Postcardioversion atrial electrophysiologic changes induced by oral verapamil in patients with persistent atrial fibrillation

OBJECTIVES: The aim of our study was to verify the effect of oral administration of verapamil on atrial electrophysiologic characteristics after cardioversion of persistent atrial fibrillation (AF) in humans. BACKGROUND: Discordant findings have been reported regarding the efficacy of verapamil in preventing the electrical remodeling induced by AF. METHODS: We determined the effective refractory periods (ERPs) at five pacing cycle lengths (300 to 700 ms) and in five right atrial sites after internal cardioversion of persistent AF (mean duration 238.1+/-305.9 days) in 19 patients. Nine patients received oral verapamil (240 mg/day) starting four weeks before the electrophysiologic study, whereas the other 10 patients were in pharmacologic washout. RESULTS: The mean ERPs were 202.0+/-22.7 ms in the washout group and 189.3+/-18.5 ms in the verapamil group (p < 0.0001). The degree of adaptation of refractoriness to rate was similar in the two groups (mean slope value in the washout group and verapamil group: 0.07+/-0.03 and 0.08+/-0.05, respectively), showing a normal or nearly normal adaptation to rate in the majority of the paced sites in both groups. The mean ERP was slightly longer in the septum than in the lateral wall and in the roof, both in the washout and verapamil groups. CONCLUSIONS: In patients with persistent AF, long-term administration of verapamil before internal cardioversion resulted in 1) shortening of atrial ERPs; 2) no change in refractoriness dispersion within the right atrium; and 3) no change in atrial ERP adaptation to rate.     

Age-related changes in arrhythmias and electrophysiologic properties

There are few data on the relationships between age and arrhythmias, except for the Wolff-Parkinson-White syndrome. In clinical practice, the most frequent arrhythmia is the atrial fibrillation (AF). It is well-known, that the prevalence of AF increases with age from 2 to 4% before 70 years up to 9 to 15% in patients older than 80 years. However, it is unknown if the increased prevalence of AF is related to the increase of the cardiac and extracardiac diseases, noted in the elderly, or to atrial electrophysiological changes. Probably, the incidence and mechanism of arrhythmia do not differ between adults and elderly patients when the other clinical data are similar.Arrhythmias in elderly patients represent most of the urgencies, consultations or hospitalizations. They could become more and more frequent because we now know that the management of most of these elderly patients should be identical to that of younger patients. However, the treatment frequently is difficult. The difficulties in elderly patients are due to the associated non-cardiac and cardiac diseases which are more frequent than in adults. Therefore, the quality of management should be particularly careful in elderly patients.     

心房颤动患者心房电生理特性的研究

目的　观察心房颤动 (房颤 )患者的心房传导性及心房不应期 ,探讨房颤发生机制。方法　以既往无房颤病史、在心脏电生理检查中出现房颤的 72例非器质性心脏病患者作为研究对象 ,测量反映心房传导的电生理参数 (P A、P CSd、S1 A1、最大S2 A2、MaxCD、CDzone)及心房有效不应期(ERPHRA) ,与同等条件下无房颤发作的患者进行比较。结果　房颤组P A、P CSd、最大S2 A2、MaxCD、CDzone显著延长 (P =0 0 0 1) ,ERPHRA 明显缩短 (P =0 0 0 1)。结论　心房传导性的降低和心房有效不应期的缩短是房颤发生的心房电生理基础     

Electrophysiological properties of the human atrium in atrial fibrillation

It has been reported that ectopic foci from the pulmonary veins can initiate atrial fibrillation (AF) and can also act as drivers for maintaining AF. However, not all patients with atrial arrhythmias initiate AF. A substrate for atrial propensity to AF is required for AF initiation and maintenance. Thus, we reviewed and discussed mainly the electrophysiological properties observed in AF. Abnormal atrial electrograms during sinus rhythm and abnormal responses of the atrium elicited by programmed stimulation have been observed more frequently in patients with paroxysmal AF than in those without. A shorter atrial effective refractory period, greater dispersion of the atrial refractoriness and atrial conduction delay are also of electrophysiologic significance in the genesis of AF. Electrical remodeling is likely to be a final common pathway that ultimately supervenes. Even if atrial electrical remodeling facilitates AF initiation and AF perpetuation, the initiation of AF requires a trigger. Further investigation into the electrophysiological properties in AF will be needed in order to contribute to the future development of an appropriate treatment.     

