贝那普利联合胺碘酮预防阵发性房颤复发的作用

目的 评价贝那普利联合胺碘酮预防阵发性房颤复发的疗效。方法随机选取阵发性房颤复律后患者66例，分为治疗组（Ⅱ组）32例和对照组（Ⅰ组）34例。Ⅰ组常规口服胺碘酮，Ⅱ组口服胺碘酮加贝那普利，观察12个月。结果Ⅱ组治疗后复发率明显下降并低于对照组（P〈0．05）有显著差异，左房内径亦有显著性缩小。结论 贝那普利联合胺碘酮能更有效预防阵发性房颤复发。     

Efficacy and safety of the additional bepridil treatment in patients with atrial fibrillation refractory to class I antiarrhythmic drugs.

BACKGROUND: Bepridil has multiple ion-channel blocking effects and is expected to be useful for managing atrial fibrillation (AF). The purpose of this study was to clarify the efficacy and safety of additional treatment with bepridil in patients with AF who had been treated with class I antiarrhythmic drugs (AADs). METHODS AND RESULTS: Bepridil (50-200 mg/day) was given to 76 patients with either paroxysmal (n=49) or persistent AF (n=27). All patients had been treated with class I AADs (1.9+/-0.9 drugs/patient) that failed to control the AF. With the addition of bepridil, the frequency of symptomatic AF episodes decreased to less than 10% in 38 (78%) patients with paroxysmal AF, and sinus rhythm was restored within 3 months and maintained during the follow-up in 20 (74%) patients with persistent AF. Efficacy was usually obtained with a small to moderate dose (50-150 mg/day) of bepridil. During a mean follow-up period of 27+/-22 months, no potential complications occurred in any of the patients. CONCLUSIONS: The addition of bepridil to class I AADs is effective and safe for AF, but careful observation using periodic ECG recordings is essential for avoiding torsades de pointes caused by QT prolongation.     

胺碘酮与普罗帕酮治疗老年阵发性心房颤动疗效与安全性研究

目的 探讨胺碘酮与普罗帕酮治疗老年阵发性心房颤动的疗效与安全性.方法 106例阵发性房颤患者随机分成胺碘酮治疗组和普罗帕酮治疗组,分别为54例和52例,随访1年,观察两组治疗前后房颤复发情况及左房内径的变化.结果 胺碘酮治疗组预防老年阵发性房颤复发3m的总有效率为88.9％,6m的总有效率为77.8％,9m的总有效率为74.1％,12 m的总有效率为70.4％;普罗帕酮治疗组3m的总有效率为73.1％,6m的总有效率为63.5％,9m的总有效率为57.7％,12m的总有效率为53.8％;胺碘酮治疗组左房内径在治疗前后发生了变化（P＜0.05）;两组药物长期应用不良反应均较为少见.结论 胺碘酮在老年阵发性房颤的治疗比普罗帕酮相对有效,两组药物合理使用不良反应均较低.     

Long-term prognosis of patients with paroxysmal atrial fibrillation depends on their response to antiarrhythmic therapy.

BACKGROUND: The rhythm control treatment strategy for persistent atrial fibrillation (AF) has been shown not to improve quality of life or prognosis any more than rate control. It is unclear whether the prognosis of the patients with paroxysmal AF (PAF) is influenced by the response to antiarrhythmic drug therapy (AAT). METHODS AND RESULTS: The relationship between the response to AAT and long-term prognosis was evaluated in 290 patients with PAF (mean age, 69 years). During a mean follow-up period of 51 months, 114 patients (39%) had no recurrence of AF (Group 1), 113 (39%) had repeated AF recurrence (Group 2), and the remaining 63 (22%) had permanent AF despite AAT (Group 3). The survival rate without any cardiovascular deaths at 60 months was 99% in Group 1, 95% in Group 2 and 94% in Group 3 (p=NS among 3 groups). Survival rate without symptomatic ischemic stroke was 99% in Group 1, 88% in Group 2 and 76% in Group 3 (p<0.05 Group 1 vs Groups 2 and 3). The annual rate of stroke in the patients with warfarin treatment was similar among the 3 groups, whereas that in the patients without warfarin was higher in Groups 2 and 3 than in Group 1. CONCLUSIONS: Long-term prognosis of patients with PAF varies with the response to AAT: When sinus rhythm is maintained, the prognosis is good even without anticoagulation therapy.     

