Radiofrequency Catheter Modification of the Sinus Node for “Inappropriate” Sinus Tachycardia
Background Radiofrequency catheter ablation is the treatment of choice for patients with paroxysmal supraventricular tachycardias refractory to medical therapy. However, in symptomatic patients with inappropriate sinus tachycardia resistant to drug therapy, catheter ablation of the His’ bundle with permanent pacemaker insertion is currently applied. We evaluated the safety and efficacy of radiofrequency modification of the sinus node as alternative therapy for patients with inappropriate sinus tachycardia.
Methods and Results Sixteen patients with disabling episodes of inappropriate sinus tachycardia refractory to drug therapy (4.2±0.3 drug trials) underwent either total sinus node ablation or sinus node modification. The region of the sinus node was identified as the region of earliest atrial activation in sinus rhythm during electrophysiological study. This region was further defined by use of intracardiac echocardiography (ICE) in 9 patients, in whom it was found that an ablation catheter could be guided reliably and maintained on the crista terminalis. Radiofrequency energy was delivered during tachycardia between either a standard 4-mm or custom 10-mm thermistor-imbedded catheter tip and a skin patch. Total sinus node ablation was performed successfully in all 4 patients in whom it was attempted and was characterized by a junctional escape rhythm. Sinus node modification was successfully achieved in all 12 patients in whom it was attempted and was characterized by a 25% reduction in the sinus heart rate. For the group as a whole, exercise stress testing after ablation revealed a gradual chronotropic response, with a significant reduction in maximal heart rate (132.8±6.5 versus 179.5±3.6 beats per minute [bpm]; P<.001) without evidence of an exaggerated heart rate response to a light workload (103.0±4.1 versus 139.5±3.5 bpm; P<.001). Twenty-four-hour ambulatory ECG monitoring revealed a significant decrease in maximal heart rate and mean heart rate after ablation (167.2±2.6 versus 96.7±5.0 bpm, P<.001, and 125.6±5.0 versus 54.1±5.3 bpm, P<.001, respectively). There was a significant decrease in the number of applications of radiofrequency energy required in patients undergoing modification of the sinus node when guided by ICE compared with fluoroscopy alone (3.6±0.8 versus 10.4±2.1; P<.01) as well as a decrease in fluoroscopy time (33.0±9.5 versus 58.5±8.4 minutes). After a mean follow-up period of 20.5±0.3 months, there were no recurrences of inappropriate sinus tachycardia in patients who underwent a total sinus node ablation. However, 2 patients who had a total sinus node ablation subsequently required permanent pacing because of symptomatic pauses, and 1 patient developed an ectopic atrial tachycardia. After a mean follow-up of 7.1±1.7 months, there were two recurrences of inappropriate sinus tachycardia in patients who underwent sinus node modification. However, no significant bradycardia or pauses were observed. Complications encountered during the study included 1 patient who developed transient right diaphragmatic paralysis and another patient who developed transient superior vena cava syndrome.
Conclusions Sinus node modification is feasible in humans and should be considered as an alternative to complete atrioventricular junctional ablation for patients with disabling inappropriate sinus tachycardia refractory to medical management. Sinus node modification may be aided by ICE.
Incessant inappropriate sinus tachycardia is an uncommon disorder that may produce total disability.1 The tachycardia resembles sinus tachycardia electrocardiographically as well as electrophysiologically. Patients with inappropriate sinus tachycardia have an abnormally high resting heart rate and a disproportionate increase in heart rate in response to minimal activity. Abnormal sinus node automaticity and a hypersensitivity to β-adrenergic stimulation have been suggested as mechanisms leading to inappropriate sinus tachycardia.2 β-Blockade is the initial treatment of choice. For medically refractory patients with inappropriate sinus tachycardia, His bundle ablation and permanent pacemaker implantation or subtotal right atrial exclusion has been used.3
Sinus node pacemaker function is widely distributed through the right atrium with its superior aspect originating at the junction of the superior vena cava and right atrial appendage and extending inferiorly along the crista terminalis toward the junction of the inferior vena cava and right atrium. The crista terminalis is a well-defined ridge on the endocardial surface of the right atrium that marks the junction of the smooth right atrium, derived from the sinus venosus, and the trabeculated appendage, derived from the primitive right atrium.4 There are predictable shifts in the earliest site of activation within the sinus node complex in response to changes in autonomic tone and pharmacological manipulations that correlate with changes in heart rate.5 6 7 In humans and dogs, the origin of the dominant sinus pacemaker group may be shifted over a distance of up to 3 cm along the region of the sulcus terminalis in response to autonomic influences.8 9 Sympathetic activation causes a cranial shift in the pacemaker location, whereas vagal stimulation results in a caudal shift along the crista terminalis. These unique properties of sinus node anatomy and physiology recently have led investigators to test the feasibility of selective sinus node ablation to control rate responsiveness in dogs using either epicardial laser irradiation10 or endocardial application of radiofrequency energy.9 11
The purpose of the present study was to evaluate the efficacy and safety of radiofrequency catheter ablation of the sinus node in a consecutive series of patients with debilitating, drug-refractory inappropriate sinus tachycardia. In addition, observations regarding the usefulness of intracardiac echocardiography (ICE) to achieve sinus node modification were made.
