Relation between history of paroxysmal atrial fibrillation and electrophysiological abnormalities of atrial muscle

Although electrophysiological abnormalities of atrial muscle have been evaluated in patients with paroxysmal atrial fibrillation (PAF), no prior study has determined the contribution of the patient's history of PAF to electrophysiological abnormalities. The study population consisted of 108 patients (71 men; mean age, 57 ± 14 years) with symptomatic and idiopathic PAF who underwent electrophysiological study. Before electrophysiological study, histories of frequency, number of PAF episodes per month, and duration, a time interval from the first episode of PAF to electrophysiological study, were examined. At electrophysiological study, endocardial electrograms from 12 right atrial sites were recorded during sinus rhythm, and the right atrial effective refractory period was determined. Longest duration of atrial electrograms, maximal number of fragmented deflections, and number of abnormal atrial electrograms recorded at the right atrial sites were significantly greater in the frequent group (> 1 PAF episode per month, n = 57) than in the infrequent group (< 1 PAF episode per month, n = 51) (98 ± 18 ms vs 88 ± 16 ms, P < 0.005; 8.7 ± 2.6 vs 7.5 ± 2.6, P < 0.05; and 2.2 ± 2.2 vs 1.4 ± 1.6, P < 0.05, respectively). Indices of atrial vulnerability were also greater in the frequent group. Duration of PAF history was significantly correlated with longest duration r = 0.52, P < 0.0001), maximal number of fragmented deflections r = 0.51, P < 0.0001), and number of abnormal atrial electrograms r = 0.58, P < 0.0001). More frequent episodes and longer history of PAF significantly increased the electrophysiological abnormalities of the atrial muscle, suggesting that PAF results in gradual electrical remodeling of the atrial muscle.     

Effects of rosuvastatin on serum asymmetric dimethylarginine levels and atrial structural remodeling in atrial fibrillation dogs

Background: Circulating asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is increased in atrial fibrillation (AF). The purpose of this study was to investigate the effects of rosuvastatin on serum ADMA levels and atrial structural remodeling in AF dogs induced by chronic rapid atrial pacing. Methods: Twenty dogs were randomly divided into the sham‐operated (n = 6), control (n = 7), or rosuvastatin (n = 7) groups. Sustained AF was induced by rapid pacing of the right atrium at 400 beats per minute for 6 weeks. Rosuvastatin was administered orally (1 mg/kg d) for 3 days before rapid pacing and was continued for 6 weeks. Transthoracic and transesophageal echocardiography were performed to detect left atrial structure and function. Serum levels of nitric oxide and ADMA were measured. Interstitial fibrosis and cardiomyocyte apoptosis in the atria were also identified. Results: After 6 weeks, compared with the control group, dramatic smaller left atrium and left atrial appendage volumes and higher atrial contractile function were observed in the rosuvastatin group. Serum nitric oxide concentration was increased, whereas ADMA was decreased in the rosuvastatin group compared with the control group. The percentages of interstitial fibrosis and atrial apoptosis in the control group were significantly higher than those in the sham‐operated group, and rosuvastatin attenuated these changes induced by atrial rapid pacing. Conclusion: A short course of rosuvastatin treatment decreased apoptosis and prevented atrial structural remodeling in association with a decrease in ADMA levels in AF dogs. PACE 2012; 35:456–464)     

Verapamil suppresses the inhomogeneity of electrical remodeling in a canine long-term rapid atrial stimulation model

Verapamil is known to suppress shortening of the atrial effective refractory period (AERP) during relatively short-term atrial pacing, although the effect of a long-term stimulation model is unclear. The effect of verapamil on electrical remodeling was evaluated in a canine rapid atrial stimulation model. The right atrial appendage (RAA) was continuously paced (400 beats/min) for 2 weeks. Four pairs of electrodes were sutured at four atrial sites; the RAA, right atrium close to the inferior vena cava, Bachmann's bundle, and LA. AERP, AERP dispersion (AERPd), conduction time, and inducibility of AF were evaluated during the pacing phase and the recovery phase. The same protocol was performed under the administration of verapamil. In five control dogs, the AERP shortening was inhomogeneous and the shortening of the AERP was most prominent in the LA. AERPd increased during the rapid pacing phase by 5 +/- 2 ms, but recovered quickly in the recovery phase. The max AERPd was 46 +/- 4 ms in the control group and was larger than that in the verapamil group (31 +/- 3 ms, P = 0.001). At the LA site, the shortening of the AERP was decreased by verapamil administration (-19 +/- 3 vs -5 +/- 2 ms, P = 0.04). However, the AF inducibility was not significantly different between the two groups. The effect of verapamil on electrical remodeling was inhomogeneous, depending on the anatomic portion. As a result, AERPd widening during the rapid pacing phase was suppressed by verapamil, while the AF inducibility was unchanged.     

