Shortening of Fast Pathway Refractoriness After Slow Pathway Ablation

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1 1103 Shortening of Fast Pathway Refractoriness After Slow Pathway Ablation Effects of Autonomic Blockade Andrea Natale, MD; George Klein, MD; Raymond Yee, MD; Ranjan Thakur, MD Background Shortening of the anterograde effective refractory period (ERP) of the fast pathway has been reported after radiofrequency ablation of the slow pathway. We hypothesized that ERP shortening may be related to autonomic changes, possibly catecholamine release, as a result of ablation. Methods and Results To test this, 10 consecutive patients with atrioventricular node reentry undergoing slow pathway ablation were given autonomic blockade before the ablation procedure. This was achieved by atropine 0.03 mg/kg and propranolol 0.15 mg/kg IV supplemented by half the initial dose after ablation and before the final study. A control group of 10 patients underwent the protocol without autonomic blockade. Before ablation, autonomic blockade did not alter the ERP of either the fast pathway (295+±22 versus 298±26 Slow atrioventricular (AV) node pathway ablation using radiofrequency energy is highly effective for patients with AV node reentrant tachycardia. Ablation can be guided either by recording "slow pathway" potentials1 or anatomically.2-4 Elimination of slow pathway physiology has been accompanied by a shortening of the fast pathway effective refractory period.3'4 Decrease of the sinus cycle length after ablation led to the suggestion3 that change in autonomic tone during the procedure was responsible for this finding. To test this hypothesis, we assessed the effects of slow pathway ablation on AV node physiology in patients with and without prior autonomic blockade. Methods The study population consisted of 20 consecutive patients (15 women and 5 men) with a mean age of 37±14 years (range, 21 to 70 years) undergoing electrophysiological study and radiofrequency catheter ablation of the slow pathway. Patients were assigned to either the experimental or the control group on the basis of laboratory schedule, taking into consideration the length of the protocol in the autonomic blockade group. Ten patients, mean age 36±+16 years (2 men, 8 women), underwent our standard ablation protocol and were used as control subjects. The other 10 patients, mean age 38±13 years (3 men, 7 women) received autonomic blockade before the ablation. All patients had symptomatic AV nodal tachycardia of the common type and had previously been treated with antiarrhythmic drugs without control of symptoms. No patient had structural heart disease. Received September 21, 1993; revision accepted November 6, From the Department of Medicine, University of Western Ontario, London, Ontario, Canada. Correspondence to Dr George J. Klein, University Hospital, 339 Windermere Rd, London, Ontario, Canada N6A SA5. milliseconds) or the slow pathway ( versus 269±38 milliseconds). Autonomic blockade obscured dual pathway physiology in 2 patients and brought it out in another 2 without dual pathway physiology initially. Slow pathway ablation shortened the ERP of the fast pathway for the group as a whole (331.5±54 versus 305.5±60 milliseconds, mean+sd, n=20, P<.04). There was no difference in degree of ERP shortening in control patients ( milliseconds) or autonomic blockade patients ( milliseconds). Conclusions These data suggest that shortening of the ERP of the fast pathway after slow pathway ablation is not mediated by autonomic changes. (Circulation. 1994;89: ) Key Words * radiofrequency * autonomic agents - physiology Electrophysiological Study Written and verbal consent was obtained from all patients. Each patient was studied in the fasting state under sedation achieved with intravenous midazolam and fentanyl. Under 2% local anesthesia, three quadripolar catheters were introduced percutaneously into the right femoral vein and advanced to the high right atrium, His bundle recording position, and right ventricular apex, respectively. An octapolar catheter was placed in the coronary sinus via the left subclavian vein. A baseline study was performed in all patients to confirm the diagnosis of AV node reentrant tachycardia5 and to measure antegrade and retrograde conduction parameters. Briefly, the study consisted of atrial and ventricular incremental pacing to block and extrastimulus testing with at least two drive cycle lengths. Presence of dual AV node physiology was established by a sudden prolongation of the atrio-his (AH) interval of at least 50 milliseconds