Progressive Anterior Ablation in the Coronary Sinus Region
Evidence to Support the Presence of a ‘Slow Pathway’ Input in Normal Patients?
Background AV node modification is an emerging approach to rate control in patients with medically refractory atrial fibrillation. The mechanism of benefit of this procedure is not completely understood.
Methods and Results Twenty-two patients (age, 65±11 years; 16 women) with medically refractory paroxysmal atrial fibrillation referred for complete AV node ablation underwent serial ablations beginning at the level of the coronary sinus os progressing in a superior and anterior direction toward the His bundle. Serial atrial extrastimulus testing was performed to determine the effect of the progressive posteroseptal ablation in the region of the coronary sinus on the AV node antegrade refractory curve. Two of 22 patients had antegrade dual AV node pathways before ablation. Three patterns of response to serial ablation were noted. In 10 patients (45%), loss of the terminal portion of the AV node antegrade refractory curve occurred without evidence of fast pathway injury. In 7 patients (32%) the curve was shifted upward and to the left, consistent with nonspecific AV node damage. In 5 patients (23%), no effect could be attained before induction of complete AV block at superior and anterior ablation sites. Clinical variables and site of ablation did not predict response to serial ablations.
Conclusions These data suggest that the mechanism of benefit of AV node modification in this population may be through elimination of “slow pathway” tissue in half of patients and nonspecific injury in the remainder. Modification without complete AV block may not be possible in a minority of patients, as the response to progressive ablation appears to be “all or none” conduction.
Ablation of the AV node has become an accepted alternative therapy in patients with atrial fibrillation who continue to have symptoms despite antiarrhythmic therapy and rate-limiting agents.1 2 3 4 5 Recent studies have suggested that ablation in the posterior and inferior AV node input zone (region of the slow pathway) as performed in patients with AV node reentrant tachycardia with dual antegrade AV node pathways can reduce the ventricular rate during atrial fibrillation without creating AV block.6 7 8 9 10 11 12 The presumed mechanism of benefit of this procedure is elimination of the short refractory input into the AV node,10 13 14 which may represent slow pathway tissue. However, it is also possible that the prolongation of AV node refractoriness indicates nonspecific injury to the AV node, a situation that may have implications for future occurrence of complete AV block. To clarify the potential mechanisms of benefit, we examined the effect of serial ablation beginning at the level of the coronary sinus orifice (“slow pathway” zone), moving progressively superior and anterior until AV block was achieved, in a population of patients referred for elective complete AV node ablation who were in sinus rhythm at the time of the study.
It is generally accepted that radiofrequency catheter ablation in the posteroseptal region at the terminal input of the crista terminalis into the AV node is curative in AV node reentry. The loss of slow pathway conduction after ablation in this region has led to the assumption that this input harbors the anatomic “slow pathway.” Perinodal dissection in patients with AV node reentry has been shown to eliminate slow pathway conduction without affecting residual fast pathway conduction or refractoriness.15 Nonspecific cryosurgical injury applied directly to the AV node region in animals has been shown to prolong both conduction time and refractoriness.16 We have shown that conventional slow pathway region ablation in patients with otherwise typical AV node reentry without evidence of dual pathways results in a clinical cure and loss of the terminal portion of the curve relating the atrial extrastimulus coupling interval to the subsequent AH interval.17 We hypothesized that radiofrequency catheter ablation in the posteroseptal (“slow pathway”) region in patients with paroxysmal atrial fibrillation, as performed in patients with AV node reentrant tachycardia, would result in elimination of the terminal portion of the AV node antegrade refractory curve (Fig 1A⇓), the putative “slow pathway” component. Alternatively, ablation in this region could shift the curve up and to the left, prolonging AV node conduction and refractoriness, consistent with nonspecific injury to the compact AV node, injury to both fast and “slow” pathway components of the node or injury to the fast pathway without affecting the “slow” pathway (Fig 1B⇓).
Patients studied had refractory paroxysmal atrial fibrillation, had failed at least two antiarrhythmic drugs, and presented for complete AV node ablation and pacemaker implantation. Patients were only included in the study if they were in sinus rhythm at the time of the ablation procedure. All antiarrhythmic agents and rate-limiting drugs were discontinued at least 5 half-lives before AV node ablation. Patients were excluded if they had received amiodarone within 1 month before the study. All patients gave informed consent for complete AV node ablation, and those who did not have a permanent pacemaker consented to its insertion.
