Cardiac sympathetic denervation for intractable ventricular arrhythmias in Chagas disease

Author’s Accepted Manuscript Cardiac Sympathetic Denervation for Intractable Ventricular Arrhythmias in Chagas Disease Luis Carlos Saenz, Federico Malavassi Corrales, William Bautista, Mahmoud Traina, Sheba Meymandi, Diego A. Rodriguez, Luis J. Tellez, Marmar Vaseghi, Fermin Garcia, Kalyanam Shivkumar, Jason S. Bradfield

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To appear in: Heart Rhythm Received date: 8 December 2015 Cite this article as: Luis Carlos Saenz, Federico Malavassi Corrales, William Bautista, Mahmoud Traina, Sheba Meymandi, Diego A. Rodriguez, Luis J. Tellez, Marmar Vaseghi, Fermin Garcia, Kalyanam Shivkumar and Jason S. Bradfield, Cardiac Sympathetic Denervation for Intractable Ventricular Arrhythmias in Chagas Disease, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2016.03.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

CARDIAC SYMPATHETIC DENERVATION FOR INTRACTABLE VENTRICULAR ARRHYTHMIAS IN CHAGAS DISEASE

1Luis

Carlos Saenz, MD; 1Federico Malavassi Corrales, MD; 1William Bautista, MD; Traina, MD; 2Sheba Meymandi, MD; 1Diego A. Rodriguez, MD; 1Luis J. Tellez, MD; 4Marmar Vaseghi, MD; 1,3Fermin Garcia, MD; 4Kalyanam Shivkumar, MD, PhD and 2, 4Jason S. Bradfield, MD 2Mahmoud

1International

Arrhythmia Center at Cardioinfantil Foundation, Bogota, Colombia View-UCLA Center of Excellence for Chagas Disease 3Division of Cardiology, Section of Electrophysiology, University of Pennsylvania Health System and School of Medicine, Philadelphia, Pennsylvania 4UCLA Cardiac Arrhythmia Center & UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, CA 2Olive

Running Title: cardiac sympathetic denervation in Chagas disease Word count: 4764 This study was supported by NIH DP2HL132356 to MV and NIH R01HL084261 Conflicts: No authors report conflict of interest for this manuscript Correspondence: Jason S. Bradfield, MD UCLA Cardiac Arrhythmia Center 100 Medical Plaza, Suite 660 Los Angeles, CA 90095 Phone: 310 267 8563 Fax: 310 794 6492

1

ABSTRACT Background: Autonomic modulation is a valuable therapeutic option for the management of ventricular arrhythmias. Bilateral cardiac sympathetic denervation (BCSD) has shown promising results in acute, intermediate and long-term management of polymorphic and monomorphic ventricular tachycardia (VT) in patients with structural heart disease. Cardiomyopathy (CM) due to Chagas disease (CD), and associated VT, is thought to be in part due to autonomic neuronal destruction and dysfunction. Objective: To assess whether BCSD is a safe and effective treatment modality in CD patients with VT storm/refractory VT. Methods: Retrospective analysis of data from patients with Chagasic CM who underwent BCSD between 2009 and 2015 at two international centers was performed Results: Of seventy-five patients who underwent BCSD for VT storm/refractory VT in the setting of CM, 7 patients had CD as the etiology of CM. All patients had monomorphic VT. Median follow-up was 7 (1-46) months. All patients either underwent previous unsuccessful catheter ablation or were not candidates for ablation. The median number of ICD shocks 1 month prior to BCSD was 4 (2-30) and decreased to 0 (0-2) in available follow-up after BCSD. When anti-tachycardia pacing (ATP) therapies were included in the analysis, the median number of ICD therapies (shocks + ATP) still decreased to 1 (0-3). Conclusion: In Chagasic CM patients presenting with refractory monomorphic VT, early evidence suggests BCSD reduces appropriate ICD therapy and may represent a valuable treatment option.

Keywords: Chagas disease, ventricular tachycardia, autonomic, sympathetic, ablation, ICD therapy

2

INTRODUCTION Antiarrhythmic therapy and radiofrequency catheter ablation (RFCA) remain the primary treatment options for recurrent ventricular tachycardia (VT) leading to implantable cardioverter-defibrillator (ICD) shocks in patients with structural heart disease. However, RFCA success rates for non-ischemic cardiomyopathy (NICM) are variable and lower than desired1, possibly due to the complex nature of this disorder with a combination of scar-based reentry and functional VT.