Sixteen patients diagnosed between April 1993 and March 1995 as having inappropriate sinus tachycardia were enrolled in the study. All patients were debilitated by their arrhythmias and had either already undergone complete atrioventricular junctional ablation and pacemaker implantation to achieve rate control but were still symptomatic because of ventricular tracking of rapid atrial rates (3 patients) or were referred for possible His bundle ablation and permanent pacemaker implantation.
Definition of Inappropriate Sinus Tachycardia
Patients underwent initial evaluation that included history, physical examination, ECG, echocardiogram, 24-hour Holter monitoring (14 patients), and exercise stress testing (15 patients). Autonomic testing by total pharmacological autonomic blockade with atropine and propranolol were performed before ablation in 11 patients.
Inappropriate sinus tachycardia was defined as1 2 (1) P-wave axis and morphology during tachycardia similar or identical to that during sinus rhythm; (2) resting heart rate of ≥100 beats per minute (bpm) or increase of heart rate ≥100 bpm with minimal exertion (eg, rising out of a chair or slow walking); (3) exclusion of secondary causes of sinus tachycardia; and (4) symptoms of palpitations and/or presyncope clearly documented to be related to resting or easily provoked sinus tachycardia. The inclusion of symptoms to the criteria for inappropriate sinus tachycardia differentiates this syndrome from severely deconditioned individuals who might fulfill the criteria for “inappropriate” sinus tachycardia based on rate alone.
Assessment of intrinsic heart rate by pharmacological autonomic blockade was performed at baseline and after the ablation procedure in 1 of 4 patients undergoing total sinus node ablation and in 10 of 12 patients undergoing sinus node modification. To obtain pharmacological autonomic denervation, propranolol (0.2 mg/kg) was administered intravenously (with a maximal infusion rate of 1 mg/min), followed by administration of atropine (0.04 mg/kg) administered intravenously over 2 minutes.12 Blood pressure and heart rate were monitored at baseline for 10 minutes, followed by monitoring during administration of propranolol and atropine. After return to baseline heart rate, patients were monitored for an additional 10 minutes. Predicted intrinsic heart rate (IHR) was calculated by use of the formula: IHR=118.1−(0.57×age).12
Exercise Treadmill Testing and Holter Monitoring
Exercise treadmill testing using a Bruce protocol was performed at baseline and 1 to 5 days after ablation. Maximal heart rate, heart rate midway through stage I of the Bruce protocol, and workload were recorded. Ambulatory ECG monitoring was performed at baseline and 1 to 5 days after ablation. The 24-hour disclosures were recorded at 3 mm/s. Maximal, minimal, and mean heart rates were determined for each 1-hour period and for the full 24-hour period. The number of pauses defined as >2 seconds were also determined at baseline and after the ablation procedure.
