (RF) ablation of typical, isthmus-dependent atrial flutter requires establishment and confirmation of bidirectional conduction block across the cavotricuspid isthmus. Low atrial pacing usually is performed from the bipoles of the 20-pole Halo catheter, septal and lateral to the cavotricuspid isthmus ablation line. However, occasionally this is difficult because of high pacing thresholds and/or saturation of the atrial electrograms recorded near the pacing catheter. OBJECTIVES: The purpose of this study was to assess if right ventricular (RV) pacing and resulting retrograde atrial activation can be used to assess conduction block from the septum to the lateral wall in a clockwise direction. METHODS: Thirty-five consecutive male patients (mean age 64 +/- 10 years; mean ejection fraction 42 +/- 13%; mean left atrial dimension 44 +/- 6 mm) with typical isthmus-dependent atrial flutter were studied. The following electrophysiology catheters were used: 20-pole catheter along the tricuspid annulus, quadripolar catheters at the His and/or RV apex, and 8-mm ablation catheter. Following RF ablation of the cavotricuspid isthmus, bidirectional conduction block was confirmed in all 35 patients by pacing at a cycle length of 600 ms from bipoles septal and lateral to the cavotricuspid isthmus ablation line. Conduction times from pacing artifact to adjacent bipolar atrial electrograms and reversal of atrial activation pattern were analyzed. RV pacing was performed and retrograde atrial activation pattern assessed. If retrograde AV nodal conduction was absent, isoproterenol was infused intravenously at 2 microg/min, and RV pacing was repeated. The conduction time between the double potentials across the cavotricuspid isthmus ablation line was measured. RESULTS: Mean conduction times across the isthmus during septal (S), lateral (L), and RV pacing were 145 +/- 21 ms, 144 +/- 24 ms, and 129 +/- 20 ms, respectively. Retrograde AV nodal conduction was present in 34 of 35 patients (isoproterenol 8 patients). Evidence of conduction block by a clear change in activation pattern across the isthmus was seen during RV pacing in 33 of 35 patients with bidirectional conduction block. CONCLUSION: RV pacing is a simple and easy maneuver that can be performed to assess isthmus conduction in most patients.     

What is the optimal electrode configuration for atrial defibrillators in man?

AIMS: To compare the atrial defibrillation threshold (DFT) for two electrode configurations in patients with drug refractory persistent atrial fibrillation (AF). METHODS AND RESULTS: 11 patients, 73% male, mean age 60.9 (range 38 to 83), underwent implantation of a Medtronic Jewel AF dual chamber defibrillator (model 7250). A step-up atrial DFT was performed in a randomized sequence for two electrode configurations: (1) Right atrial to distal coronary sinus electrode (RA > CS) and (2) defibrillator can to right ventricular and right atrial electrodes (CAN > RV + RA). The RA > CS configuration restored SR in 10 patients (91%). The CAN > RA + RV configuration restored SR in four patients (36%). The mean atrial DFT was significantly lower for the RA > CS than CAN > RA + RV configuration (10 +/- 7 Joules vs 25 +/- 6 Joules), P < 0.01. At 3 months post implantation, AF was reinduced and the protocol was repeated for the optimal electrode configuration. There was no significant difference in the atrial DFT compared with that at implant. CONCLUSION: The right atrium to coronary sinus electrode configuration significantly reduces the atrial DFT. The atrial DFT also remains stable at 3 months post-implantation. Patients with persistent AF undergoing insertion of an atrial defibrillator should have a coronary sinus electrode implanted.     

Dispersion of atrial repolarization in patients with paroxysmal atrial fibrillation.

