1 9/14/2019 EFFECT OF THORACIC EPIDURAL ANESTHESIA ON BARORECEPTOR - - PDF document

9/14/2019 1

Neuromodulatory Therapies for Ventricular Tachycardia

Marmar Vaseghi, M.D., Ph.D.

Associate Professor of Medicine Director, Clinical and Translational Research UCLA Cardiac Arrhythmia Center University of California, Los Angeles

S

BERKELEY • DAVIS • IRVINE • LOS ANGELES • RIVERSIDE • SAN DIEGO • SAN FRANCISCO SANTA BARBARA • SANTA CRUZ Sympathetic activation + Parasympathetic withdrawal ↑ Dispersion of repolarization and refractoriness Altered conduction velocity and functional block ↑ Triggered activity (EADs/DADs) ↓ ACh release due to ↑NE ↓ Baroreceptor sensitivity ↓ HR variability

RENAL/SUPRARENAL AUTONOMIC DYSREGULATION

Increased fibrosis Gap junction remodeling Increased release of catecholamines from the adrenal gland à ↑ triggered activity and dispersion of repolarization Volume overload and mechanical stretch à altered electromechanical feedback Neuroendocrine activation (ATII + aldosterone)

CARDIAC AUTONOMIC DYSFUNCTION RENAL/ADRENAL AUTONOMIC DYSFUNCTION

Efferent Sympathetic Fibers Efferent Preganglionic Vagal Fibers Brainstem

STRATEGIES FOR NEURAXIAL MODULATION OF VENTRICULAR TACHYARRHYTHMIAS

CBS VNS SCS TEA CBS SGB CSD RND Increase Parasympathetic Drive Decrease Sympathetic Drive TNS

Krokhaleva Y, Vaseghi M. Update on prevention and treatment of sudden cardiac

• arrest. Trends CV Med 2018

50 100 50 100 20 40 60 80

EFFECT OF THORACIC EPIDURAL ANESTHESIA ON HEMODYNAMIC PARAMETERS IN INFARCTED HEARTS Heart Rate LVSP RVSP

P = 0.13 P = 0.01 P = 0.6 Pre-TEA Post-TEA Pre-TEA Post-TEA Pre-TEA Post-TEA

• J. Hoang MS

Hoang J, Swid MA, Kang K, Vaseghi M. Hemodynamic and electrophysiological effects of thoracic epidural anesthesia in infarcted porcine heart. In preparation HR (bpm) LVSP (mmHg) RVSP (mmHg) Epidural Catheter Epidural Catheter

• A. Swid MD

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50 100 150 200 75 150 225 300 200 220 240 260 280 30 35 40 45 50 55

EFFECT OF THORACIC EPIDURAL ANESTHESIA ON ELECTROPYSIOLOGICAL PARAMTERS IN INFARCTED HEARTS AH Interval HV Interval AERP VERP

AH (msec) HV (msec) AERP (msec) VERP (msec)

@drive CL 450 msec

P = 0.001 P = 0.49 P = 0.001 P = 0.006 Pre-TEA Post-TEA Pre-TEA Post-TEA Pre-TEA Post-TEA Pre-TEA Post-TEA Hoang J, Swid MA, Kang K, Vaseghi M. Hemodynamic and electrophysiological effects on thoracic epidural anesthesia in infarcted porcine heart. In preparation Epidural Catheter Epidural Catheter

Ba Baror

• rece

ceptor

• r Sensit

nsitiv ivit ity Incr crease ses Post-TE TEA With h Phenyelp lphe herin ine

BRS (ms/mmHg)

Pre-TEA Post-TEA P = 0.015

EFFECT OF THORACIC EPIDURAL ANESTHESIA ON BARORECEPTOR SENSITIVITY

• J. Hoang MS

Hoang J, Swid MA, Kang K, Vaseghi M. Hemodynamic and electrophysiological effects of thoracic epidural anesthesia in infarcted porcine heart. In preparation Epidural Catheter Epidural Catheter

