Author + information
- Received June 11, 1997
- Revision received August 21, 1997
- Accepted September 2, 1997
- Published online December 1, 1997.
- Anne B Curtis, MD, FACCA,* (, )
- Luiz Belardinelli, MDA,
- David A Woodard, MDA,
- Christopher S Brown, MDA and
- Jamie B Conti, MD, FACCA
- ↵*Dr. Anne B. Curtis, University of Florida, Box 100277, 1600 SW Archer Road, Gainesville, Florida 32610.
Objectives. This study sought to evaluate the sensitivity of fast and slow atrioventricular (AV) node pathways to incremental doses of adenosine in patients with typical AV node reentrant tachycardia.
Background. Although adenosine is known to depress conduction through the AV node, the relative sensitivity to adenosine of the anterograde fast and slow pathways in patients with dual AV node pathways and typical AV node reentrant tachycardia has not previously been studied.
Methods. Sixteen patients with dual AV node physiology and typical AV node reentrant tachycardia and 10 control patients were given incremental doses of adenosine during atrial pacing.
Results. In 14 of 16 patients with dual-AV node physiology, administration of small doses of adenosine during atrial pacing led consistently to transient block of impulse conduction in the fast pathway before block in the slow pathway, resulting in abrupt prolongation of the AH interval with continued 1:1 AV conduction. The mean (±SD) doses of adenosine required to cause conduction block in the fast and slow pathways were 2.7 ± 3.0 and 7.2 ± 4.7 mg, respectively (p = 0.004). In 9 of 16 patients, administration of low dose adenosine led to initiation of AV node reentrant tachycardia. The control patients showed no abrupt increases in AH interval with administration of adenosine during atrial pacing.
Conclusions. In most patients with dual AV node pathways and typical AV node reentrant tachycardia, the fast pathway is more sensitive than the slow pathway to the effects of adenosine.
A great deal of evidence has accumulated from basic and clinical studies [1, 2]that the compact atrioventricular (AV) node has dual inputs located anteriorly and posteriorly. In patients with AV node reentrant tachycardia, the anterior pathway in general is a rapidly conducting pathway with a long refractory period, whereas the posterior pathway is slowly conducting and has a shorter refractory period .
Adenosine is an endogenous nucleoside that slows the sinus heart rate (negative chronotropic effect) as well as impulse conduction through the AV node (negative dromotropic effect). Adenosine is highly effective in terminating supraventricular tachycardias in which the AV node is part of a reentrant circuit . In typical AV node reentrant tachycardia, previous studies have shown that adenosine may terminate the tachycardia either by causing block in the anterograde slow pathway or in the retrograde fast pathway. Although observations in clinical studies have suggested that adenosine is more potent in slowing anterograde than retrograde conduction through the AV node, the relative responsiveness of anterograde fast and slow pathway conduction to adenosine has not been investigated. The purpose of the present study was to determine whether the depressant effect of adenosine on the anterograde fast pathway is more pronounced than the effect on the slow pathway in patients with typical AV node reentrant tachycardia who have demonstrable dual AV node pathways. As a corollary to this first objective, the second aim of this investigation was to determine whether low doses of adenosine, by briefly blocking fast pathway conduction, could be used to initiate AV node reentrant tachycardia.
All patients undergoing electrophysiologic studies for the diagnosis and radiofrequency ablation of supraventricular tachycardia were invited to participate in the study. The study was approved by the institutional review board of the University of Florida, and all patients gave informed consent. Patients were studied in the fasting state after all antiarrhythmic drugs had been discontinued for at least 5 half-lives. Three quadripolar catheters were inserted through sheaths in the femoral veins and advanced to the right ventricular apex, the high right atrium and the His bundle position, respectively. A decapolar catheter was placed in the coronary sinus through a subclavian vein in selected patients. Baseline atrial, AV node and ventricular refractory periods were determined in each patient, and incremental atrial and ventricular pacing were performed. Supraventricular tachycardia was induced by using atrial or ventricular extrastimuli or by atrial burst pacing. The mechanism of the tachycardia was determined using standard criteria.
All patients who had consented to participate in the study and who had dual AV node pathways and typical AV node reentrant tachycardia underwent the adenosine protocol before radiofrequency ablation of the slow pathway. Dual AV node pathwayswere considered to be present when there was a sudden increase ≥50 ms in the AH interval for a 10-ms decrement in the A1–A2 coupling interval . Eligible patients received incremental doses of adenosine during atrial pacing at a cycle length that was determined by adding ∼40 ms to the effective refractory period of the fast pathway to achieve steady state conduction over the fast pathway. Adenosine was administered at increasing doses of 1, 2, 4, 6, 9, 12 and 18 mg, or until AV block occurred. The adenosine was administered rapidly into a peripheral intravenous line, followed by an immediate saline flush. At least 2 min was allowed to elapse between injections of adenosine. In two patients in whom administration of low doses of adenosine during atrial pacing led to initiation of AV node reentrant tachycardia, atrial pacing was discontinued, and higher doses of adenosine were administered during the same episode of tachycardia to terminate it.