To study the role of the dispersion of atrial repolarization (DAR) in the genesis of atrial fibrillation (AF), monophasic action potentials (MAP) were recorded simultaneously from a catheter at the high lateral right atrium (HLRA) and a catheter moving around the high, middle and low lateral right atrium (RA) the high, anterior and posterior septal RA and the RA appendage in 15 patients with paroxysmal AF and 15 patients with atrioventricular nodal re-entry tachycardia (AVNRT) or concealed Wolff-Parkinson-White syndrome (WPW) without history of AF. After recordings during sinus rhythm (SR), MAPs were recorded during programmed stimulation (PS) via the HLRA catheter at a drive cycle length (CL) of 500 ms. Thus, MAPs were recorded simultaneously from 2 sites at a time and sequentially from 4 to 12 sites during SR, drive pacing and PS. Taking the MAP at the HLRA as reference, the dispersion of repolarization time (dispersion of RT) and its two components, the dispersions of activation time (dispersion of AT) and MAP duration (dispersion of MAP duration) among the 4 to 12 sites were calculated and taken as parameters of DAR. RESULTS: During SR and PS, the maximal dispersion of RT was significantly greater in AF than in control patients, 113+/-49 ms vs 50+/-28 ms (P<0.001) and 114+/-56 vs 70+/-43 ms (P<0.05) respectively. The increased dispersion of RT in the AF group was caused by increases in both dispersion of MAP duration and dispersion of AT. CONCLUSION: During SR and PS, DAR increased in patients with paroxysmal AF due to increases in dispersion of MAP duration and dispersion of AT, which suggests the involvement of both repolarization and conduction disturbances in the development of paroxysmal AF.     

Does the mechanism of action of biatrial pacing for atrial fibrillation involve changes in cardiac haemodynamics? Assessment by Doppler echocardiography and natriuretic peptide measurements.

AIMS: The antifibrillatory mechanism of biatrial (BI) pacing has not been fully elucidated. We investigated the role of a haemodynamic mechanism in eight patients implanted with a BI pacemaker (Chorus RM) by comparing changes in mitral Doppler flow and atrial and B-type natriuretic peptide levels (ANP, BNP) with BI pacing compared with sinus rhythm and right atrial (RA) pacing. METHODS AND RESULTS: Measurements were taken after 60 min in the supine position in each of two pairs of randomized pacing modes: (a) AAI40 beats x min(-1), (allows sinus rhythm mean rate 56 beats x min(-1), SR) vs AAI 40 beats x min(-1) with synchronized left atrial pacing (SRSync); (b) overdrive AAI RA pacing (89 beats x min(-1) (n = 6) or 70 beats x min(-1) (n = 2)) vs overdrive AAI BI pacing. Within each pair there was significant earlier activation of the left atrial Doppler signal in relation to the surface ECG P wave with BI pacing (SR 163 +/- 10 ms vs SRSync 144 +/- 21 ms (P = 0.02), and RA 232 +/- 14 ms vs BI 196 +/- 16 ms (P = 0.001)), and significant shortening of the P-R interval (SR 163 +/- 29 ms vs SRSync 148 +/- 20 (P = 0.007) and RA 261 +/- 27 ms vs BI 232 +/- 23 (P = 0.001)). The net observed effect was of no change in the atrioventricular timing sequence (delay of peak E or A to QRS/ mitral valve closure) and no change in other Doppler echo parameters. Levels of the cardiac peptides ANP and BNP were raised compared with healthy controls, but did not significantly change during the study. CONCLUSION: Acute BI pacing shortens the P-R interval and causes earlier left atrial contraction in relation to the surface electrocardiogram P wave. It does not alter the atrioventricular timing cycle, any other Doppler measurements or change cardiac peptide levels. This suggests that BI pacing does not cause haemodynamic changes that could account for any antifibrillatory properties.     

Prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia: role of right atrial linear ablation and pacing site

