Background In some patients with atrial fibrillation, the ventricularrate may be difficult to control with medications. We evaluateda radiofrequency catheter technique to modify atrioventricularconduction in atrial fibrillation in order to control the ventricularrate without creating pathologic atrioventricular block.
Methods We studied 19 consecutive patients with atrial fibrillationand uncontrolled ventricular rates refractory to drug therapy.They had had atrial fibrillation for a mean (±SD) of5.5 ±4.9 years, had had 4.9 ±0.9 unsuccessfuldrug trials, and were 62 ±15 years old. Before the procedure,the maximal ventricular rate during exercise was 180 ±39beats per minute. A total of 11 ±5 radiofrequency-energyapplications were delivered to the posterior septal or midseptalright atrium, near the ostium of the coronary sinus.
Results Successful control of the ventricular rate without pathologicatrioventricular block was achieved in 14 of the 19 patients(74 percent). Persistent third-degree atrioventricular blockrequiring a permanent pacemaker occurred inadvertently in fourpatients (21 percent). Atrioventricular conduction was intentionallyablated in one patient. The 14 patients who had successful modificationof conduction had persistent reductions in maximal ventricularrate during exercise (rate at three months, 126 ±24 beatsper minute; P<0.01). These patients had resolution of symptomsrelated to rapid rates during 8 ±2 months of follow-up.One patient had a recurrence of a rapid ventricular rate butwas again asymptomatic after a second modification procedure.One patient with dilated cardiomyopathy died suddenly, fivemonths after a successful procedure.
Conclusions A catheter technique to modify atrioventricularconduction without creating pathologic atrioventricular blockis feasible in the majority of patients with symptomatic atrialfibrillation and a rapid ventricular rate refractory to drugtherapy.
Direct-current shocks1,2,3,4,5 and radiofrequency energy6,7,8,9,10,11,12have been used to interrupt atrioventricular conduction in patientswith atrial fibrillation associated with an uncontrolled ventricularrate refractory to drug therapy. However, a technique to slowthe ventricular rate during atrial fibrillation without creatingpathologic atrioventricular block would be desirable. Untilnow, only two case reports have described patients in whom radiofrequencyenergy was successfully used to slow the ventricular rate duringatrial fibrillation without creating the need for a pacemaker13,14.This study was intended to evaluate a catheter technique tomodify atrioventricular conduction with radiofrequency energywithout creating pathologic atrioventricular block in a seriesof consecutive patients with atrial fibrillation and uncontrolledventricular rates.
Methods
Characteristics of the Patients
We studied 19 consecutive patients with atrial fibrillationand uncontrolled ventricular rates. In all the patients, medicaltherapy had failed to control the ventricular rate, and theyconsequently had rapid palpitations and limited exercise tolerance.The characteristics of the patients are shown in Table 1.
The ventricular rate during atrial fibrillation was measuredunder four circumstances. Each measurement was made before andafter the modification procedure. The resting rate was measuredafter the discontinuation of antiarrhythmic-drug therapy 48hours before the electrophysiologic study, with the patientsitting and inactive. The ambulatory rate was measured afterthe patient had walked 46 m (50 yd) at his or her usual pace.If feasible, the maximal ventricular rate during strenuous exertionwas determined with a symptom-limited exercise treadmill test.In addition, the slowest rate during atrial fibrillation wasdetermined from 24-hour ambulatory recordings.
Protocol for Radiofrequency Modification
Informed consent was obtained under a study protocol approvedby the Human Research Committee at the University of Michigan.Two quadripolar-electrode catheters were inserted into a femoralvein and positioned at the His bundle and in the right ventricle.A 7-French quadripolar-electrode catheter with a 4-mm distalelectrode, 2-to-5-mm spacing between electrodes, and a deflectabletip (Mansfield Scientific, Watertown, Mass.) was used to deliverradiofrequency energy (EP Technologies, Mountain View, Calif.)through the distal electrode; a large patch electrode (Valleylab,Boulder, Colo.) on the posterior thorax served as the indifferentelectrode. Ventricular rates were measured for one minute inthe base-line state and after a steady-state effect had beenreached during the infusion of 4 µg of isoproterenol perminute.