Intracardiac recordings were obtained throughout the period of administration of adenosine until the AH interval returned to baseline. The signals were filtered at 30 to 500 Hz and stored on an optical disk (Quinton Electrophysiology, Ontario, Canada) for later analysis. The longest AH interval achieved for each dose of adenosine was determined; in addition, any abrupt changes in AH interval were noted.
After the adenosine protocol was completed, all patients successfully underwent radiofrequency ablation of the slow pathway.
In addition to the patients with dual AV node pathways, 10 patients without known supraventricular tachycardia and with no electrophysiologic evidence for dual AV node pathways who were undergoing electrophysiologic studies for syncope or ventricular arrhythmias were also given incremental doses of adenosine during atrial pacing at cycle lengths of 50 and 100 ms longer than the Wenckebach cycle length.
1.2 Statistical Analysis
Results are expressed as mean value ± SD. The Student paired ttest was used to compare the mean doses of adenosine required to block the fast and the slow AV node pathways, with a p value ≤0.05 taken as evidence of a significant difference. Regression analysis was used to determine the correlation between the dose of adenosine required to cause conduction block of the pathway and the effective refractory period of the fast and slow pathways.
2.1 Patient Characteristics
A total of 26 patients were enrolled in the study (16 with dual AV node pathways and AV node reentrant tachycardia; 10 with no evidence for dual AV node pathways and no inducible supraventricular tachycardia). Among the 16 patients with dual AV nodal pathways (14 women, 2 men; mean age 54 ± 15 years), there was 1 woman with mitral valve prolapse 1 man with hypertrophic cardiomyopathy; the other 14 patients had structurally normal hearts. The 16 patients with dual AV node pathways were classified into two groups: Group 1 (n = 9) received incremental doses of adenosine until AV block occurred; Group 2 (n = 7) received increasing doses of adenosine only until fast pathway block occurred, with the primary aim of inducing AV node reentrant tachycardia. Baseline electrophysiologic data for both groups are summarized in Table 1. Two patients had repeated induction of AV node reentrant tachycardia with incremental atrial pacing, making it difficult to determine the Wenckebach cycle length.
2.2 Refractory Periods and Response to Adenosine
Among the 16 patients with dual AV node pathways, the mean effective refractory period of the fast pathway was 344 ± 53 ms (range 263 to 482) versus an upper limit of 272 ± 31 ms for the slow pathway (range <212 to 325). In nine of the patients studied, the effective refractory period of the slow pathway could not be precisely determined because of atrial refractoriness. There was a significant difference between the mean doses of adenosine required to block conduction through the fast and the slow AV node pathways. In Group 1, conduction in the fast pathway blocked at a mean dose of 3.1 ± 3.7 mg (median dose 2.0), whereas conduction in the slow pathway blocked at a mean dose of 7.0 ± 4.9 mg (median dose 6.0). This difference was highly significant at p = 0.009. Among all the patients, the fast pathway blocked at a mean dose of adenosine of 2.7 ± 3.0 mg (median dose 1.0).
A representative example of a patient with dual AV nodal pathways and the effect of adenosine on the AH interval is illustrated in Fig. 1. Fig. 1A depicts an abrupt increase in the AH interval at an A1–A2 coupling interval of 263 ms during the AV node refractory period determination. Fig. 1B shows that in the same patient, the AH interval was 64 ms and changed little (73 to 100 ms) during administration of 1- to 5-mg doses of adenosine while pacing the atrium at a cycle length of 350 ms. At a dose of 6 mg, there was an abrupt increase in the AH interval to 245 ms that persisted for 14 s before abruptly returning to baseline. Higher doses of adenosine (i.e., 7 to 18 mg) also led to abrupt increases in the AH interval to 245 ms. When 10 to 18 mg of adenosine was given, AV node reentrant tachycardia was initiated. In this patient, AV block was not seen, even at the 18-mg dose of adenosine. Although the effect of adenosine on fast pathway conduction that was seen in this patient was typical of that observed throughout the study, this patient required markedly higher doses of adenosine to block conduction in the fast pathway than were necessary in the other patients (Table 1).
2.3 Control Patients
Ten patients without evidence of dual AV node pathways or a history of supraventricular tachycardia were studied as well. In these patients, administration of increasing doses of adenosine was associated with little change in the AH interval, until AV block occurred at a mean adenosine dose of 7.5 ± 1.7 mg. A typical example is illustrated in Fig. 11, C and D.
2.4 Block of Fast Pathway Conduction with Adenosine
The abrupt prolongation of the AH interval caused by adenosine in the patients with dual AV node pathways is shown in Fig. 2. Fig. 2A illustrates a sudden increase in AH interval within a single beat (from 115 to 194 ms), whereas the abrupt return of the AH interval to baseline (from 180 to 95 ms) as the effect of adenosine wore off is shown in Fig. 2B.
