Ibutilide in persistent atrial fibrillation refractory to conventional cardioversion methods

BACKGROUND: Electrical cardioversion of atrial fibrillation seems to be enhanced by pretreatment with ibutilide, but only few is known about the effects of ibutilide in atrial fibrillation which failed to convert with class III antiarrhythmic agents and electrical cardioversion. The objectives of this study were to evaluate the efficacy and safety of ibutilide administration in patients with persistent atrial fibrillation refractory to long-term therapy with class III antiarrhythmic drugs and transthoracic cardioversion. METHODS: Prospective study in 22 patients (16 men and 6 women, mean age 63+/-9 years) with structural heart disease and persistent atrial fibrillation for a mean duration of 39+/-50 (range 1-145) months. All patients had failed to convert to sinus rhythm after transthoracic cardioversion while on treatment with class III antiarrhythmic drugs (amiodarone in 82%, sotalol in 18%). One milligram of ibutilide was administered in all patients and electrical cardioversion was performed again, if necessary. RESULTS: The total conversion rate to sinus rhythm was 95% (21 of 22 patients). Two patients (9%) were successfully converted after ibutilide alone and 19 patients (86%) when transthoracic cardioversion was repeated after ibutilide. The QTc intervals increased from 451+/-28 to 491+/-49 ms (p<0.001) after ibutilide. No adverse effects occurred. The rate of freedom from atrial fibrillation after 1 month of follow-up was 64%. CONCLUSIONS: The efficacy of concomitant use of ibutilide infusion and, if necessary, repeated transthoracic cardioversion for restoration of sinus rhythm in long-term persistent atrial fibrillation and previously failed antiarrhythmic and electrical cardioversion was 95%. There were no adverse effects associated with ibutilde administration. Our results suggest that this combined strategy may be safe and successful in patients with atrial fibrillation resistant to conventional cardioversion methods and may be an alternative to internal cardioversion.     

Persistent Atrial Flutter in Patients Treated for Atrial Fibrillation with Amiodarone and Propafenone:

INTRODUCTION: Antiarrhythmic drugs have been reported to promote the conversion of atrial fibrillation to atrial flutter in patients with paroxysmal atrial fibrillation. However, information about the electrophysiologic mechanism and response to radiofrequency ablation of these drug-induced atrial flutters is limited. Furthermore, the determinants of the development of persistent atrial flutter in patients treated for atrial fibrillation with antiarrhythmic drugs are still unknown. METHODS AND RESULTS: Among the 136 patients treated for atrial fibrillation with amiodarone (n = 96) or propafenone (n = 40), 15 (11%, mean age 65.5 +/- 12.3 years) were identified to have subsequent development of persistent atrial flutter based on surface ECG characteristics during antiarrhythmic drug treatment. The mean interval between the beginning of drug treatment and the onset of atrial flutter was 5.0 +/- 5.5 months. Intracardiac mapping and entrainment studies revealed that 11 patients had counterclockwise typical atrial flutter, and 4 had clockwise typical atrial flutter. All 15 patients underwent successful ablation with creation of complete bidirectional isthmus conduction block. After a mean follow-up of 12.3 +/- 4.2 months, 14 (93%) of 15 patients who underwent successful ablation and continued taking antiarrhythmic drugs have remained in sinus rhythm. Univariate analysis of clinical variables demonstrated that only atrial enlargement was significantly related to the occurrence of persistent atrial flutter. CONCLUSION: In patients with atrial fibrillation, persistent typical atrial flutter might occur during antiarrhythmic drug treatment, and atrial enlargement was a risk factor for the development of such an arrhythmia. Radiofrequency ablation and continuation of pharmacologic therapy offered a safe and effective means of achieving and maintaining sinus rhythm.     

Maintenance of sinus rhythm and recovery of atrial mechanical function after cardioversion with bepridil or in combination with aprindine in long-lasting persistent atrial fibrillation.

