The future of atrial fibrillation therapy

Today management of atrial fibrillation (AF) centers on restoration and maintenance of normal sinus rhythm or control of the ventricular rate response to AF. Current guidelines state that rhythm and rate control strategies should be considered therapeutically equivalent, but recognize that no "one size fits all," an approach consistent with growing recognition of the heterogeneity of AF. As data from the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial clearly demonstrate, conventional antiarrhythmics have a role in highly symptomatic AF accompanied by decreased quality of life. However, for many AF patients such drugs lack efficacy, have potentially serious side effects, and are poorly tolerated. In parallel with the development of more effective and safer antiarrhythmics, nontraditional approaches to prevention and treatment of AF are being explored. Treatments not considered "antiarrhythmic" that may prevent or forestall AF include aggressive antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and some, but not all, beta-blockers and calcium channel antagonists, especially when used as adjunctive therapy. Other approaches include statins, steroids, and fish oil to reduce atrial fibrosis and inflammation, and pacemakers to prevent bradycardia-mediated AF and as a pacing preventive strategy in selected patients. Ablative techniques with potential to cure AF are gaining popularity, but are not yet simple, straightforward, and risk-free procedures. In the future, treatment of AF will progress beyond today's focus on AF as a purely electrocardiographic disease toward a patient and context-specific management strategy involving multiple treatment modalities.     

Prevention of recurrences of atrial fibrillation by cardiologists established in general office practice: data from the FAUVE observatory

OBJECTIVES: Analyse the modalities of preventive therapy of recurrences of paroxysmal or persistent atrial fibrillation (AF) with Vaughan-Williams (VW) type IC antiarrhythmics. METHODS: Observational study conducted with 326 French cardiologists established in general office practice, involving on the one hand an opinion survey among the cardiologists and on the other hand a cross-sectional observatory of usual medical practice. Each cardiologist was asked to include two patients aged less than 65 with non-permanent (paroxysmal or persistent) AF without left ventricle dysfunction (LVD) and initiated on treatment with a VW type IC antiarrhythmic after cardioversion to sinus rhythm. RESULTS: The opinion survey among the cardiologists indicates that non-permanent AF constitutes 36.1% of AF cases, of which 57.8% concern LVD-free patients. Most cardiologists (85%) declare to institute a preventive therapy of AF recurrences in 70-100% of these patients after cardioversion to sinus rhythm, with a VW type IC antiarrhythmic in more than 50% of cases. Of the 633 patients included in the FAUVE observatory, mainly men, 409 (64.6%) had paroxysmal AF and 224 (35.4%) had persistent AF. Analysis of therapeutic management shows that both alteration of the previous treatment and the choice of a VW type IC antiarrhythmic are based chiefly on efficacy and on tolerability of the antiarrhythmic therapy. CONCLUSION: VW type IC antiarrhythmics constitute a therapy of choice for the maintenance of sinus rhythm in non-aged and LVD-free patients with non-permanent AF.     

Antiarrhythmic therapy--recent aspects of pharmacologic treatment

Over the last years the indication for antiarrhythmic therapy has changed due to the development of other therapeutic approaches. However, antiarrhythmics are important in the acute treatment as well as the prevention of recurrent rhythm disorders. In line with the antiarrhythmic agents of class IC and III also beta-blockers, ACE inhibitors and AT (1) antagonists can be used primarily with a lower risk of severe cardiac side effects. Recent studies demonstrate that for patients with atrial fibrillation there was no benefit of rhythm control versus rate control. However, rhythm control with antiarrhythmics is beneficial in the treatment of highly symptomatic or hemodynamically compromised patients. Hybrid therapy and the "pill in the pocket"-strategy seem to be potent new therapeutic options.     

