Sinus Node Modification in the Treatment of Inappropriate Sinus Tachycardia: A Clinical Update

   Inappropriate sinus tachycardia (IST) is a clinical syndrome defined by an increase in sinus rate out of pro- portion to physiologic needs. It is an under-appreciated etiology of persistent tachycardia often misdiagnosed as anxiety or atrial tachycardia. Prior reports of radiofrequency catheter ablation have demonstrated only moderate long- term success rates with risks of significant damage to the sinus node requiring treatment with a permanent pacemaker. Recent advances that allow real-time 3D mapping of atrial activation have allowed more precise localization of sinus pacemaker cells causing early activation possibly allowing for increased efficacy and safety profile for catheter ablation in the management of IST. We report a case of long-standing IST treated with sinus node modification utilizing St. Jude Medical’s EnSite non-contact mapping and Array catheter, allowing for ablation of three distinct sites of early atrial activation.

Case Description

   A 58-year-old female nurse presents with a greater than 40-year history of intermittent palpitations. Her heart rate (HR) would increase to 150-180 bpm, occasionally with presyncopal symptoms. The symptoms were often nocturnal or coincident with periods of emotional stress. Thyroid tests revealed no abnormalities. At age 20, she underwent an exercise tolerance test with a resting heart rate of 120 that increased to 187 with an upright p wave in the inferior leads throughout. Subsequently she underwent initial electrophysiology study at age 23 where only sinus tachycardia was reported. Trials of medical therapy, including treatment with escalating doses of beta blockers and calcium channel blockers, were ineffective. At the time of our initial evaluation, her atenolol dose had been increased to 300 mg daily with persistent breakthrough symptoms. Trial discontinuation of beta blocker therapy did not alter symptoms. In 2009, the patient underwent two EP studies with ablation of presumed ectopic atrial tachycardia located in the high right atrium with locations near the sinus node, producing improvement but not resolution of her symptoms. Physical exam at all visits was notable for intermittent tachycardia and hypertension. The remainder of her cardiovascular exam was unremarkable. Echocardiogram revealed preserved left ventricular function without evidence of underlying valvular disease. A Holter monitor placed one month after her second ablation revealed sinus rhythm with average rate of 86 bpm (minimum 67 bpm, maximum 117 bpm) and frequent unifocal atrial ectopy. Her symptoms again worsened, prompting evaluation with repeat EPS, but this time utilizing the EnSite Array catheter (St. Jude Medical, St. Paul, MN).    After written informed consent, sedation with intravenous fentanyl and midazolam was achieved. Instrumentation consisted initially of multielectrode catheters placed in the right atrium and His-bundle position via the right femoral vein. Right atrial activation was recorded on the EnSite 3D map using an EnSite 8F Array catheter, demonstrating initial early activation site in the high right atrium (Figure 1). Radiofrequency ablation at this site abruptly decreased HR from 154 bpm to 127 bpm. A second early activation site in a more caudal location was identified (Figure 2); radiofrequency ablation at this site reduced HR to 80 bpm. With brief IV isoproterenol given at 1 ug/min, persistent tachycardia restarted with a rate of 120 bpm. Mapping and ablation of a third early activation site (Figure 3) restored HR to 74 bpm with site of earliest activation as recorded by the distal electrode on the ablation catheter transitioning from the earliest site of activation to one coincident with the onset of the p wave (Figure 4). IV isoproterenol was again given at 1 ug/min with gradual increase in HR to 100 bpm returning gradually to 71 bpm after discontinuation of the medication. Electrocardiogram after sinus node modification demonstrated flattening of p waves in the inferior leads (Figure 5). There were no complications, and symptoms remained palliated after 90 days.