BACKGROUND: The aim of this study was to evaluate pharmacological cardioversion of long-lasting persistent atrial fibrillation (AF) using bepridil in terms of recovery of atrial mechanical function and maintenance of sinus rhythm. Bepridil alone or in combination with aprindine is effective for termination of persistent AF. METHODS AND RESULTS: The study group comprised 38 consecutive patients (24 men, 58.8+/-9.3 years) with successful conversion of persistent AF lasting >1 month either pharmacologically (Group I) or electrically (Group II). Fast Fourier transform analysis of fibrillation waves was performed and fibrillation cycle length (FCL) was calculated from the peak frequency. In Group I, sinus rhythm was pharmacologically restored in 22 patients after an average 30 days (7-49 days) of bepridil administration, either alone (11) or in combination with oral aprindine (11); they were followed up while using the same drugs. In Group II, electrical conversion restored sinus rhythm in 16 patients, and they were followed up with conventional antiarrhythmic drugs other than bepridil and aprindine. After bepridil treatment FCL increased and became significantly longer in Group I than in Group II (190+/-39 vs 150+/-29 ms, p<0.001). Atrial peak velocity in transmitral flow within the first week after cardioversion was greater in Group I than in Group II (68+/-35 vs 32+/-20 cm/s, p<0.05). By Kaplan-Meier analysis, 83% of Group I patients were free of AF recurrence at the 12-month follow-up, compared with 36% in Group II (p<0.005). CONCLUSIONS: In patients with long-lasting AF, pharmacological conversion with bepridil alone or in combination with aprindine recovered atrial mechanical function better and maintained sinus rhythm longer than electrical conversion.     

Effectiveness of rhythm control in persistent or permanent atrial fibrillation with overdrive atrial pacing and antiarrhythmic drugs after linear right atrial catheter ablation

Right atrial (RA) maze procedures using linear catheter ablation have had limited efficacy in paroxysmal atrial fibrillation (AF). We hypothesized that "hybrid" therapy using overdrive atrial pacing and antiarrhythmic drugs can improve efficacy of catheter RA maze and expand its role to persistent or permanent AF. Catheter RA maze procedures were performed in 26 patients with persistent or permanent AF refractory to 4.5 +/- 2.1 antiarrhythmic drugs. Overdrive dual-site RA pacing (21 patients) or high RA pacing (5 patients) was continued (n = 11) or instituted periablation (n = 15). All patients continued receiving previously ineffective antiarrhythmic drugs. Freedom from permanent AF (rhythm control), symptomatic and/or asymptomatic AF recurrences, the safety of hybrid therapy, and overall survival were assessed. There was no procedure-related mortality or stroke. Rhythm control was achieved in 24 patients (92%) within 3 months. During long-term follow-up (6 to 49 months, mean 17 +/- 10), rhythm control was maintained in 20 patients (77%). Nine patients (35%) had no AF recurrences, whereas 11 patients maintained rhythm control with infrequent AF recurrences. Device datalogs at the study cut-off point demonstrated no AF events in 6 patients, nonsustained atrial tachycardia in 2 patients, and brief asymptomatic paroxysmal AF in 12 patients. Actuarial patient survival was 95% at 1 year and 74% at 2 years of follow-up. Thus, hybrid therapy utilizing catheter RA maze procedures with overdrive atrial pacing and antiarrhythmic drugs can be performed safely and can reestablish rhythm control in selected patients with refractory persistent or permanent AF.     

Clinical characteristics of persistent lone atrial fibrillation in the RACE study

In the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study, 522 patients were randomized to either rate or rhythm control therapy. Lone atrial fibrillation (AF) was present in 89 patients. Demographics, cardiovascular mortality and morbidity, and quality of life were compared between patients with lone AF and those with underlying structural heart disease. Patients with lone AF were significantly younger (65 +/- 10 vs 69 +/- 8 years) and had fewer complaints of fatigue (p = 0.01) and dyspnea (p = 0.005). With lone AF, quality-of-life scores were higher on almost all 8 Medical Outcomes Study Short-Form health survey questionnaire subscales, and comparable to healthy, age- and gender-matched controls. Mean follow-up was 2.3 +/- 0.6 years. Cardiovascular end points occurred in 9 patients with lone AF (10%), consisting of death (all bleedings) 3%, thromboembolic complications in 3%, nonfatal bleeding in 2%, and pacemaker implantation in 2%, but no heart failure and severe adverse effects due to antiarrhythmic drugs occurred. End points occurred in 95 patients (22%) with underlying diseases. Heart failure and severe adverse effects from drugs did not occur in patients with lone AF in this study. Despite the absence of demonstrable cardiovascular and cerebrovascular disease, lone AF is associated with bleeding and thromboembolism.     

Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFE Polish Study

BACKGROUND. Patients with atrial fibrillation (AF) can be managed either by maintaining sinus rhythm using antiarrhythmic drugs and/or electrical cardioversion, or by leaving patients in AF and controlling ventricular rate without attempts to restore sinus rhythm. Which of these two strategies is superior, has not yet been definitively established. AIM. HOT CAFE Polish Study (How To Treat Chronic Atrial Fibrillation) was designed to evaluate in a randomised, multicentre and prospective manner the risks and advantages of two therapeutical strategies - rate control or rhythm control, in patients with persistent AF. METHODS. The study group consisted of 205 patients (71 females and 134 males; mean age 60.8+/-11.2 years) with a mean time of AF duration of 273.7+/-112.4 days; 101 patients were randomly assigned to rate control (Group I) whereas 104 patients were randomised to sinus rhythm (SR) restoration by DC cardioversion (CV) and subsequent antiarrhythmic drug treatment (Group II). At the end of follow-up (12 months) SR was present in 75% of patients. RESULTS. The incidence of hospital admissions was higher in group II in comparison to group I (12% vs 74%; p<0.001). Mortality was similar in both groups (1.0% versus 2.9%, NS). In both groups a significant improvement of heart failure symptoms was observed during the first 2 months (p<0.02 and p<0.001). In group II exercise tolerability measured by maximal workload during treadmill test significantly improved compared with baseline (5.2+/-5.1 vs 7.6+/-3.3 MET; p<0.0001). In patients in whom SR was restored, the left ventricular function improved and an increase in the shortening fraction was observed (29+/-7% vs 31+/-7%; p<0.01). No thromboembolic complications were observed in patients left with AF. Three patients from group II suffered ischaemic stroke; in two cases stroke was associated with CV whereas in the third patient - with late AF recurrence. CONCLUSIONS. The HOT CAFE Polish Study did not reveal significant differences in mortality between the two treatment strategies in patients with persistent AF. Although patients with SR had better improvement in some haemodynamical parameters, the hospitalisation rate was higher and the incidence of stroke was not reduced compared with the rate control group.     

Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm; a randomized study.

AIMS: The aim of this prospective, randomized study was to determine the efficacy of a serial external electrical cardioversion strategy in maintaining sinus rhythm after 12 months in patients with recurrent persistent atrial fibrillation. METHODS AND RESULTS: Ninety patients with persistent atrial fibrillation lasting more than 72 h but less than 1 year were randomized in a one to one fashion to repetition of up to two electrical cardioversions in the event of relapse of atrial fibrillation detected within 1 month of the previous electrical cardioversion (Group AGG), or to non-treatment of atrial fibrillation relapse (Group CTL). ECGs were scheduled at 6 h, 7 days, and 1 month. Clinical examination and ECGs were repeated during the 6-month and 12-month follow-up examinations. Echocardiography was repeated during the 6-month follow-up examination. Clinical and echocardiographic characteristics were similar in the two groups. All patients were treated with antiarrhythmic drugs before electrical cardioversion and throughout follow-up. After 12 months, sinus rhythm was maintained in 53% of Group AGG patients and in 29% of Group CTL patients (P<0.03). After 6 months, left ventricular ejection fraction had recovered significantly only in Group AGG (56.8 +/- 9.0% at enrollment vs 60.4 +/- 9.4% at 6 months,P <0.001). CONCLUSION: These results demonstrate that an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm after 12 months.     

Pharmacological cardioversion of persistent atrial fibrillation with and without a history of drug-resistant paroxysmal atrial fibrillation.

