Use of Noncontact Mapping and Saline-Cooled AblationCatheter for Sinus Node Modification in MedicallyRefractory Inappropriate Sinus TachycardiaDAVID LIN, M.D., FERMIN GARCIA, M.D., JASON JACOBSON, M.D.,EDWARD P. GERSTENFELD, M.D., SANJAY DIXIT, M.D., RALPH VERDINO, M.D.,DAVID J. CALLANS, M.D., and FRANCIS E. MARCHLINSKI, M.D.From the Division of Cardiology of the University of Pennsylvania Health Systems, Electrophysiology Section,Philadelphia, Pennsylvania

Background: Inappropriate sinus tachycardia (IST) is characterized by heart rate (HR) increase outof proportion to stress level. Radiofrequency (RF) modification of the sinus node (SN) is an acceptedtreatment modality for medically refractory IST. We describe a new technique using noncontact mappingand a saline irrigated catheter for SN modification.

Methods: Seven consecutive patients with medically refractory IST were referred for ablation. Intrinsicheart rate (IHR) was calculated with complete autonomic blockade by atropine and propranolol. Isopro-terenol (ISO) 1 mcg/min was initiated and increased to 10 mcg/min. Site of earliest activation was taggedat each dose of ISO once stable HR was achieved. RF ablation to target site of earliest activation at peakHR on ISO 10 mcg/min was performed. With any change in P-wave morphology, activation was reassessedand the new site of earliest activation targeted. Endpoint was a decrease in HR and change in P-wavemorphology in lead III and aVF.

Results: Five of seven patients had abnormal IHR. Mean number of RF lesions was 25 (10–52). Allpatients had either flattening of the P wave or development of negative P waves in leads III and aVF postRF associated with a decrease in HR of ≥25% from baseline off ISO. A caudal shift of the site of earlyactivation compared with baseline was observed. One patient who had a prior SN modification developedsymptomatic intermittent junctional bradycardia and required an atrial pacemaker 2 weeks later. Theother 6 patients in follow-up from 6 to 24 months had no further IST.

Conclusions: Noncontact mapping using the described technique in conjunction with the saline-cooledablation catheter for SN modification in the treatment of IST may provide effective HR control. (PACE2007; 30:236–242)

catheter ablation, mapping, clinical electrophysiology

BackgroundInappropriate sinus tachycardia (IST) is an ill-

defined clinical syndrome characterized by palpi-tations, syncope, and a heart rate increase out ofproportion to the degree of physiological stress.1–4

Radiofrequency (RF) modification of the sinusnode (SN) is an accepted treatment modality formedically refractory IST. Several techniques havebeen described for SN modification with vari-able results.5–12 Difficulties frequently encoun-tered with SN modification include the inabilityto accurately localize the site as well as the needto create extensive lesion sets due to the predomi-nantly epicardial location of the SN. We report ourobservations using a noncontact multielectrode ar-ray (MEA) and a 4-mm saline-irrigated ablation

Address for reprints: David Lin, M.D., Hospital of the Uni-versity of Pennsylvania, Division of Cardiology, 3400 SpruceStreet, 9 Founders, Philadelphia, PA 19104. Fax: (215) 662-2879; e-mail: david.lin@uphs.upenn.edu

Received June 27, 2006; revised October 30, 2006; acceptedOctober 31, 2006.

catheter for SN modification in patients who arerefractory to medical therapy and continue to havehighly symptomatic IST.

MethodsElectrophysiologic Evaluation and Ablation

Written informed consent was obtained fromall patients before the procedure. All proce-dures were performed according to the institu-tional guidelines of the University of Pennsylva-nia Health System. Preprocedure transtelephonicmonitoring demonstrated frequent episodes of nar-row complex tachycardia with a P-wave axis andmorphology consistent with a site of origin at orclose to the SN.

The patients were brought to the electrophys-iology (EP) laboratory in a fasting state. Vascularaccess was obtained via the femoral vein. Base-line electrophysiology study was performed inall patients to rule out other arrhythmias using 3standard 6-Fr nondeflectable quadrapolar Joseph-son diagnostic EP catheters (Bard Electrophysiol-ogy, Lowell, MA, USA) placed in the high right

C©2007, The Authors. Journal compilation C©2007, Blackwell Publishing, Inc.