The autonomic nervous system plays an essential role in the initiation and perpetuation of ventricular arrhythmias. Mounting evidence suggests that neuromodulation is a promising treatment option for VT, potentially stabilizing the imbalance between sympatho-excitation and impaired parasympathetic activity that occurs due to various cardiac pathologies. Bilateral cardiac sympathetic denervation (BCSD) involving the removal of the lower ½ of the stellate ganglia and T2-T4 ganglia has been shown to reduce the burden of ventricular arrhythmias in patients with structural heart disease and channelopathies.2

NICM can have multiple etiologies including viral, alcohol/drug-induced, chemotherapy-related, familial and Chagas disease (CD). CD is a major cause of CM in Latin America. CD has also been found to be a significant cause of CM in certain regions of the United States (US) that have a large immigrant population from endemic areas. The mortality-rate for Chagasic CM patients in the US is significantly higher than for other etiologies of NICM.3 The increased mortality is thought to be

3

due to an increased risk of sudden cardiac death in CD, accounting for 55-65% of deaths in this population as seen in previous studies from South America.4 In addition to epicardial (EPI) and endocardial (ENDO) myocardial fibrosis and scar formation, CD is thought to have a significant component of autonomic destruction/dysfunction contributing to CM and risk of VT.

Although BCSD has been shown to be beneficial in a mixed population of NICM patients, whether patients with CD specifically benefit from this procedure is unknown. The purpose of this study was to assess the effect BCSD on the burden of ventricular arrhythmias in patients with Chagasic CM presenting with intractable VT.

METHODS Patient Population: All CD patients who underwent BCSD for VT storm or refractory VT and recurrent ICD shocks at two centers (UCLA Medical Center, Los Angeles, CA and Cardioinfantil Foundation-Cardiac Institute, Bogota, Colombia) between 2009 and 2015 were retrospectively reviewed. Baseline characteristics, pre- and postBCSD arrhythmia burden, procedural data and complications were reviewed in all patients. Records from outpatient visits, hospital records, and ICD interrogations were used to assess pre- and post-BCSD outcomes. No patients were lost to followup. Retrospective review of data was approved by the Institutional review boards of the University of California, Los Angeles, Olive View-UCLA Medical Center and Cardioinfantil Foundation-Cardiac Institute, Bogota, Colombia.

4

Patients cared for at Olive View-UCLA Center of Excellence for Chagas Disease and UCLA Medical Center had a diagnosis of CD based on serologic testing done through the Centers for Disease Control. All samples underwent Immunofluorescence Assay and Enzyme-Linked Immunosorbent Assay (Chagatest ELISA recombinate v. 3.0, Wiener Laboratorios, Argentina) tests. Subjects were considered to be seropositive for CD only if both assays resulted positive. The same testing criteria were utilized at Cardioinfantil Foundation-Cardiac Institute, Bogota, Colombia.

Patients were excluded from this analysis if they had any history of myocardial infarction, revascularization, or obstructive coronary artery disease on invasive coronary angiography or cardiac computed tomography angiography or had other risk factors concerning for an alternative etiology for the patient’s CM.

Cardiac Sympathetic Denervation: BCSD was performed as previously described2 via video-assisted thoracic surgery. BCSD involved removal of the lower ½-1/3 of the stellate ganglia and T2-T4 thoracic sympathetic ganglia as well as the nerve of Kuntz when present. Quantification of Arrhythmia Burden: VT storm was defined as three or more episodes of sustained VT within a 24-hour period, each of which required termination by an intervention. Refractory VT was defined as recurrent ICD shocks that did not respond to antiarrhythmic, medical, or RFCA therapy.

5

The number of ICD shocks and ICD therapies (ICD shocks + ATP episodes) in the month prior to BCSD was analyzed and compared to follow up in separate analyses. Review of all device interrogations was performed to assure that no changes were made to ICD therapy settings during the course of follow-up (ICD settings are listed in Table 1). VT below the ICD detection/therapy rate that required intervention was consider equivalent to an ICD shock as to not underestimate the arrhythmia burden. Statistical analysis: Continuous variables were expressed as median (range).