• A. Swid MD

Do DH, Bradfield J, Ajijola O, Vaseghi M, Le J, Rahman S, Mahajan A, Nogami A, Boyle NG, Shivkumar K. Thoracic Epidural Anesthesia can be Effective for the Acute Management of Ventricular Tachycardia Storm. Journal

• f the American Heart Association. 2017 10.1161/JAHA.117.007080

ACUTE MANGEMENT OF VENTRICULAR TACHYCARDIA STORM-THORACIC EPIDURAL ANESTHESIA

Patient factors for which TEA could be considered Incessant VT despite 2+ antiarrhythmic agents Continued VT storm despite initial ablation attempt Decrease in VT burden to deep sedation Hypotension limiting deep sedation Long wait time anticipated before definitive therapy Absolute Contraindications Active infection Dual antiplatelet therapy Requirement for uninterrupted therapeutic anticoagulation Relative Contraindications Acute myocardial infarction Active major non-cardiac medical or surgical process

Duc Do MD

Approaches to anestheticuse for stellateganglionblock. AnestheticAgent Numberof patients Dose (Concentration,%) Volume (ml) Bupivacaine 16 0.25-0.5 9 ± 5.6 Ropivacaine 11 0.2 6 ± 5.7 Lidocaine 9 1-4 8 ± 3.8 Mepivacaine 2 2 4 ± 0.0 Type

• f

administrationof anesthetics Numberof patients Bolus injections 28 Continuousinfusion 9 Both bolusinjectionsand continuous infusion 1 Utilityof imaging guidance Numberof patients Landmark

• nlywithoutimaging

13 Ultrasound 21 Fluoroscopy 4

EFFICACY OF STELLATE GANGLION BLOCKADE IN MANAGING ELECTRICAL STORM

Meng L, Tseng CH, Shivkumar K, Ajijola OA. Efficacy of Stellate Ganglion Blockade in Managing Electrical Storm JACC Electrophys 2017 LV EF and type of cardiomyopathy does not influence efficacy Impact of stellate ganglion block on ventricular arrhythmia episodes and defibrillator shocks.

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PatientCharacteristics N = 121

Age (y) 55 ± 13 Female 26% NYHA Class 2.4 ± 0.8 LVEF 30 ± 12% ICM 27% #ICD shocks (median, IQR) 10 (5,18) Polymorphic VT 38% >1 VT Morphology 63% VT Storm 75% Hypertension 56% Hyperlipidemia 44% Afib 25% CKD 27% DMII 19% Beta-blockers 92% >1 AAD 49% Left Only 19%

International Cardiac Sympathetic Denervation Collaborative Study

Vaseghi M, Barwad P, Malavassi F, Tandri H, Mathria N, Sáenz L, Lokhandwala Y, Shivkumar K. J Am Coll Cardiol 2017

58% ICD Shock Free, Transplant Free Survival at One year

5 10 15 20 25 Pre-CSD Post-CSD

Number of ICD Shocks P < 0.01

Follow Up (months) VT/ICD Shock-Free Transplant

• Free
• Survival

1.0 0.8 0.6 0.4 0.2 0.0

• 2
• 4
• 6
• 8
• 10
• 12
• No.

at

• Risk
• 121
• 79
• 67
• 57
• 55
• 49
• 44

VT/ICD Shock-Free Transplant-Free

A

MCG & Stellate Complex

Vaseghi M, Barwad P , Malavassi F, Tandri H, Mathria N, Sáenz L, Lokhandwala Y, Shivkumar K. J Am Coll Cardiol 2017

n = 121 patient

75% had VT Storm, Mean EF 30%, 92% were on BB+1AAD, 59% on >2 AADs

ICSDC-International Cardiac Sympathetic Denervation Collaborative Group

BILATERAL CARDIAC SYMPATHECTOMY IS EFFECTIVE FOR VT CONTROL

N=121 Procedural Complications

Total (N=121) Hemothorax 3 (2.4%) Pneumothorax 6 (5%) Ptosis – mild 5 (4%)- resolved in 4 patient by 6 months Vasopressor support – ≥24 hours post-procedure 16 (13%) Incisional Cellulitis 2 (1.6%) Nausea/vomiting 1(0.8%) UTI 1 (0.8%) Multi-focal pneumonia 1 (0.8%) Procedural Complications of Cardiac Sympathetic Denervation: ICSDC Study