Impact of amiodarone on electrophysiologic properties of pulmonary veins in patients with paroxysmal atrial fibrillation

INTRODUCTION: Pulmonary veins (PVs) are the predominant location of triggers for atrial fibrillation (AF), but little is known about the electrophysiologic properties of PVs. In addition, the influence of amiodarone on the electrophysiologic properties of PVs has not been elucidated. METHODS AND RESULTS: Fifty-five patients with symptomatic and drug-resistant AF were divided into two groups: group 1 patients (n=29) without antiarrhythmic drug therapy at the time of electrophysiologic study (EPS), and group 2 patients (n=26) undergoing continuous long-term treatment with amiodarone. EPS including programmed stimulation of both atria and within the PVs was performed in both groups. In group 1, the effective refractory period (ERP) of all PVs (174 +/- 62 msec) was significantly shorter than the ERP of the left atrium ([LA] 254 +/- 30 msec, P=0.0001) and right atrium ([RA] 221 +/- 29 msec, P=0.0001). The same pattern was observed in group 2 (PV: 210 +/- 58 msec; LA: 259 +/- 35 msec, P=0.0001; RA: 246 +/- 37 msec, P=0.0255). The ERP of all stimulated PVs was significantly lower in group 1 (174 +/- 62 msec) than in group 2 (210 +/- 58 msec; P=0.0001). The ERP of the left superior and right superior PVs and RA but not the left inferior PV and LA were significantly increased in patients treated with amiodarone. Decremental conduction properties were observed in all stimulated PVs, and there were no significantly differences between the maximal decrement of both groups. CONCLUSION: The distinctive electrophysiologic properties of PVs are emphasized by amiodarone therapy. Long-term amiodarone treatment is responsible for heterogeneous alteration of the PV electrophysiology, which may account for the individual antiarrhythmic responses in a subset of patients with paroxysmal AF.     

Effect of atrial dilatation on electrophysiologic properties and inducibility of atrial fibrillation

Introduction: Atrial dilatation may play an important role in the occurrence of atrial fibrillation (AF) in clinical situations. However, the electrophysiologic characteristics of dilated atria are still unclear. Methods and results: In 18 isolated Langendorff-perfused canine hearts (14.6 ± 2.2 kg), we measured atrial effective refractory periods (ERPs) at four different sites, conduction velocity and percentage of slow conduction on the right atrium (using a high-density electrode plaque), and assessed the inducibility of AF at the baseline (0 cm H₂O) and high (15 cm H₂O) atrial pressure. The atrial ERPs did not change significantly, but the dispersion of ERP increased significantly (40 ± 18 vs 25 ± 9 vs ms, p = 0.01) during high atrial pressure. The percentage of slow conduction (< 25 cm/s) over the mapping area, and the inducibility of AF increased during high atrial pressure (23.7 ± 10.2 % vs 32.1 ± 12.5 %, p = 0.02). The AF inducibility significantly correlated with the ERP dispersion (R = 0.75, p < 0.001) and maximal percentage of slow conduction (R = 0.88, p < 0.001). Furthermore, ERPs were significantly shorter in the induced AF group than those without induced AF (68 ± 17 vs 84 ± 16 ms, P < 0.05). Conclusions: The increased inhomogenity in atrial electrophysiological properties during atrial dilatation contributed to the inducibility of AF. Received: 26 November 2001?Returned for 1. revision: 2 January 2002?1. Revision received: 11 February 2002?Returned for 2. revision: 25 March 2002?2. Revision received: 6 May 2002?Returned for 3. revision: 10 June 2002?3. Revision received: 21 August 2002?Accepted: 11 September 2002     