BACKGROUND: Suppression by antiarrhythmic drugs of the maintenance mechanisms could convert persistent atrial fibrillation (AF) to sinus rhythm (SR). Whether a history of drug-resistant paroxysmal AF (PAF) would affect the outcome of pharmacological conversion of persistent AF by bepridil or in combination with aprindine was evaluated in the present study. METHODS AND RESULTS: The study group comprised 51 consecutive patients (24 men, 61+/-8 years) undergoing pharmacological conversion of persistent AF lasting >1 month. Drug-resistant PAF was defined as AF and at least 2 ineffective antiarrhythmic drugs for suppression of AF recurrence. Fast Fourier transform analysis of fibrillation waves was used to measure fibrillation cycle length (FCL) from the peak frequency. Fifteen patients had a history of drug-resistant PAF (Group I), and the remaining 36 did not (Group II) before diagnosis of persistent AF. Ten patients (67%) in Group I and 26 patients (72%) in Group II were restored to SR by bepridil alone or in combination with aprindine after 29+/-15 days of drug administration. Before conversion to SR, bepridil increased the FCL more in Group II than in Group I. During a 12-month follow-up period, 4 of 10 patients in Group I and 2 of 26 patients in Group II (p<0.01) had recurrence of persistent AF with bepridil alone or in combination with aprindine. CONCLUSIONS: A history of drug-resistant PAF does not affect the efficacy of pharmacological conversion by bepridil or in combination with aprindine. However, recurrence of AF was significantly higher in patients with such a history.     

Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment.

AIMS: To investigate the rate of transformation of atrial fibrillation to atrial flutter in patients taking antiarrhythmic drugs for the prophylaxis of atrial fibrillation, we retrospectively analysed data from 305 consecutive patients with paroxysmal atrial fibrillation (155 male; mean age 63 +/- 11 years) treated with ventricular rate controlling drugs, antiarrhythmic drugs, or without drugs. METHODS AND RESULTS: At a mean follow-up of 9 months (range 1-24) all patients experienced recurrence of arrhythmia: 48 (14.6%, Group A) suffered Type 1 atrial flutter, and 257 (85.4%, Group B) atrial fibrillation. The relative rate of recurrence of atrial flutter vs atrial fibrillation was similar in patients without treatment or with ventricular rate controlling drugs (from 6.8% to 14.6%, P=ns). However, recurrence was higher (25%) in patients administered antiarrhythmic drug therapy. The relative risk in these patients was 3.02 times greater, compared with patients without treatment, or treated with rate controlling drugs (P<0.001). There were no differences between groups concerning the baseline clinical characteristics and the clinical consequences of the recurrence; patients with atrial flutter had a lower rate of conversion to sinus rhythm (42% vs 64%) and a higher rate of hospital admission (69% vs 36%) compared with those with atrial fibrillation. Six patients (8.5%) experienced 1:1 atrioventricular conduction during atrial flutter with a ventricular rate of 240-280 beats x min(-1). CONCLUSION: Our data suggest that the use of antiarrhythmic drugs for the prophylaxis of atrial fibrillation is associated with a threefold increase in the probability of Type 1 atrial flutter recurrence, as opposed to atrial fibrillation, which may have important clinical consequences, but which did not in our study.     

Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter.

AIMS: Catheter ablation of the inferior vena cava-tricuspid annulus isthmus and continuation of antiarrhythmic drug therapy have been shown to be an effective hybrid therapy for atrial flutter which results from antiarrhythmic drug treatment of atrial fibrillation. The aim of this study was to determine the risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. METHODS AND RESULTS: 90 patients with paroxysmal (n=46) or persistent atrial fibrillation (n=44) developed atrial flutter due to the administration of amiodarone (n=48), flecainide (n=22), propafenone (n=14) or sotalol (n=6). Recurrence of atrial fibrillation after ablation was assessed during follow-up on continued antiarrhythmic drug therapy and during long-term follow-up, irrespective of the initial antiarrhythmic medication. During the follow-up on continued antiarrhythmic drug therapy (16+/-13 months), recurrence of atrial fibrillation was documented in 24 of 90 patients (27%). The presence of accompanying pre-ablation episodes of atrial fibrillation on antiarrhythmic treatment (Odds ratio 7.1, 95% confidence interval 2.3 to 25, p=0.001) and decreased left ventricular ejection fraction (Odds ratio 3.7, 95% confidence interval 1.01 to 12.5, p=0.048) were significant and independent predictors of post-ablation atrial fibrillation. Antiarrhythmic medication was discontinued during long-term follow-up due to adverse drug effects (amiodarone, n=12; flecainide, n=1) in 13 patients (14%). During the long-term follow-up, irrespective of the initial antiarrhythmic medication (21+/-15 months), stable sinus rhythm was maintained in 60 of 90 patients (67%). CONCLUSION Hybrid therapy can be considered as the first line therapy for patients with antiarrhythmic drug-induced atrial flutter but patients should be carefully evaluated for accompanying pre-ablation episodes of atrial fibrillation and possible adverse drug effects before initiation of hybrid therapy.     

