Thromboembolic prophylaxis in nonrheumatic atrial fibrillation: utilization patterns, efficacy, and complications in a long-term follow-up of community patients

OBJECTIVES: To define the incidence, contemporary utilization patterns, efficacy, and complications of thromboembolic prophylactic treatment in patients with chronic (CAF) and paroxysmal atrial fibrillation (PAF). BACKGROUND: Although recent randomized trials with antithrombotic therapy in nonrheumatic atrial fibrillation (AF) patients emphasized the benefits of warfarin in preventing stroke, warfarin treatment is still far from optimal. METHODS: A retrospective analysis of the medical records of 506 patients with nonrheumatic PAF or CAF from 23 clinics in the north of Israel, including an interview with the patients' family physician. RESULTS: (1) The most effective treatment for preventing thromboembolic events (a reduction of 75.9%) was warfarin at an international normalized ratio (INR) intensity of 2-3. (2) After diagnosis, 26.9% of the patients were treated with warfarin. (3) During the follow-up period (not following a thromboembolic event), an additional 26.9% of the patients began treatment with warfarin. (4) Elderly patients (p<0.001), patients with limited activity of daily living (ADL) (p<0.012) or instrumental activity of daily living (IADL) (p<0.001), and patients with PAF (p<0.0001) were less likely to be treated with warfarin. (5) Three new risk factors found for thromboembolic event were limited ADL (p<0.001), limited IADL (p<0.002), and extended duration of AF (p<0.006). CONCLUSIONS: Less than optimal utilization patterns of thromboembolic prophylactic treatment with anticoagulants were found, especially regarding elderly patients, patients with limited ADL and IADL, and patients with PAF, despite the fact that their thromboembolic risk is as high or higher than that of other patients with AF.     

Risk factors for thromboembolism in patients with paroxysmal atrial fibrillation

There is some controversy concerning which clinical characteristics predict thromboembolism and whether treatment with class I antiarrhythmic drugs reduces thromboembolim in patients with paroxysmal atrial fibrillation (AF). This retrospective, multicenter study was undertaken to determine risk factor or factors for thromboembolism in patients with paroxysmal AF. Seven hundred forty patients with paroxysmal AF (mean age 56 years) without prior thromboembolic events were followed retrospectively. Cerebral thromboembolism, including transient ischemic attack and embolism of peripheral arteries, were selected as primary end points. Independent risk factors were determined with multivariate analysis, and event-free survival curves were estimated. During 3.4-year follow-up period, primary end points occurred in 55 patients (2.2% per year). Patients with thromboembolism had a higher prevalence of underlying heart disease (p <0.01), less frequent treatment with antiarrhythmic drugs (p <0.01), and received diuretics more often (p <0.01) compared with patients without thromboembolism. Age (>/=65 years, RR 3.33, p = 0.0001) and gender (male, RR = 2, p = 0.0291) emerged as predictors of thromboembolism by multivariate analysis with Cox's proportional hazard model. Treatment with antiarrhythmic drugs (RR = 0.57, p = 0.0578) and aspirin (RR = 0.52, p = 0.1094) showed trends toward reducing thromboembolic risks. It is suggested that elderly men (>/=65 years) with paroxysmal AF are at risk for thromboembolism, but the risk tended to be reduced by treatment with antiarrhythmic drugs and aspirin.     

