Adjunctive Therapies For Ventricular Arrhythmia Management

Adjunctive Thera p ies for
Ven t r i c u l a r A r r h y t h m i a
Management
Autonomic Neuromodulation—Established
and Emerging Therapies
Justin Hayase, MD, Jason S. Bradfield, MD*
KEYWORDS
Ventricular arrhythmias Electrical storm Autonomic modulation
KEY POINTS
The autonomic nervous system is a key contributor to ventricular arrhythmogenesis and provides
numerous therapeutic targets in arrhythmia management.
Mounting clinical data support the application of various autonomic modulation therapies for ven-
tricular arrhythmias including beta blockade, sedation, thoracic epidural anesthesia, stellate gan-
glion blockade, surgical cardiac sympathetic denervation, and renal artery denervation.
Emerging therapies in autonomic modulation that require more data include stellate ganglion abla-
tion, transcutaneous stellate ganglion modulation, tragus nerve stimulation, deep plexus blockade,
and ganglionated plexus ablation.
INTRODUCTION Case Presentation

Ventricular arrhythmias are an important cause of The patient was a 45-year-old man with history of
sudden cardiac death and often require a multi- coronary artery disease and reduced ejection frac-
modal approach for management.1 Therapeutic tion of 30% to 35% with single-chamber VDD
options include recognition and correction of un- implantable cardioverter-defibrillator (ICD) implan-
derlying causes (eg, electrolyte derangements, tation who presented to the hospital with 5 ICD
ischemia, toxins, and so forth), an implantable car- shocks for ventricular fibrillation (VF) over a 24-
dioverter defibrillator for secondary prevention, hour period. Coronary angiography demonstrated
goal-directed medical therapy for associated car- no targets for revascularization. His medications
diomyopathy, antiarrhythmic medications, and included metoprolol succinate 200 mg daily and
catheter ablation. Autonomic modulation is a ranolazine 500 mg twice daily in addition to maxi-
cornerstone of management of ventricular arrhyth- mally tolerated goal-directed medical therapy for
mias that can often be underappreciated. The au- ischemic cardiomyopathy. ICD interrogation
thors review the established and emerging demonstrated multiple episodes of premature
autonomic modulation therapies in this article ventricular contraction (PVC)-initiated VF, with
(Fig. 1). At the outset, they present a case that similar far-field PVC morphology for the episodes
highlights the value of autonomic modulation in (Fig. 2). A prior exercise treadmill test had showed
the management of ventricular arrhythmias. exercise-induced PVCs as well as runs of nonsus-
cardiacEP.theclinics.com
tained polymorphic ventricular tachycardia. He
UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine at UCLA, 100 Medical Plaza, Suite 660, Los
Angeles, CA, USA
* Corresponding author.
E-mail address: JBradfield@mednet.ucla.edu
Card Electrophysiol Clin - (2022) -–-

https://doi.org/10.1016/j.ccep.2022.06.004
1877-9182/22/Ó 2022 Published by Elsevier Inc.
Downloaded for saikrish nareddy (seemala123@emergentvillage.org) at CK Global Selfmanra Test from ClinicalKey.com by Elsevier on
November 03, 2022. For personal use only. No other uses without permission. Copyright ©2022. Elsevier Inc. All rights reserved.
2 Hayase & Bradfield
Fig. 1. Central illustration. Established

and emerging autonomic modulation
Established Therapies
therapies.
Thoracic Stellate
Epidural Ganglion
Anesthesia Blockade
General Cardiac
anesthesia/ Sympathec
Sedaon Denervaon
Beta Renal Artery