INTRODUCTION: Right atrial linear lesions (RALL), either alone or in combination with antiarrhythmic drug therapy, may modify the substrate for maintenance of atrial fibrillation (AF). The aim of this prospective randomized study was to determine whether RALL provides additional benefit to right atrial appendage pacing (RAAP) and/or interatrial septum pacing (IASP) and drug therapy in patients with symptomatic paroxysmal AF and sinus bradycardia requiring permanent atrial pacing. METHODS AND RESULTS: Sixty-four patients (33 men and 31 women, mean age 73 +/- 10 years) completed the 6-month follow-up. Patients were randomized to either RALL (n = 33) or non-right atrial linear lesions (NRALL), and then to either IASP (n = 32) or RAAP (n = 32). Fifteen RALL patients were paced at the IAS and 18 at the RAA. Seventeen NRALL patients were paced at the IAS and 14 at the RAA. No statistical difference was observed with regard to the mean atrial tachyarrhythmia (AT) burden between NRALL (84 +/- 169 min/day) and RALL patients (202 +/- 219 min/day). Mean AT burden was significantly lower in the IASP group (70 +/- 150 min/day) than in RAAP group (219 +/- 317 min/day; P < 0.016). In the RALL group, the mean AT burden was 99 +/- 180 min/day in the IASP patients and 288 +/- 372 min/day in the RAAP patients (P < 0.046). In the NRALL group, no statistical difference in the mean AT burden was observed between IASP patients (46 +/- 117 min/day) and RAAP patients (130 +/- 211 min/day). CONCLUSION: The results of the present study indicate that RALL did not provide any additional therapeutic benefit to combined antiarrhythmic drug therapy and septal or nonseptal atrial pacing in patients with sinus bradycardia and paroxysmal AF.     

Is There an Optimal Pacing Site to Prevent Atrial Fibrillation?: An Experimental Study in the Chronically Instrumented Goat

INTRODUCTION: Atrial pacing can reduce the number of recurrences of atrial fibrillation (AF). It is unclear the extent to which this effect is determined by the site(s) of pacing. METHODS AND RESULTS: In six electrically remodeled goats (24-hour AF), the window of inducibility of AF was determined by applying premature stimuli (S1-S2) at the right (RA) or left (LA) atrium (baseline values). Determination of the window of inducibility of AF at RA and LA was repeated during preventive pacing at four sites: RA, LA, Bachmann's bundle (BB), and RA+LA (biatrial). Mapping was used to elucidate the mechanisms of prevention of AF. At baseline, the window of inducibility of AF was 49 +/- 9 msec at RA and 45 +/- 17 msec at LA. Initiation of AF was associated with conduction block of the premature beat at BB. Preventive pacing at BB markedly shortened the window of inducibility of AF at RA (25 +/- 11 msec) and LA (17 +/- 8 msec, P < 0.01). Pacing at RA only shortened the window of inducibility of AF at LA (23 +/- 9 msec, P < 0.01), whereas pacing at LA only shortened the window of inducibility of AF at RA (23 +/- 11 msec, P < 0.01). Biatrial pacing failed to shorten the window of inducibility of AF both at RA and LA. Prevention of AF by pacing was due to prolongation of the premature interval at BB. CONCLUSION: In the caprine model of AF, BB is a critical area of conduction of premature beats and initiation of AF. Pacing at BB can prevent but not completely abolish the initiation of AF by single premature beats (shortening of the window of inducibility). Prevention of AF by pacing is based on prolongation of the premature interval at BB, thus preventing conduction block and reentry. In general, the optimal site for preventive pacing is close to the area of block and remote from the origin of premature beats.     

Prevention of atrial fibrillation by inter-atrial septum pacing guided by electrophysiological testing, in patients with delayed interatrial conduction.

