Electrophysiological mechanism of combination therapy with disopyramide and propranolol for paroxysmal atrial fibrillation

OBJECTIVES: Combined administration of propranolol and disopyramide treatment often leads to better results in patients with atrial fibrillation refractory to only disopyramide administration. The electrophysiological mechanism of this combination therapy was investigated. METHODS: Nineteen patients with paroxysmal atrial fibrillation without organic heart disease were studied. The indices for atrial vulnerability were compared in the control state, 10 min after injection of disopyramide (2 mg/kg) and 10 min after additional administration of propranolol (0.2 mg/kg). RESULTS: Administration of both drugs did not significantly change the percentage fragmented atrial activity and the interatrial conduction delay. Disopyramide increased the atrial effective refractory period and the wavelength index, defined as the ratio of the atrial effective refractory period to the interatrial conduction delay and represented the length of the reentry circuit. Additional injection of propranolol caused further increases in both values. CONCLUSIONS: Combination therapy with disopyramide and propranolol improves atrial vulnerability by increasing the wavelength.     

Acute effect of disopyramide on atrial fibrillation in the Wolff-Parkinson-White syndrome

Disopyramide was administered intravenously to 54 patients during atrial fibrillation and predominantly pre-excited QRS configuration at the time of electrophysiologic study. All patients had Wolff-Parkinson-White syndrome and no patient had coexistent heart disease. The drug was given during sustained atrial fibrillation (n = 45) or during sinus rhythm before induction of atrial fibrillation for patients whose atrial fibrillation was self-terminating in the control state (n = 9). Atrial fibrillation converted to sinus rhythm within 15 min after disopyramide in 37 (82%) of the 45 patients. The shortest RR intervals between two pre-excited cycles increased from 208 +/- 42 to 293 +/- 117 ms (p less than 0.0001). The average RR interval of all cycles prolonged from 332 +/- 60 to 396 +/- 117 ms(n = 45, p less than 0.0001). The 9 patients in whom pre-excitation was abolished after the drug had a significantly longer initial shortest RR interval than that of the 36 patients in whom pre-excitation persisted (246 +/- 47 versus 199 +/- 36 ms, p = 0.0022). No patients developed significant hemodynamic or other adverse effects after disopyramide. These data support the intravenous use of disopyramide in patients with normal ventricular function who have atrial fibrillation and a predominant ventricular response over an accessory atrioventricular pathway.     

Effect of disopyramide on initiation of atrial fibrillation and relation to effective refractory period

Electrophysiologic studies were performed before and after intravenous administration of disopyramide (2 mg/kg) to 40 patients with either documented or suspected atrial fibrillation (AF). In control studies, sustained AF (greater than 1 minute), nonsustained AF (1 to 60 seconds) and no AF were found in 14, 18 and 8 patients, respectively. After disopyramide, the ability to initiate AF was totally lost in 18 patients (group A), while 22 patients (group B) showed sustained AF (11 patients) or nonsustained AF (11 patients). The effective refractory period of the atrium was 232 +/- 41 ms in the control study and 266 +/- 49 ms after disopyramide. Atrial functional refractory periods before and after disopyramide were 282 +/- 43 and 317 +/- 48 ms, respectively. The differences and ratios of the refractory periods after and before disopyramide were higher in group A than in group B (p less than 0.001). The prolongation of atrial refractoriness after disopyramide was important to suppress the initiation of AF in group A. In some group B patients, on the other hand, the initiation of AF was promoted after disopyramide. Disopyramide may alter the atrial electrophysiologic substrate required for AF initiation.     

Effects of oral repetitive loading of disopyramide on acute-onset atrial fibrillation with concurrent monitoring of serum drug concentration

We investigated the efficacy and safety of oral repetitive loading of disopyramide, for the termination of acute-onset (i.e., therapy started within 2 days after the onset of palpitations) atrial fibrillation (AF) in 96 consecutive patients, with concurrent monitoring of the serum concentration of this agent in fifteen of the patients. Outpatients with AF verified by standard electrocardiogram (ECG) were hospitalized and received disopyramide (200 mg) every 4-6 h, with a maximal dose of 800 mg daily, until the termination of AF under ECG monitoring was obtained. Conversion to sinus rhythm occurred within the first day of treatment in 88 patients (92%), on the second day of treatment in six patients (6%), and on the third and fifth days of treatment in the remaining two patients. No major adverse effects, such as hypotension, congestive heart failure, proarrythmic events or systemic embolism were noted. The serum levels of disopyramide evaluated in fifteen of the enrolled patients were found to be maintained within the therapeutic range throughout the treatment period. In spite of the absence of any placebo-controlled group in this study, these findings suggest that repetitive oral loading of disopyramide (200 mg) with an interval of 4-6 h is effective and safe for the termination of acute-onset AF under a stable therapeutic serum drug concentration, hence offering the possibility of self-medication for patients with episodic AF.     