Informed written consent was obtained from the patient before the procedure by use of a protocol approved by the Institutional Review Board. Antiarrhythmic medications were discontinued at least five half-lives before the electrophysiological study. Patients were studied in the postabsorptive state, mildly sedated with intravenous fentanyl and midazolam. Quadripolar catheters (6F) were positioned in the high right atrium, low septal right atrium (to record the His bundle electrogram), and right ventricular apex. In 10 patients (patients 7 through 16) undergoing sinus node modification, a catheter with either 5 or 10 bipolar pairs (2 mm interelectrode distance, 5 mm interbipole distance) (Webster Laboratories) was positioned along the posterolateral wall of the right atrium approximating the crista terminalis. The second bipolar pair was positioned at the junction of the superior vena cava and right atrium, which usually defines the most superior aspect of the sinus node complex. Positioning of the second bipolar pair of electrodes was performed by passing the decapolar catheter superiorly into the superior vena cava until intracardiac electrograms were lost, then maneuvering the catheter back into the atrium until the intracardiac electrograms reappeared. Catheter position relative to the crista terminalis was confirmed with ICE (see below). Surface leads and intracardiac electrograms filtered from 30 to 250 Hz were recorded on a computer-based digital amplifier/recorder system with optical disk storage (ART, Inc). If the tachycardia rate was not >120 bpm, isoproterenol was infused until the tachycardia rate was >120 bpm or the heart rate increased by at least 30% (starting dose of 0.5 μg/min was used, with the dose increased every 5 minutes). For arrhythmias not induced by isoproterenol, aminophylline was infused at a dose of 6.0 mg/kg over 15 to 20 minutes, followed by a maintenance infusion of 0.5 mg ·kg−1 · min−1.
Electrophysiological diagnosis for inappropriate sinus tachycardia included: (1) exclusion of arrhythmias initiated or terminated by programmed atrial stimulation or overdrive pacing; (2) intracardiac atrial electrogram recordings that revealed a cranio-caudal pattern of activation, with the earliest recordings occurring at the superior aspect of the crista terminalis; (3) a gradual increase and decrease in heart rate at the initiation and termination of the tachycardia; and (4) shifts in the earliest site of activation along the crista terminalis in response to changes in the tachycardia rate.
The intracardiac imaging system and its use in humans have been described previously.13 Briefly, a 10-MHz ultrasound transducer mounted on the tip of a 10F catheter (Cardiovascular Imaging Systems) was used to visualize the crista terminalis. The intracardiac imaging catheter was advanced via a 10F sheath in the femoral vein through the inferior vena cava into the right atrium. Under echocardiographic guidance, the imaging plane for the crista terminalis was located. Optimization of the echocardiographic image was obtained by gentle manipulation of the imaging catheter.
Intracardiac Mapping and Radiofrequency Ablation
Patients were divided into two groups: (1) those in whom the modification was guided by fluoroscopy and (2) those in whom the procedure was guided by ICE. Seven patients underwent either extensive sinus node ablation (patients 1 through 4) or limited sinus node modification (patients 5 through 7) guided by fluoroscopy alone. Nine patients (patients 8 through 16) underwent sinus node modification guided by ICE.
Total sinus node ablation was defined as a reduction in heart rate of >50% of the tachycardia heart rate with a junctional escape rhythm. Sinus node modification was defined by at least a 25% reduction in the sinus heart rate under the same conditions of catecholamine infusion with either retention of the normal P-wave axis in frontal and horizontal planes or transient low atrial escape rhythm.
The crista terminalis crosses from the high anteromedial right atrium in front of the superior vena cava and down the lateral right atrial wall to terminate in the posteroinferior right atrium as the eustachian valve. An anatomical approach consisting of applying radiofrequency energy to the most superior aspect of the crista terminalis (junction of the superior vena cava and right atrial appendage) with subsequent lesions applied to progressively inferior sites along the crista terminalis was used to achieve heart-rate reduction. This approach was based on physiological studies demonstrating that sympathetic stimulation resulting in maximal heart rates is produced by activation of the more superior aspects of the crista terminalis.5 6 7 8 9 In the initial 7 patients, an attempt was made to define the supermedial aspect of the crista terminalis by use of fluoroscopy and earliest site of activation during catecholamine infusion. In patients 8 through 16, applications of radiofrequency energy were guided by ICE in a precise and systematic approach to modifying the sinus node. Applications of radiofrequency energy were initially delivered to the most superior aspect of the sinus node (the prominent ridge of the crista terminalis).