AIMS: Interatrial septum (IAS) pacing seems efficient in synchronizing atrial depolarization in patients (pts) with delayed inter-atrial conduction, but its clinical role in preventing atrial tachyarrhythmias is still debated. This study was conducted in order to evaluate the clinical efficacy of IAS pacing guided by pace mapping of the IAS, as an alternative treatment modality in pts with drug refractory paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: We evaluated 29 pts (13 male, 16 female, 60 +/- 11 years), with drug refractory PAF, normal sinus node function and prolonged inter-atrial conduction time (P wave 142 +/- 10 ms). Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle and distal coronary sinus (CS) were recorded. The IAS was paced from multiple sites. The site of IAS where the timing between HRA and distal CS was <20 ms was considered the most suitable for synchronizing the atria. This site was found to be superior to the CS os. near the fossa ovalis in all pts. An active fixation atrial lead was positioned at this site and a standard lead was placed in the right ventricle. During IAS pacing, the P wave duration decreased significantly to 107 +/- 15 ms (P<0.001). At implant, the atrial sensing was 2.3 +/- 0.7 mV, the atrial pacing threshold was 0.95 +/- 0.15 V (0.5 ms) and the impedance was 760 +/- 80 Ohm. We evaluated the pts during four periods of 3 months duration each. The first period (control) was before pacemaker implantation, while the pts were under antiarrhythmic treatment. During the subsequent two periods, we evaluated the clinical efficacy of IAS pacing to prevent PAF recurrences, in AAT (75 bpm) and AAIR (75-140 bpm) mode, with random selection of the order and after discontinuation of antiarrhythmic treatment. During the fourth period, the same AAIR mode was assessed, but antiarrhythmic drugs were also administered. We compared the arrhythmia free interval among the four periods. The proportion of atrial paced beats in AAIR pacing mode plus antiarrhythmics was significantly higher compared with the drug-free period in AAIR mode (57 +/- 9% and 49 +/- 9% respectively, P=0017) and with AAT pacing mode (44 +/- 10%,(, P<0.001). In AAT mode, the arrhythmia free interval was 24.2 +/- 5.1 days, while it was 26.2 +/- 5.7 days in AAIR mode. These intervals did not differ significantly from the pre-implantation period (24.1 +/- 6.3 days). The arrhythmia free interval in AAIR pacing in combination with antiarrhythmic drug therapy was 38.7 +/- 8.1 days and this was significantly longer than the previous periods (P<0.05). CONCLUSION: Atrial septal pacing in combination with antiarrhythmic drug therapy reduced the incidence of PAF in pts with prolonged inter-atrial conduction times. Pace mapping of the IAS is an attractive technique to assess the shortest atrial activation time between HRA and distal CS. Whether placement of the atrial lead based on the shortest HRA--distal CS time is the best place in the IAS to prevent PAF still remains to be proven.     

Mechanisms of Biatrial Pacing for Prevention of Postoperative Atrial Fibrillation—Insights from a Clinical Trial

Atrial fibrillation (AF) occurs in a high proportion of patients after cardiac surgery and is associated with increased morbidity and longer hospital stay. Beta-blockers and amiodarone have been shown to reduce the incidence, but AF still occurs in up to 25% despite pre-treatment. The mechanisms of AF after cardiac surgery are presumably multifactorial. The transient nature of postoperative AF suggests a reversible trigger in patients with susceptible underlying electrophysiological substrates such as abnormal automaticity and conduction delay due to atrial incisions, ischemia and preexisting disease). These could result in atrial premature beats (APBs) and prolonged atrial activation causing lengthening of the P wave. Prophylactic atrial pacing (single- or multi-site) is reported to be effective in patients at high risk for postoperative AF. The mechanisms are probably a combination of preventing bradycardia-induced arrhythmias, overdrive suppression of APBs, eliminating compensatory pauses after APBs and reduction of dispersion of refractoriness. By reducing non-uniform and asynchronous activation resulting from anatomic or functional block, multi-site pacing could improve local excitability and reduce the window of opportunity for AF initiation. We found that the incidence of AF after coronary bypass surgery (CABG) was significantly reduced in patients who received prophylactic biatrial overdrive pacing (BiA) compared with single site left atrial (LA) or right atrial (RA) pacing or no pacing. (BiA 12.5% versus LA 36.4%; RA 33.3% or control 41.9%; P < 0.05). BiA pacing was associated with the greatest reduction of P wave dispersion compared with single site pacing or control (BiA 42 ± 8%; LA 13 ± 6%; RA 10 ± 9%; P < 0.05). Prophylactic postoperative BiA pacing is thus a reasonable and attractive strategy for reducing the risk for postoperative AF.     