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atrium, His bundle, and right ventricular apex.β-adrenergic sensitivity was assessed by the re-sponse to graded boluses of isoproterenol (ISO)starting at 0.25 mcg and doubling each subsequentdose until an increase in heart rate (HR) of 35 bpmfrom baseline or a peak HR of 150 bpm is achievedas previously described by Morillo et al.13 The HRwas allowed to return to baseline between eachbolus. A patient was classified as having a hyper-sensitive adrenergic response if the target HR wasreached using ≤ 1mcg of isoproterenol.

After the HR returned to within 5 bpm ofbaseline, the intrinsic heart rate (IHR), definedas the heart rate activity under the simultane-ous presence of the nonselective β-blocker pro-pranolol (0.2 mg/kg) and atropine (0.04 mg/kg),was calculated and adjusted for age, based onthe previously described formula 118.1 − (0.57 ×age).14,15 The diagnostic EP catheters were thenremoved for the remainder of the mapping andablation. A steerable, decapolar 120-cm catheter(Dynamic XT, Bard) was placed in the coro-nary sinus via the femoral vein for pacing pur-poses. Mapping and ablation was performed usinga standard curve 4-mm-tip Chilli Cooled Ablationsystem (Boston Scientific, Boston MA, USA). TheEnsite Array multi-electrode catheter (EndocardialSolutions, St. Paul MN, USA) was placed in theright atrium approximately 2 cm below the supe-rior vena cava/right atrial (RA) junction with thedistal end oriented superiorly using a guidewire.Prior to insertion of the Ensite catheter, a weightbased (80 U/kg) bolus of heparin was given toachieve an ACT of >200 seconds. The ACT wasmaintained between 250 seconds and 300 secondsfor the duration of the case. Baseline right atrialgeometry was acquired. The location of earliestactivation during baseline sinus rhythm was de-termined with the low- and high-pass filters setto 1 and 300 Hz, respectively. (Fig. 1) The abla-tion catheter was initially placed into the superiorvena cava (SVC) as defined by the presence of far-field atrial signals or the loss of atrial recordingsand gradually withdrawn back into the RA until asharp atrial signal was again recorded. The sharpatrial signal was to confirm that we were in goodcontact and in the atrium at the SVC-right atrial(SVC-RA) junction rather than recording a far-fieldelectrogram deep in the SVC. Because atrial fiberscan extend into the SVC and allow for recordingof atrial signals even inside the SVC, careful fluo-roscopic observation was also made to define thelevel that the ablation catheter falls out of the SVCinto the RA during pullback. This maneuver wasperformed several times to delineate the SVC-RAjunction. (Fig. 2)

ISO infusion at 1 mcg/min was initiated andincreased to maximum dose of 10 mcg/min, in in-

Figure 1. An activation map showing initial baselinesite of earliest activation and the gradual cranial shiftwith the corresponding heart rates on incremental dosesof isoproterenol. The arrow correlates with the isopro-terenol dose.

crements of 1, 2, 3, 5, and 10 mcg/min, in all pa-tients. The site of earliest activation was labeled ateach dose of ISO once a stable HR was achieved.Once the site of earliest activation at peak HR onmaximum dose of ISO was determined and tagged,the saline irrigated ablation catheter was advancedto the most superior aspect of the site. The ISOwas then discontinued and the HR was allowed toreturn to the baseline state. Pacing from the abla-tion catheter was performed at maximum outputof 10 mA at a pulse width of 2 msec to confirm theabsence of phrenic nerve stimulation prior to eachRF lesion delivery. If phrenic nerve stimulationwas observed, the ablation catheter was moved toa slightly different location and repeat pacing wasperformed. Frequently, only minor adjustments inthe orientation of the catheter tip had to be madeto eliminate phrenic nerve stimulation. The atrialsignal on the ablation catheter was also confirmedto be earlier than the surface P wave. Once all ofthese parameters were met, RF energy was deliv-ered in the temperature controlled mode for 60seconds at a set temperature of 38◦C starting at 20W. The power was titrated starting from 20 W and