for a 10-millisecond decrement during extrastimulus testing. The stimulation sequence that most clearly demonstrated dual physiology was identified and was used as a quick reference for assessing ablation of the slow pathway. In addition, the latter sequency of pacing was repeated three or four times to assess reproducibility of dual AV node physiology and variability of fast and slow pathway effective refractory period. Autonomic Blockade Protocol After the initial study was performed, autonomic blockade was obtained by administration of 0.03 mg/kg atropine and 0.15 mg/kg propranolol.6-9 Atropine was given over a 2-minute period and immediately followed by propranolol administered over a 5-minute period. Electrophysiological study was repeated beginning 10 minutes later. Radiofrequency Ablation A 7F quadripolar deflectable catheter (Mansfield-Webster, Watertown, Mass) with a large-tip electrode was used for ablation. Radiofrequency energy was delivered by a device that operates at 350 khz and provides continuous monitoring

2 1104 Circulation Vol 89, No 3 March 1994 of current, impedance, and energy (RFG-3C, Radionics, Burlington, Mass). A power setting of 30 W was used for each ablation attempt. Current was applied for 40 seconds if junctional tachycardia was observed during the ablation. Application of energy was interrupted if junctional tachycardia did not occur within 10 seconds or if impedance rose. The approach used in our laboratory to achieve ablation of the slow pathway was described recently.4 It consists of a series of anatomically guided lesions directed to the region between the orifice of the coronary sinus and tricuspid annulus. The left anterior oblique view was used to confirm the position of the catheter in the area of interest. The end point was elimination of the slow pathway as evaluated by atrial extrastimulus testing. In the absence of dual AV node physiology, elimination of all echo beats served as the marker of successful ablation. Evaluation After Ablation Thirty to 45 minutes after the last radiofrequency ablation, the presence of slow pathway conduction was assessed by programmed atrial stimulation. If antegrade slow pathway conduction was eliminated, electrophysiological evaluation was repeated according to the same protocol as previously. In the patients subjected to autonomic blockade, half of the initial dose of atropine and propranolol was provided as a supplement, followed by electrophysiological study performed 10 minutes later. All patients were monitored continuously for 24 hours after the procedure. Patients were discharged without antiarrhythmic medication and were reevaluated at 3 months in the clinic. Follow-up electrophysiological testing was not performed unless the patient developed evidence of recurrence of tachycardia. Additional Measurements The interval from atrial activation at the His bundle recording to atrial deflection at the proximal coronary sinus (Ah- Acs) was measured during AV node reentrant tachycardia and ventricular pacing to assess whether shorter values, which may reflect closer slow and fast pathways,2 predict fast pathway effective refractory period shortening after ablation. The longest AH interval with 1:1 atrioventricular conduction during incremental pacing was obtained in the autonomic blockade group before and after ablation to assess whether this parameter provides useful information to distinguish successful slow pathway ablation even in the absence of dual AV node physiology. Statistical Analysis Statistical analysis of electrophysiological data before and after ablation and before and after autonomic blockade was performed by use of the two-tailed paired Student's t test with correction for multiple comparisons. Student's t test for independent samples was also used when appropriate. Data were expressed as mean±sd. A probability value <.05 was considered statistically significant. Results Radiofrequency ablation was successful in eliminating slow pathway conduction in all 20 patients. None of the patients included in the study developed transient or persistent AH prolongation with delivery of radiofrequency energy. The two groups did not differ with respect to age, sex, and sinus cycle length at baseline (control, 825±+ 197 milliseconds versus study group, 817±229 milliseconds). In addition, the most common site of successful slow pathway ablation was similar in the two groups, being the midseptal region in 80% of the cases. The mean number of radiofrequency appli- Electrophysiological Effects of Slow Pathway TABLE 1. Ablation in the Control Group (Group 1) Preablation Postablation SCL AH :1 Ant ±75 1:1 Ret ±90 ERPFP 361±57 338±50 ERPsp 283±48... Ret ERPAVN 268±65 348±121* SCL indicates sinus cycle length; AH, atrio-his interval; 1:1 ANT, 1:1 Ret, minimum cycle length maintaining one-to-one conduction over the atrioventricular (AV) node anterogradely and retrogradely, respectively; ERPFP, effective refractory period of the fast pathway; ERPsp, effective refractory period of the slow pathway; and Ret ERPAVN, retrograde effective refractory period of the AV node. *P< ±9 versus study group, 16±8) and the total fluoroscopy time, including the diagnostic study (control, 30±12 minutes versus study group, 28±16 minutes), were not different. Effects of Slow Pathway Ablation in the Control Group Sustained slow-fast AV node reentrant tachycardia was induced in 9 of 10 patients before ablation. In the remaining patient, nonsustained tachycardia was induced. ear evidence of dual AV node physiology was present in all patients before ablation. Sinus cycle length prolonged slightly after ablation (825 ± 197 versus 857±+177 milliseconds, P=NS). This reflected a decrease of heart rate in 6 patients and increase in 3. The effects of ablation on the refractory and conduction properties of the AV node are shown in Table 1. There was no change in the AH interval. The anterograde Wenckebach cycle length increased slightly (401±55 versus 423±75 milliseconds, P=NS). The antegrade effective refractory period of the AV node prolonged (283±48 versus 338±50 milliseconds, P<.01), whereas the effective refractory period of the remaining fast pathway shortened ( versus 338±50 milliseconds, P=.09). The average decrease of the fast pathway effective refractory period was -23.5±58 milliseconds (range, +60 to -120 milliseconds). One patient had no retrograde ventriculoatrial conduction before ablation as opposed to two after ablation. The patient who apparently lost retrograde conduction had a preablation retrograde Wenckebach cycle length equal to the postablation sinus node cycle length. Retrograde Wenckebach cycle length did not change after ablation (396±74 versus 401±90 milliseconds, P=NS), but there was an increase in the retrograde refractory period of the AV node (268±65 versus 348±121 milliseconds, P=.02). Increase of the retrograde AV node effective refractory period was usually associated with prolongation of the sinus node cycle length after ablation. Effects of Autonomic Blockade Before autonomic blockade, sustained AV node recations required for slow pathway ablation (control, entrant tachycardia was induced in 8 of 10 patients.

3 Natale et al Autonomic Blockade After Slow Pathway Ablation 1105 HL ' 100 OS. S 00 * A1A2 FIG 1. Curve relating atrio-his (AH) interval to prematurity of atrial extrastimuli in a patient. Before autonomic blockade, dual atrioventricular node pathway physiology is present (o). After autonomic blockade (e), conduction over the slow pathway is eliminated. A1A2 indicates interval between atrial deflection of the last drive cycle and the extrastimulus (at the His bundle catheter); A2H2, AH interval at the His bundle catheter after the extrastimulus. After autonomic blockade, tachycardia was still inducible in only two of these patients. A discontinuous AV node function curve was present in 8 subjects at the baseline study. Autonomic blockade brought out dual AV node physiology in 2 patients (patients 3 and 6) but obscured it in 2 others (patients 2 and 9). In patient 2, slow pathway conduction was abolished after autonomic blockade (Fig 1). In patient 9, the AV node function curve became continuous after autonomic blockade because of slower conduction of the fast pathway. This resulted in a more progressive AH interval prolongation. However, tachycardia was consistently induced with the same coupling interval that was associated with 30-millisecond prolongation of the AH interval. This was considered to be the fast pathway effective refractory period (Fig 2). When autonomic blockade revealed dual AV node physiology, this reflected a shift to the left of the slow pathway curve, which was favored by a reduction in the atrial functional refractory period in patient 3. In addition, the degree of overlap between the fast and slow pathway components of the AV node curve dimin n ot PD OS& A1 A2 FIG 2. Curve relating atrio-his (AH) interval to prematurity of atrial extrastimuli in a patient. Discontinuous curve (o) became continuous (5) because of predominant 3-blocking effect on the fast pathway, which resulted in a more progressive AH prolongation and transition from fast to slow pathway. A1A2 indicates interval between atrial deflection of the last drive cycle and the extrastimulus (at the His bundle catheter); A2H2, AH interval at the His bundle catheter after the extrastimulus. 