Radiofrequency energy was applied during atrial fibrillation,and an infusion of isoproterenol was given to permit immediateassessment of the effect of each application. If sinus rhythmwas present, atrial fibrillation was induced by rapid atrialpacing before the delivery of radiofrequency energy. The rightatrial septum adjacent to the septal leaflet of the tricuspidvalve and extending from the ostium of the coronary sinus tothe recording site at the His bundle was divided into threeregions: posterior, midseptal, and anterior15,16. After thelocation of the coronary-sinus ostium had been defined fluoroscopically,the catheter was positioned against the posterior septum, atthe level of the ostium, to record a maximal atrial-to-ventricularelectrographic ratio of 0.5 or less during a continuous recordingperiod of at least 10 seconds.
Radiofrequency energy was delivered at 12 to 38 W for up to60 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 therewas no change in the ventricular rate, the catheter was repositionedin progressively more superior and anterior positions alongthe posterior and midatrial septum. No applications were deliveredat sites where a His-bundle potential greater than 0.02 mV waspresent. The end point of the procedure was an average ventricularrate of approximately 120 beats per minute during the infusionof isoproterenol. When this objective was achieved, the ventricularrate was also determined 20 to 30 minutes after the discontinuationof the infusion.
Follow-up Evaluation
The patients underwent continuous inpatient electrocardiographicmonitoring for at least 48 hours. Twenty-four-hour Holter monitoringand exercise treadmill tests were performed two days after themodification procedure, when the patients were receiving noantiarrhythmic-drug therapy. The patients were seen on an outpatientbasis at three-month intervals. Ambulatory monitoring and treadmilltests 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. Comparisonswere performed by Student's paired t-test or by an analysisof variance with repeated measures. A two-tailed P value ofless than 0.05 was considered to indicate statistical significance.
Results
Overall Short-Term Results
In the electrophysiology laboratory, atrioventricular conductionwas modified in 17 patients (Figure 1), inadvertent third-degreeatrioventricular block occurred in 1 patient, and third-degreeatrioventricular block was induced in 1 patient in whom themodification procedure did not succeed in slowing the ventricularrate (Table 2). The mean (±SD) number of radiofrequency-energyapplications was 11 ±5 (range, 3 to 27). The averageduration of fluoroscopy was 37 ±16 minutes (range, 13to 66). The location of the effective target site was posteriorin 7 patients and midseptal in 10.
Figure 1. Modification of Atrioventricular Conduction by a 30-Second Application of Radiofrequency Energy (RF).
The energy was delivered during an infusion of 4 µg of isoproterenol per minute, and the beginning and end of the application are shown. The initial rate was 190 beats per minute, decreasing to 110 beats per minute after the energy application.
Table 2. Results of Radiofrequency Modification to Control Ventricular Rates in Patients with Atrial Fibrillation.
In 3 of the 17 patients in whom atrioventricular conductionwas modified in the electrophysiology laboratory, third-degreeatrioventricular block occurred within the first three daysafter the procedure. Therefore, over the short term, atrioventricularconduction was modified successfully in 14 of 19 patients (74percent), inadvertent atrioventricular block requiring the insertionof a permanent pacemaker occurred in 4 patients (21 percent),and ablation of the atrioventricular junction was intentionallyperformed because the modification procedure was unsuccessfulin 1 patient (5 percent).
Patients with a Successful Outcome
The 14 patients in whom atrioventricular conduction was successfullymodified had a statistically significant decrease in ventricularrates at two days and three months of follow-up (Table 3 andFigure 2).
Table 3. Ventricular Rates during Atrial Fibrillation in the 14 Patients with Successful Outcomes, before and after Radiofrequency Modification of Atrioventricular Conduction.
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.
B denotes before the procedure, the asterisk P<0.05, daggers P<0.01, double daggers P<0.001, and NS not significant.