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Figure 2. A fluoroscopic image of the Ensite Array just below the SVC-RA junction and a represen-tative site of ablation with the corresponding intracardiac electrograms. Note the early potentialon the distal ablator preceding the surface P wave. Abl = ablation catheter; B = balloon; CS =coronary sinus.

increased every few seconds to maximum of 40 Wto achieve an impedance decrease of 6 to 8 ohms.Even though the ablation was performed in thebaseline state without isoproterenol for catheterstability reasons, the earliest site tagged duringpeak ISO infusion was targeted for initial RF en-ergy delivery. With each change in HR or change inP-wave morphology, the site of earliest activationwas reassessed using the EnSite Array. The newsite of earliest activation was then targeted withRF energy and the same protocol was repeated inan effort to shift the sinus rhythm more caudallyas determined by a change in the P-wave morphol-ogy. The endpoint was achieved when there was adecrease in HR of ≥25% from baseline off ISO andan associated change in the P-wave morphology inlead III and aVF from a positive to a flat or negativedeflection consistent with a more inferior impulseorigin. Isoproterenol infusion was reinitiated postablation to demonstrate the persistent change in P-wave morphology and to show a lower site of earlyactivation as compared to preablation state at thesame dose of ISO.

Follow-up

All patients were monitored post procedurewith continuous electrocardiographic monitoringfor 24 hours as an in-patient. Upon discharge, pa-tients were monitored with a transtelephonic mon-itor (TTM) for a minimum of 14 days to 30 days.Patients were instructed to transmit at least twicedaily and with any symptoms. Patients were seenin the office 4–6 weeks post procedure and thenat 6-month intervals. A 12-lead electrocardiogram(ECG) was performed at each visit and repeat 24-hour Holter was performed at 6 months and for anyrecurrent symptoms.

ResultsPatient Characteristics

Seven consecutive patients with a mean ageof 31 years (21- to 43-year old; 1 man) withhighly symptomatic IST characterized by baselinesinus tachycardia, palpitations, syncope, presyn-cope, and unresponsive to medical therapy were

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Figure 3. These ECGs show the pre- and postablation effects on the P-wave morphology. Thetypical endpoint showing flattening of the P-wave amplitude in leads III and aVF associated witha corresponding decrease in HR.

referred for SN modification. As has been previ-ously described, the patients with highly symp-tomatic IST in our series were predominantly fe-male (6 of 7 patients) and most were health careprofessionals (5 of 7 patients).1,4,7,12 All patients in-cluded in this study had failed maximum tolerateddoses of β-blockers, calcium channel blockers, flu-drocortisone, midodrine, salt tablets, flecainide, orserotonin-selective reuptake inhibitors (SSRI) ei-ther as the sole therapy or in combination. Onepatient had a prior SN modification at another in-stitution but had recurrent IST and was referredfor a repeat ablation. Thyroid function was normalin all subjects. A 2D ECG confirmed the absenceof structural heart disease in all patients. All sec-ondary and reversible causes of sinus tachycardiawere excluded.

Outcome

Five of seven patients had an IHR greater thanthe predicted HR based on age with a mean of111 ± 8 bpm (range: 103–130). The baseline EPS inall patients demonstrated normal conduction withno inducible supraventricular tachycardia. A hy-persensitive adrenergic response was observed inall seven patients using incremental ISO boluses.The site of earliest activation demonstrated a meancranial shift of 4.7 ± 3 mm at peak HR on ISO at10 mcg/min as compared to baseline state preab-lation. The mean number of RF lesions deliveredwas 25 ± 14 (range: 10–52). The mean fluoroscopytime was 26.7 ± 10.7 minutes (range: 8.8–38.5). Allpatients had either flattening of the P-wave ampli-

tude or development of negative P waves in leadIII and aVF post RF associated with a decrease inHR of ≥25% from baseline (Fig. 3). Post ablation,a caudal shift of the site of earliest activation com-pared with baseline state was observed in all pa-tients. The mean distance between the earliest ac-tivation during baseline sinus rhythm and after SNmodification was 33.2 ± 29 mm (range: 9–70 mm).The mean baseline resting HR before SN modifica-tion was 95 bpm (range: 89–109) and decreased to72 bpm (range: 54–88) after SN modification (P =0.001). ISO infusion to 10 mcg/min post SN modi-fication demonstrated mean HR of 130 bpm (range:105–145) compared to mean HR of 152 bpm (range:125–165) preablation (P < 0.001). The mean pre-ablation resting HR compared to the resting HR at6 months follow-up was 95 bpm versus 79 bpm,P < 0.001.