Vaseghi M, Barwad P, Malavassi F, Tandri H, Mathria N, Sáenz L, Lokhandwala Y, Shivkumar K. Outcomes after cardiac sympathetic denervation for refractory ventricular arrhythmias: an international collaborative study. J Am Coll Cardiol 2017

50 yo female with non-ischemic cardiomyopathy, EF 40% and three different monomorphic ventricular tachycardias, s/p endocardial ablation at an outside hospital, s/p epicardial and endocardial ablation 3 months ago, has recurrence of ICD shock for monomorphic VT. Do you…. (A) Refer for repeat epi/endo ablation (B) Refer for cardiac sympathetic denervation (C) Refer for heart transplantation (D) Refer for renal denervation

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QUANTIFYING THE VALUE OF CSD IN PATIENTS WITH CARDIOMYOPATHY AND MONOMORPHIC VENTRICULAR TACHYCARDIA

Study Cohort (n=404) CSD Sub-group (n=69) P value Age (years) 62±13 57±13 <0.01 Female gender 52 (13) 8 (12) 1.00 Ischemic cardiomyopathy 202 (50) 12 (17) <0.01 Non ischemic cardiomyopathy

• Idiopathic
• ARVC
• Myocarditis
• Sarcoid/Inflammatory
• Hypertrophic
• Valvular
• Chagas

194 (48) 87 (22) 23 (6) 13 (3) 12 (3) 11 (3) 10 (2) 11 (3) 54 (78) 22 (32) 3 (4) 4 (6) 6 (9) 6 (9) 5 (7) 4 (6) <0.01 0.06 0.59 0.29 0.03 0.02 0.05 0.49 Diabetes mellitus 114 (28) 17 (25) 0.66 Hypertension 252 (62) 43 (62) 1.00 Hyperlipemia 235 (58) 39 (57) 0.79 Atrial fibrillation 147 (36) 28 (41) 0.50 Prior VT ablation before the index 214 (53) 53 (77) <0.01 Number of VT ablations before the index (median, IQR) 0 (IQR 0-1) 1 (IQR 0-2) 0.02 Implantable device (None, ICD, CRT-D) 27/241/136 (7, 60, 33) 1/43/25 (2, 62, 36) 0.23 LVAD 5 (1) 2 (3) 0.27 Beta-blocker 344, (85) 63, (91) 0.19 ≥ 2 AAD use 104 (26) 23 (33) 0.19 Amiodarone 232 (57) 42 (61) 0.69 VT Storm 188 (46) 49 (71) <0.01 ICD Shock(s) prior 338 (84) 65 (94) 0.03 NYHA Class (I/II/III/IV) 96/152/132/24 (24, 37, 33, 6) 10/30/28/1 (15,43,41,1) 0.10 Presentation (Elective/urgent/emergent)* 114/278/10 (28, 69, 3) 18/48/3 (26, 70, 4) 0.65 LVEF (mean±SD)* 32 ± 13 34 ± 13 0.46 CKD (Grade ≥3**) 147 (36) 21 (30) 0.04 Preoperative ECMO/IABP 7 (1) 3 (4) 0.17 Dusi V, Gornbein J, Do D, Sorg JM, Khakpour H, Krokhaleva Y, Ajijola OA, Macias C, Bradfield JS, Buch EF, Fujimura OA, Boyle NB, Yanagawa J, Lee JL, Shivkumar K, Vaseghi M. Quantifying the value of cardiac sympathetic denervation in cardiomyopathy patients with monomorphic ventricular tachycardia. Under review.

