CLINICAL STUDIES
Radiofrequency catheter ablation of inappropriate sinus tachycardia guided by activation mapping
K. Ching Man, DOa,
Bradley Knight, MDa,
Hung-Fat Tse, MDa,
Frank Pelosi, MDa,
Gregory F. Michaud, MDa,
Matthew Flemming, MDa,
S. Adam Strickberger, MD, FACCa and
Fred Morady, MD, FACCa
a Division of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Manuscript received February 2, 1999;
revised manuscript received August 16, 1999,
accepted October 18, 1999.
Reprint requests and correspondence: Dr. Fred Morady, University of Michigan Hospital, Division of Cardiology; B1-F245, Ann Arbor, Michigan 48109-0022
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Abstract
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OBJECTIVE
The purpose of this study was to evaluate the value of activation mapping for radiofrequency modification of the sinus node and the long-term success rate of the procedure in a series of patients with inappropriate sinus tachycardia.
BACKGROUND
The results of radiofrequency ablation of inappropriate sinus tachycardia have been reported in only a small number of patients.
METHODS
The subjects of this study were 29 consecutive drug-refractory patients who underwent catheter ablation of inappropriate sinus tachycardia. Target sites were selected by activation mapping during sinus tachycardia.
RESULTS
The ablation procedure was successful acutely in reducing the baseline sinus rate to <90/min and the sinus rate during isoproterenol infusion by >20% in 22 of 29 patients (76%). In 13 of 22 patients (59%) with a successful acute outcome, successive applications of radiofrequency energy at the site of earliest endocardial activation resulted in a cranial-caudal migration of earliest endocardial activation from the high lateral right atrium, along with a step-wise reduction in heart rate. In the other nine patients (41%) with a successful acute outcome, the reduction in sinus rate occurred abruptly, unaccompanied by migration of the site of earliest activation. Symptoms due to inappropriate sinus tachycardia recurred at a mean of 4.4±; 3 months after the ablation procedure in 6 of 22 patients (27%). After additional procedures in three patients, symptoms of inappropriate sinus tachycardia ultimately were successfully eliminated over the long-term in 19 of 29 patients (66%).
CONCLUSIONS
In conclusion, radiofrequency ablation is at best only modestly effective for managing patients with inappropriate sinus tachycardia. The two different responses of heart rate to radiofrequency ablation may reflect differences in the number and/or multicentricity of subsidiary sites of impulse generation within the sinus node and/or atrium in patients with inappropriate sinus tachycardia.
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Abbreviations and Acronyms
| | LV | = left ventricular | | RA | = right atrium | | RFA | = radiofrequency ablation |
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Inappropriate sinus tachycardia is characterized by an elevated resting heart rate and/or an exaggerated increase in heart rate in response to activity (1). In patients with inappropriate sinus tachycardia who are refractory to medical treatment, radiofrequency catheter modification of the sinus node may be effective in lowering the sinus rate. However, the results of radiofrequency ablation (RFA) of inappropriate sinus tachycardia have been reported in only a small number of patients (2–4). The purpose of this study was to determine the long-term results of radiofrequency modification of the sinus node guided by activation mapping in a series of 29 patients with inappropriate sinus tachycardia.
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Methods
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Patient characteristics.
Twenty-nine consecutive patients referred for catheter ablation of inappropriate sinus tachycardia. Inappropriate sinus tachycardia was defined as a heart rate >100/min at rest or with minimal exertion, with P waves during tachycardia that were identical or very similar to the P waves during sinus rhythm, and with no other identifiable causes for sinus tachycardia, such as hyperthyroidism or orthostatic hypotension. Inappropriate sinus tachycardia was distinguished from paroxysmal atrial tachycardia by a gradual onset and offset. There were 26 women and 3 men, and their mean age was 37 ± 12 years (±SD). Each of the patients was functionally limited by symptoms of palpitations, weakness and lightheadedness. Twenty-seven patients had no structural heart disease, one patient had coronary artery disease and one patient had hypertension with left ventricular (LV) hypertrophy. All patients had a normal LV ejection fraction. The mean duration of symptoms attributable to inappropriate sinus tachycardia was 7.2 ± 12.7 years. Treatment with a mean of 4.7 ± 2.1 antiarrhythmic drugs had failed to provide adequate control of symptoms. During outpatient evaluation two or more weeks before the RFA procedure, at which time all of the patients were being treated with a beta-adrenergic antagonist, calcium channel blocker or amiodarone, the mean heart rate while sitting was 93 ± 9/min, the mean heart rate after walking 50 yards was 123 ± 8/min and the mean heart rate after one minute of stair-stepping on a single step was 151 ± 8/min.
