ATRIAL FIBRILLATION
Increased AAI mode pacing threshold after termination of atrial fibrillation by acute administration of disopyramide phosphate
1 Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; 2 Department of Internal Medicine, Tsunan Hospital, Niigata, Japan
Manuscript submitted 26 August 2005. Accepted after revision 19 February 2006.
* Corresponding author. Tel: +81 3 3433 1111 ext. 3261 or 3262; fax: +81 3 3459 6043. E-mail address: anzawar{at}jikei.ac.jp
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Abstract |
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Aims We studied changes in atrial pacing threshold after termination of atrial fibrillation (AF) by acute administration of disopyramide phosphate (DP) to elucidate the suitable setting for atrial pacing output before AF termination.
Methods and results Four patients with sick sinus syndrome implanted with AAI mode pacemakers were examined. Disopyramide phosphate (2 mg/kg body weight) was injected intravenously for termination of a total of eight AF episodes. The maximal pacing threshold after AF termination (5.2±0.8 V at 0.45 ms) was significantly higher than that at baseline (1.3±0.2 V at 0.45 ms; P<0.01) and the average increment was 433±68%. During a period free from AF, an acute administration of DP did not increase the atrial pacing threshold and serum disopyramide levels were not toxic.
Conclusion The increased atrial pacing threshold observed after AF termination cannot be explained by the action of DP alone. However, our results suggest that atrial pacing output should be set at the maximum value before DP is administered to induce AF termination in patients with AAI pacemaker-dependent bradyarrhythmias.
Key Words: Antiarrhythmic drug, Atrial fibrillation, Disopyramide phosphate, Pacing failure, Pacing threshold, Sick sinus syndrome
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Introduction |
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An increased pacing threshold after administration of antiarrhythmic drugs (AADs)1
–7 is a condition that is often encountered and a severe problem for patients with pacemaker-dependent bradyarrhythmia. Most of the reports regarding this condition are about ventricular pacing threshold and chronic administration of AADs, whereas there are few studies of atrial pacing threshold or acute administration of AADs for termination of tachyarrhythmia.
We previously reported a case of atrial pacing failure following termination of atrial fibrillation (AF) by acute administration of disopyramide phosphate (DP), a class Ia AAD.8 In that patient, a dramatic increase in atrial pacing threshold was the main feature of the case; therefore, we investigated the degree and mechanism of the increase in atrial pacing threshold after AF termination by acute administration of DP in four other subjects. Further, we attempted to determine a suitable setting of atrial pacing output before administration of DP based on the degree of changes in pacing threshold.
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Methods |
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Patients
Four patients with implanted AAI pacemakers (Dash, model 292-03 R, Sulzer Intermedics Inc., Freeport, TX, USA), chosen according to the pacemaker criteria reported by Nielsen et al.,9
were enrolled in this study. When the device was implanted, atrial pacing threshold was <1.0 V at 0.45 ms in all of the patients. A total of eight episodes of paroxysmal AF was studied.
Measurement of atrial pacing threshold after AF termination by acute administration of DP
Before beginning the experiments, during the period free from AF, atrial pacing thresholds were measured (Thbase) by pulse amplitude (V) at a fixed pulse duration of 0.45 ms using a pacemaker programmer (RX 5000 programmer 522-12, Sulzer Intermedics Inc.) with the patient in a supine position. Beta-blockers were administered to control the ventricular rate of paroxysmal AF in all of the patients (Table 1).
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During each episode of paroxysmal AF, the pacing output was first set at a maximum of 8.1 V with a pulse duration of 1.0 ms. Next, DP at a dose of 2 mg/kg body weight (maximum dose, 150 mg) was administered intravenously over 10 min. Arterial blood pressure using a sphygmomanometer and QT intervals with an electrocardiographic (ECG) monitor were recorded simultaneously at 5 min intervals. After recognizing AF termination on the ECG monitor, the pacing threshold at 0.45 ms was measured in a non-invasive manner using the pacemaker programmer after 3, 5, 10, 15, and 20 min. The maximum atrial pacing threshold was defined as Thmax, whereas the increment was defined as Thmax/Thbasex100 (%). The time from AF termination to Thmax was determined as time to Thmax (min).
To measure serum levels of disopyramide, potassium, and creatinine, blood samples were obtained via the median cubital vein just after AF termination, then centrifuged at 3000 rpm for 5 min. The level of disopyramide was measured using an enzyme immunoassay.
Measurement of atrial pacing threshold after acute administration of DP during a period free from AF
One week after the second episode of paroxysmal AF in each patient, during a period free from AF, atrial pacing threshold was measured after acute administration of DP to assess the effect of DP. After the time required to terminate AF during the second episode, measurements of atrial pacing threshold were started and blood samples were obtained using the same method noted above. We measured pacing threshold before administration of DP (Thbase) and maximal pacing threshold after administration of DP (Thmax, V), and also determined the increment [Thmax/Thbasex100 (%)].
