Comparison of the acute effects of pacing the atrial septum, right atrial appendage, coronary sinus os, and the latter two sites simultaneously on the duration of atrial activation

OBJECTIVE—To compare the acute effects of right atrial appendage, atrial septal, coronary sinus os, and dual site pacing on the duration of atrial activation.
METHODS—20 patients with a variety of cardiac conditions underwent an intracardiac electrophysiological study. Electrograms were recorded from the right atrial appendage and at multiple sites within the coronary sinus. The duration of atrial activation was measured during pacing at the right atrial appendage, atrial septum, and coronary sinus os, and also during dual site stimulation.
RESULTS—The duration of atrial activation with atrial appendage pacing was notably longer (p < 0.001) than with dual site, septal, or coronary sinus os pacing, but there were no significant differences in atrial activation times between these latter three pacing modes. When stimulating the atria at a cycle length of 500 ms, the mean (SD) duration of atrial activation was 145 (37) ms for right atrial appendage pacing, 93 (26) ms for dual site pacing, 96 (28) ms for septal pacing, and 98 (28) ms for coronary sinus os pacing.
CONCLUSIONS—Assuming that the duration of atrial activation is an important determinant of predisposition to paroxysmal atrial fibrillation, atrial septal pacing or coronary sinus os pacing would appear to offer the same advantage as dual site pacing without the additional complexities associated with the latter pacing mode.


Keywords: atrial septal pacing; dual site pacing; atrial activation; atrial fibrillation     

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.     

Pronounced effect of procainamide on clockwise right atrial isthmus conduction compared with counterclockwise conduction: possible mechanism of the greater incidence of common atrial flutter during antiarrhythmic therapy

INTRODUCTION: It has been shown that the induction rates of common and reversed common atrial flutter are comparable during baseline control study, whereas the rate is significantly greater for common flutter than reversed common flutter during administration of antiarrhythmic agents. The mechanism of this discrepancy is not known. METHODS AND RESULTS: The study consisted of 15 patients (group 1) with clinically documented common atrial flutter either with (n = 10) or without (n = 5) Class I antiarrhythmic therapy, and 15 patients with paroxysmal supraventricular tachycardia (group 2). Bidirectional conduction velocity and minimal pacing cycle length of 1:1 conduction during incremental pacing from both the low lateral right atrium and coronary sinus were assessed. The response of these variables to procainamide was analyzed in correlation with the induction rate of each type of flutter during the pacing protocol. Conduction velocity in the clockwise (CW) direction was significantly slower for all pacing cycle lengths than conduction velocity in the counterclockwise (CCW) direction in group 1 but was similar in group 2. Minimal pacing cycle length of 1:1 conduction did not differ between CW and CCW conduction in either group. However, in group 1, minimal pacing cycle length of 1:1 conduction of CW conduction was prolonged to a greater degree after procainamide than that of CCW conduction. There also was a significant increase in the induction rate of common flutter. This preferential effect of procainamide on CW conduction was not observed in group 2. CONCLUSION: CW conduction over the isthmus is preferentially influenced by procainamide compared with CCW conduction, which may explain the greater incidence and induction probability of common flutter during antiarrhythmic therapy.     

Atrial dysfunction and interatrial dyssynchrony predict atrial high rate episodes: insight into the distinct effects of right atrial appendage pacing

Atrial Dysfunction and Dyssynchrony Predict Atrial High Rate Episodes . Introduction: Right atrial (RA) appendage pacing may prolong atrial conduction time (ACT). This study aimed to investigate if RA appendage pacing can induce intra‐ and interatrial dyssynchrony and if atrial dysfunction and dyssynchrony can predict atrial high rate episodes (AHREs) in the first year after pacing. Methods and Results: Patients implanted with dual‐chamber pacemakers for symptomatic bradycardia were enrolled. Cumulative percentage of RA appendage pacing (Cum%AP) during 1‐year follow‐up and AHREs were recorded. Full Doppler echocardiography studies were performed before implantation and 1 year after pacing. ACT and peak atrial velocities (Sm‐la, Em‐la, Am‐la) were measured. One hundred ten patients (age 70.5 ± 11 years; 53 males) were recruited and completed 1‐year follow‐up. ACT of both RA and left atrial (LA) were more prolonged in patients with Cum%AP > 75% than those with <25%. Intra‐ and interatrial dyssynchrony was more obvious in patients with Cum%AP > 75% (22.3 ± 12.2 milliseconds vs 9.5 ± 6.2 milliseconds; 53.9 ± 29.7 milliseconds vs 19.7 ± 17.3 milliseconds; both P < 0.001). AHREs occurred in 29% of patients. Atrial pump function and interatrial dyssynchrony independently predicted AHREs in multivariate analysis. Receiver operating characteristic curve provided a cutoff value of Am‐la <5.3 cm/s, which predicted AHREs with a sensitivity of 71% and a specificity of 75% (area under the curve, 0.822; P < 0.001). Conclusion: RA appendage pacing causes atrial conduction delay with intra‐ and interatrial dyssynchrony. Atrial dysfunction and interatrial dyssynchrony are related to AHREs in the first year after pacing.     