4 N9 300' 100 o 1 50 *. 0 S A1A2 FIG 3. Atrioventricular (AV) node function curve before (o) and after (o) autonomic blockade in a patient. Autonomic blockade disclosed dual AV node physiology, possibly by shortening slow pathway refractoriness. In addition, shortening of the functional refractory period of the atrium allowed shorter A1A2 to be achieved. A1A2 indicates interval between atrial deflection of the last drive cycle and the extrastimulus (at the His bundle catheter); A2H2, AH interval at the His bundle catheter after the extrastimulus. ished because of a rightward shift of the fast pathway effective refractory period in patients 3 (Fig 3) and 6. Sinus node cycle length was significantly shortened after autonomic blockade ( versus 624± 72 milliseconds, P=.02). Unlike the control group, ablation did not cause any heart rate change in this group (624±72 versus 629±82 milliseconds, P=NS). Effects of Autonomic Blockade on Electrophysiological Properties of the AV Node Autonomic blockade did not produce any change in AH interval (70±15 versus 71±16 milliseconds, P=NS) or minimum cycle length maintaining 1:1 antegrade ( versus milliseconds, P=NS) and retrograde conduction (313±68 versus 306±51 milliseconds, P=NS). Similarly, fast and slow pathway effective refractory periods (295±22 versus 298±26 milliseconds, P=NS and 264±36 versus 269±38 milliseconds, P=NS, respectively) as well as the retrograde AV node effective refractory period (258±50 versus 257±37 milliseconds, P=NS) were not altered. Despite autonomic blockade, the fast pathway effective refractory period shortened after ablation of the slow pathway (298±26 versus 273±50 milliseconds, P=.08). The mean shortening of the effective refractory period was -25.5±51 milliseconds, and it ranged from +50 to -90 milliseconds (Fig 4). Effects of Ablation on the Electrical Properties of the AV Node in the Presence of Autonomic Blockade No change in antegrade and retrograde AV node refractoriness and Wenckebach cycle was documented in the group with autonomic blockade. Unlike the control group, the retrograde effective refractory period of the AV node did not prolong (257±37 versus milliseconds, P=NS) (Tables 2 and 3). Additional Measurements The Ah-Acs interval was measured during AV node reentrant tachycardia as a poterntial reflection of the distance between the fast (anterior) and slow (posterior) pathways. There was no difference in this interval between patients with shortening of the fast pathway

4 1106 Circulation Vol 89, No 3 March Ce o 1 50 RE A1 A2 FIG 4. Atrioventricular node function curve before (o) and after (V) ablation in a patient undergoing autonomic blockade. After elimination of the slow pathway, shortening of the fast pathway refractoriness is observed despite autonomic blockade. A1A2 indicates interval between atrial deflection of the last drive cycle and the extrastimulus (at the His bundle catheter); A2H2, AH interval at the His bundle catheter after the extrastimulus. effective refractory period and those without (13.8±10 versus 9.1±7 milliseconds, P=NS). The longest AH interval during incremental pacing with 1:1 AV conduction appeared to be a useful indicator of persistence of the slow pathway regardless of the presence of dual AV node physiology during extrastimulus testing. After successful ablation of the slow pathway, the longest AH interval achievable systematically decreased (291±82 versus 118±26 milliseconds, P=.00005). Discussion Shortening of the fast pathway effective refractory period has been reported3,4 immediately after ablation of the slow pathway. This observation seems to depend on complete elimination of slow pathway conduction. Indeed, this finding has not been described in other series with higher percentages of residual slow pathway conduction after ablation.1,2 Kay et al3 suggested either increased sympathetic tone or selective destruction of TABLE 2. Electrophysiological Effects of Slow Pathway Ablation After Autonomic Blockade (Group 2) Preablation, Postablation, Autonomic Autonomic Preablation Blockade Blockade SCL 817± ±72* 629±82.7 AH ±16 1:1 Ant ±43 367±61 1:1 Ret ± ERPFP ±26 273±50 ERPsp 264±36 269±38... Ret ERPAVN 258± ±57 SCL indicates sinus cycle length; AH, atrio-his interval; 1:1 ANT, 1:1 Ret, minimum cycle length maintaining one-to-one conduction over the atrioventricular (AV) node anterogradely and