Effect of the Implantable Atrial Defibrillator on the Natural History of Atrial Fibrillation

INTRODUCTION: The purpose of our study was to evaluate the effect of repeated cardioversion with an implantable atrial defibrillator on the clinical outcome of patients with atrial fibrillation. METHODS AND RESULTS: The effects of the implantable atrial defibrillator on the total duration of atrial fibrillation, number of atrial fibrillation recurrences, and left atrial size were evaluated prospectively in 16 patients with atrial fibrillation (13 men and 3 women; mean age 58 +/- 11 years). Seven patients had no cardiovascular disease, 5 patients had hypertension, 3 patients had coronary heart disease, and 1 patient had congenital heart disease. Eight patients had paroxysmal atrial fibrillation for a mean duration of 80 +/- 61 months, and eight patients had persistent atrial fibrillation for a mean duration of 68 +/- 119 months. Except for one patient who received digoxin throughout the study, all patients received the same Class I or III antiarrhythmic agent throughout the study. The implantable atrial defibrillator successfully converted 50 (93%) of 54 spontaneous episodes of atrial fibrillation in 12 patients. During the initial 3 months of clinical follow-up, the atrial defibrillator documented 261 +/- 270 hours of atrial fibrillation compared with 126 +/- 172 hours (P = 0.01) during the subsequent 3 months. The left atrial size decreased from 4.4 +/- 0.7 cm at the time of atrial defibrillator implantation to 4.1 +/- 0.6 cm (P = 0.02) 6 months later. The number of atrial fibrillation recurrences did not change. These findings were observed in the absence of changes in drug therapy. No complications were observed. CONCLUSION: Restoration and maintenance of sinus rhythm in patients with atrial fibrillation by repeated cardioversion with an implantable atrial defibrillator was associated with a reduction in the total arrhythmia duration and a reduction in left atrial size. These results suggest that maintenance of sinus rhythm with the atrial defibrillator may reverse the remodeling process associated with atrial fibrillation.     

Inefficiency of renin-angiotensin inhibitors in preventing atrial fibrillation in patients with a normal heart

AIM: Recent scientific evidence has emphasized the possible role of inhibitors of the renin-angiotensin system in preventing arrhythmic relapses in patients with paroxysmal or persistent atrial fibrillation and co-existing left ventricular hypertrophy or left ventricular dysfunction. METHODS: In order to verify the effects of these drugs on patients with a normal heart, we collected a series of 187 patients admitted to our division of cardiology for paroxysmal or persistent atrial fibrillation. All patients underwent cardioversion (with antiarrhythmic drugs and/or by electrical cardioversion) and were discharged in sinus rhythm. Episodes of recurrent arrhythmia were recorded during a mean follow-up period was 2 years. Patients were subdivided into 2 groups according to therapy: group 1 comprised patients receiving renin-angiotensin system inhibitors, group 2 comprised those not receiving therapy with these agents. All 91 patients in group 1 and 76 of those in group 2 had hypertension. Among the 91 patients in the group 1, 55 were treated with angiotensin-converting enzyme (ACE) inhibitors and 36 with angiotensin receptor blockers. There were no statistically significant differences in cardiovascular risk factors or antiarrhythmic drug use between the 2 groups. RESULTS: In group 1, 83% of patients experienced <2 recurrences of atrial fibrillation during the follow-up period, while 17% had >2 episodes. In group 2, 86% of patients experienced <2 relapses during the follow-up period, while the remaining 14% had >2 relapses. There was no statistically significant difference between the 2 groups (P=0.85). A subgroup analysis showed that treatment with angiotensin receptor blockers, beta-blockers, diuretics, and calcium-channel blockers brought no advantage in sinus rhythm maintenance. CONCLUSION: In our sample of hypertensive patients with a healthy heart, treatment with ACE inhibitors showed no statistically significant advantage in the prevention of atrial fibrillation relapses.     