Noninvasive, direct visualization of macro-reentrant circuits by using magnetocardiograms: initiation and persistence of atrial flutter.

AIMS: We analysed the cardiac magnetic fields on the body surface to visualize electrical currents noninvasively during reentrant arrhythmias. METHODS AND RESULTS: Seven patients with counterclockwise atrial flutter (AFL) were studied during 17 episodes of AFL using 64-channel magnetocardiograms (MCGs) and electrophysiological study. Eight of the episodes were paroxysmal AFL, in which MCGs were recorded from the time of spontaneous onset to the time of termination. We constructed iso-magnetic field maps of the tangential components and produced MCG animations. With respect to AFL initiation, an atrial premature complex induced AFL. Prior to the initiation of AFL, atrial fibrillation (AF) transiently occurred. The cardiac magnetic fields revealed a single peak during sinus rhythm or with premature complexes but a disorganized pattern during AF. When AF transformed to AFL, the magnetic fields changed from a disorganized pattern to a single peak at first and then evolved to a circular pattern. During persistent AFL, the magnetic source moved in a counterclockwise circuit. CONCLUSION: MCG animation can be used to visualize the sequence in which a premature complex transforms sinus rhythm to AFL via AF. Our findings indicate that MCGs can be used to identify noninvasively the mechanisms responsible for atrial tachyarrhythmias.     

快速右房起搏制备猪房颤模型及其心肌组织中抗凝血酶测定的研究

目的观察快速右房起搏法制备猪房颤（AF）模型的可靠性及AF易并发血栓形成的可能机制。方法将12只健康家猪随机分为模型组和对照组各6只,模型组以闭胸法快速右房起搏建立AF模型并采用程序刺激或Burst刺激进行鉴定,对照组仅植入电极,不予起搏。两组均于心脏电生理检查结束后迅速开胸取心肌组织,采用双向凝胶电泳分离心肌差异表达蛋白,采用图像分析及质谱法测定抗凝血酶表达情况。结果模型组均成功建立AF模型,且其心肌组织中抗凝血酶表达明显低于对照组（P〈0.05）。结论快速右房起搏法制备猪AF模型稳定可靠;AF易并发血栓形成的可能机制为其心肌组织中抗凝血酶表达降低。     

Prevention of immediate reinitiation of atrial tachyarrhythmias by high-rate overdrive pacing: results from a prospective randomized trial

INTRODUCTION: Immediate reinitiation of atrial tachyarrhythmia (IRAT) is an important cause of failure to maintain sinus rhythm. IRAT prevention by overdrive pacing has not been evaluated in a prospective randomized trial. METHODS AND RESULTS: Patients with a DDDRP pacemaker offering temporary atrial overdrive pacing after AT termination (Post Mode Switching Overdrive Pacing [PMOP]) were enrolled into the prospective PIRAT (Prevention of IRAT) trial if paroxysmal AT episodes occurred after implantation. PMOP was randomly activated (120 beats/min for 2 min) or inactive. After 3 months, device memory was interrogated, symptoms and quality of life assessed, and patients crossed over to the alternative treatment arm for another 3 months. Primary study endpoint was the number of AT episodes; secondary endpoints were the cumulative time in AT (AT burden), percentage of AT episodes with IRAT, symptoms, and quality of life with PMOP active versus inactive. In 37 patients (21 men; 69 +/- 9 years), there was no difference in the median number of AT episodes (0.37 vs 0.34 per day), AT burden (both 1%), percentage of episodes with IRAT (30%vs 28%), symptoms, and quality of life during PMOP off versus on. With PMOP active, 29% of 439 ATs restarted during and 18% before PMOP intervention. The PMOP-induced rate increase appeared to be associated with IRAT in 9% of AT episodes. CONCLUSION: Automatic overdrive pacing after AT termination did not prevent IRAT, mainly due to insufficient overdrive suppression even at 120 beats/min and the delay between AT termination and PMOP intervention.     

