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Ann Thorac Surg 2002;74:2210-2217
© 2002 The Society of Thoracic Surgeons
a Department of Thoracic and Cardiovascular Surgery and Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
b Department of Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
* Address reprint requests to Dr Gillinov, Department of Thoracic and Cardiovascular Surgery, F24, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195 USA
e-mail: gillinom{at}ccf.org
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Abstract |
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 Top Abstract IntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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Introduction |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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Permanent AF is associated with doubling of all-cause mortality and of mortality from cardiovascular disease [3]; after adjusting for coexisting cardiovascular conditions, AF remains an important incremental risk factor for death [4, 5]. It is associated with a five- to sevenfold increase in the risk of stroke [6] and increases health care spending [5–7]. Therefore, development of low-risk, minimally invasive, cost-effective operations to ablate AF is of great value.
After presenting the general classification of AF and its mechanisms in relation to surgical therapy, this review describes contemporary and emerging surgical approaches to AF, synthesizes results of these operations, and proposes new standards for reporting results of AF treatment.
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Classification of atrial fibrillation |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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The joint American College of Cardiology/American Heart Association/European Society of Cardiology task force has recommended clear and precise nomenclature for classifying AF [8]. Classification begins with the first-detected episode of AF. If a patient has two or more episodes, AF is considered recurrent. Recurrent AF is designated as paroxysmal, persistent, or permanent. Paroxysmal AF lasts 7 or fewer days and terminates spontaneously. Persistent AF does not terminate spontaneously, but requires electrical or pharmacologic cardioversion to restore normal sinus rhythm; if the first-detected episode of AF does not terminate spontaneously, it is also designated persistent. Permanent AF is defined as a condition in which sinus rhythm cannot be sustained after cardioversion or the patient and physician have decided against further efforts to restore sinus rhythm.
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Mechanisms of atrial fibrillation and relationship to surgical technique |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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Allessie [11] furthered understanding of AF by observing that it induces a cycle of electrophysiologic and structural changes in the atria that lead to "domestication" of the arrhythmia. That is, AF causes electrical remodeling that favors maintenance of AF [11]. Thus, duration of AF likely influences the choice and success of therapy.
There is general agreement that AF requires a substrate and a trigger [5]. The substrate is an atrial abnormality, frequently inflammation or fibrosis, and causes atrial electrical dysfunction that favors development of AF [13]. Triggers include atrial ectopic foci, changes in atrial wall tension, and alterations in autonomic tone. Although substrate and trigger may vary, experimental and clinical evidence points to the primary importance of the pulmonary veins and left atrium in initiating and maintaining AF [14–17].
Haissaguerre and colleagues [18] demonstrated that paroxysmal AF originates from ectopic beats in the pulmonary veins in 94% of cases. This likely relates to the anatomic transition from pulmonary vein endothelium to left atrial endocardium; at this juncture, two types of tissue with different electrical properties are juxtaposed, and this may potentiate development of AF [18, 19]. Although this observation demonstrates the critical importance of pulmonary veins in patients with paroxysmal AF, it may not apply to persistent or permanent AF.
As regards persistent and permanent AF, direct evidence is lacking, but clinical experience implicates the posterior left atrium and possibly the pulmonary veins in their pathogenesis and maintenance. Harada and colleagues [20] performed intraoperative atrial activation mapping in 10 patients with persistent AF, demonstrating that for most patients, the left atrium acted as the electrical driving chamber. However, such patients also tend to have pathologic right atrial changes [21]. Treating patients with persistent AF and mitral valve disease, Sueda and colleagues [22, 23] performed a simple left atrial procedure that successfully ablated AF in 78% of patients. This procedure included encircling (isolating) the four pulmonary vein orifices, excising the left atrial appendage, and connecting lesions to the mitral valve annulus.
These observations support developing surgical procedures to ablate persistent AF that concentrate on the left atrium and pulmonary veins (Fig 1).
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Surgical techniques |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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In the Cox-Maze III operation, incisions and cryolesions are strategically made to interrupt the multiple reentrant circuits of AF (Fig 2) [24–28]. Right and left atrial incisions interrupt the most common reentrant circuits and direct the sinus impulse from the sinoatrial node to the atrioventricular node along a specified route. Multiple "blind alleys" off this main conduction pathway (the Maze analogy) allow electrical activation of the entire atrial myocardium.
