a Westmead Hospital, University of Sydney, NSW, Australia
b UCSF, California, USA
* Correspondence to: Dr Liza Thomas, FRACP, Department of Cardiology, Westmead Hospital, Darcy Road, Sydney 2145 NSW, Australia. Tel: 02/98 456 795, Fax: 02/984 583 23
E-mail address: lizat{at}westgate.wh.usyd.edu.au
Received 23 December 2002; revised 8 June 2003; accepted 21 August 2003
Abstract
Aims We determined late atrial function following a surgical linear endocardial radiofrequency (RF) ablation procedure that aimed to restore and maintain sinus rhythm (SR) in atrial fibrillation (AF). We tested the hypothesis that successful restoration of SR is accompanied by measurable mechanical atrial function that is at normal or near normal levels.
Methods Forty-seven patients who underwent the surgical RF procedure at least 6 months previously (median 2.86 years; range: 0.64.2 years) were studied using an array of echocardiographic variables. Two patient groups (SR restored [RF-SR], persistent AF [RF-AF]) and an age matched control group were studied. Among the echocardiographic variables measured were left atrial (LA) size and volume, LA active fractional emptying and mitral annular displacement corresponding to atrial contraction (A' velocity) by Doppler tissue imaging.
Results At long term follow up 29/47of patients who underwent the RF procedure were in SR with atrial contraction present echocardiographically. Of the patients initially restored to SR, the proportion remaining in SR at 3 years was 79% (SE 9%). The atrial-emptying fraction was reduced in comparison to that seen in normal controls (27±14% vs 46±10%). The A' velocity was decreased in the surgical RF cohort vs controls (4.4±1.3 vs 9.7±1.7cm/s; P=0.0001). Despite LA size preoperatively being similar in both surgical groups, atrial size decreased in those in whom SR was restored (48.6±7.6 vs 44.8±4.7mm; P=0.0001) but increased in those in whom AF persisted (48.2±8.1mm vs 52.3±7.8mm; P=0.0001).
Conclusion The radial pattern of linear radiofrequency ablation used in the present study resulted in restoration of SR and atrial function. Procedural success was independent of preoperative atrial size. Restoration of SR results in reverse atrial remodelling and improved atrial function. However atrial function remains modestly impaired, either due to the ablation lesions or pre-existing atrial disease.
Key Words: Echocardiography Atrial fibrillation Radiofrequency ablation
Atrial fibrillation (AF) occurs in 0.4% of the general population, increasing to 5% in those over 65 years of age.1AF results in loss of effective atrial contraction with chamber dilatation thereby decreasing cardiac function and increasing the risk of thromboembolism. The Cox-maze surgical procedure,2,3usually restored sinus rhythm (SR) and atrial contraction in patients with chronic AF. Recently, linear radiofrequency ablation techniques, simpler and less time consuming than the incisional maze procedure410have been developed. We have reported on such a procedure using a radial pattern of radiofrequency (RF) lesions, under direct vision, during open-heart surgery11in an attempt to maintain normal cranio caudal atrial activation and minimizeelectrical isolation of areas of the atrial myocardium. This operation was termed Star procedure because of the radial pattern of lesions (Fig. 1).
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We hypothesized that (1) atrial function would be restored at least partially following the RF procedure and (2) that persistent AF would cause further deterioration in atrial function. We evaluated atrial mechanical function extensively using traditional echocardiographic measures and in addition, the peak velocity of atrial contraction (A' velocity) using Doppler tissue imaging (DTI). This parameter may be less load dependent than traditional measures of atrial function.
From July 1995 to December 2001, 52 patients with chronic (71%) and paroxysmal (29%) AF for a mean duration of 54±41 months (range 4 months to 12 years), underwent the RF procedure. Of these, five with complex congenital heart disease had a modified RF procedure; these patients were excluded from analysis. Of the remaining 47 patients, 17 had only the RF procedure while 30 had other concomitant procedures (Table 1
).
There were two immediate deaths from pump failure (<48h: one with hypertrophic cardiomyopathy and one with a mitral valve replacement) and two later deaths (>1 month: one who had an aortic valve replacement and bypass grafting from presumed ventricular tachycardia and one from prostatic carcinoma). All four deaths occurred in the group that had the RF with concomitant procedures. In the initial cohort who underwent the RF procedure routine electrophysiological studies were performed at 6 months and 22/42 had additional RF ablation primarily for inducible atrial flutter.11Subgroup analysis of this group demonstrated no significant differences in atrial function (data not shown). Of the remaining 43 patients, 42 were reviewed by ECG and transthoracic echocardiography at 6 months after the RF procedure (median follow up time 2.86 years: range 0.64.2 years). Assessment of atrial function was difficult preoperatively because of the high proportion of patients (76%) in AF. Therefore, we compared the RF patients with 42 age matched normal controls with no history of ischaemic heart disease, significant valvular, peripheral vascular or cerebrovascular disease, hypertension or diabetes. None of the control subjects was on cardioactive medications. Among the 42 patients, 29 were in SR (two patients had back-up pacemakers) while 13 still had an arrhythmia (10 with persistent AF (two with pacemakers), one with paroxysmal AF and one with atrial flutter). Four of the 29 patients in whom SR was restored were on antiarrhythmic agents as compared to 6/13 in the AF group. Study approval was obtained from the Human Research Ethics Committee at Westmead Hospital.