Upstream therapy of atrial fibrillation

Failure of current pharmacological therapy for atrial fibrillation in maintaining sinus rhythm may be due to structural atrial remodeling caused by inflammation and fibrosis. Upstream therapy that interferes in the structural remodeling process may be effective in maintaining sinus rhythm. This article reviews upstream therapy in atrial fibrillation. Various prospective and retrospective studies demonstrate that upstream therapy, consisting of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, fish oils, glucocorticoids, or moderate physical activity, is associated with a reduced incidence of new-onset atrial fibrillation (i.e., primary prevention) and with a reduced recurrence of atrial fibrillation (i.e., secondary prevention). Larger clinical trials are required to further elucidate the position of upstream therapy in the primary and secondary prevention of atrial fibrillation.     

Parasympathetic blockade promotes recovery from atrial electrical remodeling induced by short-term rapid atrial pacing

The purpose of the present study was to assess the influence of autonomic blockade on shortening of effective refractory period (ERP) induced by short-term rapid atrial pacing (RAP) and its recovery process. Fifteen patients (8 men, 7 women, age 52 +/- 16 years) without structural heart disease and without a history of atrial fibrillation were included in this study. All patients underwent RAP at a cycle length of 300 ms for 5 minutes, after which the ERP was measured in all patients at 1, 3, 5, 7.5, and 10 minutes following cessation of RAP. In ten patients, these RAP and measurements of ERPs were repeated after administration of propranolol (P) and subsequent administration of atropine (P + A), respectively. In the remaining five patients atropine (A) was given first and then the administration of propranolol followed (P + A). Relative to the baseline value, the ERP immediately after RAP did not differ significantly from the Control(C), P, A, or P + A (C, 79%+/- 8%; P, 82%+/- 9%; A, 80%+/- 6%; P + A, 82%+/- 13%). However, the ERP 3 minutes after cessation of RAP was significantly (P < 0.05) longer in A (93%+/- 4%) and P + A (97%+/- 5%) than that in C (86%+/- 5%) and P (86%+/- 5%). The recovery time for ERP to return to pre-RAP value was significantly shorter during A and P + A than during either C or P (C, 536 +/- 161 s; P, 503 +/- 172 s; A, 282 +/- 111 s; P + A, 291 +/- 147 s; P < 0.05). Parasympathetic blockade may promote recovery from ERP shortening induced by short-term RAP.     

Left atrial appendage electrical isolation for persistent atrial fibrillation

Left atrial appendage (LAA) may be the source for initiation and maintenance of atrial fibrillation (AF). This report shows restoration of sinus rhythm in the atria during radiofrequency wide‐area LAA electrical isolation, whereas AF persists in the LAA.     

Dual-site right atrial pacing increases left atrial appendage flow in patients with sick sinus syndrome and paroxysmal atrial fibrillation

BACKGROUND: Dual-site right atrial pacing has been proposed as a promising concept for prevention of paroxysmal atrial fibrillation (PAF). Effects of this pacing configuration on left atrial appendage (LAA) flow and transmitral flow may be of prognostic and hemodynamic relevance. This study aims to characterize acute changes in left atrial flow depending on dual-site right atrial pacing. METHODS: In 12 patients (66 +/- 8.8 years, 4 women) with PAF and sinus bradycardia a pacemaker with a right atrial dual-site lead configuration (right atrial lateral and coronary sinus ostium) was implanted. Flow velocities in the left pulmonary vein (LPV), LAA, and across the mitral valve were assessed by transesophageal echocardiography and compared during sinus rhythm (SR) and dual-site (DS) pacing. RESULTS: Dual-site pacing resulted in higher maximum (SR: 0.57 m/s; pacing: 0.77 m/s; P < 0.02) and mean (SR: 0.33 m/s; DS: 0.47 m/s; P < 0.01) LAA emptying flow when compared with SR. The passive transmitral flow component (maximum E-wave velocity) was lower during dual-site pacing (SR: 0.53 m/s vs DS: 0.44 m/s, P < 0.02). The E/A ratio tended to be lower during dual-site pacing (SR: 1.21 vs DS: 1.01, P = 0,10). LPV flow velocities during SR and DS pacing did not differ. CONCLUSION: DS right atrial stimulation in patients with PAF increases the LAA emptying flow velocity and shifts the transmitral flow pattern towards a lower passive component when compared with sinus rhythm. The change in LAA flow may contribute to a lower incidence of thromboembolism and merits further investigation.     

