Prospective, randomized study of atrioventricular ablation and mode-switching, dual chamber pacemaker implantation versus medical therapy in drug-resistant paroxysmal atrial fibrillation. The PAF study. Paroxysmal Atrial Fibrillation.

We performed a prospective randomized 6-month evaluation of the clinical effects of atrioventricular junctional ablation together with placement of a DDDR mode-switching pacemaker vs pharmacological treatment in 43 patients with intolerable paroxysmal atrial fibrillation not controlled with antiarrhythmic drugs. Ablation and pacemaker treatment were highly effective and superior to drug therapy in controlling symptoms and improving quality of life. However, discontinuation of drug therapy exposed patients to further recurrences of paroxysmal atrial fibrillation and the risk of developing permanent atrial fibrillation.     

Catheter ablation or modulation of the AV node

The ablate and pace strategy may be considered a viable therapy in the palliative management of patients with medically refractory highly symptomatic atrial fibrillation (AF). The overall success rate is approaching 100%, the inhospital course is usually event free, and the procedure is a relatively safe therapeutic option. There is no doubt that one of the major findings after atrioventricular (AV) node ablation is the significant reduction of cardiac symptoms and health care use, while exercise tolerance and quality of life significantly improved after the procedure. It is also well accepted that catheter ablation and pacemaker (PM) implantation are usually associated with significant improvement in left ventricular ejection fraction, particularly in patient with AF and reduced systolic function at baseline. On the other hand, AV node ablation seems unlikely to have a negative effect on long term survival. The mortality rate in some reports have raised concerns about excess deaths (mainly sudden deaths) attributable to AV node ablation and pacing therapy. These findings are not confirmed by recent data.Modulation of the AV node has been more recently introduced in the clinical practice in order to avoid permanent complete AV block and lifetime PM dependency. AV node modulation procedure is effective in 70% of cases. The short duration of following periods does not allow to draw definitive conclusions concerning the potential evolution of AV node conduction disorders.Both AV node ablation and AV node modulation, when successful, are effective means to improve quality of life and cardiac performance in patients with medically refractory AF. The exact place of these procedures is, today, a matter of debate which is more controversial in patients with paroxysmal AF than with uncontrolled permanent AF.     

射频消融房室交界区和植入起搏器治疗心房颤动

目的 对9例阵发性心房颤动(房颤)和8例慢性房颤患者行房室交界区消融和植入起搏器(Abl+Pm)治疗,探讨这一方法的临床治疗效果。方法 经右股静脉植入4极电极导管于右心室心尖部和4极大头消融导管至房室交界区,于记录到希氏束电位处放电消融,直至出现三度房室阻滞,然后植入VVI或DDD起搏器。结果 所有患者均成功阻断房室交界区并植入起搏器。8例慢性房颤患者植入VVI起搏器,术后血流动力学稳定、临床症状改善,3个月后心胸比例由原来的0.62±0.04缩小为0.57±0.05,差异有显著性(P<0.05),心功能(NYHA分级)均提高Ⅰ级以上;9例阵发性房颤患者中,8例植入VVI起搏器,1例植入DDD起搏器,房颤发作时,8例无临床症状,1例仅有轻微心悸。随访1～47个月,无1例出现起搏器综合征、栓塞和心功能恶化。结论 房颤患者的Abl+Pm治疗可有效控制临床症状、改善心功能和提高生活质量。     

房室结消融及起搏器治疗改善心房颤动患者心功能和生活质量的研究

探讨房室结消融 +VVIR起搏器 (ABL +PM)治疗对永久性心房颤动 (简称房颤 )患者生活质量、心功能的改善及评估该治疗的安全性。选择 30例永久性房颤患者 ,14行例ABL +PM治疗 ,16例行药物治疗。治疗前及治疗后 12个月所有患者均做GWB和CSS生活质量评分 ,心脏超声测左室内径及射血分数值 ,活动平板测运动耐力 ,用Holter记录最快、最慢心率。并观察治疗后临床事件的发生。结果 :永久性房颤患者ABL +PM或药物治疗前、后组内比较 ,患者心室率、心功能、运动耐力及生活质量均得到改善 (P <0 .0 5 ) ;但ABL +PM组左室内径缩小 (P <0 .0 5 ) ,药物治疗组无改变 (P >0 .0 5 )。ABL +PM或药物治疗后 12个月组间比较 ,ABL +PM组心室率控制、左室内径、心功能、运动耐力及生活质量改善优于药物组 (P <0 .0 5 )。再次住院人次ABL +PM组较药物组减少 (P <0 .0 5 ) ,死亡、恶性室性心律失常和血栓栓塞事件两组无差异 (P >0 .0 5 )。结论 :ABL +PM或药物治疗均能改善永久性房颤患者心功能、运动耐力及生活质量 ,但ABL +PM优于药物治疗。ABL +PM是一种简单易行安全的治疗方法。     

Chronic atrial fibrillation in patients with paroxysmal atrial fibrillation, atrioventricular node ablation and pacemakers: determinants and treatment.