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2.2. Left atrial volumes and mechanical function
Left atrial end systolic volume (LAESV) (the maximum LA volume in ventricular systole) and LA end diastolic volume (LAEDV) (the minimum LA volume in ventricular diastole) were calculated from apical four- and two-chamber zoomed views of the LA, using the biplane method of discs.14LA stroke volume was estimated as the difference between LA ESV and LA EDV. Left atrial ejection fraction was measured in all patients as (LAESV-LAEDV/LAESV)x100.14In patients who were in AF, LAESV was estimated as the largest left atrial volume during ventricular systole with the mitral valve closed. LAEDV was the smallest atrial volume during ventricular diastole.15
2.3. Traditional parameters of atrial function
Mitral inflow velocity was obtained by pulsed wave Doppler examination at a sweep speed of 100mm/s from the apical four-chamber view by placing the sample volume at the tips of the mitral leaflets or at the centre of the prosthetic valve in the four patients who had mitral valve replacement. Peak velocity of atrial contraction in diastole (A-wave velocity) was measured.16The velocity time integral (VTI) of the A wave was measured and the atrial emptying fraction estimated as A VTI divided by the total VTI of mitral inflow.16
2.4. Pulsed wave Doppler tissue imaging
Traditional measures of atrial function have been criticized because of their dependence on preload. Peak velocity of mitral annular motion in late diastole secondary to atrial contraction (A') was measured in all patients using pulsed wave DTI at a sweep speed of 100mm/s.17The pulsed wave Doppler sample volume was placed on the atrial side of the mitral annulus at the basal interatrial septum in the apical four-chamber view (Fig. 2). Special attention was made to align the Doppler beam to the interatrial septum to optimize measurements. Doppler traces were obtained during end expiration to eliminate respiratory variation and an average of three beats was measured. Digital images were obtained and stored on magneto-optical discs and reviewed on a stand-alone offline measuring systems.
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2.6. Pre operative echocardiogram
All 42 RF patients had a preoperative echocardiogram. As 32/42 (76%) were in AF, only limited transmitral flow data was available. LA diameter measured by M mode was used as a preoperative marker of LA size.
2.7. Observer agreement
In 10 randomly selected studies from each group (using the SPSS for Windows version 10, random number generator), two readers independently measured the peak A' velocity. One observer re-measured the same 20 studies at a separate time to determine intraobserver agreement.
2.8. Analysis
All values are expressed as a mean±SD. Differences between groups were examined by means of a paired Students t-test. Two sided tests with a 5% significance level were used throughout. In this study an exploratory data analysis approach has been used to investigate the behaviour of many outcome variables and therefore no adjustment was made for multiple comparisons. Repeated measures analysis of variance was done to evaluate changes in left atrial size within patients after the RF procedure. The degree of linear association between A' velocity, atrial emptying fraction, LAEF, LAESV and LAEDV were quantified using Pearsons correlation coefficient. KaplanMeier survival analysis technique was used to estimate restoration of sinus rhythm. BlandAltman analysis19was performed to analyse intra and interobserver variability. Data were analysed using Statview (version 4.0) and SPSS (version 10.0).
Forty-two patients out of forty-seven were studied and compared with age matched normal controls. The patients were categorised as having sinus rhythm restored based on electrocardiographic evidence of the presence of P waves and a regular RR interval and with echocardiographic evidence of atrial contraction based on the presence of transmitral A wave secondary to atrial contraction. Ten of the 47 patients were not restored to SR after the procedure. Of the group restored to sinus rhythm initially, the KaplanMeier estimate of the proportion remaining in sinus rhythm at 3 years was 79% (SE 9%) and at 4 years was 68% (SE 13%).
The RF patients were divided into two groups on the basis of their underlying cardiac rhythm [RF-SR (n=29) and RF-AF (n=13)]. The demographic, clinical, Doppler and echocardiographic parameters in the RF and control cohorts are listed (Table 2A). An additional comparison was performed between patients with lone AF, who underwent an isolated RF procedure and were in SRat follow up, with their age matched normal controls (Table 2B).