RESULTS Baseline Characteristics: A total of 75 BCSD operations were performed at two institutions for refractory VT or VT storm between April of 2009 and March of 2015. Of 75 patients, 7 (9%) patients carried a diagnosis of Chagasic CM. Median age of these 7 patients was 51 (46-60) years and 57% were male with a median ejection fraction (EF) of 35 (1045)%. Country of origin was: 43% (3) Mexico, 43% (3) Colombia and14% (1) El Salvador. Clinical presentation was VT storm in 6 (86%) and refractory VT in 1 (14%). VT in all patients was monomorphic. All patients had recurrent arrhythmias and ICD therapies despite anti-arrhythmic medications. The patients underwent a median of 1 (0-3) VT ablation procedures prior to BCSD, though 1 patient (patient 6) was referred directly for BCSD without ablation and one (patient 3) had an incomplete ablation due to a complication. (Table 1) All patients underwent a 6

bilateral procedure. Four patients had procedures done at UCLA (patients 1-4) and 3 patients at Cardioinfantil Foundation-Cardiac Institute, Bogota, Colombia (patients 5-7).

BCSD Outcomes: Median follow-up was 7 (1-46) months. No significant changes were made in ICD therapy settings that would alter likelihood of ICD therapy delivery in any patients. The median number of ICD shocks 1 month prior to BCSD was 4 (2-30) and decreased to 0 (0-2) during follow-up after BCSD. ICD shock data before and up to 1 year after BCSD is shown in Figure 1. The only patient to receive an ICD shock after 1-month post-op was patient 6 who had not undergone previous RFCA due to recent development of left ventricular thrombus. Epicardial-only RFCA was subsequently required. When anti-tachycardia pacing (ATP) therapies that terminated VT without the need for ICD shock were included in the analysis, the median number of ICD therapies (shocks + ATP) still decreased from 4(2-30) to 1 (0-3) during available follow-up (up to 4 years). The ICD therapy (shock + ATP) data up to 1 year follow-up is shown in figure 2. Complications were noted in 1 (14%) patient. The patient developed thoracic hyperalgesia that lasted 4 months prior to resolution. No other complications were noted.

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Detailed patient histories: Patient 1: 51-year-old man originally from Mexico, EF of 35% status-post ICD for secondary prevention who presented with 2 ICD shocks for monomorphic VT. He had failed amiodarone and metoprolol and underwent combined EPI/ENDO VT RFCA with 4 VTs induced/observed during the procedure. Two months post-ablation, the patient presented with symptomatic incessant slow VT that was below the ICD detection setting and therefore did not lead to ICD therapies. He was referred for BCSD. In the first week post-BCSD the patient had recurrent VT that was managed with Mexilletine and Ranolazine. Shortly after discharge these medications were discontinued and the patient has been arrhythmia free, treated with only a betablocker for 24 months.

Patient 2: 51 year-old female originally from El Salvador, EF of 35%, status-post ICD for primary prevention that presented with VT storm (monomorphic VT) requiring 3 ICD shocks. She had failed amiodarone and metoprolol and was referred for EPI/ENDO RFCA. She underwent Impella (Abiomed, Danvers, MA) assisted RFCA due to hemodynamic intolerance of VT and 4 different VT morphologies were observed. The patient had recurrent VT and an ICD shock 6 days post-ablation and underwent BCSD. Antiarrhythmic therapy remained unchanged. The patient had no further ICD shocks within the 2 years of follow-up, but did have successful ATP therapy 2 weeks and 4 months post-op. Subsequently, she was free of ICD therapies

8

for 1.5 years, followed by a single ATP 21 months post BCSD. EF improved slightly from 35% to 45% at follow-up. The patient noted symptoms of severe thoracic hyperalgesia post-BCSD that lasted 4 months, but resolved spontaneously.

Patient 3: 46 year-old male originally from Mexico with an EF of 10% presented with recurrent monomorphic VT storm after failing amiodarone and mexiletine and had receiving 9 ICD shocks. Despite severe CM, the patient was found not to be a heart transplant candidate. EPI/ENDO RFCA was undertaken and complicated by right ventricular outflow perforation, and therefore, a complete RFCA was not performed. Nine days after attempted RFCA the patient received an ICD shock and was referred for BCSD.