Atrial electrophysiologic properties in paroxysmal atrial fibrillation. Study conducted with the stimulation of 5 atrial sites

Programmed atrial stimulation at five atrial sites was performed to evaluate electrophysiologic atrial properties in 17 control patients (14 M, 3F, mean age 61 +/- 9 years) (Group A) and in 18 patients with paroxysmal atrial fibrillation (13 M, 5 F, mean age 61 +/- 5 years) (Group B) with normal sinus node function. The mean value of the P wave duration was similar in both groups. Programmed atrial stimulation was performed at five atrial sites: high, medium and low lateral wall, and high and low medial wall. We evaluated the following parameters: A) local conduction delay measured at the functional refractory period as the difference between A1-A2 and S1-S2 intervals; B) widening of local electrogram measured at the functional refractory period as the difference between A1-A2 interval measured at the end of each local electrogram and A1-A2 interval measured at the beginning of each local electrogram. We evaluated the mean and the maximum value of the two above-mentioned parameters; C) dispersion of effective refractory period and functional refractory period, determined as the longest minus the shortest refractory period from the range of refractory periods measured in each patient; D) the mean of effective refractory periods and functional refractory periods observed at five atrial sites. Mean and maximum local conduction delay, mean effective and functional refractory periods did not present significant differences in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Natural history of patients with isolated atrial fibrillation

Sixty three patients (pts) (aged less than or equal to 50 years) with a history of "lone" atrial fibrillation (AF) and normal heart size at radiological examination were followed-up for a mean period of 95 months (range 1-360). The arrhythmia remained paroxysmal in 43 pts, became chronic in 13, while in 7 could not be reverted to sinus rhythm at the time of first observation. Clinical examination was normal in 58 pts; in 23 echocardiography disclosed mild abnormalities. In 2 pts auscultation revealed a mid-systolic apical click, i n one a mid-systolic murmur and in 2 click and murmur together. These findings were correlated to slightly pathological echocardiographic patterns. M-mode and B-mode echocardiography yielded normal results in 35 pts and showed minor pathological findings in 28 (16 with paroxysmal AF and 12 with chronic AF). Thyroid hormones, tested in 58 pts, were within normal limits in 53, showed decreased T4 in 2 and increased T3 in 3 (2 of whom in treatment with amiodarone). During the follow-up period, no patient had a deterioration of the clinical status from the cardiovascular point of view. However, one patient suffered an episode of cerebral embolism, with rapid resolution, and one a cerebral transient ischemic attack. In conclusion "lone" AF has a favourable prognosis and systemic anticoagulation is not indicated, particularly in the absence of left atrial dilatation.     

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.     

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.     

心房颤动患者心房肌乙酰胆碱兴奋钾电流通道基因和蛋白的表达

目的:探讨心房颤动(房颤)患者心房肌乙酰胆碱兴奋钾电流(Ik,Ach)通道基因和蛋白表达变化,以了解Ik,Ach通道在房颤发生中的可能作用机制.方法:入选行心脏瓣膜病手术患者作研究对象,其中并发房颤者9例(房颤组),窦性心律者13例(对照组).所有入选患者于开胸行心脏手术时切取右心耳组织,房颤组患者同期加取左心耳组织.用RT-PCR和Western-Blot检测不同心房肌组织中人Kir3.4基因及蛋白水平的表达.结果:房颤组患者IK,Aeh通道蛋白mRNA表达水平及蛋白含量均较对照组患者减少(P＜0.05).结论:Ik,Ach通道蛋白mRNA表达水平及蛋白含量较少可能是慢性房颤患者发病机制之一.     