A standard 4-mm or 10-mm customized deflectable-tip catheter with a thermistor-embedded distal electrode was used (EP Technologies). The anatomical approach consisted of applying radiofrequency energy to the most superior aspect of the crista terminalis. If the first radiofrequency lesion failed to produce the desired heart-rate response, additional applications of radiofrequency energy were delivered in a methodical stepwise approach moving inferiorly along the crista terminalis until the desired heart-rate response was achieved. After transient right diaphragmatic paralysis in patient 2, atrial pacing with 10 mA and a 2-ms pulse width was performed before delivery of radiofrequency energy to ensure that the diaphragm was not paced via stimulation of the phrenic nerve. Power was adjusted to achieve a tip-tissue interface temperature of 55° to 70°. Radiofrequency energy (500 kHz) was delivered between the distal electrode and a large surface patch. If a temperature of 50° was not achieved within the initial 15 to 20 seconds, inadequate endocardial tissue contact was assumed and the radiofrequency energy application was discontinued. If a reduction of heart rate and/or appearance of junctional rhythm was observed during the initial application of radiofrequency energy, radiofrequency energy was continued for 60 to 80 seconds. In the majority of successful applications, an initial marked increase in sinus rate was followed by a subsequent fall in heart rate. In these applications, radiofrequency energy was continued for 60 to 80 seconds.
All results are presented as mean±SEM. Comparisons were made using a two-tailed t test. A value of P<.05 was considered significant.
The patient population consisted of 16 patients with chronic, debilitating, drug-refractory inappropriate sinus tachycardia in which all identifiable causes of sinus tachycardia had been excluded. Clinical and demographic characteristics are listed in Table 1⇓. Eight of the 16 patients were healthcare-related workers. Symptoms of palpitations, fatigue, and presyncope had been present for at least 1 year. The average number of failed antiarrhythmic drugs was 4.2±0.3 (Table 1⇓). Three patients (patients 4, 7, and 15) had undergone previous atrioventricular junctional ablation and permanent pacemaker implantation as treatment for their inappropriate sinus tachycardia. They were referred for repeat evaluation because of persistence of symptoms related to ventricular tracking of sinus tachycardia by their dual-chamber implanted pacemaker systems. Patient 14 had undergone electrophysiological testing in which dual atrioventricular nodal physiology and a single echo beat during atrial extrastimuli pacing were detected. Atrioventricular nodal slow pathway ablation did not modify her symptoms or arrhythmia. Excluding patient 5 and patients with mitral valve prolapse (patients 8 and 12), patients enrolled in the study had no evidence of structural heart disease assessed by echocardiography.
Results from the electrophysiological study, radiofrequency catheter ablation procedure, and subsequent follow-up for patients who presented with inappropriate sinus tachycardia are listed in Table 2⇓. All patients had sinus tachycardia either at rest or after the infusion of isoproterenol (<1.5 μg/min) or aminophylline (250 mg infused over 15 minutes). The arrhythmias were not initiated or terminated by programmed atrial stimulation or overdrive pacing. P-wave axis and morphology during tachycardia resembled that during sinus rhythm (Fig 1A⇓) and intracardiac atrial electrogram recordings revealed a cranio-caudal pattern of activation. Extensive mapping of the right atrium demonstrated that the earliest atrial activation originated in the sinus node region. No atrial tachycardias were induced by programmed atrial stimulation or overdrive pacing. Target sites were initially identified by the earliest site of endocardial atrial activation relative to the surface P wave. However, many sites showed similar early endocardial activation times, thus limiting the usefulness of this approach. The atrial activation time measured at the site of radiofrequency ablation that created the desired heart-rate response ranged from −15 to −60 ms (23.7±3.6 ms). The average heart rate during tachycardia was 142.5±7.8 bpm.
Results of the radiofrequency catheter ablation procedure are listed in Table 2⇑. The anatomical approach used in the first four patients consisted of attempting to apply radiofrequency energy to the most superior aspect of the crista terminalis, with subsequent lesions applied to progressively inferior sites until the distal third of the crista terminalis was reached. The extensive modification technique was based on our observation that a significant caudal shift in sinus node activation did not occur until heart rates below 60 bpm were achieved, thus implying that the majority of the sinus node region is capable of producing sinus tachycardia. This more extensive technique was termed “total sinus node ablation.”
Extensive ablation procedures resulted in an unacceptably high requirement for permanent pacing. This fact, combined with demonstration of the feasibility of limited sinus node modification in the animal laboratory,9 led us to attempt a more limited procedure, sinus node modification, in the subsequent 12 patients.
Total Sinus Node Ablation
Initial success was achieved in all four patients in whom total sinus node ablation was attempted. A junctional escape rhythm was recorded in all four patients (patients 1 through 4) (Fig 1A⇑). However, by postoperative day 1, a low ectopic atrial rhythm was the predominant rhythm (Fig 1B⇑) and by 1 week after ablation, these four patients showed recovery of sinus rhythm as indicated by a normal P-wave axis and upright P waves in the inferior leads (Fig 1C⇑).
