Original Article
Radiofrequency Catheter Modification of Atrioventricular Conduction to Control the Ventricular Rate during Atrial Fibrillation
N Engl J Med 1994; 331:910-917October 6, 1994
- Abstract
Background
In some patients with atrial fibrillation, the ventricular rate may be difficult to control with medications. We evaluated a radiofrequency catheter technique to modify atrioventricular conduction in atrial fibrillation in order to control the ventricular rate without creating pathologic atrioventricular block.
Methods
We studied 19 consecutive patients with atrial fibrillation and uncontrolled ventricular rates refractory to drug therapy. They had had atrial fibrillation for a mean (±SD) of 5.5 ±4.9 years, had had 4.9 ±0.9 unsuccessful drug trials, and were 62 ±15 years old. Before the procedure, the maximal ventricular rate during exercise was 180 ±39 beats per minute. A total of 11 ±5 radiofrequency-energy applications were delivered to the posterior septal or midseptal right atrium, near the ostium of the coronary sinus.
Results
Successful control of the ventricular rate without pathologic atrioventricular block was achieved in 14 of the 19 patients (74 percent). Persistent third-degree atrioventricular block requiring a permanent pacemaker occurred inadvertently in four patients (21 percent). Atrioventricular conduction was intentionally ablated in one patient. The 14 patients who had successful modification of conduction had persistent reductions in maximal ventricular rate during exercise (rate at three months, 126 ±24 beats per minute; P<0.01). These patients had resolution of symptoms related to rapid rates during 8 ±2 months of follow-up. One patient had a recurrence of a rapid ventricular rate but was again asymptomatic after a second modification procedure. One patient with dilated cardiomyopathy died suddenly, five months after a successful procedure.
Conclusions
A catheter technique to modify atrioventricular conduction without creating pathologic atrioventricular block is feasible in the majority of patients with symptomatic atrial fibrillation and a rapid ventricular rate refractory to drug therapy.
Media in This Article
Figure 1
Modification of Atrioventricular Conduction by a 30-Second Application of Radiofrequency Energy (RF).Figure 2
Mean (±SD) Ventricular Rates during Atrial Fibrillation before and Two Days and Three Months after Radiofrequency Modification of Atrioventricular Conduction in 14 Patients with Successful Outcomes.Article Activity
- Article
Direct-current shocks1-5 and radiofrequency energy6-12 have been used to interrupt atrioventricular conduction in patients with atrial fibrillation associated with an uncontrolled ventricular rate refractory to drug therapy. However, a technique to slow the ventricular rate during atrial fibrillation without creating pathologic atrioventricular block would be desirable. Until now, only two case reports have described patients in whom radiofrequency energy was successfully used to slow the ventricular rate during atrial fibrillation without creating the need for a pacemaker13,14. This study was intended to evaluate a catheter technique to modify atrioventricular conduction with radiofrequency energy without creating pathologic atrioventricular block in a series of consecutive patients with atrial fibrillation and uncontrolled ventricular rates.
Methods
Characteristics of the Patients
We studied 19 consecutive patients with atrial fibrillation and uncontrolled ventricular rates. In all the patients, medical therapy had failed to control the ventricular rate, and they consequently had rapid palpitations and limited exercise tolerance. The characteristics of the patients are shown in Table 1Table 1
Characteristics of the Patients..Measurement of Ventricular Rates
The ventricular rate during atrial fibrillation was measured under four circumstances. Each measurement was made before and after the modification procedure. The resting rate was measured after the discontinuation of antiarrhythmic-drug therapy 48 hours before the electrophysiologic study, with the patient sitting and inactive. The ambulatory rate was measured after the patient had walked 46 m (50 yd) at his or her usual pace. If feasible, the maximal ventricular rate during strenuous exertion was determined with a symptom-limited exercise treadmill test. In addition, the slowest rate during atrial fibrillation was determined from 24-hour ambulatory recordings.
Protocol for Radiofrequency Modification
Informed consent was obtained under a study protocol approved by the Human Research Committee at the University of Michigan. Two quadripolar-electrode catheters were inserted into a femoral vein and positioned at the His bundle and in the right ventricle. A 7-French quadripolar-electrode catheter with a 4-mm distal electrode, 2-to-5-mm spacing between electrodes, and a deflectable tip (Mansfield Scientific, Watertown, Mass.) was used to deliver radiofrequency energy (EP Technologies, Mountain View, Calif.) through the distal electrode; a large patch electrode (Valleylab, Boulder, Colo.) on the posterior thorax served as the indifferent electrode. Ventricular rates were measured for one minute in the base-line state and after a steady-state effect had been reached during the infusion of 4 μg of isoproterenol per minute.