AIMS: This study examined the factors associated with the development of chronic (or permanent) atrial fibrillation (AF) in patients who had undergone atrioventricular (AV) node ablation with permanent pacing because of paroxysmal AF. METHODS: A retrospective review of case notes of all 65 consecutive patients identified as having had paroxysmal atrial arrhythmias, AV node ablation and permanent pacemaker implantation was performed. Atrial rhythm was established from all pacing records and from the surface ECG. Treatment with anti-arrhythmic drugs and with warfarin was recorded. A multivariate analysis was undertaken, using atrial rhythm on final ECG and chronic AF as outcome measures. RESULTS: During a mean follow-up of 30 months, 42% of patients with paroxysmal AF had developed chronic AF. Multivariate analysis showed that increasing age, history of electrical cardioversion and VVI pacing all contributed to the development of chronic AF. 25/62 patients were taking warfarin, and four had had strokes (2.5%/year). CONCLUSION: The majority of patients with paroxysmal atrial arrhythmias treated with AV node ablation and pacing develop chronic AF eventually. Stroke remains a risk, particularly in those who develop chronic AF.     

Cholesterol lowering and coronary artery disease: mechanisms of risk reduction

OBJECTIVE: To assess the effect of atrioventricular node ablation and implantation of a dual chamber, mode switching pacemaker on quality of life, exercise capacity, and left ventricular systolic function in patients with drug refractory paroxysmal atrial fibrillation. PATIENTS: 18 consecutive patients with drug refractory paroxysmal atrial fibrillation. METHODS: Quality of life was assessed before and after the procedure using the psychological general wellbeing index (PGWB), the McMaster health index (MHI), and a visual analogue scale for cardiac symptoms. Nine of the patients also underwent symptom limited exercise tests and echocardiography to assess left ventricular systolic function. RESULTS: The procedure allowed a reduction in antiarrhythmic drug treatment (p < 0.01). PGWB and symptom scores improved (p < 0.01) but the MHI score did not change. Left ventricular systolic function and exercise capacity were unchanged. CONCLUSIONS: Atrioventricular node ablation and implantation of a DDDR/MS pacemaker is effective treatment for refractory paroxysmal atrial fibrillation, producing improved quality of life while allowing a reduction in drug burden. The popularity of the treatment is justified, but further studies are needed to determine optimum timing of intervention.     

房室结消融联合起搏治疗老年永久性房颤患者的初步探讨

目的观察房室结消融联合起搏治疗与正规药物治疗对老年房颤患者心功能及生存质量的影响。方法选择2003年7月至2006年7月在两家3级甲等医院心内科住院且未正规口服抗心律失常药物治疗的老年永久性房颤患者52例。将患者分成两组,其中10例接受房室结射频消融联合起搏手术治疗(手术组),42例接受正规药物治疗(药物组)。采用心脏超声测量心功能,在常规二维超声切面上测量心输出量(CO)、心脏指数(CI)、每搏输出量(SV)、心搏出量指数(SVI)、左室射血分数(LVEF)。以中文版简明健康调查问卷SF-36,评估患者生存质量。首次问卷调查及心功能检查在入院后进行,随访调查在正规药物治疗6个月及起搏手术治疗后6个月进行。采用配对t检验、两个独立样本的秩和检验进行统计学分析。结果老年永久性房颤患者房室结消融联合起搏治疗与常规药物治疗后比较,患者心功能及生存质量各项指标均得到改善(P<0.01);两组组间比较分析,差异均无统计学意义(P>0.05)。结论房室结消融联合起搏治疗与药物治疗均能改善老年房颤患者的心功能及生存质量。     

Atrial fibrillation in the elderly

Atrial fibrillation is the most common arrhythmia in the United States, whose incidence is greatest in the elderly population. This rhythm disorder can be paroxysmal or chronic and is associated with a range of clinical conditions from palpitations and dyspnea to stroke and death. In the elderly the mainstay of treatment of atrial fibrillation should utilize drug therapy. The main goals of drug therapy should be effective rate control to avoid tachycardia-induced cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism, and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those patients in whom effective rate control cannot be achieved, catheter ablation of the atrioventricular node and implantation of a permanent pacemaker should be considered. Catheter ablation of atrial fibrillation by targeting pulmonary venous foci or pulmonary venous isolation currently remains investigational and we advocate its use be limited to symptomatic patients who have failed traditional therapy.     

Determinants of development of permanent atrial fibrillation and its treatment.