Predictors of atrial fibrillation recurrence in patients with long-lasting atrial fibrillation

BACKGROUND:

Limited data are available on the predictors of atrial fibrillation (AF) recurrence in patients with chronic AF.

OBJECTIVES:

To evaluate potential clinical, echocardiographic and electrophysiological predictors of AF recurrence after internal cardioversion for long-lasting AF.

METHODS:

A total of 99 consecutive patients (63 men and 36 women, mean age 63.33±9.27 years) with long-standing AF (52.42±72.02 months) underwent internal cardioversion with a catheter that consisted of two defibrillating coils. Shocks were delivered according to a step-up protocol. Clinical follow-up and electrocardiographic recordings were performed on a monthly basis for a 12-month period or whenever patients experienced symptoms suggestive of recurrent AF.

RESULTS:

Ninety-three patients (93.94%) underwent a successful uncomplicated cardioversion, with a mean atrial defibrillation threshold of 10.69±6.76 J. Immediate reinitiation of AF was observed in 15 patients (15.78%) of whom a repeated cardioversion restored sinus rhythm in 13 cases. Early recurrence of AF (within one week) was observed in 12 of 93 patients (12.90%). At the end of the 12-month follow-up period, during which seven patients were lost, 42 of the 86 remaining patients (48.84%) were still in sinus rhythm. Multivariate regression analysis showed that left atrial diameter (OR 1.126, 95% CI 1.015 to 1.249; P=0.025) and mitral A wave velocity (OR 0.972, 95% CI 0.945 to 0.999; P=0.044) were significant and independent predictors of AF recurrence, whereas age, left ventricular ejection fraction and AF cycle length were not predictive of arrhythmia recurrence.

CONCLUSION:

The present study showed that the left atrial diameter and mitral A wave velocity are the only variables associated with AF recurrence after successful cardioversion.     

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.     

植入型心房除颤器治疗心房颤动的临床应用

目的 评估入型心房除颤器（ｉｍｐｌａｎｔａｂｌｅ ａｔｒｉａｌ ｄｅｆｉｂｒｉｌｌａｔｏｒ,ＩＡＤ）治疗阵发性和持续性心房颤动（房颤）患者的有效性和安全性。方法 １１例患者（８例阵发性房颤,３例持续性房颤）安装了ＩＡＤ,型吨Ｍｅｔｒｉｘ＾ＴＭ３０００和Ｍｅｔｒｉｘ＾ＴＭ３０２０。所有的患者在室功能正常,４５％存在高血压等基础心脏病。ＩＡＤ在识别房颤和心室同步化后,通过右房－冠状静脉窦电流路线,发放     

心房颤动总是"引发"心房颤动吗?

心房颤动(AF)是临床上常见的心律失常,心房重构和AF"引发"AF概念的提出是对AF病理生理机制研究的重大进展,但临床上有关AF的诸多问题并不能都用AF"引发"AF和单纯的心房电重构来解释,本文就AF"引发"AF这一问题结合有关文献作一综述.     