Blockade Autonomic Denervaon
Neuromodulaon
for Ventricular
Stellate Ganglionated
Ganglion Arrhythmias Plexus
Ablaon Ablaon
Stellate
Deep Plexus
Ganglion
Block
Modulaon Tragus
Smulaon
Emerging Therapies
was admitted to the hospital and telemetry moni- standard recommendations in accordance with
toring showed occasional PVCs with similar Advanced Cardiac Life Support guidelines. In their
morphology, suggesting upper septal, fascicular study, patients in group 1 had a significantly
origin. He was taken to the electrophysiology lab- reduced mortality rate at 1 week compared with
oratory for attempt at PVC ablation; however, this group 2 (22% vs 82%, P 5 .0001). The use of b-
procedure was complicated by repetitive episodes blockers currently carries a class I indication for
of VF during diagnostic catheter placement and patients with ventricular arrhythmias with struc-
prolonged hemodynamic instability, so ablation tural heart disease and a class IIa recommenda-
could not be performed. He was subsequently tion for patients with ventricular arrhythmias and
referred for bilateral surgical stellate ganglionec- no structural abnormalities1; this highlights the
tomy for cardiac sympathetic denervation (CSD), importance of the autonomic nervous system
which was successfully performed via video- and its modulation for management of ventricular
assisted thoracoscopic surgery. He was able to arrhythmias.
be discharged from the hospital with no changes
to his cardiac medications, and he has done well
with no ICD shocks for more than 1 year. Sedation
Deep sedation with intubation can be considered
for patients presenting with ES refractory to antiar-
AUTONOMIC NEUROMODULATION
rhythmic medications as a means of suppressing
Established Therapies
the sympathetic overdrive that often accompanies
Medications recurrent arrhythmias as well as the repetitive ICD
In a study by Nademanee and colleagues, pub- therapies required to terminate them. In a multi-
lished in 2000, the key role of the autonomic ner- center study of 116 patients with ongoing ventric-
vous system in ventricular arrhythmias was ular arrhythmias in spite of a median of 2.0
demonstrated.2 In 49 patients presenting with antiarrhythmic medications, 47.4% of patients
electrical storm (ES), patients were either had acute termination of ventricular arrhythmias
managed by sympathetic blockade with either b- within 15 minutes of sedation.3 In another obser-
blocker or left stellate ganglion blockade (group vational study of 46 patients with ES, there were
1) or with antiarrhythmic medications (group 2). 15 patients who remained refractory in spite of
At the time, antiarrhythmic medications such as usual care, and 80% of those had abatement of ar-
lidocaine, procainamide, and bretylium were rhythmias with the use of deep sedation.4
Ventricular Arrhythmia Management 3
Fig. 2. ICD interrogation and 12-lead ECG. (A) ICD interrogation showing episode of sustained ventricular fibril-
lation initiated with PVC. (B) ICD electrograms of PVCs and nonsustained VF initiated by PVCs with similar
morphology (red circles) as PVC-triggered sustained VF episodes. (C) 12-lead ECG from prior exercise treadmill
test showing frequent exercise-induced PVCs with narrow QRS, qR morphology in V1, lead V2 pattern break,
and AVL/AVR discordance that suggests upper septal origin. ECG, electrocardiogram.
Sedation remains a universally available technique experienced providers. TEA can be performed
for autonomic modulation. via epidural needle placement at the T1-T2 or
T2-T3 interspace and epidural catheter advance-
Thoracic epidural anesthesia ment beyond the needle tip. Infusion of 0.25%
Thoracic epidural anesthesia (TEA) provides a bupivacaine or 0.20% ropivacaine can then be
rapid means of bilateral, sympathetic modulation administered and titrated to arrhythmic response.
that can be performed at the bedside by In a multicenter series of 11 patients presenting
Fig. 3. (A): Illustration of an ultrasound-guided percutaneous stellate ganglion block. (B–C) Ultrasound images of
the percutaneous approach on the right side. (B) Taken before needle insertion. Dashed arrow indicates the sym-
