Ann Thorac Surg 2006;82:357-364
© 2006 The Society of Thoracic Surgeons
Review
Current Strategies in the Management of Atrial Fibrillation
Marjan Jahangiri, FRCS
a
,
*
,
Graeme Weir, MRCS
a
,
Kaushik Mandal, FRCS
a
,
Irina Savelieva, MD
b
,
John Camm, FRCP
b
a Department of Cardiac Surgery, St. George's Hospital Medical School, London, United Kingdom
b Department of Cardiac and Vascular Sciences, St. George's Hospital Medical School, London, United Kingdom
* Address correspondence to Dr Jahangiri, Department of Cardiac Surgery, St. George's Hospital, Blackshaw Road, London SW17 OQT, United Kingdom (Email: marjan.jahangiri{at}stgeorges.nhs.uk).
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Abstract
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Treatment of atrial fibrillation (AF) has been undergoing significant changes recently. This is due partly to different mechanisms proposed for persistent and permanent AF and partly due to the introduction of energy-based techniques, providing less invasive procedures. This article aims to review the mechanisms of AF leading to the changes in clinical practice and to review the results of surgery, energy-based, and percutaneous techniques. It is difficult to compare and contrast the results of reported series in the literature due to different definitions of AF; freedom from and recurrence of it. Furthermore, in most series it is difficult to distinguish results of surgery for lone AF and AF associated with valvular heart disease and coronary artery disease.
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Material and Methods
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An English literature search using the Pubmed-Medline database between 1960 and today was carried out. Key words used included fibrillation, atrial fibrillation (AF), cardiac surgery, surgery, ablation, and percutaneous ablation. A search on energy-based techniques using the key words radiofrequency, microwave, and cryothermy was also carried out.
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Definition of AF
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The use of inconsistent terminology in different studies has made comparison and analysis of literature difficult. Some of the terms used include paroxysmal, persistent, permanent, intermittent, chronic, and continuous. The American College of Cardiology, American Heart Association, and European Society of Cardiology practice guidelines [1] recommend that when a patient has had two or more episodes, AF is considered recurrent. Once terminated, recurrent AF is designated paroxysmal and when sustained is designated persistent. Persistent AF does not terminate spontaneously and requires electrical and/or pharmacologic measures to restore sinus rhythm. However, permanent AF is not cardioverted by electrical and/or pharmacologic measures. We have previously classified AF into acute and chronic; acute having an onset within 24 to 48 hours with a high chance of cardioversion and chronic consisting of paroxysmal, persistent, and permanent [2, 3].
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Incidence of AF
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The incidence of AF, the most common cardiac arrhythmia in the general population [4], is increasing as the population ages [5, 6]. The incidence of new-onset AF doubles with each successive decade after 50 years with 10% of patients in their eighth decade suffering from this condition [7]. Independent risk factors for the development of AF include increasing age, diabetes, left ventricular hypertrophy, coronary heart disease, and valvular heart disease [8]. The Coronary Artery Surgery Study registry revealed that 116 (0.6%) of 18,343 patients with angiographically demonstrated coronary artery disease had AF [9], while 38-year follow-up data from The Framingham Study have shown that valvular heart disease is associated with a 1.8-fold increase of AF in men and a 3.4-fold increase in women [7, 8]. The prevalence of AF in patients with mitral valve disease ranges between 30% and 84% [10, 11].
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Mechanisms of AF
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Understanding the mechanisms of AF lies at the fulcrum of its treatment, especially with the recent introduction of reduced ablation lines applied percutaneously and surgically. It is important to distinguish the "triggers" from "drivers." Haissaguerre and colleagues [12] reported that paroxysmal AF is induced by triggers located in the pulmonary veins in approximately 90% of cases and lie outside the region of the pulmonary veins in the remaining 10%. Therefore, 90% of patients with paroxysmal AF should be cured with pulmonary vein isolation alone.