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Partial mazes
Several groups have reported procedures [22, 23, 32–35] that include some of the incisions and cryoablation lesions of the Cox-Maze III operation, but not all; these are categorized as partial Maze procedures. They tend to focus on the left atrium, including isolation of the pulmonary veins and excision or exclusion of the left atrial appendage. They generally ignore the coronary sinus, which increases the risk of atrial flutter [36, 37]. Kress and colleagues [38] validated a left atrial lesion pattern for intraoperative ablation of AF. This lesion set includes isolation of the pulmonary veins in pairs with connecting lesions between the sets of pulmonary veins and to the left atrial appendage. It may be used for endocardial or epicardial AF ablation.
In addition to a simplified lesion set concentrating on the left atrium, most of these procedures use alternative energy sources (Table 1). For these reasons, the partial Maze procedures take less time to perform than the Cox-Maze III [32–34].
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Radiofrequency
Radiofrequency energy uses alternating current of 350 kHz to 1 MHz to heat tissue. Experimental data demonstrate that heating tissue for approximately 1 minute at 70° to 80°C produces lesions 3 to 6 mm deep, usually sufficient to create a transmural line of conduction block [40]. The efficacy of this modality in catheter-based arrhythmia ablation [15, 17, 41, 42] led surgeons to examine the feasibility of direct application of radiofrequency energy to the heart during cardiac surgery.
In unipolar systems, the patient is grounded by an indifferent electrode applied to the skin (usually the back), and current flows from the tip of the radiofrequency catheter and resistively heats tissue in tip contact. Locally, temperatures above 100°C can occur, causing tissue vaporization and surface charring. Deeper tissue planes are heated by conduction from this region of volume heating. This mechanism can limit lesion depth. Saline-cooled radiofrequency systems may increase lesion depth while relieving surface char. A recently developed bipolar radiofrequency clamp overcomes these disadvantages, creating controlled and precise transmural lesions.
Several different radiofrequency catheter systems are available for surgical application. They include long flexible probes [40], rigid probes [43], pencil-like probes with a cooled tip [44, 45], and a probe that is configured as a bipolar clamp. The probes may be placed on either epicardial or endocardial surfaces of the heart; both techniques result in continuous and transmural lesions [40, 46]. Epicardial placement permits beating heart, or "off-pump," AF ablation [42].
Surgeons have created a variety of lesion sets for radiofrequency ablation of AF [40, 44–54]. They all include complete or nearly complete isolation of the pulmonary veins and excision or exclusion of the left atrial appendage; in addition, most include one or more connecting lesions in the posterior left atrium between the pulmonary veins and atrial appendage or between the pulmonary veins and mitral annulus. Some include right atrial lesions similar to those of the Cox-Maze III [40, 44, 48, 51].
Creation of left-sided lesion sets generally requires 10 to 20 minutes [40, 43–45, 47–54]. This amount of time contrasts with the 1 hour required to perform the Cox-Maze III procedure [55, 56].
Microwave
Interest is growing in microwave energy for creating lines of conduction block by thermal damage and subsequent scar formation. This mechanism of thermal injury is different from that of radiofrequency [57–59] ablation. High-frequency electromagnetic radiation (microwaves) causes oscillation of water molecules in tissue, converting electromagnetic energy into kinetic energy (heat). Microwave heating has an advantage over radiofrequency heating because the depth and volume of heated tissue are greater, resulting in a higher probability of transmural lesions. Microwave heating does not char the endocardial surface, which may reduce risk of thromboembolism [60]. Microwave probes are shielded, a feature that is important during epicardial ablation. At present, 2-, 4-, and 10-cm probes are available for microwave-based AF ablation [60, 61].
Lesion sets created with microwave energy are similar to those created with radiofrequency energy, generally including pulmonary vein isolation.
Surgeons who use energy sources that create thermal lesions must avoid damaging surrounding structures, particularly the esophagus [62]. The transesophageal echo probe should be removed during endocardial AF ablation. Esophageal injury has been reported with radiofrequency surgery [60, 63], but not with microwave. In addition, thermal endocardial energy application should be avoided in thin, frail patients with delicate tissues; in such patients, damage to surrounding structures may be more likely.
Cryothermy
Cryoablation is a well-established modality in arrhythmia surgery and an important component of the Cox-Maze III procedure [24–27]. Application of a nitrous oxide–based cryoprobe to atrial tissue for 2 minutes at -60°C reliably produces a transmural lesion that can be confirmed visually. Tissue architecture is preserved, leaving a smooth endocardial surface.