One patient developed symptomatic intermit-tent junctional bradycardia that persisted on mon-itoring 2 weeks post procedure and subsequentlyrequired an atrial pacemaker (Fig. 4). The other sixpatients over a mean follow-up of 13 months (6–24months) had no further IST based on postablationambulatory monitoring and no clinical symptomsthereafter, since these were all previously highlysymptomatic patients. All patients had repeat 12-lead ECGs at each clinic visit to confirm the per-sistent P-wave changes. Six-month Holter demon-strated a mean HR of 83 ± 7 bpm (range: 67–90)compared to preablation monitoring with meanHR of 106 ± 8 bpm (range: 96–117), P < 0.001. Theone patient who required an atrial pacemaker wasone who had a prior SN modification. This patient

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Figure 4. This example shows the one patient who had one prior SN modification but was stillsymptomatic with sinus tachycardia documented on Holter. The result of further modification wasan intermittent junctional rhythm (upper panel). The activation map shows a 70-mm caudal shiftin the site of earliest activation compared with baseline. This patient did well after implantationof an atrial pacemaker (lower panel).

deviated from our protocol in that we continued totarget the site of earliest activation even though theendpoint of a HR decrease and P-wave morphol-ogy change in lead III had already been achieved.However, in this particular patient, the decisionhad been made preprocedure that due to the re-current IST, the goal was to shift the sinus focusmuch lower than our defined endpoint with theunderstanding that the patient would likely needan atrial pacemaker. There were no complicationsresulting from the procedure.

Table I.

Patient Heart Rates at Baseline and with Autonomic Modulation Pre- and Postablation

Age-adjusted Preablation Postablation HR on HR on RestingIntrinsic Resting Resting ISO 10 mcg/min ISO 10 mcg/min HR at 6 Months

Patient M/F Heart Rate HR HR Preablation Postablation Follow-up

1 F Abnormal 109 75 163 125 892 M Abnormal 93 62 148 128 673 F Normal 92 54 154 138 794 F Normal 90 79 165 145 685 F Abnormal 89 68 149 132 776 F Abnormal 100 77 125 105 887 F Abnormal 95 88 158 136 85

DiscussionIST is an uncommon, yet often debilitating,

syndrome characterized by sinus tachycardia, ei-ther persistent or triggered by minimal physiologicstress. Previous studies on catheter-based RF abla-tion and/or modification of the SN have reportedvariable long-term success rates ranging from 23%to almost 70%.5–12 The mechanism of IST isnot completely understood. It has been suggestedthat this may represent a primary SN disordercharacterized by hypersensitivity to β-adrenergic

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receptors coupled with a depressed cardiovagalreflex and high IHRs.13 However, increased auto-maticity of the SN as a result of a defect in ei-ther sympathetic or vagal nerve control of the rest-ing HR, with or without an abnormal increase inIHR, has also been suggested as a mechanism.4 Ina study by Still et al.16 assessing the electrophys-iologic effects of adenosine on IST, it was foundthat in control subjects, pharmacologic autonomicblockade using β-blockers and cholinergic recep-tor blockade had minimal effect on the direct nega-tive chronotropic response to adenosine. However,in contrast, adenosine did not have any significanteffect on IST cycle length either under baselineconditions or during autonomic blockade. Giventhe accentuation of the effect of adenosine on theSN by β-adrenergic stimulation, the impaired re-sponse to adenosine makes excessive sympatheticinput less likely as the primary mechanism of IST.The fact that the clinical presentation of patientsdiagnosed with IST could have either normal orabnormally increased IHRs as well as exhibit anexaggerated chronotropic response suggests thatthere are several variables that may contribute toIST.