An issue of controversy is what comprises the drivers causing continuous AF. Is it the macro reentry circuits in the atria or the triggers in the pulmonary veins? The Cox-maze procedure has been based on the concept of the macro reentry circuits based in the atria that perpetuate AF [13]. This concept has been supported by the computer models devised by Moe and colleagues [14], where multiple wandering wavelets are present during AF. It is further supported by Allessie [15] demonstrating that AF induces both electrophysiologic and structural changes in the atria favoring its maintenance. Therefore, to abolish AF the macro reentrant circuits have to be interrupted and simple pulmonary vein isolation will have little role in the treatment of chronic AF [16].
Others believe that drivers to AF are predominantly within pulmonary veins and therefore pulmonary vein isolation for chronic AF should suffice [17]. To support this theory, Todd and colleagues [18] have reported 14 patients with chronic AF with excellent clinical outcome. However, in their study they did not solely perform pulmonary vein isolation, but also performed left atrial excision, pulmonary vein to mitral annulus line, and cryoablation of the right atrial isthmus. Sahadevan and colleagues [19] showed that a driver in the pulmonary vein may be responsible for chronic AF. Others have reported that a more circumferential isolation of the pulmonary veins, including the antrum of the pulmonary veins, increases the ablation success [20, 21]. Therefore, it may be that the drivers are not placed solely in the pulmonary veins, and by extending the ablation area into the antrum of the pulmonary veins and the left atrium, the macro reentrant circuits are interrupted.
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Surgical Procedures
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Cox-Maze
The Cox-maze procedure (CMP) was first introduced in 1991 [13] in a small series of seven patients. Follow-up studies of the first 32 patients who underwent CMP I at six months showed an increased incidence of a blunted sinus node response to maximum exercise and a high incidence of left atrial dysfunction and increased pacemaker implantation [22]. The CMP II had similar problems and required transection of the superior vena cava, and therefore it was thought technically demanding and was subsequently abandoned [23]. Therefore, surgical technique was modified and CMP III evolved [24]. This has been considered the optimum surgical technique for treatment of refractory atrial flutter and AF. Cox and colleagues, in their subsequent series [25], have reported freedom from AF at 10 years with CMP III of 89.3%, but 75.4% and 83.6% with CMP I and II, respectively [25]. The operative mortality in their series has been 1.2% to 1.8% [26] with reoperation for bleeding of up to 7%.
Similar results have been reported by the Cleveland group [27] with a 30-day mortality of 1%, restoration of sinus rhythm in 90% at a mean follow-up of three years, and perioperative pacemaker implantation of 6%. However, not all groups have matched these results. Izumoto and colleagues [28], in a series of 87 patients, have reported a mortality of 4.6%, restoration of sinus rhythm of 79.5%, and reoperation for bleeding of 8% (Table 1). Due to the technical demands and variable outcomes the CMP III has evolved with many surgical modifications, with or without energy-based techniques to simplify the original operation.
Several groups have chosen to omit some of the incisions of CMP III. This has made comparison of results difficult. The discrepancy in the results of different series and, in some reports, inferior results to CMP III may be due to the omission of some of these surgical lines or the inadequacy of energy-based techniques.
Mini-Partial Maze
These are procedures where one or more lines of ablation of the CMP III have been modified, omitted, or replaced with an energy-based technique [29, 30]. Schaff and colleagues [31], in their series of 221 patients, omitted the incision along the medial aspect of the right atrium from the tricuspid annulus to the cut edge of the right atrial appendage and instead applied lines of cryolesion to the atrial myocardium to minimize the risk of interruption of the coronary blood supply to the sinoatrial node. They have reported a mortality of 1.4%, bleeding of 5%, and a pacemaker implantation of 3.2%. In the majority of the partial maze procedures, the coronary sinus lesions are omitted, which can increase the risk of atrial flutter [32]. There are several reports of the partial maze procedures using various forms of energy.
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Energy-Based Procedures
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In an attempt to simplify CMP III, reduce cardiopulmonary bypass, cross-clamp times, and perioperative bleeding associated with CMP III and its modifications, use of energy source has replaced some or all of the incisions of the original operation. Generally, energy-based techniques are less effective than pure CMP III.