In their partial Maze procedure, Sueda and colleagues [22, 23] have used cryolesions to complete the lesion set. Others have used limited left atrial cryoablation with isolation of the pulmonary veins to cure AF. More recently, Cox and colleagues [19, 27] reported a minimally invasive approach in which the standard lesion set of the Cox-Maze III is re-created using cryoprobes (cryo-Maze). This procedure is demanding and technically difficult. A current characteristic of cryoprobes is their rigidity; however, future development of flexible probes or an array of probes of different shapes will overcome this limitation.
Lesion type and transmurality
Transmural lesions are ensured with the cut and sew technique and with cryothermy at -60°C for 2 minutes on an arrested heart [7]. Bipolar delivery of radiofrequency energy allows confirmation of transmurality by measuring changes in tissue impedance. However, lesions must be both transmural and in continuity to ensure conduction block. Unipolar radiofrequency, microwave, and epicardial cryothermy on a beating heart do not guarantee transmural lesions. Intraoperative testing for conduction across lesions may be necessary to assess lesion depth with these techniques.
Are transmural lesions desirable? Yes. A discontinuous line that is not transmural may allow AF breakthrough or potentiate development of atrial flutter. This may explain the lower success, compared with the Cox-Maze III, of new energy sources used to isolate the pulmonary veins: Electrical impulses from pulmonary vein drivers or initiators of AF may "escape" through a break in the lesions encircling the pulmonary veins.
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Results of surgery for atrial fibrillation |
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Cox-Maze III: other centers
Other centers have published results with the Cox-Maze III procedure [66–69]. In general, efficacy has been less than that reported by Cox and colleagues. At the Cleveland Clinic and Mayo Clinic, late freedom from AF is reported to be around 90% [66–68].
Although concomitant organic heart disease did not diminish the efficacy of the Cox-Maze III procedure in the experience of Cox and colleagues [31, 70], others report reduced success in that setting. In most series, combining mitral valve surgery with the Cox-Maze III cured AF in only 75% to 82% of patients [54, 56, 71, 72]. Kamata and coworkers [71–73] found that the amplitude of the atrial fibrillatory wave and diameter of the left atrium were independent predictors of sinus rhythm restoration after the Cox-Maze procedure in these patients.
Why are results of others inferior to those reported by Cox and colleagues? The answer is unclear.
Partial mazes
Several groups have reported results of partial Maze procedures [22, 23, 32–35]. They restore sinus rhythm in approximately 80% of patients [32–34]. Minor variations in the pattern of incisions and cryolesions do not appear to influence the results. Although the left-sided partial Maze procedures can eliminate atrial fibrillation, they have an increased risk of atrial flutter, which is usually of right atrial origin [63, 74, 75]. The occurrence of atrial flutter after these procedures is 5% to 10%. Atrial flutter, when it occurs, is managed easily by catheter ablation.
The radial incision approach provides results comparable to those of the Cox-Maze III; AF is cured in approximately 90% of patients [76, 77]. In addition, this approach may result in more effective restoration of atrial transport function [77].
Radiofrequency
Although lesions sets created with radiofrequency energy vary, results are similar: AF is ablated in 70% to 80% of patients [40, 43–45, 47, 48, 53]. Most treated patients have had organic heart disease and undergo a mitral valve procedure in addition to AF ablation. For them, results with radiofrequency fall just short of those reported for the Cox-Maze III procedure [31, 66–69]. Success of AF ablation is similar regardless of whether right atrial lesions are included.
Perioperative AF after radiofrequency ablation is common, occurring in approximately two thirds of patients [40, 47, 53]. Although 30% to 40% of patients leave the hospital in AF, many return to sinus rhythm over the ensuing 3 months [40, 47, 53]. Thus, discharge in AF is not necessarily an indication of procedure failure. Although some authors report that atrial size impacts success [44, 54], this finding has not been confirmed by others [40]. Atrial transport function is demonstrated in 80% to 100% of patients who return to sinus rhythm [62, 78].
Microwave
Approximately 80% of patients can be cured of AF by microwave ablation [61]. Worldwide, more than 500 such procedures have been performed, approximately 30 off pump. Because a microwave catheter has only recently become available for intraoperative treatment of AF, long-term results are unavailable.
Cryothermy
Sueda and colleagues [22, 23] reported successful ablation of AF in 78% of patients. Others have demonstrated that limited left atrial cryoablation with isolation of the pulmonary veins cures AF in approximately 70% of patients [79]. Cox and colleagues reported that results of their minimally invasive Cox-Maze III performed off pump with cryoprobes are similar to those for the standard Cox-Maze III.
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Assessing results of atrial fibrillation surgery |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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The end points of interest are development of permanent AF, surgical failure, prevalence of AF, and occurrence of other events associated with AF (Table 2).