pathetic ganglion. (C) Taken during needle insertion (arrow) and anesthetic infusion. Letter A marks the carotid
artery and letter V the jugular vein. (FUDIM, M., BOORTZ-MARX, R., PATEL, C.B., SUN, A.Y. and PICCINI, J.P. (2017),
Autonomic Modulation for the Treatment of Ventricular Arrhythmias: Therapeutic Use of Percutaneous Stellate
Ganglion Blocks. J Cardiovasc Electrophysiol, 28: 446-449. https://doi.org/10.1111/jce.13152.)
with ES, 5 (45%) had a complete response with Stellate ganglion blockade
cessation of arrhythmias following TEA and dose Numerous case reports and case series have illus-
titration.5 This therapeutic option can provide a trated the benefits of percutaneous stellate gan-
bridge to more durable treatment with either cath- glion blockade (SGB) in the management of
eter ablation or surgical CSD. refractory ventricular arrhythmias.6–8 This
Fig. 4. Anatomy of left cardiac sympathetic denervation (LCSD). (A) An anatomic drawing of the left cardiac sym-
pathetic chain after exposure through the pleura that is resected during VATS-LCSD. The stellate ganglion is
located under the superior edge of the incision. The dashed line indicates the resection of the lower half of
the left stellate ganglion occurring just above the major lower branches. (B, C) Videoscopic still frames of
Fig. 5. Representative anatomic geometry from a renal artery denervation procedure using the EnSite (Abbott
Medical, Minneapolis, MN) mapping system. (A) Right anterior oblique view (RAO). (B) Left anterior oblique
(LAO) view. Ablation lesions are represented as white dots. (From 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 E, Khakpour H, Krokhaleva Y, Macias C,
Fujimura O, Boyle NG and Shivkumar K. Renal denervation as adjunctive therapy to cardiac sympathetic dener-
vation for ablation refractory ventricular tachycardia. Heart Rhythm. 2019; with permission.)
procedure can be performed under either fluoro- management of refractory ventricular arrhyth-
scopic6 or ultrasound guidance (Fig. 3).7 SGB is mias.12 Greater benefit may be derived in patients
commonly performed with injection of 0.25% undergoing bilateral CSD (vs left-sided only), pa-
bupivacaine, with meta-analysis data demon- tients with faster ventricular arrhythmias, and
strating significant reduction in ventricular those with less severe New York Heart Association
arrhythmia burden.9 In a later single-center study functional status. Surgical CSD now carries a class
of 30 consecutive patients with ES, there was a IIb guideline recommendation for patients with
92% reduction in ventricular arrhythmias over the ventricular arrhythmias refractory to conventional
72 hours following SGB.10 This treatment can therapies.1
result in acute arrhythmia reduction with duration
of effect depending on the anesthetic agent used Renal artery denervation
and, similar to TEA, may provide a means of Renal artery denervation (RDN) may provide an
bridging to more definitive intervention. alternative target for autonomic modulation by
decreasing renal afferent signals and thus
Surgical cardiac sympathetic denervation reducing sympathetic input to the heart (Fig. 5).13
Surgical CSD has long been an effective therapy In a retrospective, propensity-matched study of
for certain channelopathies such as long QT syn- 32 patients with refractory ventricular arrhythmias,
drome or catecholaminergic polymorphic ventric- patients who underwent catheter ablation plus
ular tachycardia (Fig. 4).11 Mounting clinical RDN had greater arrhythmia reduction compared
evidence now support CSD via resection of the with those receiving catheter ablation alone.14 In
stellate ganglion in the management of refractory a case series of 10 patients who underwent RDN
ventricular arrhythmias including monomorphic following CSD, ventricular arrhythmias and ICD
ventricular tachycardia (VT). Multicenter data shocks were significantly reduced following
have shown the efficacy of this procedure for RDN.15 This effect was driven primarily by patients
=
VATS-LCSD before (B) and after (C) dissection of the pleura. VATS, video-assisted thoracic surgery. (From 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; with permission.)
