Physiologic Effects of Right-Sided Intravascular Cervical Sympathetic Nerve Stimulation

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 16, No. 7Physiologic Effects of Right-Sided Intravascular Cervical Sympathetic Nerve Stimulation Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBPhysiologic Effects of Right-Sided Intravascular Cervical Sympathetic Nerve Stimulation Timothy M. Markman, Francis E. Marchlinski, Andrew E. Epstein and Saman Nazarian Timothy M. MarkmanTimothy M. Markman Correspondence to: Timothy M Markman, MD, Hospital of the University of Pennsylvania, 1 Convention Ave, Philadelphia, PA 19104. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3155-2006 Cardiovascular Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Search for more papers by this author , Francis E. MarchlinskiFrancis E. Marchlinski https://orcid.org/0000-0001-7962-9423 Cardiovascular Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Search for more papers by this author , Andrew E. EpsteinAndrew E. Epstein https://orcid.org/0000-0003-0433-8802 Cardiovascular Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Search for more papers by this author and Saman NazarianSaman Nazarian https://orcid.org/0000-0002-8369-0259 Cardiovascular Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Search for more papers by this author Originally published26 Jun 2023https://doi.org/10.1161/CIRCEP.123.012063Circulation: Arrhythmia and Electrophysiology. 2023;16:418–419Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 26, 2023: Ahead of Print The maladaptive remodeling of sympathetic nervous system has been implicated in the pathogenesis of cardiovascular disease including ventricular arrhythmias.1 A number of strategies for neuromodulation can inhibit cardiac sympathetic tone including surgical denervation, percutaneous stellate ganglion block with local anesthetic, and transcutaneous magnetic stimulation.2,3 There are limitations to each of these techniques, and none is easily modified to enhance sympathetic tone or performed synchronous to invasive electrophysiological procedures.We have recently reported on the feasibility of a novel technique of intravascular stimulation via the left vertebral venous system for neuromodulation of the cervical sympathetic ganglia,4 which are located posteromedial to the carotid artery and anterior to the longus coli muscles at the level of the sixth and seventh cervical vertebrae.5 There is a consistent anatomic relationship between the ganglia and the vertebrae as well as the major vessels of the head and neck. Specifically, the vertebral venous system drains blood from the cervical spine, travel bilaterally as plexuses from the skull base in the transverse foramina of the cervical vertebrae before exiting at approximately level of seventh cervical vertebrae and coursing laterally and anteriorly, generally in larger vessels (Figure), which ultimately drain into the brachiocephalic veins. Therefore, these vessels consistently cross over the longus coli muscle and the cervical sympathetic chain at the location of the cervical sympathetic ganglia. This anatomic relationship presents a unique opportunity for an intravascular approach to sympathetic stimulation. In our prior work, we have demonstrated that stimulation of the left cervical ganglia with this approach resulted in reproducible hemodynamic effects with relatively selective increase in blood pressure that was transient and occurred with duration and magnitude of effect proportional to duration and amplitude of stimulation.4Download figureDownload PowerPointFigure. Intravascular stimulation of the cervical sympathetic ganglia via the right vertebral vein (VV). A, Antero-posterior and lateral fluoroscopy images showing the electrophysiology catheter in the right VV. B, Sagittal and coronal computed tomography images showing the right VV and artery (red arrows) entering the transverse foramina at the level of the seventh cervical vertebrae. C, Graph of acute % change in heart rate over time following right VV stimulation in 5 patients.All patients provided informed consent for this study, which was as approved by the Institutional Review Board of the University of Pennsylvania. In 5 patients undergoing catheter ablation for atrial fibrillation under general anesthesia, the right vertebral vein was cannulated from a femoral venous approach. Blood pressure was continuously monitored with a radial arterial catheter, and