Electrophysiologic testing.
After written, informed consent was obtained, patients were brought to the electrophysiology laboratory in the fasting state. Treatment with antiarrhythmic medications was discontinued at least five half-lives before the procedure, except in two patients in whom therapy with amiodarone was discontinued two to four weeks beforehand. Three quadripolar electrode catheters were inserted into a femoral vein and positioned in the right atrium, His bundle position and right ventricle. Leads VI, I, II and III, and the bipolar intracardiac electrograms filtered at settings of 50 to 500 Hz, were recorded on paper (Mingograph 7; Siemens-Elema, Solna, Sweden) and stored on optical disk (Quinton, Seattle, WA). Pacing was performed with a programmable stimulator (Bloom Associates, Ltd., Reading, PA) and no patient was found to have inducible paroxysmal supraventricular tachycardia.
Activation mapping and ablation.
Isoproterenol was infused at a rate of 1 to 2 µg/min to maintain a cycle length of <500 ms, except in three patients who had a baseline sinus cycle length <500 ms. Point-by-point activation mapping was performed in each patient. An 8-F quadripolar electrode catheter that had an interelectrode spacing of 2-5-2 mm, a 4-mm distal electrode with an imbedded thermistor and a deflectable tip (EP Technologies, Sunnyvale, California) was used for mapping and ablation. Radiofrequency energy was delivered at the site of the earliest bipolar electrogram relative to the surface P wave. When the P waves were obscured by the preceding T waves, short bursts of ventricular pacing at a cycle length 10 to 20 ms shorter than the sinus rate were used to uncover the P waves upon cessation of pacing.
Radiofrequency energy was delivered at a cycle length of 500 kHz by a generator that automatically adjusted the output to maintain a preset temperature of 50°C to 60°C at the electrode-tissue interface (EP Technologies). Because of injury to the phrenic nerve in one of the early patients in this series, in subsequent patients, pacing at an output of 10 mA was performed with the ablation catheter before delivery of radiofrequency energy, to rule out phrenic nerve stimulation. Applications of radiofrequency energy were up to 60 s in duration. The end points of the procedure were reduction of the baseline sinus rate to <90/min, and a 20% or greater reduction in the sinus rate during infusion of isoproterenol. The P waves were examined on a 12-lead electrocardiogram at baseline, during isoproterenol infusion and after each application of radiofrequency energy, to look for changes in configuration.
Follow-up.
Continuous electrocardiographic monitoring was performed on an inpatient basis for 24 h after the procedure. All of the patients were seen in follow-up at four to six weeks after the procedure and at subsequent six-month intervals. At the time of follow-up, the heart rate was measured while sitting, after walking 50 yards at a usual pace, and after 1 min of stair-stepping. The patients were instructed to contact one of the authors in the event of recurrent symptoms of palpitations. If necessary, patients were provided with a continuous loop monitor to document the rhythm at the time of symptoms. A telephone interview with each patient was performed at the close of the study.
Statistical analysis.
Continuous variables are expressed as mean ±SD and were compared with Student’s t-test or with a paired t-test. Values of p < 0.05 were considered statistically significant.
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Results
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Short-term results.
In the electrophysiology laboratory, the mean baseline sinus cycle length was 623 ± 135 msc, and the mean sinus cycle length during infusion of isoproterenol was 413 ± 37 msc. The ablation procedure was successful in reducing the baseline sinus rate to <90/min and the sinus rate during isoproterenol infusion by >20% (mean 26 ± 14%) in 22 of 29 patients (76%; Table 1). The mean number of radiofrequency applications was 22 ± 15 (Table 1). The mean duration of fluoroscopy was 59 ± 37 min. There were no significant differences in the preablation baseline sinus cycle length or in the sinus cycle length during isoproterenol infusion between the patients in whom the short-term outcome was successful and those in whom it was not.