retrogradely, respectively; ERPFP, effective refractory period of the fast pathway; ERPsp, effective refractory period of the slow pathway; and Ret ERPAVN, retrograde effective refractory period of the AV node. *P<.05, preablation autonomic blockade compared with preablation. parasympathetic innervation to explain the tendency of the fast pathway effective refractory period to shorten. Supporting their hypothesis was the faster heart rate after ablation. Our study demonstrates that ablation of the slow pathway induced shortening of the fast pathway effective refractory period and that the extent of this change was not affected by autonomic blockade. Recently, Lesh et ad10 proposed that an electrotonic interaction between fast and slow pathway may produce such changes. Electrotonus simply defined is a voltage change attributable to the flow of current through a structure.1" In the case of an excitable membrane, it is the change of potential produced by current flows that occur whenever a voltage difference exists between two sites within the syncytium. Cranefield and Hoffman12 first reported that the subthreshold depolarizing pulses, such as electrotonic current, applied during repolarization prolong the action potential duration of papillary muscle. Subsequently, others have demonstrated the influence of electrotonic interaction on the action potential recorded from different regions of the myocardium It appears that myocardial refractoriness and action potential duration are dependent on the pattern and the timing of activation. Therefore, the sequence of excitation and different speed of propagation affect local recovery properties through electrotonic interaction that operates during the excitation process. Electrotonic influence reflects the existence of anisotropy and nonuniform activation in the myocardium. In the case of the AV node tissue and surrounding myocardium, when the entire region has been excited, current from the last area to be activated, namely the slow pathway, may retard repolarization of areas excited earlier in the activation sequence such as the fast pathway. Loss of this interaction after ablation might then shorten refractoriness in the fast pathway. However, if this were the case, the shortening of the effective refractory period of the fast pathway should be expected in all patients, whereas it is evident in approximately 60% of them. We tried to distinguish patients susceptible to shortening of the effective refractory period of the fast pathway by analyzing the interval between the atrial activation at the His bundle region and the coronary sinus during reentrant tachycardia. A shorter Ah-Acs interval may identify a more closely spaced fast and slow pathway,2 heralding higher probability of electrical interaction. In our population, the Ah-Acs interval did not predict the effect of slow pathway ablation on fast pathway effective refractory period. However, patients in whom ablation was followed by prolongation of the fast pathway effective refractory period had a shorter Ah-Acs interval. It seems conceivable that fast pathway effective refractory period prolongation may reflect less "selective" damage to the slow pathway. Finally, acute effects of radiofrequency delivery in the relatively small triangle of Koch may also be implicated as a potential mechanism for the shortening of the fast pathway effective refractory period. In this case, transmission of heat from the site of ablation to the surrounding tissue might have influenced the conduction properties of the fast pathway fibers. In fact, increase of temperature below the values required to permanently injure the myocardial tissue has been shown to increase conduction velocity and shorten the refractory period.19

5 Natale et al Autonomic Blockade After Slow Pathway Ablation 1107 TABLE 3. Electrophysiological Effects of Slow Pathway Ablation in the Control and Autonomic Blockade Groups Retr Retr SCL SCL 1:1 Ant 1:1 Ant 1:1 Ret 1:1 Ret FPERP FPERP AVNERP AVNERP AVNERP Patient pre Abl post Abl pre Abl post Abl pre Abl post Abl pre Abl post Abl pre Abl AFPERP pre Abl post Abl Control group Autonomic blockade group SCL indicates sinus cycle length; pre Abl, before ablation; post Abl, after ablation; 1:1 Ant, 1:1 Ret, minimum cycle length maintaining one-to-one conduction over the atrioventricular (AV) node anterogradely and retrogradely, respectively; FPERP, effective refractory period of the fast pathway; AVNERP, effective refractory period of the slow pathway; AFPERP, absolute change of the fast pathway refractory period after ablation; and