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

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

Effects of the NA+ channel blocker pilsicainide on the electrophysiologic properties of pulmonary veins in patients with atrial fibrillation

INTRODUCTION: Na+ channel blockers are used to treat atrial fibrillation (AF). However, the effects of Na+ channel blockers on the electrophysiologic properties of pulmonary veins (PVs) are not well characterized. The aim of the present study was to evaluate the effect of the pure Na+ channel blocker pilsicainide on the PVs. METHODS AND RESULTS: PV mapping using a basket catheter was performed in 28 patients with paroxysmal AF. Twenty-eight PVs, including 20 left superior and 8 right superior PVs, were studied. Programmed stimulation was performed in the distal PV and PV-left atrial (LA) junction before and after infusion of pilsicainide (1 mg/kg). Pilsicainide significantly prolonged the effective refractory period (ERP) of the distal PV from 163 +/- 44 msec to 192 +/- 53 msec (P < 0.001), PV-LA junction from 227 +/- 48 msec to 235 +/- 52 msec (P < 0.05), and LA appendage from 225 +/- 55 msec to 245 +/- 48 msec (P < 0.05). Pilsicainide significantly prolonged the conduction time from the distal PV to PV-LA junction from 45 +/- 14 msec to 70 +/- 26 msec (P < 0.0001). In 3 of 5 patients who experienced AF termination with pilsicainide, PV-LA conduction block was observed just before AF termination. CONCLUSIONS: Pilsicainide can modify ERP heterogeneity and conduction properties in the PV and at the PV-LA junction. Because the PV and PV-LA junction have important roles as substrates for AF maintenance, pilsicainide may terminate AF by pharmacologic PV isolation.     

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.     

Impaired transport function of the left atrium in patients with lone paroxysmal atrial fibrillation

Background: Although lone paroxysmal atrial fibrillation (LPAF) is clinically defined as an arrhythmia that occurs in the absence of structural heart disease, it has been suggested that the presence of anatomical substrate is related to LPAF. The aim of the present study is to determine whether structural and functional remodeling of the left atrium (LA) occurs in patients with LPAF, and to identify whether frequent episodes of atrial fibrillation (AF) contribute to LA remodeling. Methods and Results: Forty‐five patients who diagnosed as LPAF and age‐, gender‐, and body mass index‐matched healthy control subjects (n = 45) were enrolled. Patients were grouped based on the frequency of AF episodes. An echocardiography was performed >2 weeks after last episode of AF without antiarrhythmic drugs. There were no statistical differences in left ventricular (LV) diastolic and systolic functions as well as baseline characteristics between patients and controls, whereas, patients had significantly larger LA volume (LAV), lower active LA emptying fraction (LAEF_active, P = 0.009) and total LAEF (LAEF_total, P = 0.005) compared with controls. Passive LAEF (LAEF_passive) was not different between patients and controls (P = 0.664). LAEF_active was significantly depressed in patients with frequent episodes of AF than the others (P = 0.034). Conclusions: Compared with healthy controls, patients with LPAF had increased LAV and depressed LAEF_active and LAEF_total without accompanying compensatory increase in LAEF_passive. LAEF_active was influenced by frequent episodes of AF. These findings may support the hypothesis that LPAF is “not‐so‐lone AF” and related to the concealed cardiac dysfunctions. (Echocardiography 2011;28:44‐51)     

ZV1,ZV5导联心室晚电位的检出率及临床意义

用Ｘ、Ｙ、Ｚ正交导联和改良的ＺＶ１、ＺＶ５导联，对３８例室性早搏病人进行心室晚电位检测。结果显示ＺＶ１、ＺＶ５导联法晚电位阳性率明显高于Ｘ、Ｙ、Ｚ正交导联法（ｕ＝４．６９，Ｐ〈０．０１），改进、弥补了Ｘ、Ｙ、Ｚ正交导联对晚电位“稀释”的不足。用ＤＣＧ同时记录，发现ＺＶ１导联法晚电位阳性与右室起源的早搏有关；ＺＶ５导联法记录的晚电位与左室起源的早搏有关。显示改良的ＺＶ１、ＺＶ５导联与传统的Ｘ、Ｙ、Ｚ