Postablation, the baseline sinus cycle length lengthened significantly to 748 ± 118 msc (p < 0.05) among the 22 patients with a successful outcome, and remained unchanged at 641 ± 106 msc (p = 0.10) among the 7 patients with an unsuccessful outcome. Likewise, the postablation sinus cycle length during infusion of isoproterenol lengthened significantly to 527 ± 81 ms (p < 0.01) among the 22 patients with a successful outcome, and remained unchanged at 436 ± 43 msc (p = 0.08) among the 7 patients with an unsuccessful outcome.
Activation times (table 1).
The earliest local atrial electrogram in each patient at sites of radiofrequency energy application preceded the P wave by a mean of 29 ± 14 ms. There was no significant difference in the earliest endocardial activation time between the patients who had a successful outcome and those who did not.
In 13 of 22 patients (59%) with a successful acute outcome, consecutive applications of radiofrequency energy at the site of earliest endocardial activation resulted in a cranial-to-caudal migratory pattern of earliest endocardial activation, starting in the high lateral right atrium (RA) and descending to the mid-lateral RA over a distance of approximately 2 to 3 cm. In these 13 patients, the reduction in sinus rate occurred in a step-wise fashion and was associated with visually apparent changes in P wave morphology (Fig. 1). A mean of 32.3 ± 11 applications of radiofrequency energy was required to achieve a successful outcome in these patients.
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Figure 1 An example of a step-wise increase in cycle length in response to radiofrequency ablation of inappropriate sinus tachycardia (patient 27, second procedure). Shown are leads I, II and III at several stages of the procedure. (A) The baseline sinus cycle length (CL) was 600 ms. (B) During infusion of isoproterenol (iso) at a rate of 1 µg/min, the cycle length shortened to 440 ms, and the P waves in lead III were larger in amplitude. The isoproterenol infusion was continued during the radiofrequency procedure. (C) After several applications of radiofrequency energy at the site of earliest endocardial activation (–35 ms) in the high lateral right atrium, the cycle length increased to 510 ms, and there was a change in P wave morphology in all three leads. (D) After additional applications of radiofrequency energy at a new site of earliest endocardial activation (–25 ms) approximately 2 cm caudal to the original ablation site, the cycle length increased to 580 ms, again with a change in P wave morphology. The 32% increase in cycle length during isoproterenol infusion was considered to be an adequate endpoint for the procedure. (E) After discontinuation of the isoproterenol infusion, the resting cycle length was 780 ms, representing a 30% increase compared with the baseline cycle length. Note that after discontinuation of the isoproterenol infusion, the P wave morphology again changed.
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In the other nine patients (41%) with a successful acute outcome, the reduction in sinus rate occurred abruptly and was not accompanied by migration of the site of earliest endocardial activation (Fig. 2). The effective target sites were in the high lateral RA within an area of approximately 1 cm2, and a mean of 7.5 ± 5.6 applications of radiofrequency energy was required to achieve a successful acute outcome.
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Figure 2 An example of an abrupt response of inappropriate sinus tachycardia to radiofrequency ablation (Patient 7). Shown are leads V1, I and II, an electrogram recorded in the right atrium (RA) near the ablation site, a recording from the ablation catheter in the high lateral right atrium (HRA) and lead III. The cycle length during a 2-µg/min infusion of isoproterenol was 400 ms, and the first five applications of radiofrequency energy at the site of earliest endocardial activation (–35 ms) had only either a temporary or no effect on the cycle length. Approximately 2 s after the onset of the sixth application of radiofrequency energy (RF), there was an abrupt and permanent 42% increase in cycle length to 570 ms. In this patient, the P wave morphology after radiofrequency ablation of the inappropriate sinus tachycardia did not change.
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Complications.
