Visualisation and Radiofrequency Ablation of Sympathetic Innervation Loci in the Left Atrium in Patients with Paroxysmal Atrial Fibrillation

Introduction: A novel cardiac gamma camera utilizes the radiopharmaceutical Iodine-123-Meta-iodobenzylguanidine (₁₂₃I-MIBG) to visualize cardiac sympathetic innervation. Physiological accumulation of ₁₂₃I-mIBG provides an anatomical quantitative determination of the structures of the autonomic nervous system (ANS) with discrete uptake areas (DUA) of sympathetic activity located in the left atrium (LA) corresponding to the main ganglionic plexi (GP) clusters that could not previously be visualized. Aim: to visualize the DUA of the heart in patients with paroxysmal atrial fibrillation (AF) and to assess the effect of radiofrequency ablation (RFA) on DUA in LA. Materials and Methods. Computed tomography (CT) of the heart and radionuclide imaging with ₁₂₃I-mIBG were performed in 15 patients with paroxysmal AF. The results of the study were combined with preliminary taken CT images to create a detailed anatomical map of the sympathetic activity of the heart. The processed images were combined with the 3D reconstruction of the LA, obtained with the navigation system (CARTO 3, CARTO RMT). In DUA, high-frequency stimulation (HFS) followed by RF ablation was performed using the current recommended parameters. Results. Forty-eight DUA (median 3 [3; 3]) were identified. Average activity of DUA was 1315 [1171; 1462] cnt / sec / ml. Positive response to HFS in the DUA was obtained in 8 (53.3 %) patients. Prior to ablation, no response was received to HFS in areas of LA outside the DUA. After ablation, there was no response to HFS in the DUA sites. At repeated scans 3 DUA (median 0 [0; 0]; p<0.001 compared with preoperative data) were observed. Activity of DUA significantly decreased to 819 [684; 955] cnt / sec / ml (p<0.001 as compared with preoperative data). Thirteen of 13 of 15 patients (87 %) had no AF / AT / AFL recurrences for 6 month follow up. Conclusion. In patients with AF, the areas of sympathetic activity in LA can be visualized by physiological localized uptake of ₁₂₃I-mIBG. Radiofrequency catheter ablation can target the identified sympathetic innervation structures in AF patients precisely and effectively.

1. Calkins H, Hindricks G, Cappato R, Kim Y-H, Saad EB, Aguinaga L et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10):e275–444. DOI: 10.1016/j.hrthm.2017.05.012

2. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016;37(38):2893–962. DOI: 10.1093/eurheartj/ehw210

3. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271(11):840–4. PMID:8114238

4. Israel CW, Grönefeld G, Ehrlich JR, Li Y-G, Hohnloser SH. Longterm risk of recurrent atrial fibrillation as documented by an implantable monitoring device. Journal of the American College of Cardiology. 2004;43(1):47–52. DOI: 10.1016/j.jacc.2003.08.027

5. Losik D.V., Romanov A.B., Shabanov V.V., Bairamova S.A., Yakubov A.A., Stenin I.G. et al. Progression of atrial fibrillation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation: a randomized comparison of antiarrhythmic drug therapy vs re-ablation. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2015;19(2):84–92.

6. Schauerte P, Scherlag BJ, Patterson E, Scherlag MA, Matsudaria K, Nakagawa H et al. Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous System. Journal of Cardiovascular Electrophysiology. 2001;12(5):592–9. DOI:10.1046/j.1540-8167.2001.00592.x

7. Scherlag BJ, Nakagawa H, Jackman WM, Yamanashi WS, Patterson E, Po S et al. Electrical Stimulation to Identify Neural Elements on the Heart: Their Role in Atrial Fibrillation. Journal of Interventional Cardiac Electrophysiology. 2005;13(S1):37–42. DOI:10.1007/s10840-005-2492-2

8. Hou Y, Scherlag BJ, Lin J, Zhang Y, Lu Z, Truong K et al. Ganglionated Plexi Modulate Extrinsic Cardiac Autonomic Nerve Input. Journal of the American College of Cardiology. 2007;50(1):61–8. DOI: 10.1016/j.jacc.2007.02.066

9. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G et al. Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia: A New Anatomic Approach for Curing Atrial Fibrillation. Circulation. 2000;102(21):2619–28. DOI: 10.1161/01.CIR.102.21.2619

10. Strel’nikov A.G., Yakubov A.A., Sergeevichev D.S., Artemenko S.N., Mikheenko I.L., Abashkin S.A. et al. Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2015;19(4):99–107.

11. Pokushalov E, Romanov A, Shugayev P, Artyomenko S, Shirokova N, Turov A et al. Selective ganglionated plexi ablation for paroxysmal atrial fibrillation. Heart Rhythm. 2009;6(9):1257–64. DOI: 10.1016/j.hrthm.2009.05.018

12. Katritsis DG, Pokushalov E, Romanov A, Giazitzoglou E, Siontis GCM, Po SS et al. Autonomic Denervation Added to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation. Journal of the American College of Cardiology. 2013;62(24):2318–25. DOI: 10.1016/j.jacc.2013.06.053

13. Erlandsson K, Kacperski K, van Gramberg D, Hutton BF. Performance evaluation of D-SPECT: a novel SPECT system for nuclear cardiology. Physics in Medicine and Biology. 2009;54(9):2635–49. DOI: 10.1088/0031-9155/54/9/003

14. Wieland DM, Brown LE, Rogers WL, Worthington KC, Wu JL, Clinthorne NH et al. Myocardial imaging with a radioiodinated norepinephrine storage analog. J Nucl Med. 1981;22(1):22–31. PMID:7452352

15. Gimelli A, Liga R, Giorgetti A, Genovesi D, Marzullo P. Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium-zinc-telluride camera: first clinical experience. European Heart Journal - Cardiovascular Imaging. 2014;15(5):575–85. DOI:10.1093/ehjci/jet258

16. Scherlag BJ, Yamanashi W, Patel U, Lazzara R, Jackman WM. Autonomically Induced Conversion of Pulmonary Vein Focal Firing Into Atrial Fibrillation. Journal of the American College of Cardiology. 2005;45(11):1878–86. DOI: 10.1016/j.jacc.2005.01.057

17. Nakagawa H, Scherlag BJ, Po SS. Abstract session 6: catheter ablation II: novel approaches to atrial fibrillation ablation. Heart Rhythm. 2004;1(1):S10–2. DOI:10.1016/j.hrthm.2004.03.006

18. Scanavacca M, Pisani CF, Hachul D, Lara S, Hardy C, Darrieux F et al. Selective Atrial Vagal Denervation Guided by Evoked Vagal Reflex to Treat Patients With Paroxysmal Atrial Fibrillation. Circulation. 2006;114(9):876–85. DOI: 10.1161/CIRCULATIONAHA.106.633560

19. Romanov A, Minin S, Breault C, Pokushalov E. Visualization and ablation of the autonomic nervous system corresponding to ganglionated plexi guided by D-SPECT 123I-mIBG imaging in patient with paroxysmal atrial fibrillation. Clinical Research in Cardiology. 2017;106(1):76–8. DOI:10.1007/s00392-016-1045-2