Atrial septal pacing in the prevention of paroxysmal atrial fibrillation refractory to antiarrhythmic drugs

BACKGROUND: Early reports have shown that pacing the atria at a site or sites other than the right atrial appendage may prevent atrial fibrillation. Our centre has shown that pacing the atrial septum reduces the duration of atrial activation which is an important determinant of predisposition to paroxysmal atrial fibrillation. Ablation of the atrioventricular (AV) node together with implantation of a pacemaker can control symptoms due to paroxysmal atrial fibrillation in patients in whom antiarrhythmic drugs have failed. The aim of this study was to investigate the effect of atrial septal pacing on patients who were candidates for AV node ablation. METHODS: Atrial septal pacemakers were implanted in 28 patients with symptomatic, paroxysmal atrial fibrillation that had been unresponsive to two or more antiarrhythmic drugs. Pacing was not indicated for any reason other than the anticipated need to proceed to AV node ablation. Change in symptoms was assessed by quality of life questionnaires and recurrence of atrial fibrillation was measured objectively by pacemaker interrogation and ambulatory electrocardiographic monitoring. RESULTS: Atrial septal pacing in combination with an antiarrhythmic agent resulted in a substantial subjective improvement in 19 patients (68%). Objective data confirmed similar findings; atrial fibrillation was completely or markedly reduced in 17 patients (60%). Six patients experienced a modest improvement in symptoms; in only four patients was it necessary to proceed to AV node ablation. CONCLUSIONS: Atrial septal pacing together with continuance of previously ineffective antiarrhythmic therapy may prevent or markedly reduce the frequency of paroxysmal atrial fibrillation and obviate the need to ablate the AV node.     

Long-term efficacy of amiodarone therapy for the prevention of recurrence of paroxysmal atrial fibrillation. Analysis based on patient characteristics

There is little information available on factors affecting the long-term prevention of paroxysmal atrial fibrillation (AF) in the Japanese population. A total of 71 patients (49 men, mean age, 68 ± 8 years) with paroxysmal AF refractory to ≥ 2 class I antiarrhythmic drugs received oral amiodarone (50-200 mg/day). All patients were observed for more than 12 months (mean follow-up period, 47 ± 26 months) and were analyzed on the basis of patient profiles. The percentage of patients with AF recurrence despite amiodarone therapy was 54% in all patients. In multivariate logistic regression analysis adjusted for age and sex, the following factors were associated with preventive efficacy for AF recurrence: left ventricular ejection fraction (LVEF) (relative risk [RR] 0.933, 95% confidence interval [CI] 0.877-0.993, P = 0.029), asymptomatic AF (RR 0.068, CI 0.005-0.870, P = 0.039), and AF occurring irrespective of circadian variation (RR 0.115, CI 0.013-0.988, P = 0.049). The percentage of patients with conversion to permanent AF despite amiodarone therapy was 31% in all patients. In multivariate logistic regression analysis adjusted for age and sex, asymptomatic AF (RR 0.085, CI 0.010-0.732, P = 0.025) was the only factor associated with preventive efficacy for conversion to permanent AF. Amiodarone appears to be effective in maintaining sinus rhythm, especially in patients with impaired left ventricular function. In contrast, amiodarone appears to be refractory in those with asymptomatic AF or AF occurring irrespective of circadian variation.     