Focal activation patterns: breaking new grounds in the pathophysiology of atrial fibrillation

Introduction: High-resolution atrial mapping studies have provided novel insights in the pathophysiology of atrial fibrillation (AF) in the last few years. Increasing attention is being drawn to the so-called focal activation patterns (FAPs); however, there is no consensus on criteria to identify and characterize these patterns.

Areas covered: In this expert review, an overview of definitions and criteria used to examine FAPs obtained from atrial mapping studies is provided and studies reporting on the underlying mechanisms are discussed.

Expert commentary: High-resolution cardiac mapping has revealed the importance of FAPs in the pathophysiology of AF. There is increasing evidence supporting the concept of endo-epicardial (E-E) asynchrony enabling transmural conduction of electrical waves resulting in FAPs. Uniform reports of FAPs in future studies are needed to provide more knowledge on its clinical importance.     

Accurate linear radiofrequency lesions guided by a nonfluoroscopic electroanatomic mapping method during atrial fibrillation

Catheter-based continuous linear lesions may become a curative procedure for AF. The accuracy of guiding the application of continuous RF lesions by a nonfluoroscopic mapping system (NFM) during AF in goats was tested. The NFM system (Carto) uses magnetic fields to determine, in real time, the location and orientation of a 7 Fr ablation catheter tip. AF was induced in nine goats by intravenous infusion of methacholine (3-4 microg x kg(-1) min(-1)) and burst pacing. The three-dimensional atrial geometry was reconstructed using the median location of the mapping catheter tip during 30 seconds when in contact with each endocardial site. Sequential RF energy (60 seconds in a temperature-controlled mode [60 degrees C]) was delivered along a predetermined path to create longitudinal lesions in both atria. Sites to which RF energy was applied were tagged on the NFM map, enabling the operator to accurately navigate the catheter tip to the adjacent sites. In all cases (n = 14) the location, shape, length, and continuity of the linear lesions on the electroanatomic maps highly correlated with the autopsy findings. Average line length on the reconstructed maps was 32.3+/-4.1 mm, which highly correlated (r = 0.98, P<.001) with the lesions created in the pathological specimen (31.7+/-3.9 mm). The NFM system can guide the application of RF linear lesions in a highly accurate manner during AF. Moreover, the ability to tag the ablation sites on the three-dimensional maps together with real-time monitoring of the ablation catheter tip location enables delivery of RF energy to create reproducible, continuous, longitudinal lesions without the use of fluoroscopy.     

Influence of reciprocating tachycardia on the development of atrial fibrillation in patients with preexcitation syndrome

BACKGROUND: We sought to evaluate the influence of atrio-ventricular reentrant tachycardia (AVRT) on atrial pressures during tachycardia and the presence of atrial fibrillation (AF) in patients with preexcitation syndrome. METHODS: The study population consisted of 88 patients (37 females, mean age 37.3 years) with left-sided accessory pathway and AVRT induced during electrophysiologic study. The AF-inducible group consisted of 32 patients with sustained episodes of AF provoked during electrophysiologic study, whereas the noninducible group comprised 56 patients without AF. RESULTS: We found significantly higher values of maximal and mean left (LAP) and right (RAP) atrial pressures in the AF group compared with noninducible group: LAP max 32.0 versus 20.8, LAP mean 21.6 versus 13.2, RAP max 15.2 versus 11.5, RAP mean 8.2 versus 6.2 respectively (P < 0.001). When analyzing the effect of AVRT on atrial pressures, we found a significant (P < 0.001) negative correlation between anterograde conduction times during tachycardia and LAP max and LAP mean in the whole population, but a significant positive correlation between retrograde conduction time and left atrial pressures. Similar effects of AVRT on the right atrial pressures were found. CONCLUSIONS: Atrial pressures during AVRT, which depend on the electrophysiological features of tachycardia, play an important role in the genesis of atrial fibrillation in patients with preexcitation syndrome.     