Patients with Atrioventricular Block
Persistent third-degree atrioventricular nodal block developedin Patient 15 in the electrophysiology laboratory during theapplication of 38 W of radiofrequency energy to a posteriorsite. Third-degree atrioventricular nodal block developed inthree patients 36 to 72 hours after the procedure. Transientthird-degree atrioventricular block lasting 10 to 27 secondshad occurred during the modification procedure in these threepatients (Figure 3). Transient atrioventricular block had alsooccurred in 2 of the 14 patients in whom the modification procedurewas successful. Each of the four patients with inadvertent,persistent third-degree atrioventricular block had a junctionalrhythm at a rate of 40 to 55 beats per minute and underwentthe implantation of a pacemaker.
Figure 3. Inadvertent Atrioventricular Block after an Application of Radiofrequency Energy (RF).
Transient complete atrioventricular block lasting 10 seconds occurred after discontinuation of the energy application. Shown are leads V, I, and II, the intracardiac electrograms from the ablation catheter and the right ventricular apex (RV), and lead III.
In Patient 4, atrioventricular conduction remained rapid after11 applications of radiofrequency energy; the atrioventricularjunction 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-termoutcomes had a marked improvement in symptoms, and the overallCanadian Cardiovascular Society functional class17 improvedsignificantly, 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 afterthe procedure and underwent a second procedure with no furtherrecurrence of symptoms.
The only death during follow-up was of Patient 2, who died inhis sleep five months after undergoing the modification procedure.He had idiopathic dilated cardiomyopathy and a left ventricularejection fraction of 0.20. When he was evaluated three monthsafter the procedure there was no evidence of bradycardia oratrioventricular block, and his ventricular rate was well controlled.Holter-monitor recordings before and after the procedure haddemonstrated three-to-six-beat episodes of asymptomatic, nonsustained,monomorphic ventricular tachycardia. At the time of death, hewas not being treated with any antiarrhythmic drug. No postmortemexamination was performed.
Discussion
Main Findings
This study shows that it may be feasible to control the ventricularrate without inducing pathologic atrioventricular block in about75 percent of patients with atrial fibrillation and uncontrolledventricular rates, by using a catheter technique in which radiofrequencyenergy is delivered to the posterior or midatrial septum nearthe ostium of the coronary sinus. Therefore, in the majorityof patients with atrial fibrillation and uncontrolled ventricularrates refractory to drug therapy, who may have been appropriatecandidates previously for ablation of the atrioventricular junctionand the insertion of a permanent pacemaker, it may be possibleto achieve adequate slowing of the ventricular rate and resolutionof symptoms without the need for a permanent pacemaker.
Ablation Compared with Modification of Atrioventricular Conduction
The conventional technique for ablation of the atrioventricularjunction uses sites located anteriorly and superiorly on thetricuspid annulus. In contrast, with the technique used in thisstudy to modify atrioventricular conduction, the target sitesare located inferiorly and posteriorly near the tricuspid annulus,close to the orifice of the coronary sinus, as in the techniqueof Fleck et al.14
Despite the absence of a His-bundle depolarization in the electrogramsat the target sites and the posterior position of the targetsites relative to the atrioventricular node, the delivery ofradiofrequency energy resulted at times in transient or permanentatrioventricular block. In an attempt to avoid atrioventricularblock, we delivered radiofrequency energy in a conservativefashion, discontinuing application of the energy whenever therewas a noticeable slowing in the ventricular rate. Because thedelivery of radiofrequency energy near the atrioventricularjunction often results in junctional ectopy,9,18 which may maskthe onset of atrioventricular block, we delivered radiofrequencyenergy in an interrupted fashion, in order to confirm the absenceof atrioventricular block. However, despite the discontinuationof applications of energy whenever there was a slowing in theventricular rate, inadvertent atrioventricular block sometimesoccurred (Figure 3). Therefore, an important limitation of thetechnique described in this study is that it may not alwaysbe possible to avoid the occurrence of atrioventricular block.