Use of bepridil in combination with Ic antiarrhythmic agent in converting persistent atrial fibrillation to sinus rhythm.

BACKGROUND: It has been reported that bepridil is as good as amiodarone in converting persistent atrial fibrillation (AF) to sinus rhythm (SR). The conversion effect of bepridil alone is not always satisfactory, however. The efficacy of pharmacological cardioversion by the combination of bepridil and a class Ic antiarrhythmic drug for persistent AF is studied. METHODS AND RESULTS: The participants comprised 37 consecutive patients in whom pharmacological cardioversion was conducted to treat persistent AF (duration 22.5+/-29.6 months). Each patient first received a class Ia or Ic antiarrhythmic drug, then bepridil alone, then a combined therapy of bepridil at 200 mg/day with a class Ic antiarrhythmic drug at a routine dose. Unaccompanied use of any of the antiarrhythmic drugs achieved pharmacological cardioversion in 14 (38%) of the 37 patients (single therapy group), whereas SR was restored by combination of bepridil and a class Ic antiarrhythmic drug in 22 (combined therapy group) of the remaining 23 patients. The duration of AF was significantly longer in the combined therapy group than in the single therapy group (28.3+/-31.0 vs 7.3+/-4.1 months). CONCLUSION: Combined therapy of bepridil and a class Ic antiarrhythmic drug is efficient for pharmacological cardioversion of refractory long-lasting persistent AF.     

Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators.

BACKGROUND AND OBJECTIVES. The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. METHODS. Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. RESULTS. In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. CONCLUSIONS. Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.     

Relationship between efficacy of antiarrhythmic drug therapy and structural remodeling in patients with paroxysmal atrial fibrillation

OBJECTIVES: To evaluate whether the response to antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation affects the development of structural remodeling in the left atrium and ventricle. METHODS: This study included 230 patients (158 men and 72 women, mean age 67 +/- 11 years) in whom antiarrhythmic drug therapy was attempted for > or = 12 months to maintain sinus rhythm (mean follow-up period 45 +/- 27 months). The patients were divided into three groups according to the response to antiarrhythmic drug therapy: group A consisted of 78 patients without recurrence of atrial fibrillation, group B consisted of 87 patients with recurrence of atrial fibrillation and electrical and/or pharmacological cardioversion to restore sinus rhythm, and group C consisted of 65 patients with permanent conversion despite antiarrhythmic drug therapy. RESULTS: In group A, left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (LVEF) did not change after antiarrhythmic drug therapy. In group B, LAD increased significantly after antiarrhythmic drug therapy (from 32.6 +/- 6.4 to 36.0 +/- 6.5 mm, p < 0.01), Whereas either LVDd or LVEF did not change after antiarrhythmic drug therapy. In group C, LAD increased significantly after antiarrhythmic drug therapy (from 37.3 +/- 7.0 to 40.5 +/- 7.9 mm, p < 0.01) and LVEF was significantly reduced after antiarrhythmic drug therapy (from 69.4 +/- 6.2% to 66.5 +/- 8.9%, p < 0.05). LVDd did not change after antiarrhythmic drug therapy. The plasma concentration of human atrial natriuretic peptide during sinus rhythm at the initiation of antiarrhythmic drug therapy in group A (30.5 +/- 26.7 pg/ml) was significantly lower than those in group B (48.0 +/- 49.7 pg/ml) and group C (49.7 +/- 39.5 pg/ml). CONCLUSIONS: The development of structural remodeling in human myocardium can be prevented with antiarrhythmic drug therapy if sinus rhythm is maintained without recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation.     