Stroke Event Rates and the Optimal Antithrombotic Choice of Patients With Paroxysmal Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The risks of stroke or systemic embolism and major bleeding are considered similar between paroxysmal and sustained atrial fibrillation (AF), and warfarin has demonstrated superior efficacy to aspirin, irrespective of the AF type. However, with the advent of novel oral anticoagulants (NOACs) and antiplatelet agents, the optimal antithrombotic prophylaxis for paroxysmal AF remains unclear.We searched Medline, Embase, CENTRAL, and China Biology Medicine up to October week 1, 2015. Randomized controlled trials of AF patients assigned to NOACs, warfarin, or antiplatelets, with reports of outcomes stratified by the AF type, were included. A fixed-effects model was used if no statistically significant heterogeneity was indicated; otherwise, a random-effects model was used.Six studies of 69,990 nonvalvular AF patients with ≥1 risk factor for stroke were included. Postantithrombotic treatment, paroxysmal AF patients showed lower risks of stroke (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.59–0.87), stroke or systemic embolism (RR, 0.74; 95% CI, 0.63–0.86), and all-cause mortality (RR, 0.75; 95% CI, 0.67–0.83), while the major bleeding risk was comparable (RR, 0.96; 95% CI, 0.85–1.08). We were unable to detect the superiority of anticoagulation over antiplatelets for paroxysmal AF (RR, 0.72; 95% CI, 0.43–1.23), while it was more effective than antiplatelets for sustained AF (RR, 0.42; 95% CI, 0.33–0.54). NOACs showed superior efficacy over warfarin and trended to show reduced major bleeding irrespective of the AF type.The AF type is a predictor for thromboembolism, and might be helpful in stroke risk stratification model in combination with other risk factors. With the appearance of novel anticoagulant and antiplatelet agents, the best antithrombotic choice for paroxysmal AF needs further exploration.     

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.     

Overview of the Management of Atrial Fibrillation:

There are three fundamental approaches to the management of atrial fibrillation (AF): rate control, rhythm control, and anticoagulation. Selecting a course of treatment requires a thorough knowledge of these therapeutic alternatives. This article explores treatment options, including the relative benefits of rate control versus rhythm control, which are complicated by the lack of highly effective and safe antiarrhythmic drugs. Anticoagulation is also an important issue in AF management, and warfarin effectively reduces the incidence of thromboembolic events in AF patients. The use of warfarin, however, presents its own complications. We conclude that individualization of therapy is paramount when treating AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. S275-S280, December 2003, Suppl.)     

Asymptomatisches Vorhofflimmern bei systematischem Screening mittels Tele-EKG

Event recorder monitoring plays an important role in the early detection and diagnosis of rhythm disorders such as atrial fibrillation (AF). In a recent study over 1000 patients with symptomatic paroxysmal AF were followed up by daily and symptom triggered ECG self monitoring. Independent of the presence of antiarrhythmic therapy, the incidence of AF was much higher than expected, since over 50% of AF episodes were asymptomatic. Therefore, patients symptoms are not a reliable surrogate parameter for the detection of AF. Moreover, antiarrhythmic therapy does not totally prevent atrial fibrillation, but raises the risk of silent AF episodes by reducing the mean heart rate. Based on these findings, effective anticoagulation should be taken into consideration in patients with paroxysmal AF independent of antiarrhythmic medication. The decision for anticoagulation with cumarine derivates or aspirin is dependent on the age, underlying diseases, and the individual thromboembolic risk in these patients.     

Does radiofrequency ablation of the slow pathway prevent atrial fibrillation in cases of re-entrant intranodal junctional tachycardia?

The aim of this study was to assess the effects of ablation of the slow pathway on the eventual occurrence of atrial fibrillation (AF) in cases of intranodal junctional tachycardia (INJT). Two hundred and fifty seven patients were admitted for recurrent paroxysmal junctional tachycardia. The ages ranged from 15 to 87 years (average 54 +/- 16 years). Tachycardia was induced in all patients and the mechanism shown to be INJT in 215 patients. Twelve of these (6%) also had spontaneous paroxysmal AF. It was possible to induce INJT and AF in 23 patients during electrophysiological study (11%): of these patients, 4 had a history of AF associated with INJT. Radiofrequency ablation of the slow pathway was successfully carried out. Patients were followed up for 1 to 6 years (average 3 +/- 2 years). None were prescribed antiarrhythmic drugs. The results showed that of the 12 patients with spontaneous AF before ablation, 8 had recurrence of paroxysmal AF which required reintroduction of an antiarrhythmic treatment and a ninth patient is currently in chronic atrial fibrillation. All but one of the patients were over 65 years of age. The AF recurred 1 month to 4 years after ablation. Of the 19 patients without previous AF but with inducible AF, 2 developed spontaneous paroxysmal AF. Of the patients without previous AF and without inducible AF, 4 aged over 65 went on to develop paroxysmal AF. The authors conclude that radiofrequency ablation of the slow pathway of patients with INJT does not seem to prevent future development of AF in elderly subjects.     