Sinus Node Modification
Initial success was achieved in all 12 patients in whom sinus node modification was attempted. Two patients (patients 6 and 7) developed a transient low ectopic atrial rhythm immediately after ablation. However, after 1 day, these patients had recovered a higher right atrial origin of activation consistent with the recovery of sinus rhythm. Eight of the patients remained in sinus rhythm after ablation. In all cases, there was a marked increase in postablation cycle length during infusion of at least 4 μg/min of isoproterenol as compared with cycle length before ablation (531.6±18.9 versus 432.0±15.4 ms; P<.001). In patients 8 through 11, there was also a change in the atrial activation sequence such that the earliest endocardial atrial electrogram was identified in a more caudal location on the crista terminalis (Fig 2D⇓).
Intracardiac Echocardiographic Observations
ICE clearly delineated the crista terminalis along its entire extent from supermedial to posteroinferior lateral right atrium. As shown in Fig 3A⇓, the superior aspect of the crista terminalis can be seen as a prominent ridge originating at the junction of the superior vena cava and right atrial appendage. The tip of the ablation catheter is seen as a fan-shaped acoustic artifact (Fig 3B⇓). Radiofrequency lesion formation detected by use of ICE appears as an area of local increase in tissue echogenicity that produces an ultrasound shadowing artifact (Fig 3C⇓).
Our initial experience with ICE as an ancillary tool for assisting in radiofrequency modification of the sinus node was in patient 7. During this procedure, ICE was used only to observe catheter positions within the sinus node region as guided by right and left anterior oblique fluoroscopic views. Although the sinus node region could be approximated fluoroscopically, it readily became apparent that many of the applications of radiofrequency energy were either too posterior or caudal to the most superior aspect of the crista terminalis. Furthermore, ICE demonstrated the acute closure of the superior vena cava caused by local edema from non–ICE guided applications of radiofrequency energy. After our experience with ICE in patient 7 and considering results from our animal studies that demonstrated the usefulness of ICE in guiding ablation to anatomic landmarks in dogs,13 as well as the performance of sinus node modifications,9 all subsequent sinus node modifications were guided by ICE.
In patient 10, who had undergone two previous attempts at sinus node modification at another institution in which more than 40 applications of radiofrequency energy were delivered, ICE was particularly useful. ICE was used to direct radiofrequency energy to the most medial extent of the crista terminalis at the superior base of the right atrial appendage, which proved to be the successful site of ablation. Previous ablation lesions were identified by ICE inferior to the successful site.
With the exception of patient 10, there was a significant decrease in the number of applications of radiofrequency energy used in patients undergoing modification of the sinus node guided by ICE compared with fluoroscopy alone (3.6±0.8 versus 10.4±2.1; P<.01) as well as a decrease in fluoroscopy time (33.0±9.5 versus 58.5±8.4 minutes).
Intrinsic heart-rate data for total sinus node ablation and sinus node modification were pooled, since intrinsic heart rate before and after total sinus node ablation was obtained in only 1 patient. The resting sinus rate before total sinus node ablation or sinus node modification was not significantly different from resting heart rate after catheter ablation of the sinus node (85.5±7.8 versus 79±4.9 bpm). The mean baseline measurement of intrinsic heart rate (118.6±8.6 bpm) was significantly higher than the mean predicted intrinsic heart rate (97.7±1.7 bpm; P<.01). However, intrinsic heart rate was within the normal range12 in 5 of the 11 patients who had baseline measurements. Mean intrinsic heart rate after ablation (70.5±7.5 bpm) was significantly lower than mean baseline intrinsic heart rate (P<.001; Fig 4⇓). Mean postablation intrinsic heart rate was not significantly different from mean postablation resting heart rate.
Exercise Stress Testing
The results of exercise treadmill testing before and after total sinus node ablation and sinus node modification are shown in Fig 5⇓. Preablation exercise stress testing showed that patients were able to achieve an average of 109±3.0% predicted heart rate. It was also observed that patients who underwent exercise treadmill testing had inappropriate chronotropic response to a light workload (mean heart rate was 141.2±5.1 bpm after 1.5 minutes of exercise during stage I of the Bruce protocol).