The effectiveness of SGLT2 inhibitor in the incidence of atrial fibrillation/atrial flutter in patients with type 2 diabetes mellitus/heart failure: a systematic review and meta-analysis

BackgroundType 2 diabetes mellitus (T2D) and heart failure (HF) are closely related to the increased risk of atrial fibrillation (AF)/atrial flutter (AFL). However, massive clinical studies have shown that sodium glucose cotransporter 2 inhibitor (SGLT2i) affects the occurrence of AF/AFL and its complications, but the promoting or inhibitory effect of SGLT2i on AF/AFL and its complications and the exact probability is not clear, meta-analysis can combine the existing research data to easily solve the clinical problems.MethodsWe performed a search in the registers of ClinicalTrials.gov from it,s inception to March 2021 to evaluate the occurrence of AF/AFL adverse events in SGLT2i in patients with T2D/HF. Almost all of the included studies were double-blind parallel allocation randomized controlled studies, and only one was open. The control groups all included placebo, some of which also included glimepiride, metformin, liraglutide, etc. Quality risk assessment of the included randomized controlled trials (RCTs) was conducted using Cochrane RoB 2.0., and the publication bias assessment was conducted using STATA 17.0. The odds ratio (OR) combined effect of 95% confidence interval (CI) was used for bivariate variables.ResultsWe included data from 22 confirmed trials that included 52,951 T2D/HF patients. The studies had no risk of bias. Analysis of the cumulative results showed that compared with placebo, SGLT2i can significantly reduce the incidence of AF/AFL by 18% (OR =0.82, 95% CI: 0.73 to 0.93, P=0.002), and reduce the incidence of arrhythmia by 14% (OR =0.86, 95% CI: 0.79 to 0.94, P=0.0006); among them, the incidence of AF/AFL in T2D patients was reduced by 20% (OR =0.80, 95% CI: 0.69 to 0.92, P=0.002); Dapagliflozin reduced the incidence of AF/AFL by 15% (OR =0.85, 95% CI: 0.74 to 0.98, P=0.03); the incidence of intracardiac thrombosis decreased by 69% (OR =0.31, 95% CI: 0.10 to 0.91, P=0.03), while the incidence of AF/AFL in women decreased by 17% (OR =0.83, 95% CI: 0.72 to 0.94, P=0.004).DiscussionThis article provides a new direction for the use of SGLT2i, and hopefully it can provide certain theoretical basis for the broader clinical indications of SGLT2i in the future.     

Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study

BackgroundAtrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.HypothesisOutcomes with dronedarone may also be impacted by duration of AF/AFL history.MethodsIn this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long).ResultsOf 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo‐treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65‐0.96]) and intermediate (0.72 [0.56‐0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66‐1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug‐related safety issues were identified.ConclusionsPatients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.     

Global burden of atrial fibrillation/flutter due to high systolic blood pressure from 1990 to 2019: estimates from the global burden of disease study 2019

Atrial fibrillation/atrial flutter (AF/AFL) has progressed to be a public health concern, and high systolic blood pressure (HSBP) remains the leading risk factor for AF/AFL. This study estimated the HSBP attributable AF/AFL burden based on the data from the Global Burden of Disease (GBD) study 2019. Numbers, age‐standardized rates (ASR) of deaths, disability‐adjusted life years (DALYs), and corresponding estimated annual percentage change (EAPC) were analyzed by age, sex, sociodemographic index (SDI), and locations. Gini coefficient was calculated to evaluate health inequality. Globally, HSBP‐related AF/AFL caused 107 091 deaths and 3 337 876 DALYs in 2019, an increase of 142.5% and 105.9% from 1990, respectively. The corresponding mortality and DALYs ASR declined by 5.8% and 7.7%. High‐income Asia Pacific experienced the greatest decrease in mortality and DALYs ASR, whereas the largest increase was observed in Andean Latin America. Almost half of the HSBP‐related AF/AFL burden was carried by high and high‐middle SDI regions, and it was experiencing a shift to lower SDI regions. A negative correlation was detected between EAPC and SDI. Females and elderly people tended to have a higher AF/AFL burden, whereas young adults (30–49 years old) experienced an annual increase in AF/AFL burden. The Gini index of DALYs rate decreased from 0.224 in 1990 to 0.183 in 2019. Despite improved inequality having been observed over the past decades, the HSBP‐related AF/AFL burden varied across regions, sexes, and ages. Cost‐effective preventive, diagnostic, and therapeutic tools are required to be implemented in less developed regions.     