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.     

Management of the older person with atrial fibrillation.

OBJECTIVE: To review the management of the older person with atrial fibrillation (AF). DATA SOURCES: A computer-assisted search of the English language literature (MEDLINE) database followed by a manual search of the bibliographies of pertinent articles. STUDY SELECTION: Studies on the management of persons with AF were screened for review. Studies of persons older than age 60 and recent studies were emphasized. DATA EXTRACTION: Pertinent data were extracted from the reviewed articles. Emphasis was placed on studies involving older persons. Relevant articles were reviewed in depth. DATA SYNTHESIS: Available data about the management of persons with paroxysmal or chronic AF were summarized CONCLUSIONS: Management of AF includes treatment of the underlying disease and precipitating factors. Immediate direct-current cardioversion should be performed in persons with AF associated with an acute myocardial infarction, chest pain caused by myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous verapamil, diltiazem, or beta-blockers should be used to slow a very rapid ventricular rate associated with AF immediately. Oral verapamil, diltiazem, or a beta-blocker should be given if a rapid ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected persons with symptomatic life-threatening AF refractory to other drug therapy. Nondrug therapies should be performed in persons with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drug therapy. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in persons with AF who develop cerebral symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds that are not drug-induced. Elective cardioversion of AF should not be performed in asymptomatic older persons with chronic AF. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct-current or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment strategy, especially in older persons, of ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Digoxin should be avoided in persons with sinus rhythm who have a history of paroxysmal AF. Older persons with chronic or paroxysmal AF who are at high risk for stroke or who have a history of hypertension and no contraindications to warfarin should receive long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Older persons with AF who are at low risk for stroke or who have contraindications to warfarin should receive 325 mg of aspirin daily.     

Management of the older person with atrial fibrillation

Atrial fibrillation (AF) is associated with a higher incidence of mortality, stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, verapamil, or diltiazem may be given to slow immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and with symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds that are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and should be continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older persons, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Digoxin should not be used to treat patients with paroxysmal AF. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should receive 325 mg of aspirin daily.     

Oral anticoagulation during atrial fibrillation ablation: Facts and controversies

On the background of population ageing atrial fibrillation (AF) has reached epidemic dimensions in developed countries. This condition is associated with major cardiovascular morbidity and mortality mainly due to its thrombo-embolic and heart failure related complications. Left atrial (LA) catheter ablation has emerged as a suitable alternative to antiarrhythmic drugs for sinus rhythm maintenance at least for paroxysmal atrial fibrillation in the settings of no/mild LA dilatation. Chronic oral anticoagulation (OAC) is helpful to prevent AF thromboembolic complications in high-risk patients. OAC is also protective around ablation procedures in patients with or without an indication for long-term OAC therapy, emphasizing a slight increase in periprocedural risk of stroke. Due to the potential catastrophic hemorrhagic complications during trans-septal LA instrumentation, traditional approach on LA ablations involved warfarin discontinuation with periprocedural heparin bridging. Recent observational data suggests that radiofrequency (RF) catheter ablation of AF under therapeutic OAC (mainly vitamin K antagonists [VKA]) may reduce the periprocedural risk of complications, mainly thromboembolic events (possibly including silent strokes). Uninterrupted OAC has been acknowledged as an alternative to heparin bridging by the recently published consensus and guidelines update on AF ablation. Currently the recommended therapeutic level of OAC during ablation is low (such as an INR of 2–2.5). In the general AF settings new OAC (NOAC) have shown non-inferiority compared to VKA for stroke prevention, with better safety. Rapidly acting NOAC seems a tempting alternative to VKA at least for the patients taken off OAC before the ablation, possibly avoiding any post-procedural heparin bridging. However, limited experience with periprocedural use of NOAC (mainly dabigatran) suggests an increased risk of bleeding or thromboembolic complications compared with VKA.     