Statistical analysis
The results are shown as mean±SE. Student's t-test was used to compare values between Thbase and Thmax within each group and an unpaired t-test was used to compare all values between the groups. Differences with a P-value of less than 0.05 were considered statistically significant.
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Results |
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Patient characteristics
The patient characteristics are shown in Table 1. Two patients had mild arterial hypertension, whereas none had a history of angina pectoris or heart failure or had been receiving AADs over the long term. Serum levels of potassium (3.9–4.5 mEq/dL) and creatinine (0.5–0.8 mg/dL) were within normal limits.
Measurement of atrial pacing threshold after AF termination by acute administration of DP
Figure 1 shows changes in atrial pacing threshold after AF termination following an acute administration of DP. A significant increase was observed in all cases, which gradually decreased. The average value of Thmax (5.2±0.8 V) was significantly higher than Thbase (1.3±0.2 V, P<0.01) (Figure 2A), while the increment was 433±68% and the time to Thmax was 4.1±0.9 min. The serum level of disopyramide was 4.4±0.6 µg/mL (Table 2).
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Measurement of atrial pacing threshold after acute administration of DP during a period free from AF
Atrial pacing threshold did not increase significantly after an acute administration of DP during the period free from AF (Figure 1). The increment was 158±14%; however, Thmax (2.3±0.6 V) was not higher than Thbase (1.4±0.2 V, P=NS) (Figure 2B). The serum level of disopyramide was 4.1±0.5 µg/mL (Table 2).
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Discussion |
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In the present study, atrial pacing thresholds were significantly increased after AF termination by acute administration of DP in patients with sick sinus syndrome and implanted permanent AAI pacemakers, whereas that given during the period free from AF did not significantly increase the thresholds significantly. The serum levels of disopyramide were similar between the two protocols. Thus, the mechanisms of increase in atrial pacing threshold seen in the present study cannot be explained by the effects of DP alone.
Several physiological6,10 and pharmacological10 factors, as well as metabolic and electrolyte disorders,6 can have an effect on pacing threshold. However, none of those was present in our patients. The effects of AADs on pacing threshold have been reported, with amiodarone, a class III AAD, not to change ventricular pacing threshold after intravenous and long-term administration.11 In contrast, class Ia12 and Ib13 AADs have been reported to increase ventricular pacing threshold after acute administration, and the class Ic AADs propafenone1,14 and flecainide3,4 were shown to cause greater increases in ventricular and atrial pacing threshold compared with other AADs. In another report, Bianconi et al.1 speculated that the increase in ventricular pacing threshold following long-term administration of propafenone was due to a depressed upstroke of the action potential (Vmax).
A case of ventricular pacing failure due to an acute administration of pilsicainide for AF termination in a patient with a DDD pacemaker has been reported,15 in which a toxic level of pilsicainide was suggested to be the cause of pacing failure. Disopyramide toxicity has also been shown to increase ventricular pacing threshold after acute intravenous administration.7 In the present study, the serum levels of disopyramide corresponded to the therapeutic level reported by Niarchos.16 Therefore, the increase in atrial pacing threshold observed in our patients was not due to disopyramide toxicity.
To assess the effect of DP alone, atrial pacing threshold was measured after an acute administration of DP during a period free from AF. We found a relatively lower increase of atrial pacing threshold as with that measured after AF termination, whereas the serum concentrations of disopyramide were similar throughout the study. The effects of AF alone on atrial pacing threshold are considered to be involved in the mechanisms that increase atrial pacing threshold. A recent report found a rise in atrial and ventricular stimulation thresholds after direct current cardioversion for AF termination,17 thus AF itself may be a cause of the increase in pacing threshold after its termination. Then, we speculated that the electrophysiological characteristics of the atrium might change in the presence of both DP and AF. Soriano et al.18 reported rate-dependent ventricular pacing failures with propafenone. The same mechanism may exist in the atrial myocardium related to reversible electrical remodelling19 in the presence of DP and AF. However, correlation between duration or rate of AF and Thmax is unclear in study patients (Table 1). Furthermore, the interaction of beta-blocker and DP should also be considered. Propranolol has been reported not to cause clinically important changes in the ventricular pacing threshold,20 but up to now, there are no published data on the interaction of beta-blocker and AADs.
In the present study, the average increment was >300% after AF termination by an intravenous administration of DP. In addition, the time to Thmax was relatively short (4.1±0.9 min). Pacing output is commonly set at two or three times the pacing threshold21 as a safety margin; however, the present results suggest that atrial pacing output should be set at maximum before administration of DP for AF termination in patients with AAI pacemaker-dependent bradyarrhythmias.
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Conclusion |
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Atrial pacing threshold was increased an average of >400% after AF termination by acute administration of DP in patients with AAI pacemakers. This phenomenon could not be explained by DP alone; however, this may have been more related to AF. Nevertheless, great care must be taken when DP is administered for AF termination in patients with AAI pacemaker-dependent bradyarrhythmias.
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References |
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