胺碘酮与氯沙坦、培哚普利联合治疗阵发性心房颤动的前瞻、随机开放研究

目的 评价氯沙坦和培哚普利与小剂量胺碘酮联合治疗心功能正常的阵发性心房颤动（房颤）维持窦性心律的长期疗效.方法 将181例阵发性房颤随机分为胺碘酮组（Ⅰ组,n=61）、胺碘酮＋氯沙坦组（Ⅱ组,n=59）,胺碘酮＋培哚普利组（Ⅲ组,n=61）,治疗随访时间为2年,研究的一级终点为房颤复发.比较三个组治疗后的窦性心律维持率以及治疗前、治疗后6、12、18和24个月的左心房内径.结果 治疗12个月后,Ⅰ组左心房内径大于Ⅱ组和Ⅲ组（P＜0.05）.治疗7个月后,Ⅰ组窦性心律的维持率明显低于Ⅱ组和Ⅲ组（P＜0.05）,而Ⅱ组和Ⅲ组间差异无统计学意义.试验终点时,Ⅰ组的窦性心律维持率为59.01%,Ⅱ组为83.05%,Ⅲ组为80.33%（P＜0.05）.Ⅲ组刺激性干咳的发生率明显高于Ⅰ组和Ⅱ组,而持续性窦性心动过缓和QT间期≥0.5 s的发生率三组间差异无统计学意义.结论 胺碘酮分别与氯沙坦和培哚普利联合治疗阵发性房颤,维持窦性心律的疗效间差异无统计学意义,但优于单用胺碘酮,并能抑制左心房的扩大.     

静脉注射胺碘酮转复阵发性房颤的疗效观察

目的观察阵发性房颤伴快速心室率患者静脉注射胺碘酮的有效性和安全性。方法对阵发性房颤伴快速心室率的64例器质性心脏病患者,首次静脉注射胺碘酮150mg,15min后无效时重复应用,然后用微泵静脉维持1mg/min,6h后改为0.5mg/min维持18h。结果负荷量为150～300(198±46)mg,转复成功率为78.1%,副作用发生率9.4%。结论静脉注射胺碘酮治疗并发器质性心脏病的阵发性房颤伴快速心室率是有效、较安全的。     

胺碘酮治疗急性心肌梗塞与非急性心肌梗塞伴阵发性房颤的疗效

目的:评价急性心肌梗塞(AMI)与非急性心肌梗塞伴阵发性心房颤动(PAF)静脉应用胺碘酮的疗效。方法:选择23例AMI及20例非AMI伴PAF患者,应用胺碘酮5mg/kg的负荷量后,给予10～20mg/kg.d维持,24h量不超过2200mg。结果:房颤转复率:AMI组100%,非AMI组70%(14/20),差异有显著性(P<0.05);转复时间:AMI组(2063±140)min,非AMI组(215±138)min,两组差异无统计学意义(P<0.05)。结论:胺碘酮治疗AMI并发阵发性房颤患者转复率高,安全、可靠,可作为首选用药。     

螺内酯联合胺碘酮治疗非瓣膜病阵发性心房颤动的临床研究

目的观察螺内酯联合胺碘酮治疗非瓣膜病阵发性心房颤动的效果。方法68例非瓣膜病阵发性心房颤动患者，随机分为合用组（螺内酯加胺碘酮）32例及单用组（单用胺碘酮）36例。两组均常规给予胺碘酮，合用组在此基础上加用螺内酯20mg／d，观察6个月，观察两组的左心房内径、复发率及不良反应。结果合用组的左心房内径较单用组减小[（36．3±6．56）mm比（45．2±7．43）mm]，两组比较差异有统计学意义（P〈O．05）。合用组复发率28．1％（9／32），单用组复发率52．8％（19／36），两组比较差异有统计学意义（P〈O．05）。结论螺内酯联合胺碘酮可抑制左心房结构重构，减少阵发性房颤的复发。     

Clinical profiles, efficacy of antiarrhythmic drug therapy, and cardiovascular prognosis in patients with first detected paroxysmal atrial fibrillation