Patients were studied in the electrophysiology laboratory and were given local anesthetic and intravenous sedation with midazolam and fentanyl. Standard multipolar recording catheters were inserted from the right femoral vein and placed in the high right atrium, His bundle recording position, and right ventricular apex.18 An octapolar coronary sinus recording catheter was also inserted from the left subclavian vein if a permanent pacemaker had not previously been implanted in the left pectoral region. The coronary sinus orifice was identified using a deflectable ablation catheter inserted through the right femoral vein in those patients with a left-sided permanent pacemaker.
After the baseline electrophysiology study (see below), a 4-mm-tip, 7F deflectable ablation catheter (Mansfield/Webster) connected to a radiofrequency generator (Medtronic Atakr) was introduced from the right femoral vein and positioned on the tricuspid annulus at the level of the coronary sinus. The anatomic approach to slow pathway ablation used in our laboratory has been previously described.19 In summary, an electrogram characterized by a large ventricular and small atrial deflection was obtained along the tricuspid annulus at the level of the coronary sinus (Fig 2⇓, level 1). Radiofrequency energy was delivered at 30 W for 10 seconds. If junctional rhythm was observed, energy delivery was continued for 40 seconds unless an impedance rise occurred, the catheter became unstable, or antegrade or retrograde AV block was observed. If junctional rhythm was not observed, the catheter was withdrawn to achieve a slightly larger atrial deflection and the process was repeated. If junctional rhythm was not observed along that “line,” progressively more anterior and superior “lines” were attempted until junctional rhythm was observed or there was a ≥30 ms prolongation of the AV node effective refractory period or Wenckebach cycle length with repeat testing (Fig 2⇓, lines 2 and 3). The site of effective ablation was estimated using a “clock” position on the tricuspid annulus as viewed in the left anterior oblique projection, utilizing the His recording position as “1 o’clock” and the coronary sinus orifice as “5 o’clock.”
A baseline electrophysiological study was performed using standard pacing techniques to characterize AV node function.18 Progressively premature atrial extrastimuli were delivered after a train of 8 pacing beats at a drive cycle length of 600 ms until block in the AV node occurred. A drive cycle length of 500 ms was used when the sinus cycle length was shorter than 600 ms. From these data, standard AV node antegrade refractory curves plotting the A1A2 interval on the x-axis and the H1H2 interval on the y-axis were constructed. The AV node effective refractory period (ERP) was defined as the longest A1A2 measured at the His recording position that failed to conduct over the AV node. The AV node functional refractory period (FRP) was defined as the shortest H1H2 resulting from conduction over the AV node. Dual pathways were defined as a ≥50 ms prolongation of the AH interval with a 10-ms decrement in the atrial extrastimulus coupling interval. Dual pathways were also defined when there was sudden prolongation of the AH interval during incremental atrial pacing. A second atrial extrastimulus (S3) was not used to search for evidence of dual pathways. Neither isoproterenol nor autonomic blockade was given. The shortest cycle length maintaining 1:1 conduction was defined as the shortest A1A2 interval that conducted 1:1 over the AV node during incremental atrial pacing. Retrograde AV node function was assessed using a similar technique with pacing from the right ventricular apex. The retrograde AV node ERP was defined as the longest V1V2 measured at the right ventricular apical catheter which failed to conduct over the AV node before block during extrastimulus testing. The shortest cycle length maintaining 1:1 retrograde conduction was defined as the shortest V1V2 interval which conducted 1:1 over the AV node during incremental ventricular pacing.
Repeat testing of AV node function was performed after each “line” of energy application. Upon completion of testing, all patients went on to complete AV node ablation because a clinical decision was made before the procedure to proceed with complete ablation. A permanent pacemaker was implanted in those patients who did not previously have one.
Continuous variables were compared using Student’s t test. Paired t tests were used to compare baseline and postablation variables. Categorical variables were compared using a χ2 test. A value of P<.05 was considered significant.
Twenty-two patients with a history of paroxysmal atrial fibrillation who were in sinus rhythm at the time of AV node ablation were studied. The mean age was 65±11 years, and 16 patients were women (73%). Ninety- one percent of patients were over age 50, and 68% had structural heart disease. Of the 15 patients with structural heart disease, 5 had a history of hypertension, 4 had valvular heart disease, 4 had ischemic heart disease (3 angina, 1 with previous myocardial infarction), 2 had a history of congestive heart failure, and 1 patient had hypertrophic cardiomyopathy. The mean duration of symptoms was 8.1±5.7 years, and patients had failed a mean of 2.6±1.0 antiarrhythmic drug trials. No patient had a history of syncope, documented bradycardia, or AV node reentrant tachycardia. Two patients had evidence of dual antegrade AV node pathways at baseline study. The other 20 patients had a smooth antegrade AV node refractory curve illustrated as “baseline” in Fig. 1⇑. Neither AV node echoes nor AV node reentrant tachycardia was inducible at electrophysiological study in any patient.