Transmural lesions are believed to be necessary to prevent escape of energy resulting in breakthrough of AF. The lesions produced have to be in continuity directly or have additional surgical lines to avoid breakthrough of AF. The ideal source of energy and device should achieve transmurality, cause no damage to the neighboring structures, provide fast application, and have malleable, nonbulky probes.
Radiofrequency
This type of energy uses alternating electrical current of 100 KHz to 1 MHz to heat tissue, reaching temperatures of 80°C in one minute [33]. There are several studies reporting on the use of radiofrequency (RF) energy in the treatment of AF. As stated earlier, it is difficult to compare and contrast these studies due to variable classification of AF, methodology, and follow-up. Furthermore, pacemaker implantation rate is reported at different follow-up intervals. The results of some of these studies are shown in Table 2. The average freedom from AF varies between 70% and 90%. The majority have used unipolar RF ablation. Sie and colleagues [34] have used unipolar irrigated, Gillinov and McCarthy [35] and Mokadam and colleagues [36] have used bipolar, and Khargi and colleagues [37] have used unipolar irrigated systems.
Unipolar Versus Bipolar Radiofrequency
The unipolar probe drives the current from an active electrode to an indifferent electrode and back to the generator. The current is converted into thermal energy and the high temperatures produced at tissue level can cause vaporization and charring. With the unipolar probe, energy travels both through the tissue and in a multidirectional manner. The latter can result in damage of the neighboring structures [38] like the esophagus and coronary arteries [39, 40]. A further disadvantage of the unipolar probe is the uncertainty of transmurality, especially when used on the beating heart [41]. Sie and colleagues [42] used the unipolar probe and performed a complete CMP III, achieving 78% freedom from AF. These are comparable with other surgical series [43, 44].
The bipolar system provides both epicardial and endocardial therapy. Prasad and colleagues [45] have demonstrated several advantages of bipolar in animal experimentation. With bipolar, the tissue receives just enough energy to produce a transmural lesion and shortening ablation time. It also decreases thermal spread and thus reduces the amount of nearby tissue subject to contracture and subsequent stenosis. Contracture and pulmonary vein stenosis are seen with percutaneous catheter ablation [46]. In addition, a bipolar system would avoid damage to the mediastinal structures at the back of the heart.
Irrigated Versus Nonirrigated Radiofrequency
Irrigated systems using saline-irrigated cooled tip catheters or bipolar probes allow delivery of a higher amount of energy due to improved conductivity created by the use of saline. The normal saline irrigation cools the surface tissue and lowers the impedance at the tissue-electrode interface, improving efficacy [47, 48].
Microwave
The mechanism of ablation using microwave is by heating. Microwaves cause oscillation of water molecules in tissue, converting electromagnetic energy into heat. The microwave energy penetrates the tissues at different depths depending on the type of probe. There are several articles on microwave ablation for surgical treatment of AF [49–51], reporting success rates of 70% to 90%. The epicardial approach is less commonly applied.
Cryothermy
Cryothermy ablates tissue as intracellular ice crystals disrupt cell membranes while leaving collagen structure intact. Lesions created by cryothermy heal by fibrosis, leaving a dense homogenous lesion. It has long been in use by both cardiologists and surgeons [13, 22]. Cox and Ad have [32] reported its use in ablation of the coronary sinus. Nakajima and colleagues [52] have shown that the use of cryothermy can decrease cardiopulmonary bypass and cross-clamp time with significantly less chest tube drainage. It can be applied both endocardially and epicardially and produces no char. The original cryoprobes were rigid, making their use difficult. However, the new probes have a flexible 6-cm cooling segment that can be shaped to different anatomic structures.
Gillinov and colleagues [53] have compared and contrasted these various forms of energy and have concluded that assessment of transmurality is really only available for radiofrequency and not for microwave and cryothermy. However, the latter two forms of energy do not produce any charring compared with radiofrequency. Several other issues and alternatives of the CMP III pattern, which are thought to influence the outcome of surgery, are discussed below.