Fig. 6. (A) The positioning of the electrode for stimulation of the right tragus. (B) Before stimulation, sinus cycle
length is 783 ms. (C) During stimulation at 5 mA, there is an increase in the sinus cycle length to 813 ms. (D) Low-
level tragus stimulation (LL-TS) or sham LL-TS was started once the patient arrived in the catheterization room
and lasted for 2 h after balloon dilatation (reperfusion). (From Yu L, Huang B, Po SS, Tan T, Wang M, Zhou L,
Meng G, Yuan S, Zhou X, Li X, Wang Z, Wang S and Jiang H. Low-Level Tragus Stimulation for the Treatment
of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-
Concept Study. JACC Cardiovasc Interv. 2017;10:1511-1520; with permission.)
who had an observed effect after CSD, with RDN magnetic stimulation resulted in significantly fewer
resulting in incremental arrhythmia suppression. ventricular arrhythmia episodes compared with
If patients did not have benefit from CSD, then sham control (4.5 vs 10.7, P < .001).19 Should
less benefit was observed with RDN as well. these treatment options prove effective in future
studies, these therapies could become life-
saving tools to use at the bedside of critically ill
Emerging Therapies
patients.
Stellate ganglion ablation and transcutaneous
modulation Tragus stimulation
As discussed earlier, SGB can provide acute relief The auricular branch of the vagus nerve courses
for ventricular arrhythmias, especially in the throes through the tragus and offers a potential noninva-
of ES. Based on case report data, more durable ef- sive target for autonomic modulation. Animal
fect might be achieved with percutaneous stellate model data have shown the impact of intermittent
ganglion ablation using either radiofrequency en- low-level tragus nerve stimulation in a postinfarc-
ergy16 or cryoablation17; however, these methods tion canine study20; this was further evaluated in
require further study. Alternative means of nonin- a proof-of-concept randomized trial of patients
vasive stellate ganglion modulation are also being undergoing percutaneous coronary intervention
investigated. In a pilot study involving healthy vol- for acute ST elevation myocardial infarctions,
unteers, the application of phototherapy using a which resulted in significant reduction in reperfu-
low-level laser resulted in reduction in serum sion ventricular arrhythmias in the treatment arm
adrenaline levels. In a follow-up of 11 patients (Fig. 6).21
with ES, complete arrhythmia suppression was
achieved in 7 patients using phototherapy.18 In a Deep plexus block
double-blind, sham-controlled randomized The deep plexus represents a convergence of
controlled trial of 26 patients, transcutaneous sympathetic nerves from bilateral stellate ganglia
Fig. 7. EBUS-guided transtracheal blockade of cardiac plexus. (A) Ultrasound real-time imaging of the aortopul-
monary (AP) window allows for safe positioning of injection needle into the pretracheal space (illustration). (B)
EBUS needle is advanced through the trachea anterior wall into the space between the aortic arch and pulmo-
nary artery. Injection of a contrast-lidocaine solution into the site of block (AP window) demonstrates the absence
of either systemic (intravascular) or intrapericardial inadvertent assessment (lower right). Stellate ganglia stimu-
lation catheters are shown in the background. AO, aorta (arch); EBUS, endobronchial ultrasound; PA, pulmonary
artery; (PA), posteroanterior projection; (RAO), right anterior oblique projection; red circle, right paratracheal
space. (From Assis FR, Yu DH, Zhou X, Sidhu S, Bapna A, Engelman ZJ, Misra S, Okada DR, Chrispin J, Berger R,
Mandal K, Lee H and Tandri H. Minimally invasive transtracheal cardiac plexus block for sympathetic neuromo-
dulation. Heart Rhythm. 2019;16:117-124; with permission.)
in the aortopulmonary window anterior to the tra- response to either right or left stellate ganglia in a
chea. Transtracheal lidocaine injection into the porcine model (Fig. 7).22 In a case report of a sin-
deep plexus was able to inhibit sympathetic gle patient with incessant VT, endobronchial
ultrasound-guided deep plexus lidocaine and bot- DISCLOSURE