Three patterns of response to the serial ablation procedure were noted. In 10 patients (45%), ablation resulted in elimination of the terminal portion (“tail”) of the AV node antegrade refractory curve with prolongation of refractoriness without a significant change in conduction at each extrastimulus coupling interval (group 1, Figs 3⇓ and 4⇓). In 7 patients (32%), ablation resulted in a shift of the AV node antegrade refractory curve up and to the left with prolongation of refractoriness and prolongation of the conduction time at each extrastimulus coupling interval (group 2, Fig 5⇓). Patients were included in this group if they demonstrated at least a 30-ms prolongation of the H1H2 interval at the same A1A2 coupling interval in the lower portion of the curve. In 5 patients (23%), junctional tachycardia could not be induced, and no change in AV node refractoriness or conduction was noted until complete AV block occurred. All of these patients developed AV block during ablation in midseptal or more anterior positions after demonstrating no response at more posterior and inferior sites. All ablation sites in these 5 patients were estimated between the 1 and 2 o’clock positions.
There was no difference between group 1 and 2 in their age and sex. The duration of symptoms was 4.9±3.2 years in group 1 patients and 11.7±5.8 years in group 2 (P=.01). There was no difference between groups in the number of radiofrequency energy applications or the estimated site of successful ablation. The sinus cycle length was not significantly different after ablation in both groups. The AH interval was not significantly prolonged in either group as a result of ablation (both P>.2).
The shortest cycle length maintaining 1:1 antegrade conduction increased by 59±45 ms in group 1 (P=.004) and 101±69 ms in group 2 (P=.008) (Table⇓). The degree of prolongation was greater in group 2 but failed to reach statistical significance (P=.16). Similarly, the functional refractory period increased 48±33 ms in group 1 patients (P=.001) and 96±51 ms in group 2 (P=.002). The change in AV node functional refractory period was significantly greater in group 1 compared with group 2 (P=.03). The effective refractory period increased by 87±48 ms in group 1 patients (P=.0003) and by 124±78 ms in group 2 patients (P=.006). This difference in increase was not significant between groups. Retrograde conduction was present in 3 patients in each group before ablation. The retrograde effective refractory period was not significantly prolonged in either group.
AV node modification has emerged as an effective means of rate control in patients with refractory atrial fibrillation. This procedure is associated with a significant risk for complete AV block and subsequent permanent pacemaker dependence, and the long-term safety with respect to need for pacing is unknown.7 8 12 Initial experience with posteroseptal region ablation in patients with refractory atrial fibrillation was obtained while patients were in atrial fibrillation.7 8 Although this provided clinical demonstration of efficacy by slowing of the ventricular response during ablation, it was not possible to make comparative measures of change in electrophysiological properties as a result of ablation. Subsequent studies have examined change in electrophysiological parameters in patients with AV node reentrant tachycardia undergoing slow pathway ablation with induced atrial fibrillation.12 13 14 19 These studies showed that slow pathway ablation resulted in a slowing of ventricular response in induced atrial fibrillation. This observed slowing was also present in patients with evidence of persistent slow pathway conduction13 and was unaffected by autonomic blockade but was abolished by isoproterenol infusion.19 These studies are limited by the lack of clinical atrial fibrillation in the study population and the presence of “pathological” dual pathways capable of sustained AV node reentry.
Chen et al10 studied the effect of posteroseptal ablation in patients similar to ours with refractory paroxysmal atrial fibrillation. They studied patients under autonomic blockade with an isoproterenol infusion and found that isoproterenol did not reverse the change in ventricular response rate as Strickberger et al19 had observed. Eighteen of 27 patients without dual pathways at baseline demonstrated prolongation of the AV node effective refractory period and Wenckebach block cycle length after posteroseptal region ablation with no change in the AH interval. In those patients with dual pathways, 4 of 10 patients did not achieve a sufficient drop in ventricular response rate (25% to 30% reduction, average rate less than 120 to 130 during isoproterenol infusion), which was achieved after further posterior and mid septal burns. They concluded that slow pathway elimination was only a part of the explanation for the clinical benefit of the procedure in all patients. We have further studied those patients as described by Chen et al10 with paroxysmal atrial fibrillation without dual pathways with no change in AH interval by applying the same technique we have previously described for elimination of slow pathway conduction in AV node reentry. The identical technique using junctional tachycardia as a marker for successful ablation that was used in the current study has previously been shown to eliminate slow pathway conduction in all 25 patients with AV node reentry who were ablated at our center.20 21 The present study demonstrated that loss of the terminal portion of the AV node refractory curve is possible in some patients with paroxysmal atrial fibrillation but that a significant proportion of patients (32% of those modified) also demonstrate a shift of the curve upward and to the left. This shifted curve may either represent nonspecific damage to both the fast and “slow” pathway components of the curve, damage to the compact AV node, or a combination of fast pathway injury and ongoing “slow pathway” conduction. The latter explanation seems less likely because of the prolongation of the ERP suggesting injury to the “short-refractory” component of the AV node.