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: rate and rhythm management

The goals of atrial fibrillation (AF) and atrial flutter (AFL) arrhythmia management are to alleviate patient symptoms, improve patient quality of life, and minimize the morbidity associated with AF and AFL. Arrhythmia management usually commences with drugs to slow the ventricular rate. The addition of class I or class III antiarrhythmic drugs for restoration or maintenance of sinus rhythm is largely determined by patient symptoms and preferences. For rate control, treatment of persistent or permanent AF and AFL should aim for a resting heart rate of <100 beats per minute. Beta-blockers or nondihydropyridine calcium channel blockers are the initial therapy for rate control of AF and AFL in most patients without a history of myocardial infarction or left ventricular dysfunction. Digoxin is not recommended as monotherapy for rate control in active patients. Digoxin and dronedarone may be used in combination with other agents to optimize rate control. The first-choice antiarrhythmic drug for maintenance of sinus rhythm in patients with non structural heart disease can be any one of dronedarone, flecainide, propafenone, or sotalol. In patients with abnormal ventricular function but left ventricular ejection fraction >35%, dronedarone, sotalol, or amiodarone is recommended. In patients with left ventricular ejection fraction <35%, amiodarone is the only drug usually recommended. Intermittent antiarrhythmic drug therapy ("pill in the pocket") may be considered in symptomatic patients with infrequent, longer-lasting episodes of AF or AFL as an alternative to daily antiarrhythmic therapy. Referral for ablation of AF may be considered for patients who remain symptomatic after adequate trials of antiarrhythmic drug therapy and in whom a rhythm control strategy remains desired.     

Do we need pharmacological therapy for atrial fibrillation in the ablation era?

Management of atrial fibrillation (AF) remains one of the most difficult problems of modern cardiology. Pharmacological antiarrhythmic therapy is used both for termination of episodes of AF and for prevention of AF recurrences. Recently, major trials have compared the strategy of maintenance of sinus rhythm, called rhythm control, with the strategy of heart rate control during AF and found that the rhythm control strategy was not superior to rate control in terms of mortality. Although subsequent analysis identified rhythm control as a factor of improved survival, these large trials have markedly influenced the management of AF. One of the hypotheses explaining the non-superiority of the rhythm control strategy was that the benefit of sinus rhythm was offset by the side effects of antiarrhythmic agents. As a consequence, attention was directed to non-pharmacological therapies, particularly to catheter ablation of the trigger or/and the atrial substrate using radiofrequency current or cryothermia. However, despite the reported good results of various types of interventions in the hands of highly qualified teams, catheter ablation cannot be applied to all patients with AF or to all types of AF. Furthermore, catheter ablation of AF requires sophisticated electrophysiologic laboratories equipped with expensive imaging techniques and a well-trained staff that cannot be available in sufficient number to cover the growing epidemic of AF with acceptable efficacy and safety even in rich countries. Therefore, there is still a need for pharmacological therapy aimed at the prevention of AF recurrences for the majority of AF patients. So far, attempts to provide the physician with efficient antiarrhythmic agents having a good safety profile have not been successful. However, recent research resulted in promising new approaches including prevention of AF using converting enzyme inhibitors or angiotensin 2 receptor blockers, new antiarrhythmic agents with multichannel effects such as dronedarone and tedisamil and atrial specific agents that theoretically should have no ventricular proarrhythmic effect as they target specific atrial channels such as I_KAch and I_Kur which are absent at the ventricular level. Other possible mechanisms of AF that represent potential targets, such as modification of stretch-activated ion channels, intervention of altered connexin expression and altered gap-junctional conductance, are currently investigated.     

Angiotensin Receptor Blocker as Adjunctive Therapy for Rhythm Control in Atrial Fibrillation: Results of the Irbesartan-Amiodarone Trial

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of stroke and mortality. The early appearance of electrical remodeling is followed by structural remodeling of the atrial tissue. Direct current cardioversion of persistent AF is the most effective treatment for the restoration of sinus rhythm, but it is hampered by a high percentage of recurrences. Recurrences may be the consequence of both electrical and structural remodeling. A study on the use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent AF showed that this angiotensin II receptor blocker combined with amiodarone prolonged sinus rhythm after cardioversion. Irbesartan may have antifibrotic effects due not only to the ability to diminish the synthesis of collagen type I molecules but also to its capacity to stimulate the degradation of collagen type I fibers, as has been demonstrated with losartan, another angiotensin II receptor blocker. This suggests that efforts to reduce the structural changes that occur during AF may be more useful in preventing recurrences than efforts designed to minimize the electrical changes alone. The AFFIRM trial compared two approaches to the treatment of AF: cardioversion with antiarrhythmic drugs to maintain sinus rhythm and the use of rate-controlling drugs. The results show that management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy. However, non-antiarrhythmic drugs to prevent recurrences, like irbesartan, were not controlled and amiodarone was used in a low percentage of the patients. The treatment strategies proposed in both AFFIRM and RACE, in our opinion, may not be the optimal. The modern clinical approach to AF involves an early intervention to restore sinus rhythm, therefore preventing atrial remodeling. The pretreatment of patients with AF who undergo electrical cardioversion is very important and will be the subject for continuous improvement.     