Due to the severity of his CM and given that he was not a transplant or hemodynamic support candidate, his hospital course was complicated by ischemic bowel and an ischemic limb with associated sepsis. The patient had a prolonged hospital course with multiple vascular and GI surgeries. During this period the patient had two episodes of VT 6 days and 28 days post-BCSD requiring ICD shock on an unchanged antiarrhythmic regimen. Ultimately the patient and family decided to withdraw care and the patient died 43 days after BCSD.

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Patient 4: 48 year-old male originally from Mexico with an EF of 30%, who had undergone a Dor procedure for apical aneurysm resection and ICD implantation for secondary prevention, presented with three ICD shocks. He had failed two previous VT RFCA procedures at an outside facility and was on amiodarone and carvedilol. He underwent ENDO ablation with six different VT morphologies induced. Due to previous cardiac surgery, only ENDO mapping and ablation could be undertaken. The primary clinical VT was found to be intra-septal and not amendable to ablation, and therefore the patient was referred for BCSD. The patient had no ICD therapy in the first year post-BCSD. Over the subsequent 3 years of follow-up, the patient has had 3 ATPs and no ICD shocks on the same antiarrhythmic regimen.

Patient 5: 60 year-old female from Colombia (EF 15%) status-post ICD for secondary prevention who presented with VT storm and 5 ICD shocks after failing amiodarone and metoprolol. She underwent EPI/ENDO RFCA with 3 VT morphologies noted. Despite extensive ablation on both ENDO and EPI surfaces, the patient experienced recurrent ICD therapy 1 day post-procedure and was referred for BCSD. The patient has been ICD therapy-free for 7 months on continued amiodarone therapy and increased metoprolol (50mg bid from 25 mg bid).

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Patient 6: 55 year-old female with an EF of 25% status-post primary prevention ICD presented with VT storm with 3 ICD shocks after failing amiodarone and metoprolol. Echocardiogram detected an apical LV thrombus, and therefore, the patient was referred for BCSD due to the concern of thromboembolism during RFCA. The patient was without ICD therapies for >3 months after BCSD, despite never undergoing an RFCA procedure on stable amiodarone dosing and increased metoprolol dose (50 mg bid from 25 mg bid). At 4 months post-CSD the patient had recurrence of VT (CL 350 ms), which had a slower CL than her original presenting arrhythmia. The patient was taken for epicardial-only ablation and has been free of VT since ablation (1 month).

Patient 7: 52 year-old man with an EF of 35% status-post ICD for primary prevention presented with VT storm after undergoing a previous EPI/ENDO RFCA 6 months prior. The patient received 30 shocks for monomorphic VT while on amiodarone and metoprolol and was referred directly for BCSD given recurrence after a previous ablation procedure. The patient has been arrhythmia free for 4 months following BCSD on a stable drug regimen.

DISCUSSION Major findings: BCSD appears to show promising initial results for patients with CM secondary to CD presenting with intractable monomorphic VT.

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CD is a highly arrhythmogenic disease, with evidence of a higher arrhythmogenic burden than in patients with ischemic CM.5 Ventricular arrhythmia episodes are typically monomorphic in this patient population6, which has led to the utilization of RFCA as a valuable therapy. However, due to the complex nature of VT in CD, including endocardial, mid-myocardial and/or epicardial circuits, RFCA often requires a combined EPI/ENDO approach. Given this complexity, therapies/interventions complimentary to currently available pharmacologic and RFCA modalities would be beneficial. BCSD, which reduced ICD therapies in this series of patients with monomorphic VT, may be one such approach.

The potential benefit of BCSD for CD patients may be related to autonomic dysregulation, involving both sympathetic and vagal denervation, which has long been described in CD patients and in animal models.7-21 Cardiac ganglionic damage may occur because of a complex interplay of direct parasitism, autoimmune destruction and local inflammation22, 23 that begins during the acute phase with subsequent consolidation during the chronic stage of the disease. Extra-cardiac effects have been shown to involve the cervical ganglia as well.24 Thus, if the increased arrhythmogenicity seen in Chagasic CM is due to this autonomic dysregulation, then these patients may derive significant benefit from treatment modalities targeting the autonomic nervous system such as BCSD, as suggested by the results of our study. However, a direct link between these changes and clinical events has not been proven.