Exercise treadmill testing after total sinus node ablation (patients 1 through 4) showed significantly lower chronotropic response to exercise without evidence of tachycardia (mean heart rate at 1.5 minutes of exercise was 94.0±8.1 bpm, P<.007; mean maximal heart rate was 127.3±8.3 bpm; P<.01). However, chronotropic response to exercise was achieved by initiation of either a junctional tachycardia or an ectopic atrial tachycardia, demonstrating the instability and inability of the sinus node to be the effective dominant pacemaker.
After sinus node modification, patients 5 through 16 demonstrated appropriate but significantly lowered chronotropic response (mean heart rate at 1.5 minutes of exercise was 107.0±4.8 bpm, P<.001; mean maximal heart rate was 135.3±7.6 bpm, P<.001). There was no evidence of either junctional tachycardia or ectopic atrial tachycardia in this group of patients.
Ambulatory ECG monitoring data for both total sinus node ablation patients and sinus node modification patients are presented in Table 3⇓. All patients demonstrated a high variability in upper heart rates, which were blunted after the ablation procedure. However, patients did maintain normal diurnal variation before and after modification to the sinus node.
All of the patients in the total sinus node ablation group had a significant reduction of maximal heart rate except for patient 1, who had documented episodes of atrial tachycardia to heart rates of up to 178 bpm. Recorded atrial rhythms were characterized by more than one P-wave morphology. The dramatic effects of total sinus node ablation on sinus rhythm are demonstrated by the significant reduction in 24-hour mean heart rate. Patients who underwent a total sinus node ablation also showed a significant decrease in the minimum heart rate that reflected sinus pauses and episodic junctional rhythm. In patient 1, significant pauses and junctional rhythm were noted after total sinus node ablation, with the longest pause being 6.3 seconds, associated with symptoms of presyncope. In patient 2, there were frequent pauses of 2 to 4 seconds, which were unchanged from her baseline ambulatory ECG recording.
Patients in the sinus node modification group had significant reductions in maximal heart rate and 24-hour mean heart rate. There was no difference in minimum heart rate before or after sinus node modification. Pauses and junctional rhythm were not observed in this group of patients.
Patients or their primary cardiologists were contacted periodically. If patients became symptomatic, ambulatory ECG monitoring was obtained to determine if symptoms correlated to sinus tachycardia. In addition, exercise stress testing was performed to determine if the chronotropic response to exercise was similar to the preablation exercise stress testing. A patient was considered to have had a recurrence of their inappropriate sinus tachycardia if they fulfilled the criteria of inappropriate sinus tachycardia and their symptoms corresponded to increases in heart rate. Patients with marked improvement but not total elimination of their symptoms were considered a partial success. These included patients with palpitations not corresponding to sinus tachycardia and patients who had occasional palpitations but no longer had presyncope associated with sinus tachycardia.
Total Sinus Node Ablation
All 4 patients in whom it was attempted had initial successful total sinus node ablation (patients 1 through 4). There were no recurrences of symptoms associated with inappropriate sinus tachycardia with a mean follow-up of 20.5±0.3 months. However, patient 1 developed ectopic atrial tachycardias that eventually required His bundle ablation.
Permanent pacemakers were implanted in two patients who underwent total sinus node ablation. Patient 1 had symptoms of presyncope, with documented pauses of up to 6.3 seconds. In patient 2, a pacemaker was implanted at a different institution after this patient experienced continued symptoms of fatigue and presyncope. Repeated Holter monitoring in patient 2 demonstrated pauses of 2 to 4 seconds and no evidence of tachycardia. There was no change in the incidence of these pauses after ablation. Furthermore, her symptoms of fatigue and presyncope were not clearly correlated to pauses or bradycardia. Patient 2 also had transient right diaphragmatic paralysis, which eventually resolved within 1 month.
Sinus Node Modification
Initial success was achieved in all 12 patients who underwent sinus node modification (patients 5 through 16). There were 2 recurrences (patients 5 and 6) as documented by 24-hour ambulatory ECG, which occurred 1 and 2 weeks after the initial ablation procedure (mean follow-up, 8.3±1.8 months), and there were 5 partial successes. The recurrence of inappropriate sinus tachycardia in patient 5 has been treated medically with amiodarone. However, the patient remains symptomatic. The recurrence in patient 6 was treated with His bundle ablation and permanent pacemaker implantation. However, she still complains of symptoms of palpitations associated with heart rates >100 bpm.