左心房追踪技术评价高血压心房颤动和孤立性心房颤动患者左心房功能

目的应用左心房追踪技术(LAVT)评价高血压心房颤动(房颤)和孤立性房颤患者左心房功能。方法实验组为50例房颤患者,分为孤立性房颤组24例,高血压房颤组26例,对照组为25例健康成人,用M型超声测量左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、舒张末期室间隔厚度(IVSTd)、舒张末期左心室后壁厚度(LVPWTd),用校正立方体积法(Teich)计算左心室射血分数(LVEF);二维超声测量患者收缩末期左心房前后径(LAD1)、上下径(LAD2)、横径(LAD3),收缩末期右心房上下径(RAD1)、横径(RAD2),应用LAVT测量左心房最大面积(LAAmax)、左心房最大容积(LAVmax)、最小容积(LAVmin)、收缩期左心房充盈速率峰值(dv/dtS)、舒张早期左心房排空速率峰值(dv/dtE)及舒张晚期左心房排空速率峰值(dv/dtA),并计算左心房排空分数(LAEF)。比较左心房的收缩及舒张功能。结果孤立性房颤组LAD1:(42.43±4.24)mm、LAD2:(60.22±5.79)mm、LAD3:(47.90±4.86)mm、RAD1:(55.04±5.06)mm、RAD2:(43.25±2.56)mm、LAAmax、LAVmax、LAVmin、dv/dtE与正常对照组LAD1:(33.81±2.96)mm、LAD2:(47.29±6.79)mm、LAD3:(39.04±3.53)mm、RAD1:(44.34±4.12)mm、RAD2:(36.06±3.16)mm、LAAmax、LAVmax、LAVmin、dv/dtE比较均明显升高(均为P<0.05),孤立性房颤组LAEF、dv/dtS、dv/dtA与正常对照组比较均明显减低(均为P<0.05),LVEDD、LVESD、IVSTd、LVPWTd、LVEF与正常对照组比较差异均无统计学意义(均为P>0.05)。与正常对照组比较,高血压房颤组的LAD1:(45.47±7.33)mm、LAD2:(61.35±7.39)mm、LAD3:(49.27±5.25)mm、RAD1:(56.18±4.36)mm、RAD2:(45.13±3.21)mm、LAAmax、LAVmax、LAVmin、dv/dtE均明显升高,LAEF、dv/dtS、dv/dtA均明显减低(均为P<0.05),LVEDD、LVESD、IVSTd、LVPWTd、LVEF差异均无统计学意义(均为P>0.05)。与孤立性房颤组相比,高血压房颤组LAAmax、LAVmax、LAVmin均明显升高(均为P<0.05),LAEF、dv/dtS、dv/dtE、dv/dtA均明显减低(均为P<0.05),LVEDD、LVESD、IVSTd、LVPWTd、LVEF、LAD1、LAD2、LAD3、RAD1、RAD2差异均无统计学意义(均为P>0.05)。结论 AF患者左心房功能明显下降高血压房颤患者左心房功能损害较孤立性房颤患者明显。LAVT能准确、快速的反映房颤患者左心房大小及功能的变化,在评价左心房功能方面有较高的重复性。     

Electroanatomic characteristics of atrial premature beats triggering atrial fibrillation in patients with persistent versus paroxysmal atrial fibrillation

APBs in Persistent Versus Paroxysmal AF. BACKGROUND: Although the electrical disconnection between the left atrium (LA) and pulmonary veins (PVs) by radiofrequency catheter ablation has been proven to be effective in controlling atrial fibrillation (AF), the recurrence rate is higher in patients with persistent AF (PeAF) than with paroxysmal AF (PAF). We hypothesized that the origin of the atrial premature beats (APBs) that trigger AF and the pattern of their breakthrough into the LA differ between PAF and PeAF. METHODS: We mapped 75 APBs (53 APBs triggering AF, 22 isolated APBs) from the LA and PVs in 26 patients with AF (age: 49.5 +/- 9.6, males: 23, PAF = 17, PeAF = 9), using a noncontact endocardial mapping (NCM) system. The location of the preferential conduction (PC) sites and their conduction velocity (CV) were compared. RESULTS: In patients with PeAF, the earliest activation (EA) site and exit of the PC were more frequently located on the LA side of the LA-PV junction as compared with PAF (P < 0.001). Eighty-one percent of the PCs were located in the area between the left and right superior PVs. The incidence of PCs was similar between the PeAF and PAF patients (P = NS). PCs were more commonly found with APBs inducing AF (63.3%) than with those not inducing AF (35.2%, P = 0.01). The CV of the PC was slower for PeAF than PAF (P < 0.001). The CV in the LA during sinus rhythm was also slower for PeAF than PAF (P < 0.01). CONCLUSION: PeAF was more frequently triggered by APBs from the LA side of the LA-PV junction than PAF and resulted in slower conduction than did PAF. These findings may help explain the higher potential for recurrence after electrical PV isolation in patients with PeAF.     

Electrophysiology and endocardial mapping of induced atrial fibrillation in patients with spontaneous atrial fibrillation

We analyzed the patterns of atrial activation and characterized the electrophysiologic properties of regional atrial sites in the, right atrium and left atrium at the onset of atrial fibrillation (AF) induced with programmed right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps during AF, and the stability and reproducibility of atrial activation sequences at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of intracardiac electrograms with surface electrocardiographic morphology was attempted. Maximum intraatrial conduction delay for high RA premature beats was observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or interatrial septum (n = 15). The return cycle lengths for the first AF cycle showed increasing conduction delay with increasing prematurity of the last extrastimulus in most patients. Suprisingly, discrete atrial electrograms with regular or irregular cycle lengths were present at the onset of electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p = 0.001). The atrial activation sequence at the onset of the induced AF elicited by high RA extrastimuli usually showed the earliest activation site at the crista terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced AF elicited from other RA sites usually showed earliest atrial activation at the septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation sequences for the first induced AF cycle were usually reproducible in most patients. Atrial activation patterns during the first 10 cycles for AF were stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We conclude that pacing induced AF elicited by RA premature beats commences as a regular or irregular rapid atrial tachycardia consistent with a transitional, but often organized, arrhythmia. The activation sequence and electrophysiologic behavior of the first induced AF cycle is consistent with intraatrial reentry and reproducible in most patients. More than 1 atrial activation sequence can sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant circuits.     