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Autonomic modulation therapies, have become a promising treatment modality for refractory ventricular arrhythmias. BCSD, spinal cord stimulation, thoracic epidural anesthesia and renal denervation are techniques utilized in hopes of stabilizing autonomic dysregulation. Estes and Izlar reported the first case of BCSD in humans for treatment of ventricular arrhythmias25, though the technique garnered limited interest26-30 for patients with structural heart disease over the ensuing decades.

Cardiac sympathetic denervation, predominantly limited to a left-sided procedure, was utilized for the treatment of life-threatening arrhythmias in patients with Long QT syndrome and catecholaminergic polymorphic VT 31-33 34. Subsequent data demonstrated that left cardiac sympathetic denervation had a potential benefit in patients with scar-related VT in the setting of structural heart disease, even in highrisk patients who had already failed RFCA of VT.35 Further study, and scientific understanding of the cardiac innervation of the left and right stellate and neural remodeling, suggested the importance of a bilateral approach. Recent clinical data demonstrated that BCSD might improve the likelihood of VT-free survival, with promising acute, intermediate and long-term results.2, 36, 37 Survival free of ICD shocks in this study was 48% at mean follow-up of 367 days. However, 90% of patients demonstrated a decrease in ICD therapies.2

While the rationale for the utilization of this technique to treat patients with CD and VT has a clear scientific basis in the literature, little direct clinical data exists. A case

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report by Guiterrez and colleagues38 in 2007 reported the successful use of BCSD acutely for a CD patient with recurrent polymorphic VT and syncope. In this case, although BCSD acutely controlled the arrhythmia, the patient died suddenly one month later. An ICD had not been implanted prior to discharge, and therefore, correlation with rhythm abnormalities was not available and recurrent VT as the cause of death is possible.

Renal denervation (RDN), another neuromodulatory technique to address sympatho-excitation in the setting of CM, has shown potential beneficial outcomes in patients with CM and refractory VT.

39, 40

In a recent study41, six of 10 patients

had Chagasic CM and the median number of ICD shocks decreased from 28.5 to 1 at one month and 0 at six months follow-up, providing further evidence that autonomic modulation may have promise in this population.

If future data continues to support the value of BCSD in CD patients with monomorphic VT, a new avenue of treatment may become available for patients presenting to centers in Latin America and elsewhere that do not have the capabilities of performing percutaneous epicardial RFCA, but do have a trained thoracic surgeon. Given the limited number of centers that perform epicardial RFCA world-wide, BCSD has the potential to be a first-line therapy for CD patients in these regions. However, BCSD for monomorphic VT has been predominantly performed in the setting of failed ablation. Therefore, the utility of BCSD as a first-line treatment requires further study.

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Limitations This is a small case series and three patients had limited clinical follow-up. Changes in antiarrhythmic regimens in the peri-procedure period were at the discretion of the treating physician, given the retrospective nature of this study. Therefore, a contribution of these changes (predominantly small increases in beta blocker dose) to the decrease in arrhythmia burden cannot be excluded. Further, while no significant changes were made in ICD programming, the programming was not standardized and we cannot rule out slow VT episodes falling below the ICD detection zones, leading to under reporting of VT. The relative utility of BCSD for CD patients compared to other patients with CM cannot be assessed given the lack of direct comparison.

CONCLUSION Preliminary findings suggest BCSD may be a promising therapy for recurrent monomorphic VT in patients with CD. Further study is warranted to define the role and timing of BCSD in this population.