Patient 8 had documented narrow-complex tachycardia 5 months after her sinus node modification. Initially, it was thought that she had had a recurrence of inappropriate sinus tachycardia. However, repeat evaluation revealed (1) 24-hour mean heart rate of 63 bpm (pre–sinus node modification mean 24-hour heart rate of 96 bpm); (2) gradual increase in heart rate during exercise stress test, with a maximal heart rate of 164 bpm (194 bpm pre–sinus node modification); and (3) maximal heart rate of 160 bpm after infusion of isoproterenol (4 μg/min) and atropine (1 mg), with the earliest activation on the crista at the midright atrium. It was concluded that patient 8 most likely had an ectopic atrial tachycardia that could not be induced during repeat study. Patient 8 continues to have palpitations that do not consistently correlate to Holter-documented tachycardias. She is being treated with calcium channel blockers for palpitations and syndrome X. In contrast, before her sinus node modification, symptoms of palpitations and presyncope were correlated to sinus tachycardia. In addition, after the sinus node modification, patient 8 was totally asymptomatic for 4 months.
Four patients (8, 10, 12, and 13) reported brief episodes of palpitations that were documented by ambulatory ECG to correspond to heart rates between 90 and 130 bpm. Before their sinus node modification procedures, these patients complained of sudden increases in heart rate (>150 bpm) associated with palpitations and presyncope. After sinus node modification, these patients’ symptoms of presyncope resolved. Patient 10 has been treated with sotalol with almost complete elimination of her symptoms. Patient 12 has been successfully treated with β-adrenergic blockers for palpitation, which before sinus node modification were completely ineffective, and patients 8 and 13 have not required any medical therapy.
Patient 7 had transient superior vena cava syndrome immediately after ablation that resolved within 1 hour after ablation. Coincidentally, this patient had 19 applications of radiofrequency energy and also had a dual-chamber pacemaker because of prior atrioventricular junction ablation. The endocardial pacing leads may have contributed to acute occlusion of the superior vena cava.
In this prospective study, we attempted to achieve modification of the sinus node to relieve symptoms associated with inappropriate sinus tachycardia. Direct application of radiofrequency energy to the superior aspect of the crista terminalis achieved significant reductions in sinus rates, demonstrated during treadmill exercise and ambulatory ECG. Control of sinus rate was accompanied by improvement in symptoms in the majority of patients and preservation of normal chronotropic response in those with modified sinus node function.
Unlike surgical excision, sinus node exclusion, or modification of the sinus node with lasers,3 10 radiofrequency catheter modification of the sinus node does not require an open chest surgical procedure. Our initial results suggest that sinus node modification rather than total sinus node ablation is the preferred procedure for achieving heart rate control in patients with disabling inappropriate sinus tachycardia. Similar observations have been made in dogs undergoing complete excision of the sinus node and crista terminalis or after total sinus node ablation with radiofrequency catheter ablation.9 11 In view of the complications observed after total sinus node ablation, we modified the procedure on the basis of experience gained in the animal laboratory.
Sinus node modification appears to preserve the dominance of the sinus node and achieve heart-rate control without producing significant pauses and without the need for permanent pacemaker implantation. Exercise stress testing after sinus node modification demonstrated that patients had an appropriate chronotropic response without any evidence of pacemaker instability. Furthermore, exercise stress testing clearly demonstrated that the sinus node had been modified because the maximal heart rate after modification was significantly lower than before sinus node modification. Twenty-four-hour ambulatory ECG monitoring also demonstrated a significant decrease in both the maximal and 24-hour mean heart rate without a significant change in the minimum heart rate or observation of significant sinus pauses.
The use of multiple simultaneous electrograms for the crista terminalis to determine atrial activation sequence and the use of ICE clearly helps to define the most superior aspect of the sinus node, both anatomically and electrophysiologically, and aids in achieving successful sinus node modification. Multiple electrograms demonstrating a caudal shift in the atrial activation sequence with successful ablation of the most superior aspect of the crista terminalis further aid in confirming a successful modification when combined with the desired heart-rate response. In patients in whom ICE guided the application of radiofrequency energy to the superior aspect of the sinus node, the no. of applications of radiofrequency energy and the fluoroscopy time were reduced. In addition, there were no complications or recurrent symptoms requiring atrioventricular junction ablation and permanent pacemaker implantation in the ICE–guided group of patients.