Double atrial responses to a single ventricular impulse due to simultaneous conduction via two retrograde pathways

Electrophysiologic studies were performed in two patients. In one patient (Case 1) with ventricular pre-excitation and paroxysmal supraventricular tachycardia, studies after diltiazem administration showed two QRS responses to a single atrial stimulus during atrial pacing at a cycle length of 300 ms. The first QRS response with full pre-excitation and short PR interval was consistent with accessory pathway conduction, while the second QRS response with a normal duration and an atrio-His bundle interval of 350 ms was consistent with normal pathway conduction. The second QRS response was followed by initiation of supraventricular tachycardia. Studies after verapamil administration on a separate day disclosed two atrial responses to a single QRS complex during ventricular pacing at cycle lengths between 330 and 280 ms, suggesting simultaneous retrograde accessory and normal pathway conduction. In Case 2 with a supraventricular tachycardia using a fast atrioventricular nodal pathway for anterograde and a slow ventriculoatrial pathway for retrograde conduction, two atrial responses to a single QRS complex were observed during ventricular pacing at cycle lengths between 500 and 400 ms. The first atrial response showed a stimulus to atrial interval of 120 ms and an atrial activation sequence with the low septal right atrium being earlier than other atrial sites, suggesting retrograde fast pathway conduction. The second atrial response showed a stimulus to atrial interval of 505 ms and an atrial activation sequence with low septal right atrium being simultaneous with the proximal coronary sinus, suggesting retrograde slow pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of biatrial pacing, right atrial pacing, and no pacing in patients with drug refractory atrial fibrillation.

It has been suggested biatrial pacing may prevent the recurrence of atrial fibrillation (AF). To further evaluate this hypothesis, we performed a randomized, single-blinded study in 19 patients with drug refractory AF. The study compared biatrial pacing with conventional right atrial (RA) pacing and a control period of inhibited pacing. The pacing modes utilized were DDD with a base rate of 70 beats/min for biatrial and RA pace (with and without biatrial resynchronization, respectively) and 40 beats/min for the control period. The duration of each pacing mode was 3 months. The number of AF episodes and their duration were obtained from pacemaker Holter memory (Chorus RM ELA Medical). Comparison of the control period (n = 11) with either pacing strategy showed a significant decrease in the total duration of AF (control 27 +/- 35 days, biatrial 8 +/- 15 days p = 0.02, RA 11 +/- 27 days p = 0.04). However, there was no effect on the number of AF episodes (control 79 +/- 108, biatrial 36 +/- 75 p = 0.32, RA 41 +/- 80 p = 0.11). The total percentage of atrial pacing also significantly increased when the control period (6 +/- 9%) was compared with both RA pace (62 +/- 33%, p = 0.008) and biatrial pace (63 +/- 31, p = 0.003). When biatrial pacing was compared with RA pace (n = 19), there was no significant difference in either the duration of AF (biatrial 16 +/- 26 days vs RA 19 +/- 31 days, p = 0.7) or the number of AF episodes (biatrial 56 +/- 91 vs RA 87 +/- 106, p = 0.34). In conclusion, pacing (either type) at a base rate of 70 beats/min has an antifibrillatory effect when compared with inhibited pacing at 40 beats/min. No additional benefit of biatrial pacing over right atrial pacing was demonstrated in this study.     

Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia

INTRODUCTION: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF. METHODS AND RESULTS: A total of 298 patients (age 70 +/- 10 years; 61% male) from 35 centers were implanted with a DDDRP pacing system including three AT/AF prevention pacing algorithms. Lead site was randomized at implant to right atrial septal or nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on intention-to-treat in 277 patients (138 septal) with complete follow-up. No changes in device-recorded AT/AF frequency or burden were observed with algorithms OFF versus ON or between patients randomized to septal versus nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF prevention pacing resulted in decreased atrial premature contractions in both the septal (1.9 [0.2-8.7] vs 3.3 [0.3-10.6]x 103/day; P < 0.01) and nonseptal groups (0.9 [0.2-3.3] vs 1.3 [0.3-5.5]x 103/day; P < 0.001). Patients with septal leads had fewer symptomatic AT/AF episodes ON versus OFF (1.4 +/- 3.0 vs 2.5 +/- 5.2/month, P = 0.01). CONCLUSION: The combination of three atrial prevention pacing algorithms did not decrease device classified atrial tachyarrhythmia frequency or burden during a 3-month cross-over period in bradycardic patients and septal or nonseptal atrial pacing leads. Prevention pacing was associated with decreased frequency of premature atrial contractions and with decreased symptomatic atrial tachyarrhythmia frequency in patients with atrial septal leads.     