Little information is available concerning clinical profiles and outcomes of treatment in Japanese patients with first detected atrial fibrillation (AF). In the present study, 459 patients with paroxysmal AF (309 males, mean age, 66 ± 12 years) were divided into a first detected AF group (group A, n = 143) and a non-first detected AF group (group B, n = 316). Clinical profiles, prophylactic efficacy of antiarrhythmic drug therapy (AAD), and cardiovascular prognosis during a mean follow-up period of 50 ± 35 months were compared between the two groups. The number of AF recurrences in the individual patients regardless of AAD were significantly lower in group A than in group B (0.8 ± 1.4 versus 1.7 ± 1.9)(P < 0.05). The percentages of patients free from conversion to chronic AF at 12, 36, 60, and 120 months were significantly higher in group A (98%, 96%, 93%, and 91%, respectively) than in group B (95%, 86%, 83%, and 79%, respectively)(P < 0.01). The annual rates of hospitalization for thromboembolism, heart failure, and cardiovascular death did not differ between group A (2.2%, 1.1% and 1.0%, respectively) and group B (2.2%, 1.9% and 1.1%, respectively). In multivariate logistic regression analysis, a CHADS? score ≥ 2 points (odds ratio 13.1, 95% confidence interval 3.36-51.0, P = 0.001), nocturnal AF onset (OR 0.201, 95% CI 0.050-0.815, P = 0.025), left ventricular diastolic dimension (LVDd) ≥ 50 mm (OR 3.845, 95% CI 1.078-13.71, P = 0.038), and conversion to chronic AF (OR 3.547, 95% CI 1.002-13.64, P = 0.048) were associated with cardiovascular events in group A. Rhythm control therapy with antiarrhythmic drugs was shown to be more effective for patients in group A than in group B. It is particularly important to prevent cardiovascular events in first detected AF patients with a CHADS? score ≥ 2 points, LVDd ≥ 50 mm, and conversion to chronic AF.     

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.     

Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation

To determine whether treatment with antiarrhythmic drugs could be cost-effective in preventing thromboembolic events in patients with paroxysmal atrial fibrillation (AF), 4 groups of patients without prior thromboembolism were studied. Group A: 193 patients with paroxysmal AF receiving antiarrhythmic drugs, but not antiplatelets or warfarin; Group B: 228 patients with paroxysmal AF not receiving antiarrhythmics, antiplatelets or warfarin; Group C: 284 patients with chronic AF receiving warfarin; Group D: 394 patients with chronic AF not receiving antiplatelets or warfarin. Direct costs for treatment of AF were determined. During a follow-up period of 4.6 years, the prevalence of thromboembolic episodes was lower by 70% in Group A and by 47% in Group C than in each control group. To prevent one thromboembolic event annually with antiarrhythmic drugs in patients with paroxysmal AF, an extra cost of 6.16 million yen was required. This less favorable cost-effectiveness was mainly because of physician's preference for new antiarrhythmic drugs. In contrast, treatment with warfarin required an extra cost of 1.09 million yen to prevent one thromboembolic event annually in patients with chronic AF. Antiarrhythmic drugs are less cost-effective in preventing thromboembolic events in patients with paroxysmal AF when new, expensive drugs are preferentially selected.     

阵发性心房颤动患者心房及肺静脉不应期离散度的变化

目的探讨阵发性房颤患者房颤相关组织的电生理特性改变情况。方法选取阵发性房颤患者10例(房颤组)和无房颤病史的左侧旁路有显性预激波患者15例(对照组)。将大头电极分别放置在两组患者左上肺静脉、左下肺静脉、右上肺静脉、右下肺静脉开口及左心房顶壁、前壁、后壁、高位右心房,分别测定各部位有效不应期(EPR)。结果①房颤组心房及肺静脉EPR离散度指数(DI)为0.117±0.028,对照组为0.074±0.029,两组比较,P<0.05。②房颤组左心房ERP为(234.00±28.72)ms,肺静脉ERP为(230.75±32.69)ms;对照组左心房ERP为(248.00±25.99)ms,肺静脉ERP为(244.33±26.78)ms,两组比较,P均<0.05。结论阵发性房颤患者DI明显增大,左心房、肺静脉ERP显著缩短。     