Antiarrhythmic drug therapy for atrial fibrillation: Are the guidelines guiding clinical practice?

The AFFIRM study showed no clear survival advantage for a rhythm versus rate control strategy in patients with atrial fibrillation (AF). However, rhythm control with antiarrhythmic drugs (AADs) is appropriate in a large number of patients with AF. The American College of Cardiology/ American Heart Association/European Society of Cardiology AF management guidelines include a safety-based algorithm for selection of AAD therapy. Class 1C agents are recommended as first-line therapy in patients without or with minimal structural heart disease. However, market research and clinical study data indicate a growing use of class III agents (mainly amiodarone) despite long-term safety and tolerability concerns, suggesting that clinical practice does not adhere to current guidelines.     

Implication from Randomized Trials of Rate and Rhythm Controls on Management of Patients with Persistent Atrial Fibrillation

Recently, several randomized trials were published on the issue of rate or rhythm control for patients with atrial fibrillation (AF). Patients were typically minor symptomatic, relatively old, with age above 70, presenting with a recurrence of AF and suffering from only mild to moderate underlying heart disease. The main outcome of these trials is that rate control is not inferior to rhythm control for the management of patients with AF concerning morbidity and mortality. Also patients' quality of life did not differ significantly in follow‐up in these trials. However, rhythm control is not redundant in the treatment of AF. Focus is now on subgroups of patients who could still have benefit being in sinus rhythm. For severely symptomatic patients, patients presenting with the first episode of AF and probably those with severe congestive heart failure, to restore and maintain sinus rhythm should still be the goal. With the failure of antiarrhythmic therapy, nonpharmacological approaches such as pulmonary vein isolation can be performed. Another finding of the randomized trials is that being in sinus rhythm does not prevent from the occurrence of thromboembolic complications. This means that for patients with AF, with risk factors for thromboembolic events, adequate anticoagulant therapy is indicated irrespective of the current heart rhythm. As with antiarrhythmic therapy, the search for new and safer anticoagulant therapy is underway. This review will focus on the key aspects we have learned from the randomized trials on rate and rhythm controls for patients with AF.     

Oral class III antiarrhythmics: what is new?

PURPOSE OF REVIEW: This review describes the latest developments in the clinical usage of class III antiarrhythmics. It also discusses some new studies providing insight into the mechanism of action of these drugs. RECENT FINDINGS: New data suggest that amiodarone is one of the most effective drugs for management of ventricular as well as supraventricular tachyarrhythmias. As over the years we have learned to deal with the toxic side effects of this drug, the risk of bradyarrhythmias requiring placement of a pacemaker is becoming more significant. Sotalol was approved for treatment of atrial fibrillation and atrial flutter (AF). It was also found to be effective in management of postoperative AF. Dofetilide has been approved for the conversion and maintenance of sinus rhythm in AF; its role in ventricular arrhythmias remains unclear. Data are emerging regarding clinical efficacy of azimilide and dronedarone. SUMMARY: Management of arrhythmias in patients with structural heart disease remains a challenge. Class III antiarrhythmics are the mainstay of treatment in this group of patients.     