Transient Atrioventricular Block
About two thirds of the patients who had transient atrioventricularblock in relation to the procedure later had persistent atrioventricularblock, with an onset 36 to 72 hours after the procedure. Itmay be that transient thermal injury to the atrioventricularconduction system results in an inflammatory reaction that isresponsible for the delayed occurrence of permanent injury.Regardless of the mechanism, if transient atrioventricular blockoccurs during an attempt to modify atrioventricular conduction,continuous electrocardiographic monitoring on an inpatient basisis appropriate for a period of three to four days, to watchfor a recurrence of atrioventricular block.
Long-Term Results
Although the mean resting, ambulatory, and minimal ventricularrates during atrial fibrillation remained stable during an intervalfrom two days to three months after the modification procedure,the mean maximal ventricular rate increased by 25 percent duringthis period. The increase in this rate during exercise at threemonths as compared with two days of follow-up may reflect partialrecovery of atrioventricular conduction from the immediate effectsof radiofrequency energy. Nevertheless, the mean maximal ventricularrate during exercise at three months of follow-up was stillapproximately 25 percent lower than at base line, a degree ofattenuation adequate to result in the persistent resolutionof symptoms.
In several patients, the maximal rate during exercise at threemonths of follow-up was within 10 beats per minute of the correspondingvalue before the modification procedure. Nevertheless, thesepatients reported relief of symptoms attributable to an uncontrolledventricular rate. Such resolution of symptoms despite littlechange in the maximal rate during exercise may be explainedin some patients by an increase in the duration of exercise.For example, Patient 11 attained a maximal rate of 165 beatsper minute with a 20-MET workload at three months of follow-up,as compared with a maximal rate of 161 beats per minute withonly a 10-MET workload before the procedure. Furthermore, eventhough the maximal rates during exercise may have been similar,the ventricular rates at comparable submaximal levels of effortwere consistently lower three months after the procedure thanat base line. For example, in Patient 11 the ambulatory rateat three months of follow-up was only 84 beats per minute, ascompared with 140 beats per minute at base line.
Mechanism of Rate Control
The sites at which radiofrequency energy was delivered in thisstudy were located in the posterior and middle septum, the samearea targeted for ablation of the slow pathway in patients withatrioventricular nodal reentrant tachycardia15,16,19,20,21,22,23,24,25,26.These sites correspond to the location of the posterior atrionodalinputs to the atrioventricular node,27 raising the possibilitythat the ventricular rate was controlled by the ablation ofsome or all of these posterior atrionodal inputs. This wouldcontrol the rate only if conduction was slower through the anterioratrionodal inputs than through the posterior inputs.
The fact that transient or permanent third-degree atrioventricularblock occurred in 6 of the 19 patients in this study indicatesthat target sites near the orifice of the coronary sinus maybe close enough to the compact atrioventricular node to injurethat structure. Because the sites that resulted in a successfuloutcome were in the same location as the sites that resultedin atrioventricular block, it may be that the rate was controlled,at least in some patients, by partial injury to the compactatrioventricular node. This would be consistent with the resultsof Huang et al., who demonstrated that persistent incompleteatrioventricular block could be achieved with radiofrequencyenergy in 13 of 20 dogs by partially injuring the compact atrioventricularnode28.
Injury to the bundle of His is an unlikely explanation for thecontrol of the ventricular rate, for two reasons. First, His-bundledepolarization was nonexistent or negligible in the target-siteelectrograms. Second, in the patients who had transient or permanentatrioventricular block, the location of the block was alwaysabove the bundle of His.