Discussion

   Inappropriate sinus tachycardia is a clinical syndrome defined by a fast sinus rate out of proportion to physiologic needs. It is not associated with underlying structural heart disease or any secondary causes of sinus tachycardia. Symptoms include palpitations, dyspnea, chest discomfort, and presyncope. The condition is found primarily in young women, with a disproportionate number who work in health care, as is the case with our patient.^1-3 The underlying etiology is unknown but thought to be related to primary sinus node pathology that includes a high intrinsic heart rate, depressed efferent cardiovagal reflex, and β-adrenergic hypersensitivity.¹² A single study suggests a link between circulating anti-β receptor antibodies and IST.³ It is differentiated from other forms of supraventricular tachycardia on the basis of ECG findings and EPS demonstrating sites of early activation located within the sinus node.¹ A population-based study conducted by Still et al suggests that higher ambulatory blood pressures and an increased hostility score on personality testing may be linked with IST. During a mean follow up of 5 years, none of the subjects developed any clinical or echocardiographic evidence of cardiomyopathy in spite of persistent palpitations.⁴    The mainstay of therapy has traditionally included use of beta blockers or non-dihydropyridine calcium channel blockers, although there has been increased use of sinus node modification for management of persistently symptomatic IST, as was done in our patient.⁸ The initial description of radiofrequency ablation of IST in a single patient was published by Waspe et al in 1994.¹⁰ In a larger case series by Lee et al, patients underwent either complete sinus node ablation or sinus node modification with an anatomically guided ablation approach consisting of radiofrequency ablation of the superior most aspect of the crista terminalis, with subsequent lesions applied to progressively inferior locations, until the desired heart rate was achieved. This anatomical approach was based upon physiological studies demonstrating the maximal heart rate response to sympathetic stimulation results from activation of this region.⁵ A subsequent study by Man et al utilized activation mapping during periods of sinus tachycardia. In this study of 29 patients, isoproterenol was utilized to maintain a cycle length 6 The success rates for these ablations have ranged from 23-70%.^1,2,5-7    Leonelli et al published an initial case series of two patients with 3D non-contact mapping utilizing Biosense Webster’s CARTO processor unit in an attempt to facilitate rapid and precise anatomic identification to the area of earliest activation.¹¹ A subsequent case series was published by Marrouche et al utilizing the same technology in a total of 39 patients (of which two had already undergone atrioventricular junctional ablation and implantation of VVIR pacemaker without improvement in symptoms). Infusion of isoproteronol or aminophylline demonstrated migration of the site of earliest activation cranially in all patients. Ablation was performed at the site of earliest activation and extended in 5 mm in each direction. Any drop in heart rate prompted acquisition of a new right atrial 3D map. When a shift in site of earliest activation was observed, ablation at that site proceeded in a cranial to caudal manner until heart rate with isoproteronol infusion was 1 There was a subsequent case report of 2 patients followed by a case series of 7 patients utilizing the EnSite contact map and EnSite Array catheter as was done in our patient.^7,9 In this series of 7 patients by Lin et al, isoproteronol was infused in 5 increments with labeling of the site of earliest activation with stable HR on each dose. Radiofrequency ablation utilizing a 4-mm tip Chilli cooled ablation catheter (Boston Scientific, Natick, MA) was performed at site of earliest activation on isoproterenol map once confirmed to be earlier than the surface p wave. Mapping was repeated after a change in HR with the same protocol utilized to attempt the sinus rhythm more caudally as demonstrated by a change in p wave morphology. The endpoint was achieved with decreasing HR 25% from baseline off of isoproterenol and a change in p wave morphology. In this series, all patients had a decrease in resting heart rate that was durable at 6 months. A single patient required an AV pacemaker; however, this patient had undergone prior sinus node modification and had a more aggressive approach to the second ablation given severe refractory symptoms. Our patient provides an additional outcome for this approach.

Conclusion

   This report illustrates the under-recognized diagnosis of IST in a patient who carried a diagnosis of ectopic atrial tachycardia versus sinus tachycardia for many years and who had been refractory to all medical therapy. In the past, ablation of this dysrhythmia would have incurred a higher risk of complete destruction of the sinus node; varying reports of long-term success rates have been reported.    Use of the EnSite technology allowed real-time 3D mapping and precise localization of the areas of earliest activation, and safe radiofrequency ablation of three distinct areas without damage to the overall pacemaker function of the sinus node. In this case, the three distinct areas of early activation provided clarity in the diagnosis that was previously felt to be atrial tachycardia. Though current published case series lack long-term outcomes, it appears that use of the EnSite contact map and EnSite Array catheter to guide radiofrequency ablation of sites of earliest activation may simplify sinus node modification and possibly lead to more durable long-term outcomes in the treatment of IST.

References

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