Management of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. It is common in the elderly and those with structural heart disease. Clinical classification can be helpful in treatment decisions and the most widely accepted classification scheme (first episode, recurrent paroxysmal, recurrent persistent, permanent) is found in the ACC/AHA/ESC guidelines. The pathophysiology of AF remains unclear at this time. It is unlikely that a single pathophysiology is operative in all or even a majority of cases. Therapies to be considered for AF include prevention of thromboembolism, rate control, and restoration and maintenance of sinus rhythm. These therapies and specific treatments for these purposes are discussed under these headings, including a section on the relative merits of the rate control and rhythm control strategies. Risk stratification is a fundamental part of the treatment for thromboembolism. When risk warrants treatment, prevention of thromboembolism is achieved either pharmacologically with aspirin, or with warfarin or new agents like ximelagatran, or by nonpharmacological approaches. Schema to assist in risk stratification and selection of appropriate antithrombotic therapy are provided. Recent trials comparing the strategy of rate control to the strategy of rhythm control failed to demonstrate that the rhythm control approach is superior to the rate control approach in patients and therapies studied so far. Rate control is an acceptable primary line of therapy in many patients, particularly the elderly with persistent AF who are not highly symptomatic. However, the risk and benefit of each treatment modality should be individualized according to the patient circumstances and comorbidity. Algorithms to help individualize which of the two strategies to use are provided. There are a number of pharmacologic and nonpharmacologic therapies available for rhythm management of AF. Pharmacologic cardioversion is an alternative to electrical cardioversion for recent onset AF but the latter is preferred for persistent AF. Current drug therapy to maintain sinus rhythm is neither highly effective nor completely safe. An algorithm to guide selection of the most appropriate antiarrhythmic drug for an individual patient is provided. Nonpharmacologic therapies for maintenance of sinus rhythm include surgery, radiofrequency ablation, devices, and hybrid (combination) therapies. Much remains to be learned about the role and application of such therapies. Pharmacologic heart rate control can be achieved for most patients with available agents and, when it cannot, there are effective nonpharmacologic therapies. A few specific situations in which AF occurs and for which there are some special considerations are described.     

Atrial fibrillation in heart failure: catheter and surgical interventional therapies

Atrial fibrillation and heart failure commonly coexist in the same patient. Each may adversely affect the other. Atrial fibrillation leads to heart failure exacerbation, left ventricular function deterioration and an increase in thrombo-embolic risk. Therapeutic options targeting atrial fibrillation in heart failure patients include pharmacological and non-pharmacological means. Pharmacological therapy is directed at either rate control using nodal blocking agents or rhythm control using anti-arrhythmic agents, of which the options are limited in patients with heart failure. The landmark AF–CHF trial did not show any benefit of rhythm control strategy as opposed to rate control in patients with heart failure and atrial fibrillation. However, patients in this trial as well as in others used mostly amiodarone for rhythm control. This might have negated any positive effects of achieving normal sinus rhythm. Non-pharmacological therapy both for rate and rhythm control is appealing. This includes AV node ablation for rate control, catheter ablation of atrial fibrillation and surgical therapy of atrial fibrillation. This review will address non-pharmacologic treatment of AF in heart failure patients.     

Systematic review of the management of atrial fibrillation in patients with heart failure.

AIMS: To systematically review the management of atrial fibrillation (AF) in patients with heart failure. METHODS: Studies investigating the management of AF in patients with heart failure published between 1967 to 1998 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. RESULTS: Eight studies pertaining to acute and twenty-four pertaining to chronic AF were identified. For patients with acute AF ventricular rate control, anticoagulation and treatment of heart failure should be pursued simultaneously before cardioversion is attempted. Digoxin is relatively ineffective at controlling ventricular response and for cardioversion. Intravenous diltiazem is rapidly effective in controlling ventricular rate and limited evidence suggests it is safe. Amiodarone controls ventricular rate rapidly and increases the rate of cardioversion. There are insufficient data to conclude that immediate anti-coagulation, trans-oesophageal echocardiography to exclude atrial thrombi followed by immediate cardioversion is an appropriate strategy. Patients with chronic AF should be anti-coagulated unless contra-indications exist. It is not clear whether the preferred strategy should be cardioversion and maintenance of sinus rhythm with amiodarone or ventricular rate control of AF combined with anticoagulation to improve outcome including symptoms, morbidity and survival. Electrical cardioversion has a high initial success rate but there is also a high risk of early relapse. Amiodarone currently appears the most effective and safest therapy for maintaining sinus rhythm post-cardioversion. Digoxin is fairly ineffective at controlling ventricular rate during exercise. Addition of a beta-blocker reduces ventricular rate and improves symptoms. Whether digoxin is required in addition to beta-blockade for the control of AF in this setting is currently under investigation. If pharmacological therapy is ineffective or not tolerated then atrio-ventricular node ablation and permanent pacemaker implantation should be considered. CONCLUSION: There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.     