QUANTIFYING THE VALUE OF CARDIAC SYMPATHETIC DENERVATION IN PATIENTS WITH CARDIOMYOPATHY AND MONOMORPHIC VENTRICULAR TACHYCARDIA

Dusi V, Gornbein J, Do D, Sorg JM, Khakpour H, Krokhaleva Y, Ajijola OA, Macias C, Bradfield JS, Buch EF, Fujimura OA, Boyle NB, Yanagawa J, Lee JL, Shivkumar K, Vaseghi M. Quantifying the value of cardiac sympathetic denervation in cardiomyopathy patients with monomorphic ventricular tachycardia. Under review.

QUANTIFYING THE VALUE OF CARDIAC SYMPATHETIC DENERVATION IN PATIENTS WITH CARDIOMYOPATHY AND MONOMORPHIC VENTRICULAR TACHYCARDIA

Dusi V, Gornbein J, Do D, Sorg JM, Khakpour H, Krokhaleva Y, Ajijola OA, Macias C, Bradfield JS, Buch EF, Fujimura OA, Boyle NB, Yanagawa J, Lee JL, Shivkumar K, Vaseghi M. Quantifying the value of cardiac sympathetic denervation in cardiomyopathy patients with monomorphic ventricular tachycardia. Under review.

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2 4 6 8 10 12 14 VT recurrence Follow up (months) Incidence of VT recurrence Expected after CSD Observed after CSD

(B)

HR Ratio observed/expected= 0.68, p <0.001

• No. at Risk

Observed 69 54 44 41 40 39 36 33 HR observed/expected = 0.68, p < 0.001 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2 4 6 8 10 12 14 Sustained VT/ICD shock Follow up (months) Incidence of Sustained VT/ICD shock Expected after CSD Observed after CSD HR Ratio observed/expected= 0.67, p <0.001

(C)

• No. at Risk

Observed 69 54 46 44 41 40 38 34 p < 0.001 HR observed/expected = 0.67, p < 0.001 After VT ablation (n=404) After CSD (n=69) Crude rate (100 person-mos) Crude rate (100 person-mos) Observed VT recurrence 3.88 4.07 1.05 Sustained VT/ICD Shock 2.94 3.16 1.08 Expected (Model) VT recurrence 5.98 1.54 Sustained VT/ICD Shock 4.70 1.60 VT ABLATION CSD Hazard ratio

(A)

QUANTIFYING THE VALUE OF CSD IN PATIENTS WITH CARDIOMYOPATHY AND MONOMORPHIC VENTRICULAR TACHYCARDIA

Dusi V, Gornbein J, Do D, Sorg JM, Khakpour H, Krokhaleva Y, Ajijola OA, Macias C, Bradfield JS, Buch EF, Fujimura OA, Boyle NB, Yanagawa J, Lee JL, Shivkumar K, Vaseghi M. Quantifying the value of cardiac sympathetic denervation in cardiomyopathy patients with monomorphic ventricular tachycardia. Under review.

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Sympathetic activation + Parasympathetic withdrawal ↑ Dispersion of repolarization and refractoriness Altered conduction velocity and functional block ↑ Triggered activity (EADs/DADs) ↓ ACh release due to ↑NE ↓ Baroreceptor sensitivity ↓ HR variability

RENAL/SUPRARENAL AUTONOMIC DYSREGULATION

Increased fibrosis Gap junction remodeling Increased release of catecholamines from the adrenal gland à ↑ triggered activity and dispersion of repolarization Volume overload and mechanical stretch à altered electromechanical feedback Neuroendocrine activation (ATII + aldosterone)

CARDIAC AUTONOMIC DYSFUNCTION RENAL/ADRENAL AUTONOMIC DYSFUNCTION

Remo BF, Preminger M, Bradfield J, Mittal S, Boyle N, Gupta A, Shivkumar K, Steinberg J, Dickfeld T. Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy. Heart Rhythm 2014

6-Month Outcomes in Patients With Implantable Cardioverter-Defibrillators Undergoing Renal Sympathetic Denervation for the Treatment of Refractory Ventricular Arrhythmias