Do All Patients Have Dual Pathways?
Animal studies support the presence of functionally discrete anteroseptal and posteroseptal inputs into the compact AV node.22 23 24 25 These data demonstrate slower conducting tissue in more posterior and inferior sites with shorter refractoriness in the absence of demonstrable distinct dual pathways using traditional atrial extrastimulus or burst pacing techniques. Human data also support the presence of dual pathways in some normal patients. Denes et al25 found evidence of dual pathways in 41 of 397 (10%) patients undergoing electrophysiological testing. Of those 41 cases, 24 did not have a history of AV node dependent–supraventricular tachycardia (6% of total). Similarly, Casta et al26 found evidence of dual pathways in 35% of 78 children with congenital heart disease undergoing cardiac catheterization and electrophysiologic evaluation who were free of arrhythmias. These studies support the presence of overt dual pathways in the minority of normal patients. In 22 patients with atrial fibrillation, an assessment of RR intervals suggested that a bimodal distribution was present in 16 of 22 patients.27 The authors concluded that the findings supported the presence of a “slower” pathway in the majority of their patients consistent with dual pathways, speculating this was related to dual AV nodal inputs.
In patients with otherwise typical AV node reentrant tachycardia who do not demonstrate discontinuity of the AV node antegrade refractory curve, Sheahan et al17 reported loss of the terminal portion of the curve after anatomic slow pathway ablation that was identical to that used in the current study. They concluded that the absence of discontinuity of the curve was related to insufficient differences in the conduction and refractory characteristics of the fast and slow pathways. Our study was designed to test the hypothesis that all patients have a “functional” slow pathway even though the AV node antegrade refractory curve is continuous. Our data suggest that in 45% of patients, the terminal portion of the curve can be eliminated with serial inferior and posterior ablations in the coronary sinus region. This inferior and posterior input into the AV node may have characteristics similar to the conventional concept of a slow pathway with short refractoriness and slow decremental conduction.
The findings illustrated in Fig 3⇑ suggest that the terminal portion of the AV node refractory curve, classically defined as the “slow pathway” in AV nodal reentrant tachycardia, may be a physiological component of the posterior AV node input. In this patient, it was possible to eliminate the conventional slow pathway portion of the AV node antegrade refractory curve with ablation at a site just above the coronary sinus and subsequently eliminate the terminal portion of the normal curve with more anterior ablation. The conventional slow pathway and the terminal portion of the curve eliminated by the second series of burns may represent the normal inferior inputs into this patient’s AV node.
In effect, the normal AV node antegrade refractory curve may represent a continuum of fast and “slow” pathway components. The latter can be selectively eliminated in some patients with this ablation technique. The range of inputs with their characteristic conduction and refractoriness is likely to vary between individuals, influencing their response to an anatomical posteroseptal ablation. In patients with a wide anatomic separation between fast and slow pathway regions, slow pathway elimination may be possible without affecting the fast pathway. In patients with less separation, the fast pathway will be injured as seen in group 2. The final group of 5 patients without change in conduction or refractoriness before complete AV block may not have adequate separation of the posterior and anterior AV node inputs so that global AV node injury is all that is possible with the current ablation technique, or that the short-refractory input into the AV node is not in the posteroseptal region but lies elsewhere, such as the left atrial input. These patients most likely represent injury to the compact AV node, since ablation in these individuals took place at relatively anterior sites with abrupt cessation of AV node conduction.
This study demonstrated that AV node modification may benefit patients with paroxysmal atrial fibrillation by one of two mechanisms, either by eliminating the terminal portion of the AV node refractory curve (which may represent “slow pathway” tissue) or by a nonspecific injury to the AV node causing a shift of the curve up and to the left. Although both responses demonstrated prolongation of refractoriness with resultant prolongation of the shortest cycle length maintaining 1:1 conduction, the degree of prolongation of the functional refractory period was greater in patients with nonspecific injury, as was the conduction time of a given atrial extrastimulus. The degree of prolongation of the effective refractory period and shortest cycle length maintaining 1:1 conduction was also greater in patients with group 2 patients but did not achieve statistical significance. In group 1 patients it was possible to eliminate the terminal portion of the AV node refractory curve with its attendant short refractory period without significantly affecting either conduction time or refractoriness at longer cycle lengths. This finding is consistent with elimination of the tissue responsible for the terminal portion of the curve, which we have termed the slow pathway. A greater degree of prolongation of refractoriness was achieved in group 2 patients, accompanied by a prolongation of conduction time, even at longer cycle lengths.