A complication occurred in 2 of 29 patients (7%). Patient 4 presented with near-syncope four days after the procedure and was found to have sinus pauses up to 4 s in duration. A dual-chamber pacemaker was implanted and the patient was asymptomatic until 10 months after the procedure, at which point inappropriate sinus tachycardia recurred. Radiofrequency ablation of the atrioventricular junction was performed, with resolution of symptoms. One other patient, who had received 25 applications of radiofrequency energy in the high lateral RA, developed paralysis of the right hemidiaphragm. The patient has remained asymptomatic during 41 months of follow-up, despite persistence of diaphragmatic paralysis.
Clinical follow-up (table 1).
After a mean duration of follow-up of 32 ± 12 months (range 12 to 50 months), 16 of the 22 patients (73%) in whom the procedure was acutely successful either have remained free of recurrent symptoms in the absence of drug therapy, or have had mild symptoms not bothersome enough to require drug therapy. At the time of the most recent outpatient evaluation (12 to 42 months postprocedure), the heart rates at rest, after walking 50 yards and after 1 min of stair-stepping were 80 ± 8, 93 ± 9 and 121 ± 9/min, respectively, in these 16 patients. These mean heart rates were significantly lower than the respective mean heart rates before the RFA procedure (p < 0.01).
Symptoms documented to be due to inappropriate sinus tachycardia recurred at a mean of 4.4 ± 3 months (range 2 weeks to 8 months) after the ablation procedure in 6 of the 22 patients (27%) in whom the procedure was acutely successful. A successful long-term outcome was achieved with an additional procedure in two patients, and with two additional procedures in one patient. Overall, among the 29 patients in this series, the radiofrequency procedure was successful in eliminating symptoms of inappropriate sinus tachycardia requiring drug therapy over the long term in 19 patients (66%).
Among the 10 patients in whom the ablation procedure was not successful, five patients continued to have severe symptoms attributable to inappropriate sinus tachycardia and underwent RFA of the atrioventricular junction and implantation of a pacemaker; relief of symptoms was complete in four of these patients and partial in one. The other five patients who had an unsuccessful outcome have had their symptoms partially controlled by treatment with beta-blockers.
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Discussion
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Major findings.
In this study, a successful long-term reduction in the sinus rate and relief of symptoms without the use of pharmacologic therapy was achieved by RFA at the sites of earliest atrial activation in approximately two-thirds of patients with drug-refractory, inappropriate sinus tachycardia. Two types of responses of the sinus tachycardia to RFA were observed. In approximately 60% of patients, there was a step-wise reduction in sinus rate, and this was associated with migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall. In the remaining patients, the heart rate dropped abruptly in response to RFA at a focal site of earliest atrial activation. These two different responses of the heart rate to RFA may reflect differences in the number and/or multicentricity of subsidiary sites of impulse generation within the sinus node and/or atrium in patients with inappropriate sinus tachycardia.
Activation mapping of inappropriate sinus tachycardia.
The sinus node impulse may have a multifocal origin, and prior studies have demonstrated that the site of impulse origin may shift inferiorly within the sinus node and surrounding atrium as the rate decreases (5–7). This type of pattern was observed in approximately 60% of the patients in this study, in whom activation mapping demonstrated a cranial-caudal migration of the earliest site of endocardial activation with successive applications of radiofrequency energy. The inferior shift in the site of earliest endocardial activation was associated with a step-wise reduction in the heart rate, consistent with the physiologic behavior of the sinus node noted in prior studies (5–7). This type of response also was noted in a recent report of two patients who underwent modification of the sinus node guided by a three-dimensional nonfluoroscopic mapping system; with tridimensional mapping, the earliest site of atrial activation was demonstrated to shift caudally from the original sinus node location by 1.8 to 2.3 cm (8).
In the other 40% of patients in this study in whom the ablation procedure was successful acutely, activation mapping demonstrated a clustering of early sites of activation within a small area in the high lateral RA. In these patients, the end point of the ablation procedure was achieved abruptly instead of in a step-wise fashion. This suggests that in some patients, inappropriate sinus tachycardia is generated by a single pacemaker site within or adjacent to the sinus node. It is also possible that there were two or more pacemaker sites with similar rates in close proximity to each other in these patients.