all patients were monitored on continuous telemetry. After cannulation of the right vertebral vein, a 2Fr octapolar electrophysiological catheter (1.3–1.5 mm electrodes, 5 mm electrode spacing) was advanced toward the cervical vertebrae. With pacing at 20 Hz and 2 to 15 mA for up to 4 minutes, reproducible hemodynamic changes were observed (Figure). Each patient had a transient increase in heart rate (range, 11–32 bpm) and an increase in systolic blood pressure was noted in 3 patients (10, 17, and 32 mm Hg, respectively). Following stimulation, both blood pressure and heart rate returned to baseline levels and no durable effects were observed. One patient was noted to cough during stimulation at 7 mA. When the output was decreased to 5 mA, no additional coughing was noted. There were no complications although it is important to note that this technique was performed by experienced operators in an investigational setting. Routine use of vertebral venous cannulation and stimulation is not encouraged at this time.A transvenous approach to direct sympathetic nerve stimulation has the potential to produce both acute and chronic effects on nerve activity. The acute effects of right-sided cervical sympathetic ganglia are predominately on heart rate, consistent with principal atrial innervation. We propose that direct cervical sympathetic stimulation through the right vertebral venous system is feasible to perform and has important potential applications. This is especially true for use at the time of invasive electrophysiological procedures, where selective modulation of atrial autonomic innervation can be valuable, for example, to aid in induction of clinical arrhythmias without causing hypotension. This technique is the focus of ongoing investigations by our group to understand the mechanistic effect of vertebral vein stimulation and to optimize its approach for therapeutic use.ARTICLE INFORMATIONSources of FundingDr Markman is supported by National Institutes of Health, National Heart, Lung, and Blood Institute grant K23HL161349, the Mark Marchlinski EP Research & Education Fund, and the Pennsylvania Steel Company EP Research Fund.Disclosures Drs Markman and Nazarian and the University of Pennsylvania hold intellectual property rights on methodology for intravascular sympathetic nerve stimulation. Dr Nazarian is a consultant for CardioSolv and Circle CVI; and principal investigator for research funding from Biosense Webster, ImriCor, Siemens, ADAS software, and the US National Institutes of Health. Dr Marchlinski has served as consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 419.Correspondence to: Timothy M Markman, MD, Hospital of the University of Pennsylvania, 1 Convention Ave, Philadelphia, PA 19104. Email timothy.markman@pennmedicine.upenn.eduReferences1. Cao JM, Fishbein MC, Han JB, Lai WW, Lai AC, Wu TJ, Czer L, Wolf PL, Denton TA, Shintaku IP, et al. Relationship between regional cardiac hyperinnervation and ventricular arrhythmia.Circulation. 2000; 101:1960–1969. doi: 10.1161/01.cir.101.16.1960LinkGoogle Scholar2. Fudim M, Boortz-Marx R, Patel CB, Sun AY, Piccini JP. Autonomic modulation for the treatment of ventricular arrhythmias: therapeutic use of percutaneous stellate ganglion blocks.J Cardiovasc Electrophysiol. 2017; 28:446–449. doi: 10.1111/jce.13152CrossrefMedlineGoogle Scholar3. Markman TM, Pothineni NVK, Zghaib T, Smietana J, McBride D, Amankwah NA, Linn KA, Kumareswaran R, Hyman M, Arkles J, et al. Effect of transcutaneous magnetic stimulation in patients with ventricular tachycardia storm: a randomized clinical trial.JAMA Cardiol. 2022; 7:445–449. doi: 10.1001/jamacardio.2021.6000CrossrefMedlineGoogle Scholar4. Markman TM, Marchlinski FE, Epstein AE, Nazarian S. Feasibility of intravascular cervical sympathetic nerve stimulation.JACC Clin Electrophysiol. 2023;S2405-500X(23)00202-5. doi: 10.1016/j.jacep.2023.03.005. Online ahead of printCrossrefMedlineGoogle Scholar5. Carron H, Litwiller R. Stellate ganglion block.Anesth Analg. 1975; 54:567–570. doi: 10.1213/00000539-197509000-00002CrossrefMedlineGoogle Scholar eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails July 2023Vol 16, Issue 7 Advertisement Article Information Metrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.123.012063PMID: 37357770 Originally publishedJune 26, 2023 Keywordscardiovascular diseasecathetersdenervationhemodynamichypotensionPDF download Advertisement Subjects Electrophysiology