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. METHODS AND RESULTS: Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.     

Treatment of atrial fibrillation and atrial flutter: Part II

Atrial fibrillation (AF) is often complicated by a life-threatening ventricular response, and emergency electrocardioversion and/or drug therapy to reduce the rapid ventricular rate may be necessary. However, patients with AF and Wolff-Parkinson-White syndrome should not be given digoxin or calcium channel blockers. Elective direct current (DC) cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct current or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older patients, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an international normalized ratio of 2.0-3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should be treated with aspirin 325 mg daily. Management of atrial flutter is similar to management of AF.     

Warfarin use and outcomes in patients with advanced chronic systolic heart failure without atrial fibrillation, prior thromboembolic events, or prosthetic valves

Warfarin is often used in patients with systolic heart failure (HF) to prevent adverse outcomes. However, its long-term effect remains controversial. The objective of this study was to determine the association of warfarin use and outcomes in patients with advanced chronic systolic HF without atrial fibrillation (AF), previous thromboembolic events, or prosthetic valves. Of the 2,708 BEST patients, 1,642 were free of AF without a history of thromboembolic events and without prosthetic valves at baseline. Of these, 471 patients (29%) were receiving warfarin. Propensity scores for warfarin use were estimated for each patient and were used to assemble a matched cohort of 354 pairs of patients with and without warfarin use who were balanced on 62 baseline characteristics. Kaplan-Meier and Cox regression analyses were used to estimate the association between warfarin use and outcomes during 4.5 years of follow-up. Matched participants had a mean age ± SD of 57 ± 13 years with 24% women and 24% African-Americans. All-cause mortality occurred in 30% of matched patients in the 2 groups receiving and not receiving warfarin (hazard ratio 0.86, 95% confidence interval 0.62 to 1.19, p = 0.361). Warfarin use was not associated with cardiovascular mortality (hazard ratio 0.97, 95% confidence interval 0.68 to 1.38, p = 0.855), or HF hospitalization (hazard ratio 1.09, 95% confidence interval 0.82 to 1.44, p = 0.568). In conclusion, in patients with chronic advanced systolic HF without AF or other recommended indications for anticoagulation, prevalence of warfarin use was high. However, despite a therapeutic international normalized ratio in those receiving warfarin, its use had no significant intrinsic association with mortality and hospitalization.     

持续性与阵发性心房颤动导管射频消融肺静脉电隔离的抗凝治疗

目的探讨持续性心房颤动(简称房颤)患者导管射频消融肺静脉电隔离前后的抗凝治疗。方法2004年7月到2006年1月连续收治行射频消融治疗的持续性房颤64例,导管射频消融前需华法林抗凝治疗的阵发性房颤患者84例。所有患者术前华法林抗凝治疗使国际标准比率2.0~3.0维持至少3周。术中完成房间隔穿刺后,静脉给予肝素5000~8000U或75~100U/kg,以后每小时追加1000U或12U/kg。术后华法林抗凝治疗至少3个月。结果持续性房颤患者中1例术中心腔内超声发现消融时消融导管顶端血栓形成,术后无血栓栓塞表现,3例术后出现血栓栓塞表现,血栓栓塞发生率4.7%。阵发性房颤患者中未见血栓形成和栓塞表现。两组病例血栓形成和栓塞比较有显著差异(4/64vs0/84,P=0.033)。结论持续性房颤患者行导管射频消融肺静脉电隔离术易血栓形成和栓塞,应加强术中及术后肝素抗凝治疗。     

Clinical outcome of very late recurrence of atrial fibrillation after catheter ablation of paroxysmal atrial fibrillation