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Detection
Detection of permanent AF requires at least two electrocardiogram (ECG) examinations separated by 7 days or more, and documented failure of cardioversion or a decision to leave the patient in AF [8].
Data analysis and reporting
Atrial healing and stabilization of rhythm may take up to 6 months after surgery [28]. Therefore, patients are not at risk, in theory, of being diagnosed with permanent AF until 6 months or more after surgery. Time zero, then, is 6 months after AF operation, and the cohort at risk comprise all patients alive at 6 months.
Data analysis is by time-related events methodology. This includes Kaplan–Meier nonparametric analysis and possibly multiphasic parametric analysis [81]. Potential incremental risk factors for permanent AF include all preoperative and intraoperative variables.
Surgical failure
Definition
Failure of surgery for AF is presence of AF at 6 months or more after operation that is [1] permanent (see above) or [2] paroxysmal and unresponsive to antiarrhythmic medications. If a patient can be maintained in sinus rhythm with antiarrhythmic medications, AF surgery has not failed. Similarly, requirement for a pacemaker does not constitute failure. If a patient requires an additional surgical or percutaneous procedure for AF or atrial flutter ablation, this is noted as failure of the initial procedure. However, subsequent interventions may restore sinus rhythm, representing ultimate success of combined therapy for AF.
Detection
Detecting permanent AF is described above. Detecting paroxysmal AF is more difficult, requiring a combination of patient history, ECG, and, frequently, a Holter monitor [8].
Data analysis and reporting
Time-related methods of analysis and formats of reporting are identical to those described for permanent AF, including setting time zero to 6 months after operation. This result may also be reported using competing risk models, accounting simultaneously for patient death and surgical failure [82].
Prevalence of atrial fibrillation
Definition
Prevalence of AF at any time after surgery is the proportion of a cohort of patients in AF at the time of inquiry. This includes patients with any classification of AF—paroxysmal, persistent, or permanent.
Detection
Two practical strategies for detection are proposed, both relying on serial ECG recordings. First, ECG rhythm status of a cohort of patients may be ascertained at specific intervals after surgery (anniversary method); second, ECG rhythm status may be ascertained on a given calendar date in the cohort (cross-sectional method). Both strategies have merit. The anniversary method yields easily interpretable ECG-verified status of patients at specific times after AF surgery. Cross-sectional follow-up can reveal the underlying pattern of AF because of the more uniformly distributed time points sampled.
Using either strategy, a decision must be made regarding the appropriate interval of follow-up. In principle, assessment should be spaced in time such that when changes are occurring rapidly, spacing is narrower, and when changes are occurring slowly, spacing is farther apart. Currently, insufficient data exist to suggest a set of specific time intervals. Until these can be established, cross-sectional follow-up, perhaps yearly, is an appropriate strategy.
Data analysis and reporting
The ideal method for analyzing serial rhythm status of a group of patients would be a multiphase longitudinal one [81]; however, such a method has not yet been devised. In its absence, the most appropriate modern method is longitudinal data analysis [83]. A logistic function would be used in which "time after AF surgery" (or appropriate transformations thereof) would be incorporated along with other risk factors, and specifically, each factor would be tested for time-related modulation (interaction with time of ECG). Because ECG observations are repeated in some patients, lack of independence of observations would be incorporated into the variance calculations (mixed modeling).
The reporting mechanism from a longitudinal data analysis is mean prevalence of AF at specific times after surgery and its confidence limits. This presentation would demonstrate prevalence of AF as a function of time after surgery, like a "snapshot"; it would not reveal either the chronicity or episodic nature of AF in individual patients. The presentation could be risk-unadjusted (overall prevalence) or adjusted for identified risk factors. Patient-specific predictions would be possible because of the completely parametric nature of the statistical model.
Other events associated with atrial fibrillation
Definitions
Other sequelae associated with AF include stroke, pacemaker implantation, and atrial dysfunction. Stroke from thromboembolism is defined according to the recommendations of Edmunds and colleagues [84]. Permanent pacemakers are required in 5% to 20% of patients after surgical treatment of AF [31, 66]. In most cases, the indication for pacemaker implantation is preexisting sick sinus syndrome. Atrial dysfunction is reduction or absence of atrial contractility.
Detection
Detection of stroke and of pacemaker implantation are straightforward. Detection of atrial dysfunction is at present controversial. Return of sinus rhythm restores some atrial function in most patients [31, 66]. However, postsurgical atrial function is influenced by many factors, including the specific atrium (right versus left), preoperative atrial size, interval since surgery, and technique of assessment. Currently, there are no uniform guidelines for detection. Until such recommendations exist, atrial function should be graded as present or absent and the method of detection specified.