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Effect of Concomitant Surgery
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Cox and colleagues [54] report their results of CMP III in 83 patients who underwent 96 valve procedures with an overall mortality of 6% compared with 1.9% in those not having valve surgery. The incidence of perioperative atrial arrhythmias was the same in both groups. Multivariate analysis of the cohort showed that concomitant valve surgery was not an independent risk factor. Others have reported a lower freedom from AF with concomitant procedures, but this may be due to different surgical techniques and incomplete CMP III [28]. The cardiopulmonary bypass and cross-clamp times have been longer in concomitant procedures, but these results are from earlier studies and generally these times have been reduced in more recent studies especially with the use of energy-based techniques [41]. The type of lesions required for the treatment of AF should be determined according to the type of AF and not according to the need for concomitant procedure.
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Is Pulmonary Vein Isolation Sufficient?
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Is pulmonary vein isolation (PVI) sufficient for treatment of all forms of AF and does it provide as good a freedom from AF compared with CMP III? The answer to this question lies with whether the drivers of AF causing chronicity are within the pulmonary vein [17] or are the macro reentrant circuits within the atria [15]. If the former theory holds, the PVI should be sufficient for treatment of all forms of AF. In a recent (between 2000 and 2002) worldwide survey of catheter ablation for AF where disconnection of multiple pulmonary veins was performed, success rates of freedom from antiarrhythmic drugs were the following: 52.7% in 65 centers including patients with paroxysmal AF; 48.5% in 17 centers including patients with paroxysmal or persistent AF; and 57.3% in 8 centers including patients with all forms of AF [55]. In this report significant pulmonary vein stenosis and strictures occurred in 1.3% and 0.2% of patients, respectively. The overall incidence of major complications was 6%. Half of the patients with pulmonary vein stenosis required interventional treatment, a method that does not necessarily abolish symptoms [56]. Therefore, it seems that PVI may be inadequate for persistent-permanent AF. However, if the driver theory holds, pure PVI for paroxysmal AF should suffice for the majority of the patients. For the minority of patients with paroxysmal AF, patients who may have different foci outside the pulmonary veins, additional lesions will be required.
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Patients With Large Atria
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Lammers and colleagues [57] have demonstrated that the left atrial refractory period is shorter than the right atrial. Therefore, the maintenance of AF in the right atrium will probably be possible only if it is enlarged. In patients with normal size atria, the treatment of AF can be directed to the left atrium avoiding recurrence due to its shorter refractory periods. However, in patients with large right atriums, additional right atrial ablation lines will be required.
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Importance of the Coronary Sinus Lesion
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In most studies it is difficult to elicit whether coronary sinus ablation has been performed. Cox and Ad [32] have emphasized the importance of coronary sinus ablation. Furthermore, Nakagawa and colleagues [58] have emphasized the importance of the isthmus line between the coronary sinus and the tricuspid valve, responsible for the majority of atrial flutters. Chauvin and colleagues [59] carried out a study of ten necropsied hearts, where they showed striated muscle around the coronary sinus connecting inferior right atrium to left atrium. This anatomy was shown to have variable morphology, which may account for inconsistent results reported for left atrial isolation.
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Endocardial Versus Epicardial Ablation
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In recent years, minimally invasive techniques have been developed that use epicardial beating heart ablation [60–62]. The effectiveness of epicardial beating heart surgery is affected by the epicardial fat and cooling effect of circulating blood, compared with endocardial ablation on the arrested heart. In a study using RF energy in ovine myocardium with different wall thickness, Thomas and colleagues [63] showed that epicardial fat has a negative effect on lesion formation. Even when fat was absent, epicardial RF energy resulted in smaller lesions compared with endocardial application. Similarly, Santiago and colleagues [64], in their in vitro experiments of human atrial walls and analysis of left atrial lesions in patients undergoing mitral valve surgery using epicardial RF ablation, showed that the thickness and composition of the epicardium and the myocardium play an important role in the formation of the myocardial lesion. Furthermore, Accord and colleagues [65], performing histologic analysis of epicardial lesions of three postmortem cases, showed that transmurality was not achieved in the majority of the samples and the extent of myocardial damage was variable. These findings may have implications in patients undergoing redo surgery and those with mitral valve disease and thickened atria.