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: catheter ablation for atrial fibrillation/atrial flutter

Catheter ablation of atrial fibrillation (AF) offers a promising treatment for the maintenance of sinus rhythm in patients for whom a rhythm control strategy is desired. While the precise mechanisms of AF are incompletely understood, there is substantial evidence that in many cases (particularly for paroxysmal AF), ectopic activity most commonly located in and around the pulmonary veins of the left atrium plays a central role in triggering and/or maintaining arrhythmic episodes. Catheter ablation involves electrically disconnecting the pulmonary veins from the rest of the left atrium to prevent AF from being triggered. Further substrate modification may be required in patients with more persistent AF. Successful ablation of AF has never been shown to alter mortality or obviate the need for oral anticoagulation; thus, the primary indication for this procedure should be improvement of symptoms caused by AF. The success rate of catheter ablation for AF is superior to the efficacy of antiarrhythmic drugs, but success is still in the range of 75%-90% after 2 procedures. Ablation is also associated with a complication rate of 2%-3%. Thus, ablation should primarily be used as a second-line therapy after failure of antiarrhythmic drugs. In contrast to AF, catheter ablation of atrial flutter has a higher success rate with a smaller incidence of complications. Thus, catheter ablation for atrial flutter may be considered a first-line alternative to antiarrhythmic drugs.     

Present concepts in management of atrial fibrillation: From drug therapy to ablation

Atrial fibrillation (AF) management requires knowledge of its pattern of presentation, underlying conditions, and decisions about restoration and maintenance of sinus rhythm, control of the ventricular rate, and anti-thrombotic therapy. Maintenance of sinus rhythm is a desirable goal in AF patients because the prevention of recurrence may improve cardiac function, relieve symptoms and reduce the likelihood of adverse events. Anti-arrhythmic drug therapy is the first-line treatment for patients with paroxysmal and persistent AF based on current guidelines. However, currently used drugs have limited efficacy and cause cardiac and extracardiac toxicity. Thus, there is a continued need to develop new drugs, device and ablative approaches to rhythm management. Additionally, simpler and safer stroke prevention regimens are needed for AF patients on life-long anticoagulation, including occlusion of the left atrial appendage. The results of the Randomized Evaluation of Long-Term Anticoagulant Therapy study are encouraging in these settings. Knowledge on the pathophysiology of AF is rapidly expanding and identification of focally localized triggers has led to the development of new treatment options for this arrhythmia. Conversely, the clinical decision whether to restore and maintain sinus rhythm or simply control the ventricular rate has remained a matter of intense debate. In the minority of patients in whom AF cannot be adequately managed by pharmacological therapy, the most appropriate type of non-pharmacological therapy must be selected on an individualized basis. Curative treatment of AF with catheter ablation is now a legitimate option for a large number of patients. The evolution of hybrid therapy, in which two or more different strategies are employed in the same patient, may be an effective approach to management of AF. In any case, planning a treatment regimen for AF should include evaluation of the risks inherent in the use of various drugs as well as more invasive strategies.     

Rate versus rhythm control strategies for AF

Optional statement The safest long-term management strategy for elderly patients with persistent or recurrent episodes of atrial fibrillation (AF) is careful rate control with medications in conjunction with appropriate oral warfarin anticoagulation. Atrioventricular junctional ablation, with pacemaker implantation, may be necessary in patients who cannot have their rate controlled adequately, or have marked fluctuations in rate with standard medical therapies. Maintenance of sinus rhythm with repeat cardioversions, antiarrhythmic medications, device therapy, or atrial ablation approaches are appropriate to consider for younger patients and those elderly patients who suffer from substantial symptoms shown to be related directly to AF.     