Retr AVNERP, retrograde effective refractory period of the AV node. However, other unknown effects of radiofrequency energy on the adjacent tissues cannot be excluded. Regardless of the mechanism, any such effect of radiofrequency delivery should be transient and should disappear with time. Although we did not obtain electrophysiological data at long-term follow-up, results from others20 support this explanation, with a tendency of the fast pathway effective refractory period to prolong with time.20 Effects of Autonomic Blockade on Cardiac Electrical Properties Kay and colleagues3 have shown that slow pathway ablation in the absence of autonomic blockade may be accompanied by a reduction of the sinus cycle length. This is consistent with either increased sympathetic tone or selective destruction of parasympathetic innervation. In the present study, both increase and decrease of the heart rate were noted in individuals in the control group after ablation. This may be related to variable degrees of sedation in individuals. This was clearly autonomically mediated, being completely obscured by autonomic blockade. However, autonomic blockade was unable to modulate the shortening of fast pathway effective refractory period after slow pathway ablation. Although incomplete sympathetic blockade at the AV node level may be theorized, this is unlikely, considering that autonomic blockade achieved in our study completely blunted the postablation sinus node response. Since the sinus node and the AV node have similar sensitivity and response to autonomic blockade,2' it is probable that the same degree of autonomic inhibition was achieved at the AV node level. In most patients, administration of propranolol and atropine before ablation reduced the sinus cycle length, suggesting a predominant effect of the parasympathetic system on this region In contrast, autonomic blockade did not result in significant change in fast and slow pathway properties, implying a balanced innervation to the AV node. After autonomic blockade, however, sustained reentrant tachycardia was inducible in only two patients. It is possible that sympathetic activation during tachycardia is important in the maintenance of the arrhythmia. Interestingly, autonomic blockade obscured dual pathway physiology (ie, the discontinuous curve) in some patients and made it manifest in others. Discontinuous curves became continuous after autonomic blockade in two patients. In one of them, this reflected a reduction of conduction velocity over the fast pathway, which allowed a more progressive AH prolongation with a smoother transition from the fast to the slow

6 1108 Circulation Vol 89, No 3 March 1994 pathway. This behavior supports a predominant 13-blocking effect. In another patient, a continuous curve after autonomic inhibition was the result of complete abolition of slow pathway conduction, which suggests that the sympathetic component of the autonomic system or the,3-blocking effects prevailed on the slow conducting pathway. In two patients, dual physiology became manifest only after autonomic blockade. In one of them, the fast pathway curve shifted to the right and the slow to the left after autonomic blockade. This suggested a more pronounced 1-blocking effect on the fast pathway and a predominant vagolytic effect on the slow pathway (Fig 3). In the second patient, both fast and slow pathway curves shifted to the left after autonomic blockade, suggesting vagolytic modulation on both pathways. Shortening of slow pathway effective refractory periods was more pronounced, reducing the degree of overlap of the two function curves. A different response of fast and slow pathways to autonomic blockade, suggesting unbalanced autonomic innervation to different portions of the AV node region, is consistent with previous reports after selective inhibition of one of the two autonomic limbs An unexpected observation was the tendency of ablation to prolong retrograde AV node refractoriness in the control group. This was not evident after autonomic blockade, suggesting that the latter effect is autonomically mediated. Conclusions In summary, radiofrequency ablation of the slow pathway is frequently followed by changes in sinus rate and shortening of the fast pathway effective refractory period. After autonomic blockade, the former was eliminated, whereas the latter persisted. The fast pathway effective refractory period shortening documented in our study and by other investigators reflected mechanisms other than autonomic modulation. 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