The sinus node is a complex structure that is at least partially insulated from the surrounding atrial myocardium, and the exit site of an impulse from the sinus node may not coincide with the site of impulse origin (9). A failure of the exit site from the sinus node to coincide spatially with the site of impulse origin may in part explain the large number of applications of radiofrequency energy needed to achieve a successful outcome in the patients in this study. It may be that successive applications of radiofrequency energy resulted in small shifts in the exit site, until the exit site was close enough to the site of impulse origin to allow its destruction, or until complete exit block was achieved. In the patients in whom the procedure was ineffective, it is possible that the exit sites identified by activation mapping never were close enough to the sites of impulse origin to allow for their destruction.
Another limitation of activation mapping in patients with inappropriate sinus tachycardia is that adjacent sites may have very similar endocardial activation times, and it may be difficult to precisely identify the site of earliest endocardial activation. This limitation of activation mapping also has been noted when mapping other tachycardias that may be automatic in nature, such as idiopathic ventricular tachycardia arising in the right ventricular outflow tract (10,11). In the case of idiopathic ventricular tachycardia arising in the right ventricular outflow tract, pace mapping has proven to be an effective alternative for identifying effective target sites for ablation (10,11). However, because P wave morphology is not sensitive to changes in the site of impulse origin of up to 3 cm, pace mapping is not a viable technique for identifying target sites for ablation in the atrium (12).
Comparison with previous studies.
In the only other published series of patients who underwent radiofrequency catheter ablation of inappropriate sinus tachycardia, Lee et al. (4) reported a successful long-term outcome in 83% of 12 patients who underwent radiofrequency modification of the sinus node. Although this success rate appears to be higher than the 66% long-term success rate achieved among the 29 patients in the present study, the apparently higher success rate may be attributable to a smaller sample size in the prior study. In fact, in a more recent preliminary report from the same laboratory, long-term follow-up over a mean of 8 ± 5 months demonstrated a recurrence rate of 77% among an expanded group of 22 patients who underwent radiofrequency modification of the sinus node using the same techniques as in the original report (13).
While target sites were identified by activation mapping in all of the patients in the present study, Lee et al. (4) used intracardiac echocardiography to identify target sites on the crista terminalis in more than 50% of their patients. This methodological difference may provide an explanation for the 77% recurrence rate of inappropriate sinus tachycardia in the preliminary report from the same laboratory (13), compared with the 27% recurrence rate in the present study. Because subsidiary atrial pacemakers that lie outside the sinus node may play a role in generating inappropriate sinus tachycardia, an anatomic approach to modification of the sinus node using intracardiac echocardiography to identify sites on the crista terminalis may not be as reliable as activation mapping, in which target sites are not necessarily restricted to the crista terminalis or sinus node.
Complications.
One of the complications encountered in this study was paralysis of the right hemidiaphragm, presumably caused by thermal injury to the right phrenic nerve, which lies on the outside of the RA. The occurrence of this complication indicates that the lesion created in the RA with a conventional ablation catheter is at least sometimes transmural. After encountering this complication in one of the early patients in this series, additional instances of hemidiaphragmatic paralysis were avoided by high-output pacing at potential target sites, to rule out phrenic nerve stimulation.
The other complication in this study was symptomatic junctional bradycardia, reflecting excessive injury to the sinus node and an absence of an atrial escape rhythm. This complication was not manifest until four days after the ablation procedure, indicating that injury to the sinus node may be progressive after the procedure has been completed. Also of note is that the delayed onset of symptomatic bradycardia in the patient who had this complication could not have been predicted from events during the ablation procedure. Therefore, it is likely that the occasional need for a permanent pacemaker after radiofrequency modification of the sinus node will not be avoidable.
Study limitations.
The precise anatomic location of each application of radiofrequency energy could not be determined. The sinus node lies beneath the crista terminalis (14), which can be visualized by intracardiac echocardiography (4). Because mapping in this study was based on analysis of local electrograms and was guided by fluoroscopy but not intracardiac echocardiography, whether the effective target sites were limited to the crista terminalis or also encompassed other sites is unknown. Therefore, this study does not clarify the extent to which extranodal pacemakers contribute to the syndrome of inappropriate sinus tachycardia.