Time-related methods of analysis and formats for reporting are identical to those described for permanent AF surgical failure, except that time zero is the time of AF surgery.
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Today and the future |
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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The immediate future will see increasingly widespread application of surgery for AF and continued refinement in energy sources, lesion sets, and surgical approaches. Simple and more rapid techniques for delivery of radiofrequency and microwave energy are under development. Laser and ultrasound may be introduced as alternative energy sources to create lesions [57, 60]. The optimal lesion set has not yet been defined, although there appears to be little difference in outcome produced by minor variations.
Minimally invasive off-pump ablation of AF is on the horizon. Cox [78] has demonstrated that a cryo-Maze procedure can be performed through right thoracotomy. The left atrial appendage can be excised or excluded using surgical staplers [85]. In the near future, it is likely that new probes, coupled with thoracoscopic stapling instruments, will facilitate off-pump epicardial ablation of AF performed through thoracoscopy.
New procedures will have low morbidity and offer the possibility of minimally invasive, permanent restoration of sinus rhythm to patients afflicted with AF. As these procedures are developed, documentation of results will be important for standardized, fair comparisons. Amplification of methods for longitudinal data analyses to include decomposition of prevalence into time frames, each with its own set of risk factors, will facilitate these comparisons. Analysis of results will enable us to choose the appropriate option for each patient, whether it be medical therapy, percutaneous ablation, or surgical ablation.
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TopAbstractIntroductionClassification of atrial...Mechanisms of atrial...Surgical techniquesResults of surgery for...Assessing results of atrial...Today and the futureReferences |
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N. A. Mokadam, P. M. McCarthy, A. M. Gillinov, W. H. Ryan, M. R. Moon, M. J. Mack, S. L. Gaynor, S. M. Prasad, S. A. Wickline, M. S. Bailey, et al. A Prospective Multicenter Trial of Bipolar Radiofrequency Ablation for Atrial Fibrillation: Early Results Ann. Thorac. Surg., November 1, 2004; 78(5): 1665 - 1670. [Abstract] [Full Text] [PDF]
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S. J. Choo, N. H. Park, S. K. Lee, J. W. Kim, J. K. Song, H. Song, M. G. Song, and J. W. Lee Excellent results for atrial fibrillation surgery in the presence of giant left atrium and mitral valve disease Eur. J. Cardiothorac. Surg., August 1, 2004; 26(2): 336 - 341. [Abstract] [Full Text] [PDF]
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M. Ruel, F. D. Rubens, R. G. Masters, A. L. Pipe, P. Bedard, and T. G. Mesana Late incidence and predictors of persistent or recurrent heart failure in patients with mitral prosthetic valves J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 278 - 283. [Abstract] [Full Text] [PDF]
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G. Troise, M. Cirillo, F. Brunelli, G. Tasca, A. Amaducci, Z. Mhagna, M. Dalla Tomba, and E. Quaini Mid-term results of cardiac autotransplantation as method to treat permanent atrial fibrillation and mitral disease Eur. J. Cardiothorac. Surg., June 1, 2004; 25(6): 1025 - 1031. [Abstract] [Full Text] [PDF]
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G. J. Hankey, C. J.M. Klijn, and J. W. Eikelboom Ximelagatran or Warfarin for Stroke Prevention in Patients With Atrial Fibrillation? Stroke, February 1, 2004; 35(2): 389 - 391. [Full Text] [PDF]
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N. M. van Hemel and J. A.M.T. Defauw Maze procedure Ann. Thorac. Surg., January 1, 2004; 77(1): 381 - 381. [Full Text] [PDF]
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M. Ruel, F. D. Rubens, R. G. Masters, A. L. Pipe, P. Bedard, P. J. Hendry, B. K. Lam, I. G. Burwash, W. G. Goldstein, M. P. Brais, et al. Late incidence and predictors of persistent or recurrent heart failure in patients with aortic prosthetic valves J. Thorac. Cardiovasc. Surg., January 1, 2004; 127(1): 149 - 159. [Abstract] [Full Text] [PDF]
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A. M. Gillinov, E. H. Blackstone, and P. M. McCarthy Reply Ann. Thorac. Surg., January 1, 2004; 77(1): 381 - 382. [Full Text] [PDF]
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 A. L. Waldo Stroke Prevention in Atrial Fibrillation JAMA, August 27, 2003; 290(8): 1093 - 1095. [Full Text] [PDF]
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