We evaluated the rate of progression of permanent atrial fibrillation (AF) and identified clinical factors that predict this event in 63 consecutive patients who had undergone AV junctional ablation and DDDR pacemaker implantation for drug-refractory paroxysmal atrial fibrillation/ flutter. Immediately after ablation, anti-arrhythmic drugs were discontinued in all cases. Permanent AF was considered to have developed if AF was present on two consecutive 6-monthly examinations with no interim documented sinus rhythm. During a mean follow-up of 23 +/- 16 months, 22 (35%) of the 63 patients developed permanent AF. The actuarial estimate of progression of permanent AF was 22%, 40% and 56%, respectively, 1, 2 and 3 years after ablation. Age and underlying heart disease were independent predictors of progression of permanent AF. Only one (6%) of 16 patients with idiopathic AF had permanent AF (low risk group). Among the 47 patients with structural heart disease, permanent AF developed in 18 (62%) of the 29 who were aged >75 years or had >12 arrhythmic episodes per year and a symptom duration >4 years (high risk group), but only in three (17%) of the remaining 18 patients who did not (intermediate risk group). In conclusion, during a 3-year follow-up period, about half of the patients with a history of drug-refractory paroxysmal AF did not develop permanent AF after AV junctional ablation and dual-chamber pacemaker implantation, even in the absence of anti-arrhythmic drug therapy. Moreover, subgroups of patients whose risk of permanent AF progression differed were identified on the basis of simple baseline clinical variables. The results of this study form the necessary background for the correct management of patients after AV junction ablation and for the planning of future trials in this field.     

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.     

An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation.

AIMS: Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. METHODS AND RESULTS: In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16+/-4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P=0.02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations (P=0.05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. CONCLUSION: Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing.     

A review on atrioventricular junction ablation and pacing for heart rate control of atrial fibrillation

Atrioventricular junction ablation with permanent pacemaker implantation is a highly effective treatment approach in patients with atrial fibrillation and high ventricular rates resistant to other treatment modalities, especially in the elderly or those with severe comorbidities. Compared with pharmacological therapy alone, the so-called “ablate and pace” approach offers the potential for more robust control of ven-tricular rate. Atrioventricular junction ablation and pacing strategy is associated with improvement in symptoms, quality of life, and exercise capacity. Given the close relationship between atrial fibrillation and heart failure, there is a particular benefit of such a rate control in patients with atrial fibrillation and reduced systolic function. There is increasing evidence that cardiac resynchronization therapy devices may be beneficial in selected populations after atrioventricular junction ablation. The present review article focuses on the current recommendations for atrioventricular junction ablation and pacing for heart rate control in patients with atrial fibrillation. The technique, the optimal implanta-tion time, and the proper device selection after atrioventricular junction ablation are also discussed.     

Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial

The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.     

进一步推进我国导管消融治疗心房颤动的临床研究

目前,心房颤动（房颤）治疗的研究方向主要有两个,一是导管消融,电生理学家力图通过不断改进消融术式,获取更好的消融效果,以期达到最终根治房颤的目的;二是药物治疗,许多药理学家则希望研制出副作用小、见效快、能长期抑制房颤的抗心律失常药物（AAD）,部分对导管消融治疗房颤效果有疑虑的临床医师也对此抱有很大希望。     

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) ≤40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 ± 10 years; 45 men), LVEF was 26% ± 8% and 34% ± 13% (p <0.001) before and after ablation, respectively. During follow-up (40 ± 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (≥45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.     

Indications and nonindications for ablation of atrioventricular conduction in the elderly: is it sensible to destroy normal tissue?

Atrial fibrillation is common in later life. The goals of therapy are maintenance/restoration of sinus rhythm and control of ventricular rate when atrial fibrillation occurs. The only nonpharmacologic therapy of proven benefit is atrioventricular junction ablation and pacing, but this approach is irreversible and requires clear guidelines for patient selection. In paroxysmal atrial fibrillation, ablation and pacing carries a high risk of progression to permanent atrial fibrillation within 6 months but is indicated only when at least two appropriate drug strategies have failed. In persistent atrial fibrillation, ablation and pacing will inevitably result in permanent atrial fibrillation; this may influence the decision for pacemaker type and the timing of the procedure. In permanent atrial fibrillation, there is clear evidence for benefit, especially in those with reduced left ventricular function. In conclusion, ablation and pacing offers symptomatic and functional benefit to patients with drug-refractory atrial fibrillation. Timing of the intervention relates to response to other pharmacologic therapy.     