Characterization of atrial fibrillation in man: studies following open heart surgery.

The nature of localized atrial activation during atrial fibrillation was characterized in 34 patients following open heart surgery. Bipolar atrial electrograms (AEG) recorded in each patient with atrial fibrillation exhibited a myriad of sizes, shapes, polarities, amplitudes, and beat-to-beat intervals. On the basis of the AEG morphology and the nature of its baseline, we have classified the recordings into four Types. Type I was characterized by discrete AEG complexes separated by an isoelectric baseline free of perturbation, Type II by discrete AEG complexes but with perturbations of the baseline between complexes, Type III by AEGs which failed to demonstrate either discrete complexes or isoelectric intervals, and Type IV in which AEGs of Type III alternated with periods characteristic of Type I and/or Type II. In 22 patients, the AEGs were recorded a second time, and in 11 of these patients the type of atrial fibrillation changed between the first and second recording period. An atrial flutter-fibrillation pattern in the ECG was associated with a relatively ordered atrial activation pattern and a relatively slow atrial rate. Human atrial fibrillation is not an electrophysiologically homogeneous process when compared among different patients or ad seriatim in the same patient.     

The renin-angiotensin system: a therapeutic target in atrial fibrillation

There is growing evidence to suggest a role for the renin-angiotensin system (RAS) in the pathogenesis of atrial fibrillation (AF). Experimental animal data suggest RAS-dependent mechanisms for the development of a structural and electrophysiologic substrate for AF. This is consistent with clinical data demonstrating the effectiveness of RAS blockade in preventing new-onset or recurrent AF in a variety of patient populations including patients with hypertension and left ventricular hypertrophy, congestive heart failure, and those undergoing electrical cardioversion for AF. This review summarizes experimental and clinical evidence to date relating to the role of RAS in the pathogenesis of AF, and the efficacy of its inhibition in managing this common arrhythmia.     

Action potential remodeling in the human right atrium with chronic lone atrial fibrillation

It has been shown in animal experiments that recurrent induction of atrial fibrillation (AF) or long-lasting atrial pacing causes a shortening of the atrial effective refractory period (ERP) and action potential duration (APD) and a loss of their physiological adaptation to rate. Much remains to be clarified as to the electrical remodeling in human patients with chronic AF. We recorded monophasic action potentials (MAPs) from the right atrium at pacing cycle lengths (CLs) of 300, 333, 400, 500, 600, and 750 ms after external cardioversion in 13 patients with chronic lone AF. Their configuration was compared with those obtained from 13 control patients. APDs at 50% and 90% repolarization (APD50, APD90) at the shortest CL (300 ms) in control and AF patients were 131 +/- 14, 211 +/- 19 ms and 136 +/- 12, 210 +/- 22 ms, respectively (mean +/- SD). APDs in control patients increased linearly with increases of CL, reaching maximal values of 174 +/- 30 ms (APD50) and 277 +/- 38 ms (APD90) at a CL of 750 ms. In AF patients, the steady-state CL-APD relation was shifted downward and flattened at CLs > 500 ms; APD50 and APD90 at a CL of 750 ms were 158 +/- 19 ms, 232 +/- 28 ms, respectively. APD90s at CLs of 600 and 750 ms were significantly shorter in AF than in control patients. No statistically significant difference was obtained in APD50 between the two groups at any CL tested. MAP configuration in AF patients was characterized by an acceleration of the late repolarization. The difference between APD90 and APD50 (APD90-50) in control patients was increased with increases of CL, reaching a plateau at a CL of 600 ms. This CL dependent slowing of the late repolarization of MAPs was abolished in AF patients. The atrial ERP, measured at CLs of 400 and 600 ms, showed changes parallel to those of APD90. ERP at a CL of 600 ms in AF patients (224 +/- 13 ms) was significantly shorter than that in control patients (247 +/- 25 ms). We conclude that chronic lone AF leads to electrical remodeling in the human atrium, which causes a loss of rate response of the late repolarization of action potential, leading to a shortening of APD and ERP at slower heart rates.     