ulinum toxin injection resulted in acute termination
of VT.23 VT ultimately recurred and the patient suc- J. Hayase: consultant (NeuCures).
cumbed to their arrhythmias, but this nonetheless
serves as an illustration of feasibility of the
procedure. REFERENCES
1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al.
Ganglionated plexus ablation
AHA/ACC/HRS guideline for management of pa-
The ganglionated plexi (GP) are epicardial struc-
tients with ventricular arrhythmias and the preven-
tures that facilitate afferent and efferent autonomic
tion of sudden cardiac death: executive summary:
nervous system effects on cardiac electrophysio-
a report of the american college of cardiology/amer-
logical and mechanical properties. The GPs have
ican heart association task force on clinical practice
been implicated in the pathogenesis of atrial fibril-
guidelines and the heart rhythm society. J Am Coll
lation24 and in neurocardiogenic syncope,25 but
Cardiol 2017;72(14):1677–749.
their role in ventricular arrhythmias is less under-
2. Nademanee K, Taylor R, Bailey WE, et al. Treating
stood. In general, GP ablation has aimed primarily
electrical storm : sympathetic blockade versus
at decreasing parasympathetic effects on the
advanced cardiac life support-guided therapy. Cir-
heart; however, in a canine study, ablation of the
culation 2000;102:742–7.
GP at the ligament of Marshall had similar effects
3. Martins RP, Urien JM, Barbarot N, et al. Effective-
as ablation of the left stellate ganglion in modula-
ness of deep sedation for patients with Intractable
tion of ventricular effective refractory period,
electrical storm refractory to antiarrhythmic Drugs.
markers of sympathetic tone, and in postinfarction
Circulation 2020;142:1599–601.
ventricular arrhythmias.26 However, ES following
4. Bundgaard JS, Jacobsen PK, Grand J, et al. Deep
atrial fibrillation cryoablation has also been re-
sedation as temporary bridge to definitive treatment
ported,27 and given the primary focus of ablation
of ventricular arrhythmia storm. Eur Heart J Acute
of GPs as a means for parasympathetic inhibition,
Cardiovasc Care 2020;9:657–64.
tremendous caution is warranted for the study of
5. Do DH, Bradfield J, Ajijola OA, et al. Thoracic
GPs as a therapeutic target for ventricular
epidural anesthesia can Be effective for the Short-
arrhythmias.
Term management of ventricular tachycardia storm.
J Am Heart Assoc 2017;6.
SUMMARY 6. Hayase J, Patel J, Narayan SM, et al. Percutaneous
stellate ganglion block suppressing VT and VF in a
Modulation of the autonomic nervous system rep-
patient refractory to VT ablation. J Cardiovasc Elec-
resents an essential component in the manage-
trophysiol 2013;24(8):926–8.
ment of ventricular arrhythmias. There are now
7. Fudim M, Boortz-Marx R, Patel CB, et al. Autonomic
numerous treatment modalities available to the
modulation for the treatment of ventricular arrhyth-
clinician, which has helped to improve patient out-
mias: therapeutic Use of percutaneous stellate gan-
comes with these life-threatening arrhythmias. In
glion blocks. J Cardiovasc Electrophysiol 2017;28:
addition, many new therapies are in development
446–9.
and show promise. Neurocardiac intervention
8. Cardona-Guarache R, Padala SK, Velazco-Davila L,
has a bright future.
et al. Stellate ganglion blockade and bilateral car-
diac sympathetic denervation in patients with life-
CLINICS CARE POINTS threatening ventricular arrhythmias. J Cardiovasc
Electrophysiol 2017;28:903–8.
9. Meng L, Tseng CH, Shivkumar K, et al. Efficacy of
stellate ganglion blockade in managing electrical
The autonomic nervous system is a key player storm: a Systematic review. JACC Clin Electrophy-
in the pathogenesis of ventricular arrhythmias siol 2017;3:942–9.
Autonomic modulation plays a key therapeu- 10. Tian Y, Wittwer ED, Kapa S, et al. Effective use of
tic role in the management of patients with percutaneous stellate ganglion blockade in patients