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.     

Evaluation of right atrial and biatrial temporary pacing for the prevention of atrial fibrillation after coronary artery bypass surgery

OBJECTIVES

The purpose of this study was to determine if atrial pacing is effective in reducing postoperative atrial fibrillation (AF).

BACKGROUND

Atrial fibrillation after coronary artery bypass grafting (CABG) is a common problem for which medical management has been disappointing. Atrial-based pacing has become an attractive nonpharmacologic therapy for the prevention of AF.

METHODS

Sixty-one post-CABG patients (mean age = 65 years) were randomized to one of three groups: no atrial pacing (NAP), right atrial pacing (RAP) or biatrial pacing (BAP). Each patient had one set of atrial wires attached to both the right and left atria, respectively, at the conclusion of surgery. Patients in the RAP and BAP groups were continuously paced at a rate of 100 pulses per minute for 96 h or until the onset of sustained AF (>10 min). All patients were monitored with Holter monitors or full disclosure telemetry to identify the onset of AF. The primary end point of the study was the first onset of sustained AF.

RESULTS

There was no significant difference in the proportion of patients developing AF in the three groups (NAP = 33%; RAP = 29%; BAP = 37%; p > 0.7). However, for the subset of patients on beta-adrenergic blocking agents after CABG, there was a trend toward less AF in the paced groups. There were no serious complications related to pacing, although in three patients the pacemaker appeared to induce AF by pacing during atrial repolarization.

CONCLUSIONS

Continuous right or biatrial pacing in the postoperative setting is safe and well tolerated. We did not find that post-CABG pacing prevented AF in this pilot study; however, the role of combined pacing and beta-blockade merits further study.     

Rationale and design of ATHENA: A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter

Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, predominantly affecting elderly patients. There is a continued need for new antiarrhythmic drugs to treat the ever-increasing number of patients with this arrhythmia. Dronedarone is a new antiarrhythmic compound currently being developed for treatment of AF.
Methods: The ATHENA trial ( A placebo-controlled, double-blind, parallel arm T rial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular H ospitalization or death from any cause in pati EN ts with A trial fibrillation/atrial flutter) is the largest single antiarrhythmic drug trial ever conducted. More than 4,600 patients with a history of AF or atrial flutter (AFL) have been randomized to receive dronedarone 400 mg bid or matching placebo. The primary study endpoint is time to first cardiovascular hospitalization or death from any cause. The study has completed patient enrollment in December 2006 and is expected to end follow-up 1 year later.
Conclusion: ATHENA will be the largest efficacy and safety trial of dronedarone, a multichannel blocker compound with properties from class I, II, III, and IV antiarrhythmic drugs developed to treat patients with AF.     

Entrainment of atrioventricular nodal reentrant tachycardias during overdrive pacing from high right atrium and coronary sinus: With special reference to atrioventricular dissociation and 2:1 retrograde block during tachycardias

Entrainment was attempted during electrophysiologic evaluation of 8 patients with atrioventricular (AV) nodal reentrant tachycardia. Entrainment could be performed while pacing from the high right atrium in 35 of 35 episodes, from proximal coronary sinus in 9 of 21 episodes and from distal coronary sinus in 10 of 20 episodes. The minimal rates required were 8 to 40 beats/min faster than those of the tachycardias. That the atria (as defined in electrophysiologic studies) were not a necessary component of the reentry circuit was suggested by the occurrence, during tachycardia, of short episodes of AV dissociation and of 1 episode of 2:1 retrograde block. For the tachycardia to be interrupted, the pacing rate usually had to be slightly faster than that required to entrain, as well as sufficiently rapid to produce anterograde block of an atrial impulse in the slow AV nodal pathway. Moreover, termination of tachycardia apparently was a function of the pacing site. In some episodes, either because of a proximity effect or because of a preferential input into the upper common pathway, coronary sinus pacing terminated the tachycardia at slower rates or with fewer stimuli than high right atrial pacing. Thus, patients with drug-resistant AV nodal reentrant tachycardias may benefit from recently introduced pacing techniques for termination of tachycardia through entrainment.