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Innervation of the Pulmonary Veins and Atria: Effect on AF Ablation
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Abnormal conduction of the autonomic nervous system can trigger or perpetuate AF [66]. Both the adrenergic and cholinergic systems may be involved in initiation and maintenance of AF. There is accumulating evidence that the activation of autonomic ganglia, specifically of the ganglion plexus at the base of the right superior pulmonary vein, may serve as a mediating factor for initiation of AF by pulmonary vein depolarization [67]. About one third of patients undergoing left atrial circumferential ablation demonstrated ganglion plexus involvement. Application of RF at these sites may increase the success rate of ablation. Furthermore, there are reports of autonomic dysfunction after AF ablation [68, 69]. Chevalier and colleagues [70] carried out a quantitative study of the innervation of the left atrium and pulmonary veins. They showed that the most densely innervated sites are the left and posterior parts of the atrium and the antrum of the pulmonary veins. These innervation gradients may contribute to the electrical propagation during AF. There are reports of neural ablation using RF for the treatment of AF [71, 72]. In addition, Pappone and colleagues [67] and Lonnerholm and colleagues [68] have demonstrated that denervation improves AF ablation. Therefore, targeting the most innervated areas should increase the success of ablation using surgical and percutaneous techniques.
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Catheter Ablation of AF
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Following the landmark observation by Haissaguerre and colleagues [12], demonstrating that impulses originating in the pulmonary veins could initiate AF, several groups developed percutaneous catheter ablation of AF [55]. In general, three different approaches for the treatment of AF have been suggested: (1) focal ablation within the pulmonary veins guided by the endocardial activation time [73]; (2) anatomically based pulmonary vein isolation by circumferential ablation at their ostia [74]; and (3) segmental isolation of pulmonary veins guided by the detection of high-frequency depolarizations within the ostia (pulmonary vein potentials) [75]. Separate encirclement of left-sided and right-sided pulmonary veins (antral ablation) is a modification of circumferential ablation. Focal ablation within veins guided by activation mapping has been abandoned because of unreliable provocation of focal firing, modest success rates, and risk of pulmonary vein stenosis.
The results of several catheter ablation studies are summarized in Table 3. Similar to surgical reports, it is difficult to compare and contrast these studies due to different classification, patient cohorts, technique used, and follow-up period. Freedom from atrial fibrillation achieved is significantly better for paroxysmal AF (59–85%) compared with permanent-persistent AF (5–25%). The complications associated with catheter ablation include pericardial effusion and tamponade secondary to perforation (
5%), stroke and transient ischemic attacks (4%), pulmonary vein stenosis (3–42%), and sinus node dysfunction.
Some of the limitations of the percutaneous ablation include achieving transmurality and continuity of the ablation lines, and prolonged procedural time, sometimes up to five hours [76]. Multiple gaps in the ablation line may result not only in recurrent AF, but also promoting new arrhythmias such as left atrial macro reentry, often requiring additional intervention. In canine experiments, gaps as narrow as 2 mm demonstrated normal conduction during atrial pacing. Employing three-dimensional anatomic mapping and double Lasso catheters in combination with adenosine provocation may improve identification of gaps in left atrial lines [71].
In summary, the type of lesion required for treatment of AF should be determined according to the type of AF, irrespective of the need for concomitant procedures. For patients with paroxysmal AF, PVI should suffice in approximately 90% of patients and the remainder will need additional lines of ablation performed. Both catheter ablation and surgical results indicate that in patients with permanent-persistent AF, PVI is insufficient and additional surgical lines are required, like right atrial ablation lines in patients with large right atria.
The future directions should determine the balance and efficacy of epicardial and endocardial approaches in the treatment of both permanent- persistent AF. Further studies, such as identification of triggers outside the pulmonary veins and the role of autonomic innervation, are required to improve the understanding of mechanisms of AF. Advances in these fields would enable surgeons and cardiologists to further the management of AF with improved results, and using minimal access techniques [77, 78] including robotic surgery with or without the use of cardiopulmonary bypass.86
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Abstract
Material and Methods