ventricular arrhythmias with electrical storm. Circ Arrhythm Electrophysiol
Autonomic targets for ventricular arrhythmia 2019;12:e007118.
management primarily aim to decrease sympa- 11. Schwartz PJ. Cardiac sympathetic denervation to
thetic or increase parasympathetic tone prevent life-threatening arrhythmias. Nat Rev Cardiol
2014;11:346–53.
12. Vaseghi M, Barwad P, Malavassi Corrales FJ, et al. 20. Yu L, Wang S, Zhou X, et al. Chronic intermittent low-
Cardiac sympathetic denervation for refractory ven- level stimulation of tragus reduces cardiac auto-
tricular arrhythmias. J Am Coll Cardiol 2017;69: nomic remodeling and ventricular arrhythmia induc-
3070–80. ibility in a post-infarction canine model. JACC Clin
13. Bradfield JS, Vaseghi M, Shivkumar K. Renal dener- Electrophysiol 2016;2:330–9.
vation for refractory ventricular arrhythmias. Trends 21. Yu L, Huang B, Po SS, et al. Low-level tragus stimu-
Cardiovasc Med 2014;24:206–13. lation for the treatment of ischemia and reperfusion
14. Evranos B, Canpolat U, Kocyigit D, et al. Role of Injury in patients with ST-Segment elevation myocar-
adjuvant renal sympathetic denervation in the treat- dial infarction: a proof-of-concept study. JACC Car-
ment of ventricular arrhythmias. Am J Cardiol 2016; diovasc Interv 2017;10:1511–20.
118:1207–10. 22. Assis FR, Yu DH, Zhou X, et al. Minimally invasive
15. Bradfield JS, Hayase J, Liu K, et al. Renal denerva- transtracheal cardiac plexus block for sympathetic
tion as an adjunctive therapy to cardiac sympathetic neuromodulation. Heart Rhythm 2019;16:117–24.
denervation for ablation refractory ventricular tachy- 23. Yu DH, Assis FR, Lerner AD, et al. Endobronchial
cardia. Heart Rhythm 2019;17(2):220–7. ultrasound-guided transtracheal cardiac plexus
16. Hayase J, Vampola S, Ahadian F, et al. Comparative neuromodulation for refractory ventricular tachy-
efficacy of stellate ganglion block with bupivacaine cardia. HeartRhythm Case Rep 2020;(6):370–4.
vs pulsed radiofrequency in a patient with refractory 24. Stavrakis S, Po S. Ganglionated plexi ablation: Phys-
ventricular arrhythmias. J Clin Anesth 2016;31: iology and clinical applications. Arrhythm Electro-
162–5. physiol Rev 2017;6:186–90.
17. Chatzidou S, Kontogiannis C, Tampakis K, et al. Cry- 25. Pachon JC, Pachon EI, Pachon JC, et al. Cardio-
oablation of stellate ganglion for the management of neuroablation"–new treatment for neurocardiogenic
electrical storm: the first reported case. Europace syncope, functional AV block and sinus dysfunction
2021;23:1105. using catheter RF-ablation. Europace 2005;7:1–13.
18. Nonoguchi NM, Adachi M, Nogami A, et al. Stellate 26. Liu S, Yu X, Luo D, et al. Ablation of the ligament of
ganglion phototherapy using low-level laser: a novel Marshall and left stellate ganglion similarly reduces
rescue therapy for patients with refractory ventricu- ventricular arrhythmias during acute myocardial
lar arrhythmias. JACC Clin Electrophysiol 2021;7: infarction. Circ Arrhythm Electrophysiol 2018;11:
1297–308. e005945.
19. Markman TM, Pothineni NVK, Zghaib T, et al. Effect 27. Munkler P, Wutzler A, Attanasio P, et al. Ventricular
of transcutaneous magnetic stimulation in patients tachycardia (VT) storm after cryoballoon-based pul-
with ventricular tachycardia storm: a randomized monary vein isolation. Am J Case Rep 2018;19:
clinical trial. JAMA Cardiol 2022;7(4):445–9. 1078–82.

Adjunctive Therapies For Ventricular Arrhythmia Management

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Adjunctive Therapies For Ventricular Arrhythmia Management

Uploaded by

Copyright:

Available Formats

Adjunctive Thera p ies for

INTRODUCTION Case Presentation

tained polymorphic ventricular tachycardia. He

Card Electrophysiol Clin - (2022) -–-

Fig. 1. Central illustration. Established

Beta Renal Artery

ultrasound-guided deep plexus lidocaine and bot- DISCLOSURE

You might also like