Radiofrequency energy was applied during atrial fibrillation, and an infusion of isoproterenol was given to permit immediate assessment of the effect of each application. If sinus rhythm was present, atrial fibrillation was induced by rapid atrial pacing before the delivery of radiofrequency energy. The right atrial septum adjacent to the septal leaflet of the tricuspid valve and extending from the ostium of the coronary sinus to the recording site at the His bundle was divided into three regions: posterior, midseptal, and anterior15,16. After the location of the coronary-sinus ostium had been defined fluoroscopically, the catheter was positioned against the posterior septum, at the level of the ostium, to record a maximal atrial-to-ventricular electrographic ratio of 0.5 or less during a continuous recording period of at least 10 seconds.
Radiofrequency energy was delivered at 12 to 38 W for up to 60 seconds, depending on the response of the ventricular rate. Whenever there was an abrupt lengthening of the RR interval, the application of energy was immediately discontinued. If there was no change in the ventricular rate, the catheter was repositioned in progressively more superior and anterior positions along the posterior and midatrial septum. No applications were delivered at sites where a His-bundle potential greater than 0.02 mV was present. The end point of the procedure was an average ventricular rate of approximately 120 beats per minute during the infusion of isoproterenol. When this objective was achieved, the ventricular rate was also determined 20 to 30 minutes after the discontinuation of the infusion.
Follow-up Evaluation
The patients underwent continuous inpatient electrocardiographic monitoring for at least 48 hours. Twenty-four-hour Holter monitoring and exercise treadmill tests were performed two days after the modification procedure, when the patients were receiving no antiarrhythmic-drug therapy. The patients were seen on an outpatient basis at three-month intervals. Ambulatory monitoring and treadmill tests were performed three months after the modification procedure. All the patients were followed for at least five months.
Statistical Analysis
Continuous variables are expressed as means ±SD. Comparisons were performed by Student's paired t-test or by an analysis of variance with repeated measures. A two-tailed P value of less than 0.05 was considered to indicate statistical significance.
Results
Overall Short-Term Results
In the electrophysiology laboratory, atrioventricular conduction was modified in 17 patients (Figure 1Figure 1
Modification of Atrioventricular Conduction by a 30-Second Application of Radiofrequency Energy (RF).), inadvertent third-degree atrioventricular block occurred in 1 patient, and third-degree atrioventricular block was induced in 1 patient in whom the modification procedure did not succeed in slowing the ventricular rate (Table 2Table 2
Results of Radiofrequency Modification to Control Ventricular Rates in Patients with Atrial Fibrillation.). The mean (±SD) number of radiofrequency-energy applications was 11 ±5 (range, 3 to 27). The average duration of fluoroscopy was 37 ±16 minutes (range, 13 to 66). The location of the effective target site was posterior in 7 patients and midseptal in 10.In 3 of the 17 patients in whom atrioventricular conduction was modified in the electrophysiology laboratory, third-degree atrioventricular block occurred within the first three days after the procedure. Therefore, over the short term, atrioventricular conduction was modified successfully in 14 of 19 patients (74 percent), inadvertent atrioventricular block requiring the insertion of a permanent pacemaker occurred in 4 patients (21 percent), and ablation of the atrioventricular junction was intentionally performed because the modification procedure was unsuccessful in 1 patient (5 percent).
Patients with a Successful Outcome
The 14 patients in whom atrioventricular conduction was successfully modified had a statistically significant decrease in ventricular rates at two days and three months of follow-up (Table 3Table 3
Ventricular Rates during Atrial Fibrillation in the 14 Patients with Successful Outcomes, before and after Radiofrequency Modification of Atrioventricular Conduction. and Figure 2Figure 2Mean (±SD) Ventricular Rates during Atrial Fibrillation before and Two Days and Three Months after Radiofrequency Modification of Atrioventricular Conduction in 14 Patients with Successful Outcomes.).Patients with Atrioventricular Block
Persistent third-degree atrioventricular nodal block developed in Patient 15 in the electrophysiology laboratory during the application of 38 W of radiofrequency energy to a posterior site. Third-degree atrioventricular nodal block developed in three patients 36 to 72 hours after the procedure. Transient third-degree atrioventricular block lasting 10 to 27 seconds had occurred during the modification procedure in these three patients (Figure 3Figure 3
Inadvertent Atrioventricular Block after an Application of Radiofrequency Energy (RF).). Transient atrioventricular block had also occurred in 2 of the 14 patients in whom the modification procedure was successful. Each of the four patients with inadvertent, persistent third-degree atrioventricular block had a junctional rhythm at a rate of 40 to 55 beats per minute and underwent the implantation of a pacemaker.In Patient 4, atrioventricular conduction remained rapid after 11 applications of radiofrequency energy; the atrioventricular junction was intentionally ablated, and a pacemaker was implanted.