3.1. Restoration of sinus rhythm
Twenty nine out of 47 (62%) patients were in SR at long-term follow-up with echocardiographic atrial contraction (peak A velocity >0.2m/s). The restoration of SR was similar in patients undergoing the RF procedure in isolation (71%; 12/17) compared to the group where other concomitant surgical procedures were performed (68%; 17/25; P=ns). At late follow-up, two patients, both of whom had remained in AF had transient neurological deficits. No cerebrovascular events were reported in the group restored to sinus rhythm.
3.2. Atrial volumes
The mean LA diameter for all RF patients was 48.5±7.7mm preoperatively, and 47±6.7mm at follow-up. Both pre and postoperative measurements were significantly larger than age matched controls (post operative LA diameter in RF group vs controls: 47±7 vs 36.6±5mm; P=0.0001). The LAESV (65.7±26 vs 38.7±10ml; P=0.0001) and LAEDV (45.6±21 vs 18.7±4.9ml; P=0.0001) were significantly larger in the post RF cohort than age matched controls. The LASV showed no significant difference between groups. Similar results were obtained when a subgroup of lone AF patients who underwent the RF procedure were compared with age matched normals (Table 2B).
3.3. Atrial function
Peak A wave velocity and VTI in the RF-SR group suggested partial recovery of atrial function when compared with age matched normals (Table 2A). The atrial emptying fraction (27±14 vs 46±10; P=0.0001) and LAEF (32±14 vs 51±7%; P=0.0001) were lower in the RF-SR group compared to controls.
3.4. A' velocity as a measure of atrial function
A' velocity, similar to the atrial fraction and LAEF, was lower in the RF- SR group compared to normal controls (4.4±1.3 vs 9.7±1.7cm/s; P=0.0001). A' velocity showed a modest but significant correlation to atrial emptying fraction (r=0.61; P=0.0001) and LAEF (r=0.64; P=0.0001) (Fig. 3). A' velocity demonstrated an inverse correlation to LAESV (r=0.53; P=0.0001) and LAEDV (r=0.61; P=0.0001), thus demonstrating that in this population, atrial enlargement is associated with a decrease in atrial contractile force.
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This study comprehensively evaluates atrial mechanical function after restoration of SR following a linear RF procedure for treatment of AF. The main findings of this study were that the radial RF procedure resulted in effective atrial contraction in all patients in SR at late follow up. At follow up, a decrease in atrial size was noted in the group with restored SR. In contrast, persisting AF was associated with continued increase in LA size.
4.1. The RF (Star) procedure
The RF procedure design11differs from the conventional maze procedure in two respects; (i) it uses RF ablation rather than surgical incision and (ii) uses the radial pattern of lesions that maintains craniocaudal activation with lines of ablation placed, where possible, parallel to the normal direction of wavefront propagation. The area of electrical isolation in the posterior LA is also minimized. The proportion of patients maintained in SR at late follow up is similar to published reports2024with the incisional maze procedure (6178%) performed either in isolation or in combination with other surgical procedures.
Ninety-three percent of patients were restored to SR in a recent study4where RF was performed for AF in the absence of associated cardiac disease.
Several previous studies of curative surgery and RF procedures for AF demonstrated worse outcomes in patients with larger atria.8,10,20,24In our cohort, procedural success was independent of LA size, similar to the findings reported by William et al.5While the reason for this is unclear, the number, spacing and spatial arrangement of lesions in the RF procedure may contribute to its success, making it an effective therapeutic option even with LA enlargement.
4.2. Atrial rhythm and structural remodelling
A decrease in atrial size was noted in patients successfully restored to SR. Post-operative decrease in LA diameter following the maze and RF procedures has been reported.4,9,2124Benussi et al.9and Chen et al.24demonstrated a significant difference in LA size postoperatively based on rhythm. However, patients in both reports had mitral valve disease and a postoperative decrease in LA diameter was noted in both groups, irrespective of rhythm. This decrease in atrial size may be secondary to correction of the underlying valve disease, as no significant difference was noted between the SR and AF group24at long-term follow-up (>12 months).
The present data in contrast demonstrates a decrease in LA diameter in the RF-SR group with a corresponding increase in LA diameter in the RF- AF group compared with preoperative values (Fig. 4). Thus although both groups had a similar intervention that in itself may cause a reduction in atrial size due to scarring resulting from linear ablation, achievement of SR was necessary to achieve a late reduction in LA size. These results are in agreement with previous reports that cardioversion is associated with a reduction in LA size25while persistence of AF26resulted in LA enlargement. Thus reverse atrial remodelling consequent from restoration of SR appears to be an important determinant for postoperative reduction in LA size.