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30. Nademanee K, Taylor R, Bailey WE, Rieders DE and Kosar EM. Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy. Circulation. 2000;102:742-7. 31. Collura CA, Johnson JN, Moir C and Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm. 2009;6:752-9. 32. Schwartz PJ, Locati EH, Moss AJ, Crampton RS, Trazzi R and Ruberti U. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report. Circulation. 1991;84:503-11. 33. Bos JM, Bos KM, Johnson JN, Moir C and Ackerman MJ. Left cardiac sympathetic denervation in long QT syndrome: analysis of therapeutic nonresponders. Circ Arrhythm Electrophysiol. 2013;6:705-11. 34. De Ferrari GM, Dusi V, Spazzolini C, Bos JM, Abrams DJ, Berul CI, Crotti L, Davis AM, Eldar M, Kharlap M, Khoury A, Krahn AD, Leenhardt A, Moir CR, Odero A, Olde Nordkamp L, Paul T, Roses INF, Shkolnikova M, Till J, Wilde AA, Ackerman MJ and Schwartz PJ. Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation. Circulation. 2015;131:2185-93. 35. Bourke T, Vaseghi M, Michowitz Y, Sankhla V, Shah M, Swapna N, Boyle NG, Mahajan A, Narasimhan C, Lokhandwala Y and Shivkumar K. Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation. Circulation. 2010;121:2255-62. 36. Ajijola OA, Lellouche N, Bourke T, Tung R, Ahn S, Mahajan A and Shivkumar K. Bilateral cardiac sympathetic denervation for the management of electrical storm. J Am Coll Cardiol. 2012;59:91-2. 37. Ajijola OA, Vaseghi M, Mahajan A and Shivkumar K. Bilateral cardiac sympathetic denervation: why, who and when? Expert Rev Cardiovasc Ther. 2012;10:947-9. 38. Gutierrez O, Garita E and Salazar C. Thoracoscopic sympathectomy for incessant polymorphic ventricular tachycardia in chronic chagasic myocarditis--a case report. Int J Cardiol. 2007;119:255-7. 39. Remo BF, Preminger M, Bradfield J, Mittal S, Boyle N, Gupta A, Shivkumar K, Steinberg JS and Dickfeld T. Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy. Heart Rhythm. 2014;11:541-6. 40. Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, Sobotka PA, Gawaz M and Bohm M. Renal sympathetic denervation for treatment of electrical storm: first-in-man experience. Clin Res Cardiol. 2012;101:63-7. 41. Armaganijan LV, Staico R, Moreira DA, Lopes RD, Medeiros PT, Habib R, Melo Neto J, Katz M, Armaganijan D, Sousa AG, Mahfoud F and Abizaid A. 6-Month Outcomes in Patients With Implantable Cardioverter-Defibrillators Undergoing Renal Sympathetic Denervation for the Treatment of Refractory Ventricular Arrhythmias. JACC Cardiovasc Interv. 2015;8:984-90.

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Table 1: Baseline characteristics P t

Ag e

Se x

Origin

E F ( % ) 45

Presentat ion

1

51

M

Mexico

2

51

F

3

46

4

Previo us Ablati on

ES

1

PreBCS D Shoc ks 2

El Salvad or

35

ES

1

M

Mexico

10

ES

48

M

Mexico

35

5

60

F

Colom bia

6

55

F

7

52

M

Pre-BCSD AAD

PostBCSD ADD

ICD Settings

Amio 200 qd Coreg 25 bid

Coreg 25 bid

4

Amio 200 bid MTP 25 bid

unchan ged

VT 139171 bpm VT2 171214 bpm VF>214 bpm VT 184222 bpm VF>222 bpm

1

9

unchan ged

rVT

3

3

Amio 200 bid Mexiletine 150 tid Amio 200 bid Coreg 3.125 bid

15

ES

1

6

Amio 200 qd MTP 25 bid

Amio 200 qd MTP 50 bid

Colom bia

25

ES

0

3

Amio 200 qd MTP 25 bid

Amio 200 qd MTP 50 bid

Colom bia

35

ES

1

30

Amio 200 qd MTP 50 bid

Amio 200 qd MTP 25 tid

unchan ged

VT 139222 bpm VF>222 bpm VT 140160 bpm VT2 160200 bpm VF>200 bpm Monitor 145-167 bpm VT 167188 bpm FVT 188250 bpm VF>188 bpm Monitor 145-167 bpm VT 167188 bpm FVT 188250 bpm VF>188 bpm Monitor 145-167 bpm VT 167188 bpm FVT 188250 bpm VF>188 bpm

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AAD=antiarrhythmic drug, Amio=amiodarone, BCSD= bilateral cardiac sympathetic denervation, BPM= beats per minute, EF=ejection fraction, ES=electric storm, FVT= fast ventricular tachcyardia; ICD= implantable cardioverter-defibrillator, MTP= metoprolol, Pt=patient, rVT=refractory ventricular tachycardia, VF= ventricular fibrillation, VT= ventricular tachycardia

FIGURE LEGEND: Figure 1: ICD shocks in the 1 month prior to BCSD and the subsequent available 12 months post procedure for all 7 patients. Figure 2: ICD therapy (shocks + ATP) in the 1 month prior to BCSD and the subsequent available 12 months post procedure for all 7 patients.

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