Long-Term Clinical Outcomes
During a mean follow-up period of 8 ±2 months (range, 5 to 13), each of the 14 patients with successful short-term outcomes had a marked improvement in symptoms, and the overall Canadian Cardiovascular Society functional class17 improved significantly, from 3.1 ±0.5 to 1.6 ±0.5 (P<0.001, Table 1 and Table 2). Patient 10 had a recurrence of palpitations, weakness, and an uncontrolled ventricular rate nine weeks after the procedure and underwent a second procedure with no further recurrence of symptoms.
The only death during follow-up was of Patient 2, who died in his sleep five months after undergoing the modification procedure. He had idiopathic dilated cardiomyopathy and a left ventricular ejection fraction of 0.20. When he was evaluated three months after the procedure there was no evidence of bradycardia or atrioventricular block, and his ventricular rate was well controlled. Holter-monitor recordings before and after the procedure had demonstrated three-to-six-beat episodes of asymptomatic, nonsustained, monomorphic ventricular tachycardia. At the time of death, he was not being treated with any antiarrhythmic drug. No postmortem examination was performed.
Discussion
Main Findings
This study shows that it may be feasible to control the ventricular rate without inducing pathologic atrioventricular block in about 75 percent of patients with atrial fibrillation and uncontrolled ventricular rates, by using a catheter technique in which radiofrequency energy is delivered to the posterior or midatrial septum near the ostium of the coronary sinus. Therefore, in the majority of patients with atrial fibrillation and uncontrolled ventricular rates refractory to drug therapy, who may have been appropriate candidates previously for ablation of the atrioventricular junction and the insertion of a permanent pacemaker, it may be possible to achieve adequate slowing of the ventricular rate and resolution of symptoms without the need for a permanent pacemaker.
Ablation Compared with Modification of Atrioventricular Conduction
The conventional technique for ablation of the atrioventricular junction uses sites located anteriorly and superiorly on the tricuspid annulus. In contrast, with the technique used in this study to modify atrioventricular conduction, the target sites are located inferiorly and posteriorly near the tricuspid annulus, close to the orifice of the coronary sinus, as in the technique of Fleck et al.14
Despite the absence of a His-bundle depolarization in the electrograms at the target sites and the posterior position of the target sites relative to the atrioventricular node, the delivery of radiofrequency energy resulted at times in transient or permanent atrioventricular block. In an attempt to avoid atrioventricular block, we delivered radiofrequency energy in a conservative fashion, discontinuing application of the energy whenever there was a noticeable slowing in the ventricular rate. Because the delivery of radiofrequency energy near the atrioventricular junction often results in junctional ectopy,9,18 which may mask the onset of atrioventricular block, we delivered radiofrequency energy in an interrupted fashion, in order to confirm the absence of atrioventricular block. However, despite the discontinuation of applications of energy whenever there was a slowing in the ventricular rate, inadvertent atrioventricular block sometimes occurred (Figure 3). Therefore, an important limitation of the technique described in this study is that it may not always be possible to avoid the occurrence of atrioventricular block.
Transient Atrioventricular Block
About two thirds of the patients who had transient atrioventricular block in relation to the procedure later had persistent atrioventricular block, with an onset 36 to 72 hours after the procedure. It may be that transient thermal injury to the atrioventricular conduction system results in an inflammatory reaction that is responsible for the delayed occurrence of permanent injury. Regardless of the mechanism, if transient atrioventricular block occurs during an attempt to modify atrioventricular conduction, continuous electrocardiographic monitoring on an inpatient basis is appropriate for a period of three to four days, to watch for a recurrence of atrioventricular block.
Long-Term Results
Although the mean resting, ambulatory, and minimal ventricular rates during atrial fibrillation remained stable during an interval from two days to three months after the modification procedure, the mean maximal ventricular rate increased by 25 percent during this period. The increase in this rate during exercise at three months as compared with two days of follow-up may reflect partial recovery of atrioventricular conduction from the immediate effects of radiofrequency energy. Nevertheless, the mean maximal ventricular rate during exercise at three months of follow-up was still approximately 25 percent lower than at base line, a degree of attenuation adequate to result in the persistent resolution of symptoms.
In several patients, the maximal rate during exercise at three months of follow-up was within 10 beats per minute of the corresponding value before the modification procedure. Nevertheless, these patients reported relief of symptoms attributable to an uncontrolled ventricular rate. Such resolution of symptoms despite little change in the maximal rate during exercise may be explained in some patients by an increase in the duration of exercise. For example, Patient 11 attained a maximal rate of 165 beats per minute with a 20-MET workload at three months of follow-up, as compared with a maximal rate of 161 beats per minute with only a 10-MET workload before the procedure. Furthermore, even though the maximal rates during exercise may have been similar, the ventricular rates at comparable submaximal levels of effort were consistently lower three months after the procedure than at base line. For example, in Patient 11 the ambulatory rate at three months of follow-up was only 84 beats per minute, as compared with 140 beats per minute at base line.