心脏再同步治疗术后患者死亡原因分析

目的探讨心力衰竭患者心脏再同步治疗（CRT）术后的死亡原因及相关影响因素。方法对110例行CRT的心力衰竭患者[其中7例植入带有心脏再同步治疗除颤器（CRT—D）]进行长期随访,观察患者术后的转归情况,以及死亡患者的死亡原因、生存时间和相关影响因素。结果110例患者中有92例患者完成随访研究,随访1～132（48±28）个月,共死亡30例,死亡率为32．6％,5年生存率为66．9％±5．8％。24例为心脏性死亡,占总体死亡的80％,其中包括11例为心力衰竭恶化导致的死亡,13例为心脏性猝死（SCD）,其余6例为非心脏性死亡。14例行CRT的持续性心房颤动（房颤）患者中有8例死亡;71例行CRT的窦性心律患者中死亡22例;前组的中位生存时间短于后组（50比87,P=0．013）;7例植人CRT—D的患者均无死亡;3组患者的死亡率差异有统计学意义（P=0．01）。合并慢性肾功能衰竭的CRT患者死亡率（66．7％）较无肾功能不良者（20．6％）高（相对危险度：3．24,95％CI1．88～5．59,P〈0．001）。结论CRT患者的主要死亡原因是心脏性死亡,其中包括心力衰竭恶化和SCD。CRT—D和CRT两组患者之间的死亡率差异有统计学意义,接受CRT的窦性心律患者较持续性房颤患者有显著的生存获益。合并慢性肾功能衰竭的CRT患者预后较差。对于合并持续性房颤的CRT患者同时给予房室结消融有可能进一步提高生存率。     

Atrial fibrillation ablation

Atrial fibrillation is the commonest cardiac arrhythmia, with significant morbidity related to symptoms, heart failure, and thromboembolism, which is associated with excess mortality. Over the past 10 years, many centers worldwide have reported high success rates and few complications after a single ablation procedure in patients with paroxysmal atrial fibrillation. Recent studies indicate a short-term and long-term superiority of catheter ablation as compared with conventional antiarrhythmic drug therapy in terms of arrhythmia recurrence, quality of life, and arrhythmia progression. As a result, catheter ablation is evolving to a front-line therapy in many patients with atrial fibrillation. However, in patients with persistent long-standing atrial fibrillation catheter ablation strategy is more complex and time-consuming, frequently requiring repeat procedures to achieve success rates as high as in paroxysmal atrial fibrillation. In the near future, however, with growing experience and evolving technology, catheter ablation of atrial fibrillation may be extended also to patients with long-standing atrial fibrillation.     

Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients

BACKGROUND. Atrial fibrillation is common in advanced heart failure, but its prognostic significance is controversial. METHODS AND RESULTS. We evaluated the relation of atrial rhythm to overall survival and sudden death in 390 consecutive advanced heart failure patients. Etiology of heart failure was coronary artery disease in 177 patients (45%) and nonischemic cardiomyopathy or valvular heart disease in 213 patients (55%). Mean left ventricular ejection fraction was 0.19 +/- 0.07. Seventy-five patients (19%) had paroxysmal (26 patients) or chronic (49 patients) atrial fibrillation. Compared with patients with sinus rhythm, patients with atrial fibrillation did not differ in etiology of heart failure, mean pulmonary capillary wedge pressure on therapy, or embolic events but were more likely to be receiving warfarin and antiarrhythmic drugs and had a slightly higher left ventricular ejection fraction. After a mean follow-up of 236 +/- 303 days, 98 patients died: 56 (57%) died suddenly, and 36 (37%) died of progressive heart failure. Actuarial 1-year overall survival was 68%, and sudden death-free survival was 79%. Actuarial survival was significantly worse for atrial fibrillation than for sinus rhythm patients (52% versus 71%, p = 0.0013). Similarly, sudden death-free survival was significantly worse for atrial fibrillation than for sinus rhythm patients (69% versus 82%, p = 0.0013). By Cox proportional hazards model, pulmonary capillary wedge pressure on therapy, left ventricular ejection fraction, coronary artery disease, and atrial fibrillation were independent risk factors for total mortality and sudden death. For patients who had pulmonary capillary wedge pressure of less than 16 mm Hg on therapy, atrial fibrillation was associated with poorer 1-year survival (44% versus 83%, p = 0.00001); however, in the high pulmonary capillary wedge pressure group, atrial fibrillation did not confer an increased risk (58% versus 57%). CONCLUSIONS. Atrial fibrillation is a marker for increased risk of death, especially in heart failure patients who have lower filling pressures on vasodilator and diuretic therapy. Whether aggressive attempts to maintain sinus rhythm will reduce this risk is unknown.     