Both responses were achieved without a significant effect on fast pathway conduction in the resting state, evidenced by the lack of change in the AH interval at a similar sinus cycle length to that before ablation. The resting AH interval may remain unchanged at longer cycle lengths. Fast pathway injury is most sensitively examined by careful examination of the curve relating the atrial extrastimulus coupling interval to the H1H2 interval. In contrast to group 1, group 2 patients did show evidence of prolonged antegrade conduction time with relatively late coupled atrial extrastimuli as assessed by the AV node refractory curve, indicating fast pathway injury. Although we arbitrarily divided patients’ responses into these two categories, the spectrum of prolongation of conduction and implied nonspecific injury is likely a continuum, since some group 1 patients demonstrated a minor degree of prolongation and a wide range of prolongation was seen in group 2 patients.
Our data suggest that the benefit of posteroseptal ablation in prolonging refractoriness without evidence of fast pathway injury can only be realized in approximately half of patients presenting for AV node modification, and only in those patients whose slow pathway refractoriness is significantly shorter than that of the fast pathway. The benefit in the remainder of patients is likely to represent nonspecific injury, where ablation must be more aggressive and is associated with a higher risk of short and potentially long-term AV block. Intuitively, patients in group 1 would appear to be at low risk for late AV block since the fast pathway was unaffected. In contrast, group 2 patients may be at higher risk and may warrant careful follow-up with more prolonged in-patient monitoring or empiric pacing. Finally, AV node modification may not be possible in a significant minority of patients (23% in our series). This is in keeping with the initial experience with AV node modification for refractory atrial fibrillation, where the reported range of AV block and pacemaker dependence was 21% to 30%.7 8 Recent series have suggested a lower risk of AV block and pacemaker dependence.6 9 10 12 These series report on small numbers of patients, and the maximum follow-up is 19 months, so that the long-term risk of AV block has not been accurately determined. The outcome of patients with different responses to AV node modification needs to be studied in larger numbers of patients who do not go on to complete AV node ablation.
The first limitation of this study is that the described changes in AV node physiology may not represent findings in the normal AV node, since these patients presumably had underlying atrial pathology leading to atrial fibrillation. Although it is possible that atrial stretch or fibrosis affects inputs into the AV node, no patient had abnormal AV node conduction at baseline study, and the patients studied represent the population of interest with respect to effect of AV node modification. Furthermore, these changes were also noted in 5 of 9 group 1 patients and 3 of 7 group 2 patients who did not have structural heart disease based on transthoracic echocardiography. Second, it is possible that the “slow pathway” may have been missed in group 2 and 3 patients. This is unlikely because the technique used is identical to that used in AV node reentrant tachycardia, which has a high success rate for slow pathway ablation. In addition, a similar site of ablation was estimated by the operator in both groups. Third, although autonomic blockade has been shown not to affect the observed changes in postablation refractoriness,19 28 a blunting of response in the presence of isoproterenol infusion has been observed in the smaller of two reported series.10 19 It is possible that isoproterenol infusion may have altered the observed nonspecific injury in our series. Fourth, we did not induce atrial fibrillation and correlate our findings with ventricular response rate. Previous studies have shown a strong correlation between the AV node refractory period, Wenckebach cycle length, and ventricular response rate in atrial fibrillation.10 11 13 14 Furthermore, since all patients were conscious, we chose not to induce atrial fibrillation to minimize the need for DC cardioversion and to facilitate completion of the protocol with attendant measurement of the refractory curves. Last, we did not routinely use a second atrial extrastimulus or drive cycle length to rule out conventional dual pathways before ablation. Although some patients may have had more overt discontinuity of the antegrade AV node refractory curve, it was still possible to eliminate the terminal portion of the AV node antegrade refractory curve by our anatomic ablation approach.
Modification of the AV node for rate control has become an accepted therapy in patients with medically refractory atrial fibrillation. The mechanism of benefit of this procedure is likely through elimination of slow pathway conduction with or without fast pathway injury. Careful follow-up of patients with evidence of fast pathway injury as assessed by extrastimulus testing after ablation may be necessary to determine risk for subsequent symptomatic bradycardia.
- Received June 11, 1997.
- Revision received July 28, 1997.
- Accepted August 5, 1997.
- Copyright © 1997 by American Heart Association
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