Chronic Atrial Fibrillation

ABSTRACT One hundred consecutive patients admitted in 1980–82 for direct current conversion of chronic atrial fibrillation (AF) were followed. The first attempt to convert was made without the institution of class I antiarrhythmics. If AF relapsed, patients were selected for further conversions, in connection with which quinidine or disopyramide treatment was instituted. The proportion of patients maintaining sinus rhythm (SR) one and two years after the first conversion was 23% and 16%, after the second conversion 40% and 33% and after any number of conversions [1–12] 54% and 41%. Fifty-three per cent of the patients were symptomless before at least one conversion. Of the patients maintaining SR two years after conversion, 46% did not receive antiarrhythmic therapy. More than two conversions should be exceptional since symptoms of AF are often absent and the additional effect of further conversions is minor. A first attempt to convert without antiarrhythmics identifies a substantial proportion of patients maintaining SR without any prophylactic antiarrhythmic therapy.     

Non-antiarrhythmic medications for atrial fibrillation: From bench to clinical practice

Many treatment modalities have been developed over the years for the management of atrial fibrillation (AF). While they are still considered the first line of treatment for suppression of AF, antiarrhythmics often lead to treatment failure, complications and undesired consequences. Pulmonary vein ablation is an invasive procedure which is not always curative. Recently, there have been a variety of studies reporting the potential antiarrhythmic effects of various nonantiarrhythmic agents. This paper aims to provide a comprehensive review of the findings reported thus far about the antiarrhythmic effects of agents which are not antiarrhythmic drugs themselves, but which have been found to offer promise in the prevention and treatment of AF.     

“Pills and Pulses”: Hybrid Therapy for Atrial Fibrillation

Hybrid Therapy for Atrial Fibrillation. Nonpharmacologic techniques are being increasingly applied to the treatment of atrial fibrillation (AF). None of these techniques (other than maze surgery) begins to approach 100% efficacy for long‐term elimination of arrhythmia. This review examines the evidence for “hybrid” therapy, using combinations of drug and nonpharmacologic treatments. The immediate success rate of electrical cardioversion can be increased with amiodarone or ibutilide, and a number of drugs reduce the risk of AF recurrence. Preventing or reversing electrical atrial remodeling is an attractive strategy for maintenance of sinus rhythm. However, the available evidence (relating to the use of verapamil) is limited and conflicting. Ablation of the cavotricuspid isthmus is effective when antiarrhythmic drugs given for AF give rise to typical flutter. Isthmus and other right atrial linear lesions are poor as a sole therapy for AF, but better when drugs are added. Better still is the combination of left atrial linear lesions with drugs. In patients with AF recurrence following focal ablation/pulmonary vein isolation procedures, drugs are an alternative to extensive linear ablation. Some studies indicate that pacing to prevent AF may be effective, but rarely without continued antiarrhythmic drug therapy. This may represent a specific effect or simply improved drug tolerance. Drugs also might assist pacemaker therapy by increasing the proportion of atrial arrhythmias that are highly organized and thus amenable to antitachycardia pacing. This and other forms of hybrid therapy will remain the subject of conjecture in the absence of controlled clinical trials, which are urgently needed.     

Long-term rhythm control of drug-refractory atrial fibrillation with "hybrid therapy" incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation

We evaluated the long-term efficacy, safety, and applicability of a "hybrid" therapy strategy for rhythm control in atrial fibrillation (AF), incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation. One hundred thirteen patients (paroxysmal AF [n = 70], persistent/permanent AF [n = 43]) with refractory symptomatic AF were treated with this strategy and followed for 1 to 81 months (mean 30 +/- 23). All-cause mortality, AF recurrences, and progression to permanent AF were monitored and recorded by implanted device data logs. There was no procedural mortality. Rhythm control was achieved in 90% of all patients at 3 and 5 years, with comparable efficacy in subpopulations with paroxysmal (98%), persistent, or permanent AF (87%, p >2). Overall survival was 84% at 3 years and 80% at 5 years, and was higher in patients with paroxysmal AF than in patients with persistent or permanent AF (86% vs 67% at 4 years, p <0.001). Patients with persistent or permanent AF had a greater need for cardioversion (p <0.004) and right atrial ablation (p <0.04) than patients with paroxysmal AF to achieve comparable rhythm control. A hybrid therapy strategy can provide safe and effective long-term rhythm control in patients with drug-refractory AF, and can be implemented in subpopulations presenting with paroxysmal, persistent, or permanent AF.