房颤中心房钾离子通道重构机制及相关药物的研究进展

心房颤动(简称房颤)是临床上最常见的持续性快速心律失常之一,可以引起心房内血栓、脑栓塞等严重并发症,是我国70岁以上老年人发病率较高、致死率较高的一种疾病。房颤的发生机制较为复杂,大量研究表明,心脏离子钾通道重构在房颤的发生和持续存在中发挥极其重要的作用。作用靶点位于钾离子通道的药物已应用于心房颤动,虽有一定的疗效但仍存在效果欠佳,并发症较多等缺点,现阶段关于心房钾离子通道重构及新型钾离子通道药物已经成为房颤研究中的热点之一。     

Relation of age and sex to atrial electrophysiological properties in patients with no history of atrial fibrillation

Although atrial fibrillation is a common arrhythmia, especially in elderly men, little is known about age related changes in atrial electrophysiological properties or gender differences. The aim of this study was to analyze the effects of aging on vulnerability to atrial fibrillation and assessed gender differences in those age related changes. An electrophysiological study was performed on 73 patients with no history of atrial fibrillation, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiological function, including 25 women (mean age 49 +/- 18 years; range 12-84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (A2/A1 x 100), effective refractory period, wavelength index (effective refractory period/A2), and inducibility of atrial fibrillation. There were no significant differences in percent maximum atrial fragmentation (143 +/- 28 vs 142 +/- 35%), effective refractory period (241 +/- 39 vs 238 +/- 50 ms), wavelength index (2.9 +/- 0.8 vs 3.1 +/- 0.9), induction of atrial fibrillation (10 [21%] vs 7 [28%]), or age (50 +/- 17 vs 49 +/- 20 years) between men and women. Age was not statistically different between those patients with and without induction of atrial fibrillation in men (48 +/- 14 vs 50 +/- 18 years) and women (48 +/- 18 vs 49 +/- 21 years). Percent maximum atrial fragmentation and effective refractory period were directly correlated with age in men (r = 0.35, P = 0.01; r = 0.46, P < 0.001, respectively) and women (r = 0.42, P = 0.04; r = 0.45, P = 0.02, respectively), though wavelength index did not correlate with age in men (r = -0.04) or women (r = -0.04) with no history of atrial fibrillation. Considering these findings, the authors conclude that the mechanism triggering atrial fibrillation may be different between older and younger patients with atrial fibrillation, because younger patients who have no marked substrate for atrial fibrillation may need many trigger beats to induce atrial fibrillation.     

Noninvasive time and frequency predictors of long-standing atrial fibrillation early recurrence after electrical cardioversion

Background: Several clinical factors have been studied to predict atrial fibrillation (AF) recurrence after electrical cardioversion (ECV) with limited predictive value. Methods: A method able to predict robustly long‐standing AF early recurrence by characterizing noninvasively the electrical atrial activity (AA) with parameters related to its time course and spectral features is presented. To this respect, 63 patients (20 men and 43 women; mean age 73.4 ± 9.0 years; under antiarrhythmic drug treatment with amiodarone) who were referred for ECV of persistent AF were studied. During a 4‐week follow‐up, AF recurrence was observed in 41 patients (65.1%). Results: RR variability and the studied AA spectral features, including dominant atrial frequency (DAF), its first harmonic and their amplitude, provided poor statistical differences between groups. On the contrary, f waves power (fWP) and Sample Entropy (SampEn) of the AA behaved as very good predictors. Patients who relapsed to AF presented lower fWP (0.036 ± 0.019 vs 0.081 ± 0.029 n.u.², P < 0.001) and higher SampEn (0.107 ± 0.022 vs 0.086 ± 0.033, P < 0.01). Furthermore, fWP presented the highest predictive accuracy of 82.5%, whereas SampEn provided a 79.4%. The remaining features revealed accuracies lower than 70%. A stepwise discriminant analysis (SDA) provided a model based on fWP and SampEn with 90.5% of accuracy. Conclusions: The fWP has proved to predict long‐standing AF early recurrence after ECV and can be combined with SampEn to improve its diagnostic ability. Furthermore, a thorough analysis of the results allowed outlining possible associations between these two features and the concomitant status of atrial remodeling. PACE 2011; 34:1241–1250)