Mechanism of Rate Control
The sites at which radiofrequency energy was delivered in this study were located in the posterior and middle septum, the same area targeted for ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia15,16,19-26. These sites correspond to the location of the posterior atrionodal inputs to the atrioventricular node,27 raising the possibility that the ventricular rate was controlled by the ablation of some or all of these posterior atrionodal inputs. This would control the rate only if conduction was slower through the anterior atrionodal inputs than through the posterior inputs.
The fact that transient or permanent third-degree atrioventricular block occurred in 6 of the 19 patients in this study indicates that target sites near the orifice of the coronary sinus may be close enough to the compact atrioventricular node to injure that structure. Because the sites that resulted in a successful outcome were in the same location as the sites that resulted in atrioventricular block, it may be that the rate was controlled, at least in some patients, by partial injury to the compact atrioventricular node. This would be consistent with the results of Huang et al., who demonstrated that persistent incomplete atrioventricular block could be achieved with radiofrequency energy in 13 of 20 dogs by partially injuring the compact atrioventricular node28.
Injury to the bundle of His is an unlikely explanation for the control of the ventricular rate, for two reasons. First, His-bundle depolarization was nonexistent or negligible in the target-site electrograms. Second, in the patients who had transient or permanent atrioventricular block, the location of the block was always above the bundle of His.
Sudden Death
Patient 2, who died suddenly five months after the modification procedure, had idiopathic dilated cardiomyopathy and a left ventricular ejection fraction of 0.20. It is possible that this patient's death resulted from a delayed complication of the modification procedure, such as pause-dependent polymorphic ventricular tachycardia19. It is also possible that his death was a result of his underlying heart disease. Sudden death is known to be a frequent complication of dilated cardiomyopathy that is associated with a depressed left ventricular ejection fraction29. A large number of patients with atrioventricular nodal reentrant tachycardia have undergone ablation of the slow pathway and have received applications of radiofrequency energy at sites in the posterior and middle septum similar to the sites used in this study, with no reports of ventricular arrhythmias or sudden death as a complication of the procedure15,16,20-26. Also, whereas the three patients in this study who had the delayed onset of atrioventricular block had transient episodes of atrioventricular block during the modification procedure, the patient who died suddenly never had atrioventricular block during the procedure and underwent ambulatory monitoring three months afterward that revealed no evidence of bradycardia, making atrioventricular block an unlikely cause of death.
Limitations
The majority of patients in this series had structural heart disease; therefore, the results may not apply to other populations of patients. Although control of the ventricular rate has been maintained for up to 13 months at this writing, follow-up has not yet reached 1 year in the majority of patients; longer follow-up is needed to confirm that the benefits of the modification procedure are permanent.
Because almost all the patients in this study had chronic atrial fibrillation, atrioventricular nodal conduction and refractoriness could not usually be measured. Therefore, another limitation of this study is that the effects of the radiofrequency-energy applications on the properties of the atrioventricular node could not usually be assessed.
Clinical Implications
Atrial fibrillation is a common arrhythmia that is often associated with uncomfortable symptoms. Despite therapy with antiarrhythmic agents and electrical cardioversion, atrial fibrillation may persist. In patients with persistent atrial fibrillation, the ventricular rate can usually be controlled pharmacologically with negative dromotropic agents, such as digitalis, calcium-channel-blocking agents, or beta-blockers. However, some patients have symptoms that cannot be controlled with medications. In such patients, catheter ablation of the atrioventricular junction has proved to be effective at eliminating the symptoms caused by a rapid ventricular rate, but at the cost of complete atrioventricular block and irreversible dependency on a permanent pacemaker. As compared with ablation of the atrioventricular junction, the catheter technique described here has the advantage that it results in adequate control of the ventricular rate in most patients without creating the need for a permanent pacemaker. Therefore, it may be appropriate to attempt first to modify atrioventricular conduction in patients with atrial fibrillation and rapid ventricular rates who are appropriate candidates for ablation of the atrioventricular junction. Because the risk of inadvertent complete atrioventricular block is approximately 20 percent, the use of the procedure should be limited at present to patients with atrial fibrillation who are symptomatic enough for ablation of the atrioventricular junction and implantation of a permanent pacemaker to be justified.
We are indebted to Betty Plunkett and Heidi Williams for their assistance in the preparation of the manuscript.
Source Information
From the Division of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0022, where reprint requests should be addressed to Dr. Morady.
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