The data for the patients with dual AV node pathways in Group 1 in whom both fast and slow pathway responsiveness to adenosine were tested are summarized in Fig. 3. In eight of nine patients, conduction block occurred in the fast pathway before the slow pathway, as depicted by the abrupt increase in AH interval with a small increment in the dose of adenosine. This greater responsiveness of the fast than the slow pathway to adenosine was also observed in six of seven patients in Group 2 tested primarily to induce AV node reentrant tachycardia. Hence, adenosine caused fast pathway conduction block before slow pathway conduction block in 14 of the 16 patients studied. The two patients who did not show this pattern had clear evidence of dual AV node pathways at baseline, yet they showed only a gradual increase in AH interval with increasing doses of adenosine until AV block occurred at adenosine doses of 18 and 9 mg, respectively.
The relation between the dose of adenosine required to block conduction in the fast or the slow AV node pathway and the effective refractory period of each pathway is shown in Fig. 4. There was a clear inverse correlation between the effective refractory period of the pathway and the dose of adenosine required to block the pathway, with a correlation coefficient of 0.94. That is, the longer the refractory period of the pathway, the lower the dose of adenosine required to cause block.
2.5 Induction of AV Node Reentrant Tachycardia with Adenosine
Of interest was the observation that in many patients, administration of doses of adenosine lower than those required to cause AV block actually led to the induction of AV node reentrant tachycardia. For instance, 9 of the 16 patients with dual AV node pathways developed AV node reentrant tachycardia with the administration of 1 to 10 mg of adenosine (mean 3.2 ± 2.9, ≤4 mg in all but 1 patient), respectively, whereas 1 additional patient showed single echo beats after administration of 2 and 4 mg of adenosine. In two of the patients, after adenosine was given during atrial pacing to initiate AV node tachycardia, atrial pacing was discontinued, and a higher dose of adenosine was given, which led to termination of the same tachycardia (Fig. 5).
The results of the present study demonstrate that the fast and the slow AV node pathways are not equally responsive to adenosine. In most patients with dual AV node pathways, the anterograde fast pathway is more responsive to the effects of adenosine than the anterograde slow pathway. In addition, because of this differential responsiveness of the fast and slow pathways, adenosine can be used both to initiate and to terminate AV node reentrant tachycardia.
3.1 Effects of Adenosine on Anterograde and Retrograde AV Node Conduction
Previous investigators have shown that adenosine can terminate typical AV node reentrant tachycardia by causing conduction block either in the anterograde slow pathway or the retrograde fast pathway, or both. Other studies have suggested that adenosine is more potent in blocking anterograde conduction through the AV node than retrograde conduction. Adenosine decreases the amplitude and duration of the action potentials of AN and N cells in the AV node, but not NH cells . The N zone of the AV node is the most likely site of conduction block caused by adenosine. Hence, the fact that adenosine markedly decreases the amplitude and shortens the action potential duration of AN cells but not NH cells is consistent with the observation that adenosine is more potent in blocking anterograde than retrograde conduction.
3.2 Effects of Adenosine on Anterograde Fast and Slow AV Node Pathways
Impulse propagation through the anterograde fast and slow AV node pathways enters into the compact AV node. Given the longer conduction time of the slow pathway than the fast pathway and the known site of action of adenosine in the AV node, it could be predicted that the slow AV node pathway would be more sensitive to the effects of adenosine than the fast pathway. Our results show just the opposite. It is thus possible that either the fast pathway involves the compact AV node to a greater extent than previously realized, or that the relative amount of input of each pathway into the compact AV node is irrelevant in explaining its responsiveness to adenosine.
A recent preliminary study on the effect of adenosine on anterograde fast and slow pathway conduction found that a higher dose of adenosine was required to cause AV block before slow pathway ablation than after ablation was accomplished. This finding and the observation by the same investigators that administration of adenosine caused an abrupt increase in the AH interval without induction of AV block are both consistent with the results of our study.
3.3 Refractoriness and Response to Adenosine
An alternative explanation for the greater sensitivity of the fast pathway to adenosine may be that refractoriness of the pathway rather than conduction is the more important determinant of responsiveness to adenosine. This hypothesis is supported by our finding that conduction through pathways with long effective refractory periods is blocked with lower doses of adenosine than pathways with shorter refractory periods. In support of this explanation, it is known that adenosine and A1 adenosine receptor agonists increase refractoriness in AV node tissue [10, 11]. However, it should be noted that the significant inverse relation between the refractory period of an AV node pathway and the dose of adenosine required to block conduction through that pathway does not in itself prove causality.
3.4 Mechanism of Action of Adenosine in AV Node Reentrant Tachycardia
A hypothesis to explain the induction of AV node reentrant tachycardia with adenosine is that low doses of adenosine that selectively and briefly block fast pathway conduction allow conduction antegradely through the slow pathway only. Retrograde conduction up the fast pathway then sets up the reentrant circuit for AV node reentry. That induction of AV node reentrant tachycardia is not often seen clinically is simply due to the fact that large doses of adenosine are routinely administered that cause unselective conduction block of both AV node pathways and, thereby, termination of AV node reentrant tachycardia.
☆ Dr. Woodard was the recipient of a Research Fellowship from the American Heart Association, Dallas, Texas.
- Received June 11, 1997.
- Revision received August 21, 1997.
- Accepted September 2, 1997.
- The American College of Cardiology
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