Effect of diltiazem and metoprolol on left atrial appendix functions in patients with nonvalvular chronic atrial fibrillation.

OBJECTIVES: Thrombo-embolic events are the important cause of mortality and morbidity in patients with chronic atrial fibrillation (CAF). The origin of thromboembolism is often the left atrial appendix (LAA). Flow rate velocity (FRV) inside the LAA is the major determinant of thrombus formation. The aim of our study was to investigate the effects of diltiazem and metoprolol used for ventricular rate control on FRV of the LAA in CAF patients and thus to evaluate the positive or negative effects of these two drugs on thromboembolic events. METHODS: Sixty-four patients were included in the study. All patients were suffering from CAF for more than a year. The patients were allocated to two groups according with agent used for rate control- metoprolol (Group 1; n=31) and diltiazem (Group 2; n=33). Transesophageal echocardiography was applied to all patients and LAA FRV was measured by a pulse wave Doppler in the 1/3 proximal portion of the LAA. The measurements were repeated after applying 5 mg metoprolol to Group 1 and 25 mg diltiazem to Group 2 via venous cannula. RESULTS: In Group 1 after metoprolol LAA flow velocity changed from 0.25 +/- 0.90 m/s to 0.25 +/- 0.10 m/s (p>0.05). In group 2 after diltiazem left atrial appendix FRV decreased from 0.21 +/- 0.9 m/s to 0.19 +/- 0.6 m/s (p>0.05). CONCLUSIONS: In patients with CAF metoprolol used for ventricular rate control had no effect on LAA flow velocity and the observed decrease in LAA flow rate velocity with intravenous diltiazem was insignificant.     

Echocardiographic changes and predictors of arrhythmia recurrence after long-term use of the atrial defibrillator

BACKGROUND: The patient-activated atrial defibrillator allows patients to cardiovert themselves from atrial fibrillation soon after the onset of symptoms. The long-term effects of early cardioversion from persistent atrial fibrillation on left ventricular performance and left atrial size are unknown. METHODS: Eighteen patients, mean age 63.4, 83% male, had the Jewel((R)) AF atrial defibrillator implanted for persistent atrial fibrillation only. Transthoracic echocardiography was performed 3-monthly following implant. Parasternal long axis measurements were taken using conventional M-mode techniques. RESULTS: Over follow-up of 28.0+/-9 months, 377 episodes of persistent atrial fibrillation were terminated by patient-activated cardioversion (median 15 per patient). Echocardiographic measurements at implant were; left atrium 44+/-6 mm, left ventricular end-diastolic diameter 49+/-7 mm, left ventricular end-systolic diameter 34+/-7 mm, fractional shortening 33+/-10% and ejection fraction 65+/-17%. After 1 year there had been a significant decrease in mean left atrial size to 41+/-6 mm (P=0.02) and an increase in mean ejection fraction to 73+/-8% (P=0.04). At long-term follow-up however, all parameters reverted to pre-implant levels. Baseline echocardiographic variables did not predict which patients would demonstrate serial increases in sinus rhythm duration between shocks during long-term follow-up. Patients on antiarrhythmic drug therapy however were more likely to demonstrate "sinus rhythm begetting sinus rhythm". CONCLUSIONS: Use of the atrial defibrillator for spontaneous persistent atrial fibrillation is associated with a medium-term (1 year) reduction in left atrial size and an increase in ejection fraction. These changes were not maintained in the long-term. Synergistic therapy with antiarrhythmic drugs may prolong periods of sinus rhythm between arrhythmia recurrences.