Another limitation of this study is the absence of well-defined criteria for assessing the short- and long-term outcomes of the radiofrequency procedure. The criteria used to define acute efficacy in this study (resting heart rate <90/min and a >20% reduction in heart rate during infusion of isoproterenol) were chosen arbitrarily, did not take into account the presence or absence of symptoms and were not prevalidated. However, when these criteria were met in the electrophysiology laboratory, the need for long-term drug therapy usually was eliminated, suggesting that these criteria, albeit arbitrary, were reasonable.
During the ablation procedures, isoproterenol was infused at a rate of 1 to 2 µg/min, resulting in a mean heart rate of approximately 150/min during mapping. It is possible that the use of a higher dosage of isoproterenol would have affected the results of mapping.
Regarding the assessment of long-term efficacy, this was based on relief of symptoms, which may be subjective and patient specific. For example, despite a similar heart rate during effort, a given patient may describe symptoms as being absent or minimal, while another patient may experience symptoms severe enough to warrant drug therapy. Furthermore, in contrast to other arrhythmias such as atrioventricular nodal reentrant tachycardia or atrial flutter, sinus tachycardia is a continuum, without a well-defined boundary between "inappropriate" and "physiologic." A formal assessment of the impact of the ablation procedure on quality of life was not performed in this study.
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Conclusions
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Radiofrequency ablation is at best only a modestly effective technique for managing patients with inappropriate sinus tachycardia. Compared with RFA of accessory pathways (15), atrioventricular nodal reentrant tachycardia (15) atrial flutter (15) or the atrioventricular junction (16), RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy, has a low success rate and is associated with a high recurrence rate. These limitations of the procedure may be attributable to the complex physiology of the sinus node, the inability to precisely target sites of impulse origin, the large size of the sinus node relative to the size of the lesion created by conventional RFA and/or to the possible contribution of shifting, extranodal pacemaker sites to generation of inappropriate sinus tachycardia. It is possible that larger lesions, such as those created with a saline-cooled ablation catheter (17), will improve the success rate, but larger lesions also may result in a higher rate of complications, including the need for a permanent pacemaker.
Because of the suboptimal results of RFA of inappropriate sinus tachycardia, this procedure should be considered only in drug-refractory patients who have severe symptoms. If a successful outcome cannot be achieved with this technique, RFA of the atrioventricular junction and implantation of a pacemaker may provide an effective alternative. In the present study, symptoms usually were relieved after atrioventricular junction ablation in association with either dual-chamber pacing and an upper rate limit of 120/min, or rate-responsive ventricular pacing. Given the technical ease and reliable long-term success of atrioventricular junction ablation (16), further studies to compare outcomes of radiofrequency modification of the sinus node and radiofrequency ablation of the atrioventricular junction in patients with inappropriate sinus tachycardia may be justified.
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24(20):
1857 - 1897.
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S. Yusuf and A. J. Camm
Sinus Tachyarrhythmias and the Specific Bradycardic Agents: A Marriage Made in Heaven?
Journal of Cardiovascular Pharmacology and Therapeutics,
June 1, 2003;
8(2):
89 - 105.
[Abstract]
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D Sanchez-Quintana, R H Anderson, J A Cabrera, V Climent, R Martin, J Farre, and S Y Ho
The terminal crest: morphological features relevant to electrophysiology
Heart,
October 1, 2002;
88(4):
406 - 411.
[Abstract]
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N. F. Marrouche, S. Beheiry, G. Tomassoni, C. Cole, D. Bash, T. Dresing, W. Saliba, A. Abdul-Karim, P. Tchou, R. Schweikert, et al.
Three-dimensional nonfluoroscopic mapping and ablation of inappropriate sinus tachycardia: Procedural strategies and long-term outcome
J. Am. Coll. Cardiol.,
March 20, 2002;
39(6):
1046 - 1054.
[Abstract]
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W. Singer, W.-K. Shen, T. L. Opfer-Gehrking, B. R. McPhee, M. J. Hilz, and P. A. Low
Evidence of an Intrinsic Sinus Node Abnormality in Patients With Postural Tachycardia Syndrome
Mayo Clin. Proc.,
March 1, 2002;
77(3):
246 - 252.
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Abstract
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