Predictors of atrial rhythm after atrioventricular node ablation for the treatment of paroxysmal atrial arrhythmias

OBJECTIVE: To assess the natural history of the atrial rhythm of patients with paroxysmal atrial arrhythmias undergoing atrioventricular node ablation and permanent pacemaker implantation. DESIGN AND SETTING: A retrospective cohort study of consecutive patients identified from the pacemaker database and electrophysiology records of a tertiary referral hospital. PATIENTS: 62 consecutive patients with paroxysmal atrial arrhythmias undergoing atrioventricular node ablation and permanent pacemaker implantation between 1988 and July 1996. MAIN OUTCOME MEASURES: (1) Atrial rhythm on final follow up ECG, classified as either ordered (sinus rhythm or atrial pacing) or disordered (atrial fibrillation, atrial flutter or atrial tachycardia). (2) Chronic atrial fibrillation, defined as a disordered rhythm on two consecutive ECGs (or throughout a 24 hour Holter recording) with no ordered rhythm subsequently documented. RESULTS: Survival analysis showed that 75% of patients progressed to chronic atrial fibrillation by 2584 days (86 months). On multiple logistic regression analysis a history of electrical cardioversion, increasing patient age, and VVI pacing were associated with the development of chronic atrial fibrillation. A history of electrical cardioversion and increasing patient age were associated with a disordered atrial rhythm on the final follow up ECG. CONCLUSIONS: Patients with paroxysmal atrial arrhythmias are at high risk of developing chronic atrial fibrillation. A history of direct current cardioversion.     

Total atrioventricular nodal ablation increases atrial fibrillation burden in patients with paroxysmal atrial fibrillation despite continuation of antiarrhythmic drug therapy

INTRODUCTION: Total atrioventricular nodal (TAVN) ablation and pacing is an accepted and safe treatment for patients with drug-refractory paroxysmal atrial fibrillation (AF). Many patients develop permanent AF within the first 6 months after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic drug therapy. We hypothesized that TAVN ablation itself creates an atrial substrate prone to AF. METHODS AND RESULTS: Patients participating in the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained on stable antiarrhythmic drug therapy throughout follow-up were included in this analysis. AF burden and the development of persistent AF in the preablation period were compared to two consecutive postablation periods. Echocardiographic changes also were evaluated. Twenty-two patients remained on stable drug therapy (9 men and 13 women, age 59 +/- 3 years). One patient developed persistent AF preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0 +/- 1.2 hours/day and increased to 10.4 +/- 2.2 hours/day and 11.8 +/- 2.3 hours/day in the two postablation follow-up periods (P < 0.05). In patients with fractional shortening (FS) >30% prior to ablation, FS decreased significantly from 39.4% +/- 1.3% to 36.4%+/- 1.7% (P < 0.05). In contrast, in patients with a FS < or =30% prior to ablation, FS increased from 27% +/- 0.8% to 33.6 +/- 1.7% (P < 0.05). CONCLUSION: TAVN ablation increases AF burden and facilitates the development of persistent AF in patients with paroxysmal AF despite the continuation of antiarrhythmic drugs. Loss of AV and/or interventricular synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch and increasing AF burden.     

Selection of Pacing Mode after Interruption of Atrioventricular Conduction for Atrial Fibrillation: Observations from the PA3 Clinical Trial

The optimal pacing mode for patients with paroxysmal atrial fibrillation (AF) following AV junction ablation remains the subject of some debate. Recent clinical trials have not demonstrated a superior advantage of maintenance of sinus rhythm over the rate control approach. However, clinical trials in pacemaker populations have demonstrated that physiologic pacing reduces the probability of paroxysmal and persistent AF compared to ventricular pacing. In the second phase of the PA(3) study, patients were randomized to DDDR versus VDD pacing in a cross over study design. Of the 67 patients randomized, 42% developed permanent AF within one year following ablation. AF frequency and burden increases early following AV junction ablation suggesting that ventricular pacing even in an atrial synchronous mode promotes AF. Given the high probability of permanent AF developing early following ablation, VVIR pacing appears to be the appropriate pacing mode for symptomatic patients undergoing total AV junction ablation.     

Resynchronization therapy in the context of atrial fibrillation: Benefits and limitations

Atrial fibrillation (AF) and heart failure often coexist and are believed to directly predispose to each other. Cardiac resynchronization does not prevent or increase the induction of AF. However, new onset of AF does not seem to diminish the beneficial effects of CRT on symptoms, cardiac function and, more importantly, all-cause mortality if appropriate ventricular rate control by beta-blockers and digoxin is being achieved. While a pharmacological approach to control ventricular rate may be sufficient in most patients with paroxysmal AF or AF of shorter duration in those with permanent AF ablation strategies may be necessary. Observational studies and one randomized trial indicate a potential benefit of CRT in heart failure patients with chronic AF; particularly, biventricular pacing was superior compared to conventional right-univentricular stimulation. However, recent results suggest that even relatively high percentage biventricular capture may be inadequate, and that the benefits of CRT may only be extended to chronic AF patients with previous AV junctional ablation. Well designed and powered clinical trials are required before pacemaker dependency is created in large numbers of heart failure patients.