Sudden Death
Patient 2, who died suddenly five months after the modificationprocedure, had idiopathic dilated cardiomyopathy and a leftventricular ejection fraction of 0.20. It is possible that thispatient's death resulted from a delayed complication of themodification procedure, such as pause-dependent polymorphicventricular tachycardia19. It is also possible that his deathwas a result of his underlying heart disease. Sudden death isknown to be a frequent complication of dilated cardiomyopathythat is associated with a depressed left ventricular ejectionfraction29. A large number of patients with atrioventricularnodal reentrant tachycardia have undergone ablation of the slowpathway and have received applications of radiofrequency energyat sites in the posterior and middle septum similar to the sitesused in this study, with no reports of ventricular arrhythmiasor sudden death as a complication of the procedure15,16,20,21,22,23,24,25,26.Also, whereas the three patients in this study who had the delayedonset of atrioventricular block had transient episodes of atrioventricularblock during the modification procedure, the patient who diedsuddenly never had atrioventricular block during the procedureand underwent ambulatory monitoring three months afterward thatrevealed no evidence of bradycardia, making atrioventricularblock an unlikely cause of death.
Limitations
The majority of patients in this series had structural heartdisease; therefore, the results may not apply to other populationsof patients. Although control of the ventricular rate has beenmaintained for up to 13 months at this writing, follow-up hasnot yet reached 1 year in the majority of patients; longer follow-upis needed to confirm that the benefits of the modification procedureare permanent.
Because almost all the patients in this study had chronic atrialfibrillation, atrioventricular nodal conduction and refractorinesscould not usually be measured. Therefore, another limitationof this study is that the effects of the radiofrequency-energyapplications on the properties of the atrioventricular nodecould not usually be assessed.
Clinical Implications
Atrial fibrillation is a common arrhythmia that is often associatedwith uncomfortable symptoms. Despite therapy with antiarrhythmicagents and electrical cardioversion, atrial fibrillation maypersist. In patients with persistent atrial fibrillation, theventricular rate can usually be controlled pharmacologicallywith negative dromotropic agents, such as digitalis, calcium-channel-blockingagents, or beta-blockers. However, some patients have symptomsthat cannot be controlled with medications. In such patients,catheter ablation of the atrioventricular junction has provedto be effective at eliminating the symptoms caused by a rapidventricular rate, but at the cost of complete atrioventricularblock and irreversible dependency on a permanent pacemaker.As compared with ablation of the atrioventricular junction,the catheter technique described here has the advantage thatit results in adequate control of the ventricular rate in mostpatients without creating the need for a permanent pacemaker.Therefore, it may be appropriate to attempt first to modifyatrioventricular conduction in patients with atrial fibrillationand rapid ventricular rates who are appropriate candidates forablation of the atrioventricular junction. Because the riskof inadvertent complete atrioventricular block is approximately20 percent, the use of the procedure should be limited at presentto patients with atrial fibrillation who are symptomatic enoughfor ablation of the atrioventricular junction and implantationof a permanent pacemaker to be justified.
We are indebted to Betty Plunkett and Heidi Williams for theirassistance 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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Writing Committee Members, , Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., Wann, S., ACC/AHA Task Force Members, , Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., ESC Committee for Practice Guidelines, , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L.
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Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., Wann, S.
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Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., Wann, S.
(2006). ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society . J Am Coll Cardiol
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[Full Text]
Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., Wann, S., ACC/AHA TASK FORCE MEMBERS, , Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., ESC COMMITTEE FOR PRACTICE GUIDELINES, , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L.
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Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J.-Y., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., Wann, S., ACC/AHA TASK FORCE MEMBERS, , Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., ESC COMMITTEE FOR PRACTICE GUIDELINES, , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L.
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Fuster, V., Ryden, L. E., Asinger, R. W., Cannom, D. S., Crijns, H. J., Frye, R. L., Halperin, J. L., Kay, G. N., Klein, W. W., Levy, S., McNamara, R. L., Prystowsky, E. N., Wann, L. S., Wyse, D. G., Gibbons, R. J., Antman, E. M., Alpert, J. S., Faxon, D. P., Fuster, V., Gregoratos, G., Hiratzka, L. F., Jacobs, A. K., Russell, R. O., Smith, S. C. Jr, Klein, W. W., Alonso-Garcia, A., Blomstrom-Lundqvist, C., De Backer, G., Flather, M., Hradec, J., Oto, A., Parkhomenko, A., Silber, S., Torbicki, A.
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A correction has been published: N Engl J Med 1995;332(7):479.
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