Armaganijan L et al. J Am Coll Cardiol Cardiovasc Interv 2015;61:457-464

NEURAL MODULATION WITH RENAL DENERVATION

Bradfield JS, Hayase J, Liu K, Moriarty J, Kee ST, Do D, Ajijola OA, Vaseghi M, Gima J, Sorg J, Cote S, Pavez G, Buch EF, Khakpour H, Krokhaleva Y, Macias C, Fujimura O, Boyle NG, Shivkumar K. Renal denervation as an adjunctive therapy to cardiac sympathetic denervation for ablation of ventricular tachycardia. Heart Rhythm 2019, in press

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RENAL DENERVA TION AS AN ADJUNCTIVE THERAPY TO CARDIAC SYMPA THETIC DENERVA TION FOR ABLA TION OF REFRACTORY VENTRICULAR TACHYCARDIA

Bradfield JS, Hayase J, Liu K, Moriarty J, Kee ST, Do D, Ajijola OA, Vaseghi M, Gima J, Sorg J, Cote S, Pavez G, Buch EF, Khakpour H, Krokhaleva Y, Macias C, Fujimura O, Boyle NG, Shivkumar K. Renal denervation as an adjunctive therapy to cardiac sympathetic denervation for ablation of ventricular tachycardia. Heart Rhythm 2019, in press

RENAL NERVES SURROUNDING THE ARTERIS ARE NOT EVENTLY DISTRIBUTED Fudim M, Sobotka AA, Yin YH, Wang JW, Levin H, Esler M, Wang J, Sobotka PA. Selective vs. Global Renal Denervation: a Case for Less Is More. Curr Hyperten Rep 2018.

Congenital Heart Disease & Pediatric EP: Jeremy Moore MD Kevin Shannon MD Cardiomyopathy & Transplantation: Ali Nsair MD Tamara Horwich MD Daniel Cruz MD Arnold Baas MD Gregg C. Fonarow MD ACHD: Jamil Aboulhosn MD Gentian Lluri MD Leigh Reardon MD Ravi Mandapati MD Pamela Miner RN NP Cardiac Surgery: Reshma Biniwale MD Hillel Laks MD Murray Kwon MD Richard Shemin MD Peyman Benharash MD Curtis Hunter MD Jeffrey L. Ardell PhD (Dir)

• J. Andrew Armour MD PhD

Pradeep Rajendran PhD John Tompkins PhD Maria Jordan MD Amiksha Gandhi BS Amer Swid MD Sarah Sayari PhD Cardiac Pathology: Michael C. Fishbein MD Gregory A. Fishbein MD EP Nurse Practitioners: Shelly Cote RN MN NP Jean Gima RN MN NP Geraldine Pavez RN MN NP Research Administration: Julie M. Sorg RN MSN (clinical) Scott John PhD (basic) Radiology:

• J. Paul Finn MD PhD

Stephen J. Kee MD John Moriarty MD Stefan Ruehm MD Administrative: Jewel Casillas Cecilia Flores Ashley Nunez Carmen Mora Dara Belarmino Center Director Kalyanam Shivkumar MD PhD Co-Directors Noel G. Boyle MD PhD Jeffrey L. Ardell PhD Specialized Program for AF & EP Labs Eric F. Buch MD, MS (Dir) Specialized Program for VT Jason Bradfield, MD (Dir) Clinical & Translational Research Marmar Vaseghi MD PhD (Dir) Implanted Devices Clinic Osamu Fujimura MD (Dir) Cardiac EP, UCLA Olive View Carlos Macias, MD (Dir) Specialized Program for Clin Autonomics: Olujimi A. Ajijola MD PhD (Dir) Electrophysiology Faculty: Zenaida Feliciano MD (Dir, West LA VAMC EP) Malcolm Bersohn MD Janet Han MD Houman Khakpour MD Yuliya Krokhaleva MD EP Fellows/trainees: Duc Do MD Peter S. Hanna MD Evangelos Diamantakos MD Guillermo Cortes MD Siamak Salavatian PhD Koji Yoshie MD Naoko Yamaguchi MD Pradeep Rajendran PhD (MSTP) Cardiac Anesthesia: Komal Patel MD Jonathan Ho MD Nir Hoftman MD Health System: Paul Watkins JD Erick Ascencio CVT

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