INTRODUCTION: High recurrence rate is still a major problem associated with ablation of paroxysmal atrial fibrillation (AF). Most of the recurrences occur within 6 months after ablation. The characteristics of very late recurrent AF (>12 months after ablation) have not been reported. METHODS AND RESULTS: Two hundred seven patients with drug-refractory AF underwent successful focal ablation or isolation of AF foci. After the first ablation procedure, Holter monitoring and event recorders were used to evaluate symptomatic recurrent AF. A second ablation procedure was recommended if the antiarrhythmic drugs could not control recurrent AF. During long-term follow-up (mean 30 +/- 11 months, up to 51 months), 70 patients had recurrent AF, including 13 patients (6%) with very late (>12 months) recurrent AF (group 1) and 57 patients (28%) with late (within 12 months after ablation) recurrent AF (group 2). Group 1 patients had a significantly lower incidence of multiple (> or = 2) AF foci (23% vs 63%, P = 0.02) than group 2 patients. In addition, the incidence of antiarrhythmic drugs use (38% vs 84%, P = 0.001) to maintain sinus rhythm after the first episode of recurrent AF was significantly lower in group 1 than group 2 patients, and the incidence of a second intervention procedure (8% vs 35%, P = 0.051) tended to be lower in group 1 than group 2 patients. CONCLUSION: The incidence of very late recurrent AF after ablation of paroxysmal AF is very low, and the clinical outcome of patients with very late recurrent AF is benign.     

New concepts for old drugs to maintain sinus rhythm in patients with atrial fibrillation.

Atrial fibrillation (AF) is a chronic, often progressive disease. Despite the ongoing concerted effort to improve AF therapy, often there is no remedy for curing AF and preventing the deleterious effects of the arrhythmia on health. Antiarrhythmic drug therapy is likely to remain the mainstay of therapy for many patients in the foreseeable future. Available antiarrhythmic drugs are moderately effective, which is important for patients who respond, especially given the chronic and often progressive nature of the disease. This article describes emerging concepts under clinical evaluation that attempt to improve the safety of available antiarrhythmic drugs in the treatment of recurrent AF. Two concepts are reviewed: (1) combination of an antiarrhythmic drug with a calcium channel blocker to reduce proarrhythmic side effects, and (2) "intelligent" reduction of the duration of antiarrhythmic drug therapy targeted to periods of symptomatic or likely AF recurrence.     

Early Antiarrhythmic Therapy Is No Better than Rate Control Therapy Alone for Suppression of Atrial Fibrillation After Cardiac Surgery

Background: Despite recent advances in therapy for atrial fibrillation (AF) following cardiac surgery, the potential superiority of antiarrhythmics over rate control therapy for suppression of AF has not been convincingly demonstrated. We sought to determine whether early treatment of AF following cardiac surgery with antiarrhythmics improves clinical outcome, as measured by recurrence rate, length of stay, and adverse events. Methods: Out of 1100 consecutive patients undergoing cardiovascular surgery from July 1997 to June 1998, AF was identified in 425 (38.6%) prior to discharge. Patients with a history of chronic AF prior to cardiovascular surgery and patients who died within 48 hours of cardiovascular surgery were excluded from the analysis; 365 patients were studied. Group I patients received rate control alone; Group II received antiarrhythmic drugs within 24 hours of the first onset of AF. Results: With the exception of frequency of pulmonary disease (4 vs 17, P = 0.009), CABG rate (35 vs 45%, P = 0.045), and rate of valve surgery (24 vs 15%, P = 0.028), there were no significant differences in clinical characteristics between the two groups. The rate of return to sinus rhythm within 24 hours (80 vs 82%), and the percentage of patients leaving the hospital in sinus rhythm (90 vs 92%) were similar between the two groups, as were total length of stay (10.6 ± 6.0 vs. 11.4 ± 5.8, P = 0.159) and postoperative length of stay (8.4 ± 15.0 vs. 9.4 ± 5.3, P = 0.061). Embolic event rates were similar in both groups (eight in Group I and three in Group II). Proarrhythmia occurred in two patients receiving early antiarrhythmic therapy. Conclusion: Traditional use of early antiarrhythmic therapy appears to provide no clear advantage to rate control after cardiovascular surgery in terms of length of stay, freedom from AF at discharge, and other common clinical outcomes. Routine use of antiarrhythmics for suppression of AF should be carefully reconsidered. A.N.E. 2000;5(4):365–372     

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.