左旋氨氯地平对阵发性房颤并高血压患者房颤的影响

目的观察左旋氨氯地平对阵发性房颤并高血压患者P波离散度（Pd）、左房内径、高敏C反应蛋白（hs—CRP）水平、房颤发作情况的影响。方法将阵发性房颤并高血压患者100例随机分为治疗组（50例）和对照组（50例）。降压药物治疗组给予左旋氨氯地平,对照组给予坎地沙坦,随访1年,观察治疗前后Pd、左房内径、hs—CRP水平及房颤发作情况。结果至随访结束,在长期应用胺碘酮的患者中,对照组房颤复发17例,占81．0％,治疗组房颤复发22例,占95．7％,两组之间差异无统计学意义（x^2=1．122,P〉0．05）。未长期应用胺碘酮的患者,对照组、治疗组在7-12个月时房颤发作次数均较治疗前减少（t=2．823,P〈0．01;t=2．655,P〈0．05）,但两组之间差异无统计学意义（t=0．594,P〉0．05）。与治疗前比较,对照组、治疗组的Pd、左房内径、hs—CRP均降低（t=4．025-13．546,P〈0．01）,治疗后两组之间Pd、左房内径、hs—CRP比较,差异无统计学意义（t=1．234-1．514,P〉0．05）。结论左旋氨氯地平可减少阵发性房颤并高血压患者房颤的复发,降低Pd、左房内径和hs—CRP水平,其效果与坎地沙坦没有差异。     

Relationship between duration of arrhythmia and subsequent preventive effect of disopyramide after cardioversion in patients with symptomatic paroxysmal and persistent atrial fibrillation

OBJECTIVES: The relationship between the duration of arrhythmia and the subsequent long-term efficacy of disopyramide in preventing atrial fibrillation was investigated in patients with symptomatic paroxysmal and persistent atrial fibrillation. METHODS: A total of 60 patients (39 men, 21 women, mean age 65 +/- 11 years) were given disopyramide (300 mg/day) after electrical and pharmacological cardioversion based on American Heart Association Task Force on Practice Guidelines. The patients were divided into two types based on the duration of atrial fibrillation: conversion within 48 hr (group A, n = 35) and more than 48 hr (group B, n = 25) after the episode. Mean follow-up period was 47.1 +/- 28.7 months. RESULTS: Patient characteristics showed no statistically significant difference between groups A and B. The actuarial rates of maintenance of sinus rhythm at 1, 3, 6, 12, 18 and 24 months were 88.6%, 77.1%, 57.1%, 48.6%, 42.9% and 37.1%, respectively, in group A, and 72.0%, 44.0%, 28.0%, 16.0%, 12.0% and 8.0%, respectively, in group B. There was a significant difference in the rate at 24 months between groups A and B (p < 0.05). The periods for maintenance of sinus rhythm in groups A and B were 20.9 +/- 3.9 and 6.7 +/- 2.1 months, respectively, with a significant difference between groups A and B (p < 0.01). CONCLUSIONS: The efficacy of disopyramide in preventing the recurrence of atrial fibrillation varies with the duration of the previous episode. These results demonstrate that it is important to convert to normal sinus rhythm earlier to prevent the recurrence of atrial fibrillation in the long term.     

Postoperative atrial fibrillation in patients with left atrial myxoma

Paroxysmal atrial fibrillation (AF) is the most common arrhythmia following cardiac surgery such as coronary artery bypass grafting (CABG), and often occurs between the second and fourth postoperative days.1,2 The reported incidence of paroxysmal AF after CABG surgery varies widely, from five to 40%, which is lower than in cases of valvular cardiac surgery.3,4 Although this arrhythmia is usually benign and self-limiting, it may also be associated with increased risk of embolic events, haemodynamic instability, haemorrhagic complications, prolonged hospital stay and higher rates of re-admissions, increasing the healthcare costs.5-7Several risk factors have been proposed for paroxysmal AF after CABG or valvular cardiac surgery, such as advanced age, genetic predisposition, chronic obstructive pulmonary disease, heart failure or increased peri-operative ischaemia.8-10 In addition, certain echocardiographic parameters such as left atrial (LA) diameter or left ventricular (LV) function, and electrocardiographic parameters including P-wave duration and P-wave dispersion (Pd) have been shown to be associated with postoperative AF.11-13Although postoperative AF and its predictors after CABG and valvular surgery have been well researched, no study has been performed to explore the incidence or predictors of postoperative AF in patients with LA myxoma. The aim of this study was to identify the prevalence and predictors of postoperative AF in a pure cohort of patients with LA myxoma.