Heart-rate control may have been achieved by either the destruction of pacemaker tissue, interruption of autonomic neural inputs, or both. Histological examination of the canine sinus node after radiofrequency catheter ablation demonstrated an area of fibrosis with complete loss of both nodal cells and sympathetic innervation.9 The demonstration of a decreased intrinsic heart rate after radiofrequency ablation is consistent with destruction of sinus nodal cells and/or sympathetic innervation to the sinus node complex.
The basic mechanism of inappropriate sinus tachycardia is not well understood. Inappropriate sinus tachycardia may be due to an intrinsic increased automaticity of sinus node cells, derangement of the autonomic nervous system, or both. Morillo et al2 recently suggested that the mechanism leading to inappropriate sinus tachycardia is related to a primary sinus node abnormality characterized by a high intrinsic heart rate, β-adrenergic hypersensitivity, and depressed efferent cardiovagal reflex. However, Bauernfeind et al1 originally demonstrated that inappropriate sinus tachycardia was due to increased automaticity of the sinus node as a result of a defect in either sympathetic or vagal nerve control of resting heart rate, with or without an abnormal increase in intrinsic heart rate. Our observations of an exaggerated chronotropic response during the first 1.5 minutes of exercise corroborate the hypothesis of Morillo et al2 of enhanced sensitivity to β-adrenergic stimulation. However, we also observed that patients with inappropriate sinus tachycardia could have either normal or abnormally increased intrinsic heart rates. The variability in findings leading to inappropriate sinus tachycardia suggests a spectrum of mechanisms producing inappropriate sinus tachycardia and highlights the need for further investigation of the diathesis of inappropriate sinus tachycardia.
Long-term follow-up of patients who underwent total sinus node ablation showed subjective improvement in symptoms without recurrence of inappropriate sinus tachycardia. However, permanent pacemakers were subsequently implanted in 2 patients. One of the 2 patients requiring a permanent pacemaker also developed an ectopic atrial tachycardia and subsequently underwent His bundle ablation. During the follow-up period for patients undergoing sinus node modification, there were two recurrences (patients 5 and 6) within 2 weeks of the procedure. The initial observed short-term success may have been due to edema caused by the application of radiofrequency energy to a site caudal to or not on the superior aspect of the crista terminalis, since ICE was not used. Sinus node modification in 4 patients (patients 8, 10, 12, and 13) resulted in a partial success. Their symptoms of palpitations were markedly improved, and their symptoms of presyncope were eliminated. One patient (8) appears to have symptoms of palpitations partially attributable to ectopic atrial tachycardia. The observation that 2 of 11 patients have developed ectopic atrial tachycardias after modification of sinus function suggests that patients with inappropriate sinus tachycardia may have abnormal automaticity not limited to the sinus node. Further long-term follow-up is required to determine whether patients will develop sinus node dysfunction or have an increased incidence of atrial arrhythmias after sinus node modification.
Although our initial experience appears to be favorable, with the vast majority of patients benefiting from modification of the sinus node, the incidence of other arrhythmias, recurrence of symptoms, and possible need for pacemaker therapy suggest that this procedure should be reserved only for highly symptomatic patients for whom drug therapy fails. Additionally, patients with “functional symptoms” of palpitations and presyncope, in which symptoms appear disproportionate to the degree of tachycardia, may appear to have inappropriate sinus tachycardia, thus further emphasizing the need for careful patient selection for sinus node modification.
The present study describes a technique for altering sinus node function that was in evolution during the course of this study. This has led to the comparison of small groups of patients for total sinus node ablation versus sinus node modification and patients undergoing sinus node modification with and without the use of ICE. However, despite the relatively small no.s in each group, the present study clearly demonstrates that sinus node modification is feasible in humans and should be considered as an alternative to complete atrioventricular junctional ablation for patients with disabling inappropriate sinus tachycardia refractory to medical management.
Sinus node modification is feasible in humans and should be considered as an alternative therapy for patients with disabling inappropriate sinus tachycardia refractory to medical management. The risk of need for permanent pacing increases with complete sinus node ablation. ICE aids in directing ablation to the superior aspect of the crista terminalis, thus reducing the risk of complications while preserving sinus function.
Dr Kalman was supported by a Ralph Reader overseas research fellowship of the National Heart Foundation of Australia and a Telectronics traveling grant of the Royal Australian College of Physicians.
- Received April 10, 1995.
- Revision received August 23, 1995.
- Accepted September 12, 1995.
- Copyright © 1995 by American Heart Association
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