Effect of Bachmann's bundle pacing on atrial fibrillation: electrophysiologic assessment

BACKGROUND: It has recently been reported that simultaneous multisite atrial pacing, Bachmann's bundle (BB) pacing, and coronary sinus (CS) pacing are useful for preventing the induction of atrial fibrillation (AF). HYPOTHESIS: We investigated whether a simple pacing approach via BB could reduce the induction of AF by extrastimuli (S2) from the right atrial appendage (RAA). METHODS: Programmed electrical stimulation was performed from the RAA and the area of BB at the superior aspect of the atrial septum, and bipolar recordings were obtained from the RAA, BB, and CS in 14 patients. RESULTS: In five patients, AF was induced with critically timed RAA-S2 delivered during RAA pacing. However, AF was not induced in any patient when RAA-S2 was delivered during BB pacing. The duration of the P wave during BB pacing was significantly shorter than that during RAA pacing and sinus rhythm (BB 80 +/- 16 ms vs. RAA 106 +/- 36 ms vs. sinus rhythm 100 +/- 24 ms, p < 0.05). The intra-atrial conduction time to the distal coronary sinus (CSd) caused by early S2 at the RAA was significantly reduced by BB pacing (BB 114 +/- 22 ms vs. RAA 157 +/- 35 ms, p < 0.001). CONCLUSION: Bachmann's bundle pacing reduces atrial conduction time caused by RAA-S2 and may be useful for preventing the induction of AF.     

Interatrial septum pacing guided by three-dimensional intracardiac echocardiography

OBJECTIVES: Currently, the interatrial septum (IAS) pacing site is indirectly selected by fluoroscopy and P-wave analysis. The aim of the present study was to develop a novel approach for IAS pacing using intracardiac echocardiography (ICE). BACKGROUND: Interatrial septum pacing may be beneficial for the prevention of paroxysmal atrial fibrillation. METHODS: Cross-sectional images are acquired during a pull-back of the ICE transducer from the superior vena cava into the inferior vena cava by an electrocardiogram- and respiration-gated technique. Both atria are then reconstructed using three-dimensional (3D) imaging. Using an "en face" view of the IAS, the desired pacing site is selected. Following lead placement and electrical testing, another 3D reconstruction is performed to verify the final lead position. RESULTS: Twelve patients were included in this study. The IAS pacing was achieved in all patients including six suprafossal (SF) and six infrafossal (IF) lead locations all confirmed by 3D imaging. The mean duration times of atrial lead implantation and fluoroscopy were 70 +/- 48.9 min and 23.7 +/- 20.6 min, respectively. The IAS pacing resulted in a significant reduction of the P-wave duration as compared to sinus rhythm (98.9 +/- 19.3 ms vs. 141.3 +/- 8.6 ms; p < 0.002). The SF pacing showed a greater reduction of the P-wave duration than IF pacing (59.4 +/- 6.6 ms vs. 30.2 +/- 13.6 ms; p < 0.004). CONCLUSIONS: Three-dimensional ICE is a feasible tool for guiding IAS pacing.     

Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation

The purpose of the present study was to evaluate the effect of angiotensin II type 1 receptor (AT1R) antagonist on chronic structural remodeling in atrial fibrillation (AF). BACKGROUND: We previously reported that an AT1R antagonist, candesartan, prevents acute electrical remodeling in a rapid pacing model. However, the effect of candesartan on chronic structural remodeling in AF is unclear. METHODS: Sustained AF was induced in 20 dogs (10 in a control group and 10 in a candesartan group) by rapid pacing of the right atrium (RA) at 400 beats/min for five weeks. Candesartan was administered orally (10 mg/kg/day) for one week before rapid pacing and was continued for five weeks. The AF duration, atrial effective refractory period (AERP) at four sites in the RA, and intra-atrial conduction time (CT) from the RA appendage to the other three sites were measured every week. RESULTS: The mean AF duration in the control group after five weeks was significantly longer than that with candesartan (1,333 +/- 725 vs. 411 +/- 301 s, p < 0.01). The degree of AERP shortening after five weeks was not significantly different between the two groups. The CT from the RA appendage to the low RA after five weeks with candesartan was significantly shorter than that in the control (43 +/- 14 vs. 68 +/- 10 ms, p < 0.05). The candesartan group had a significantly lower percentage of interstitial fibrosis than the control group (7 +/- 2% vs. 16 +/- 1% at the RA appendage, p < 0.001). CONCLUSIONS: Candesartan can prevent the promotion of AF by suppressing the development of structural remodeling.     

Increased AAI mode pacing threshold after termination of atrial fibrillation by acute administration of disopyramide phosphate.

AIMS: We studied changes in atrial pacing threshold after termination of atrial fibrillation (AF) by acute administration of disopyramide phosphate (DP) to elucidate the suitable setting for atrial pacing output before AF termination. METHODS AND RESULTS: Four patients with sick sinus syndrome implanted with AAI mode pacemakers were examined. Disopyramide phosphate (2 mg/kg body weight) was injected intravenously for termination of a total of eight AF episodes. The maximal pacing threshold after AF termination (5.2+/-0.8 V at 0.45 ms) was significantly higher than that at baseline (1.3+/-0.2 V at 0.45 ms; P<0.01) and the average increment was 433+/-68%. During a period free from AF, an acute administration of DP did not increase the atrial pacing threshold and serum disopyramide levels were not toxic. CONCLUSION: The increased atrial pacing threshold observed after AF termination cannot be explained by the action of DP alone. However, our results suggest that atrial pacing output should be set at the maximum value before DP is administered to induce AF termination in patients with AAI pacemaker-dependent bradyarrhythmias.     

Mapping of atrial activation during sustained atrial fibrillation in dogs with rapid ventricular pacing induced heart failure: evidence for a role of driver regions

INTRODUCTION: Dogs with rapid ventricular pacing (RVP)-induced congestive heart failure (CHF) have inducible atrial tachycardia, flutter, and fibrillation (AF). We tested the hypothesis that rapid atrial activation in multiple regions and at different rates is responsible for sustained AF in this CHF model. METHODS AND RESULTS: We studied 12 episodes of sustained (>10 minutes) AF induced in 12 dogs with CHF produced by 3-6 weeks of RVP at 230 beats/minute. High-density mapping of AF was performed using 382 unipolar atrial electrograms recorded simultaneously from epicardial electrodes on the right (RA) and left atria (LA) and Bachmann's bundle. AF mechanisms were based on Fast Fourier Transform (FFT) analysis and activation sequence mapping. A driver was defined as a rapid stable activation region with a single dominant frequency peak in FFT analysis. During AF, three FFT and activation patterns were seen: (1) a single LA driver (7.8 +/- 1.1 Hz) near the pulmonary veins (PVs) with irregular activation in the rest of the atria (n = 4); (2) simultaneous, multisite, biatrial drivers at differing frequencies (LA vs RA dominant frequency gradient: 1.3 +/- 0.8 Hz) near the PVs (8.4 +/- 0.3 Hz) and high RA (8.5 +/- 1.5 Hz) (n = 7); and (3) biatrial irregular activation with multiple and/or broadband frequency peaks without a dominant frequency. (LA: 7.1-11.4 Hz; RA: 5.9-7.7 Hz) (n = 1). Atrial drivers had either a focal activation pattern or were due to a macroreentrant circuit around the PVs. CONCLUSIONS: In this CHF model, FFT analysis and activation sequence mapping demonstrate that sustained AF is characterized by single and multiple, stable LA and RA drivers with predominant sources in the PVs and high RA causing fibrillatory conduction.     

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.