Effect of clonazepam and antiarrhythmic drugs on heart rate variability in patients with paroxysmal atrial fibrillation

AIM: To study direction and intensity of autonomic changes in patients with paroxysmal atrial fibrillation (PAF) treated with clonazepam and their dynamics during antiarrhythmic therapy. MATERIAL: Patients with nonrheumatic PAF during effective clonazepam monotherapy or ineffective antiarrhythmic therapy (n=95), untreated patients with PAF (n=22), healthy persons (n=10). METHODS: Clinical cardiological and neurological examination, assessment of the state of autonomic nervous system, emotional sphere, patterns of sleep, and spectral analysis of heart rate variability (HRV). RESULTS: Effective monotherapy with clonazepam was associated with clinical and psychovegetative improvement, positive changes of autonomic tone and normalization of vegetative support of activity of patients with PAF. Analysis of HRV showed that ineffective (insufficiently effective) antiarrhythmic therapy was associated with stabilization of cardiac rhythm and domination of ergotropic activation which correlated with severity of psychovegetative syndrome. This could be considered as indication for supplementary use of clonazepam. CONCLUSION: Analysis of HRV confirmed expediency of the use of clonazepam in patients with PAF both as monotherapy and in combination with ineffective antiarrhythmic therapy.     

伊布利特治疗阵发性房颤的疗效及安全性

目的：观察新型Ⅲ类抗心律失常药物伊布利特转复心房纤颤的疗效。方法：选择32例房颤患者,随机分为两组：伊布利特组（18例）,伊布利特1mg,于15min内静注,如无效30min后再给予1mg静注;胺碘酮组（14例）,胺碘酮150mg,于15min内静注,如无效30min后再给予150mg静注。观察两组房颤转复情况及时间。结果：伊布利特组90min内转复房颤率明显高于胺碘酮组（77．8％比28．6％）,4h内转复房颤率亦明显高于胺碘酮组（100％比71．4％）,P〈0．01。结论：伊布利特是一种转复房颤的快速、安全、有效的药物。     

Long-term efficacy of combination therapy using antiarrhythmic agents and angiotensin converting enzyme inhibitor in patients with paroxysmal and persistent atrial fibrillation: importance of the timing of administration

OBJECTIVES AND METHODS: This study examined the long-term efficacy of combination therapy using antiarrhythmic agents and angiotensin converting enzyme inhibitor (ACE-I) to maintain sinus rhythm in patients with paroxysmal and persistent atrial fibrillation (Paf). There were 246 patients (176 men, 70 women, mean age 67.3 +/- 11.7 years, mean follow-up period 48.9 +/- 29.3 months) divided into two groups: the ACE-I(+) group (n = 74) and the ACE-I(-) group (n = 172). RESULTS: The incidence of hypertension and underlying heart disease in the ACE-I(+) group (85.1% and 34.3%, respectively) was significantly higher than those in the ACE-I(-) group (37.8% and 25.0%, respectively) (both p < 0.01). Left ventricular ejection fraction in the ACE-I(+) group (65.6 +/- 12.5%) was significantly lower than that in the ACE-I(-) group (71.9 +/- 8.9%) (p < 0.01). The actuarial rate of the maintenance of sinus rhythm at 48 months in the ACE-I(+) group (86.5%) was similar to that in the ACE-I(-) group (83.1%). Among the 104 patients who had suffered from Paf for < 3 months after the first episode, the actuarial rate of maintenance of sinus rhythm at 48 months in the ACE-I(+) group (97.1%, n = 35) was significantly higher than that in the ACE-I(-) group (82.6%, n = 65), and the period of maintenance of sinus rhythm in the ACE-I(+) group (54.8 +/- 30.8 months) was significantly longer than that in the ACE-I(-) group (28.4 +/- 20.5 months) (both p < 0.05). CONCLUSIONS: ACE-I must be additionally administered within 3 months of the first Paf episode to maintain normal sinus rhythm in patients with Paf.