4.3. Left atrial function
While atrial function was restored in the RF cohort, it was reduced compared to age matched controls. This reduction in function could result from atrial scarring and loss of atrial myocardial mass from ablation to the atrium as previously demonstrated in a canine model.27Another plausible explanation is permanent mechanical remodelling caused by preoperative AF or loss of contractile function due to underlying structural disease.
Studies evaluating the surgical maze procedure have demonstrated a decrease in post operative LA function2022,28with an atrial emptying fraction between 1720%. In comparison, atrial function after the RF procedure showed a better atrial emptying fraction of 27%. This improved contractility may be the result of reduced LA damage from RF compared with surgical incisions. The posterior atrial wall represents 36% of the surface area of left atrial muscle.29The RF procedure described does not isolate the posterior wall of the LA. This, combined with the radial pattern of lesions to improve craniocaudal activation is a significant change from previously described techniques and is consistent with data generated using the new incisional radial approach.30
4.4. The A' velocity
A novel echocardiographic measure of atrial function, the A' velocity, using Doppler tissue imaging was also used to evaluate atrial function. While peak A velocity may be decreased in atrial dysfunction, transmitral flow is significantly influenced by LV relaxation and loading conditions.31The A' velocity which measures intrinsic atrial longitudinal contraction, may be a more robust marker of atrial function being preload independent. We measured septal A' velocity since no significant difference was demonstrated previously between septal and lateral peak A' velocity.32The atrial volume demonstrated an inverse correlation to A' velocity. Thus atrial remodelling with SR may decrease LA size with a resultant improvement in effective atrial contractile function.
4.5. Left atrial compliance
Blunted systolic forward pulmonary vein flow consequent to decreased atrial compliance has been demonstrated in AF.33Decreased atrial compliance, similar to this study, was demonstrated following the incisional maze procedure.28Atrial relaxation may be decreased by an atrial myopathic process secondary to AF. Scarring resulting from the radiofrequency ablation may result in splinting of the atria, further decreasing left atrial filling.
4.6. Limitations
The RF procedure was performed in a heterogeneous cohort; patients had paroxsymal and chronic AF and a significant percentage had underlying cardiac disease. While subgroup analysis demonstrated no significant differences between these groups in relation to atrial size or function (Table 4and Table 5), the numbers in each subgroup are relatively small.
This was a cross sectional study in that patients were recruited at varying times for their postoperative follow-up. However, previous reports have demonstrated that the most significant change in atrial size occurred within the first 6 months.4,24As the aim of this study was to evaluate atrial function at late follow up (>6 months), we believe that the results presented possibly reflect a significant degree of the improvement in atrial function after a curative intervention for AF. Longer term follow up would be required to evaluate further changes in atrial function with restoration of SR.
In this study an exploratory data analysis approach has been used to investigate the behaviour of many outcome variables. Since no adjustment was made for multiple comparisons, it is possible that some spurious positive results may have been identified.
Age matched normals were used for comparison. Thus the effect of underlying cardiac disease as well as effects of cardiac surgery could be additive effects on atrial function. While the aim of the study was to evaluate restoration of atrial function in the RF group, we are unable to determine the extent to which correction of the underlying cardiac disease would have contributed to reduction in atrial size.
We did not evaluate right atrial function. Previous studies have demonstrated that right atrial function is not significantly altered after the maze procedure.20,21,28Right atrial function may be restored even when left atrial function is absent,21,28but the converse has never been observed. Further, left atrial contraction is more important since it relates to maintenance of cardiac output and prevention of systemic thromboembolism.
Four of the 29 patients in SR were on antiarrhythmic agents (sotalol, amiodarone, flecainide). These mediations may affect the atrial function in these four patients, but as 86% in SR were not on antiarrhythmic therapy, its effect may not significantly alter the results of the group.
The RF procedure is an effective procedure for restoring SR in patients with predominantly chronic AF at late follow up. Atrial emptying fraction is improved and is higher than that reported with the traditional surgical maze procedure. This improvement may be due to the more physiological function obtained with the radial patterns of lesions. Restoration of sinus rhythm causes reverse atrial remodelling with a resultant decrease in atrial size while persistent AF causes further atrial enlargement.
Acknowledgments
We acknowledge the assistance of Dr Richard Chard, Dr Ian Nicholson, Dr Graham Nunn, Dr Hugh Patterson (Department of CardioThoracic Surgery) and Dr Duncan Guy (Department of Cardiology). Dr Karen Byth, PhD, DIC, C. Stat. RSS, provided assistance with statistical analysis. Craig Campbell provided assistance with the figures. Dr Liza Thomas is a post graduate medical scholar supported by the Gustav Nossal Scholarship awarded by the National Health & Medical Research Council (NH&MRC) of Australia.
References