The mainstay of therapy for patients with ISTis medical therapy with β-blockers. Aggressive hy-dration and liberalization of salt intake may alsomitigate some of the symptoms. However, despite“optimal” medical therapy, some patients remainhighly symptomatic and, not uncommonly, to thepoint of debilitation. In these select patients whoare refractory to medical therapy, nonpharmaco-logic therapy may play a role. It is important to re-alize that sinus tachycardia is only one of the manyfindings associated with the IST “syndrome.” Pa-tients can and often continue to experience vary-ing degrees of palpitations, presyncope, and evenfrank syncope despite adequate HR control. In ourseries, the patients who underwent SN modifica-tion were patients whose predominant symptomswere related to tachycardia based on correlationwith Holter monitoring.

Furthermore, the procedure is not without itsinherent risks, including SVC occlusion, phrenicnerve paralysis, permanent pacemaker require-ment, and other complications related to catheter-based ablations.6,7,17,18 As such, patients need to beadequately counseled and modification of the SNshould be reserved to patients refractory to medi-cal therapy. Patients who benefit the most from SNmodification are those whose predominant symp-toms correlate with the sinus tachycardia.

Earlier experience with total ablation of theSN frequently resulted in significant requirementfor implantation of permanent pacemakers.7 Withmore recent strategies of SN modification in lieu oftotal ablation, the results are improved but still far

from ideal. Despite strategies utilizing activationmapping, intracardiac echocardiographic guid-ance, three-dimensional electroanatomic map-ping, and the use of larger tip ablation catheters,SN ablation procedure remains time-consuming,frequently requiring multiple RF lesions, lengthyfluoroscopy times, and are associated with highrecurrence rates. Several factors related to theanatomy of the SN may explain the difficulties fre-quently encountered in SN ablations. The densityof the matrix of connective tissue surrounding thespecialized sinoatrial cells and the potential cool-ing effects of the nodal artery may prevent deliveryof effective lesions.19–21 Furthermore, the thick-ness of the crista terminalis, especially the caudalportion, can result in a large mass of the SN tissuebeing relatively distant from the endocardium. Ina series reported by Sanchez-Quintana et al.,20 thedistance from the most caudal boundaries of thenodal body to the endocardium was > 3.5 mm.Boineau and colleagues had previously reportedtheir observation several decades ago—the widelydistributed atrial “pacemaker complex” in caninemodels.22 In their study, they observed that the sizeof the region over which the impulse could be ini-tiated in a canine model was almost twice the sizeof the histologically defined SN. This observationwas later confirmed in patients undergoing surgi-cal ablation of Wolff-Parkinson-White syndromewith intraoperative mapping of the atria utilizingbipolar recordings. This finding may explain partof the difficulties in determining the “optimal” ab-lation site. With increasing rate, the site of impulseinitiation shifted superior and anterior to the SNregion, and, with decreasing rate, it shifted infe-rior to the SN.23 Our findings in this study alsoconfirmed the dynamic shift of the site of origin ofthe sinus impulse with varying rates in response toISO infusion. The dynamic shift of the site of ori-gin may also in part contribute to the challengesin mapping and ablation of the SN.

Use of the noncontact MEA mapping systemallows a more “tailored” ablation strategy. Ratherthan just anatomically targeting the superior por-tion of the crista terminalis, the mapping catheterallows for more specific targeting of the site of ear-liest activation. Because the site of sinus impulsegeneration can and frequently shifts with RF deliv-ery, the use of noncontact mapping allows one tomore effectively ablate this “moving target.” In ourseries of patients, the use of noncontact mappingand saline irrigated ablation proved to be safe andeffective in control of highly symptomatic sinustachycardia unresponsive to medical therapy. Fur-thermore, compared with our prior experience us-ing intracardiac echocardiography (ICE) guidance,the current experience with the noncontact map-ping may suggest that the number of RF lesions

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required for a successful endpoint could conceiv-ably be less (mean of 41 RF lesions using ICE vs 25RF lesions using noncontact mapping).9

ConclusionsThe initial enthusiasm for ablating the SN may

have been tempered by the relatively high rates ofcomplications and long-term recurrence. In our se-ries of patients who underwent modification of theSN guided by “real-time” activation mapping, this

more tailored approach seemed to decrease the rateof recurrence and the associated comorbidities andmay possibly offer an alternative to patients withhighly symptomatic, medically refractory IST thatis both safe and can effectively target the site of ear-liest activation to control HRs. However, becausethis is a relatively small series, the long-term safetyand effectiveness requires further investigation ina larger population followed for a longer period oftime.

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