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Hanna DB, Karimianpour A, Mamprejew N, Fiechter C, Verghese D, Navas V, Sharma D. The role of cardiac sympathetic denervation for ventricular arrhythmias: an updated systematic review and meta-analysis. J Interv Card Electrophysiol 2025:10.1007/s10840-025-01997-x. [PMID: 39875720 DOI: 10.1007/s10840-025-01997-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/09/2025] [Indexed: 01/30/2025]
Abstract
INTRODUCTION The role of the sympathetic nervous system in the initiation and continuation of ventricular tachyarrhythmias (VTA) is well established. However, whether CSD reduces implantable cardioverter-defibrillator (ICD) shocks and recurrent VTA is still uncertain. METHODS A comprehensive literature search was performed at Medline and Embase until March 2023. The primary outcome was the rate of ICD shocks and VTA per patient-year in our pooled analysis of all included articles. Analyses were conducted using Comprehensive Meta-Analysis software. RESULTS Initial search yielded 1324 scientific studies with a total of 15 studies fitting our inclusion criteria. ICD shocks at 1 year post-CSD revealed an event rate of 69.8% (95% CI, 56.4-80.4% with 50% heterogeneity) (I2 statistic). ICD shocks at 6 months had an event rate of 59.1% (95% CI, 46.9-70.4%; 47 I2). Analysis of our pooled studies showed that 64.3% of individuals achieved freedom from VTA at 1 year post-CSD (95% CI, 42.3-81.5%; 26% I2), while 62.3% were free from recurrent VTA 6 months post-CSD (95% CI, 51.2-72.2%; 40% I2). Time to mortality directly caused by recurrent VTA post-CSD was subdivided into short-term (0-30 days), intermediate-term (31-364 days), and long-term (≥ 365). Mortality for the short-term tertile was 8.9% (95% CI, 5.0-15.4%; 0% I2), medium-term was 5.3% (95% CI, 2.4-11.3%; 0% I2), and long-term 5.2% (95% CI, 2.4-10.9%; 0% I2). CONCLUSION CSD seems to be promising as an acceptable treatment strategy for recurrent VTA refractory to traditional pharmacological or ablation therapy.
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Affiliation(s)
- Daniel B Hanna
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA.
| | | | - Nicole Mamprejew
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA
| | - Chris Fiechter
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA
| | - Dhiran Verghese
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA
| | - Viviana Navas
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA
| | - Dinesh Sharma
- Rooney Heart Institute, 311 9th St N #201, Naples, FL, 34102, USA
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Kanthasamy V, Ang R, Sridhar A, Vyas S, Whittaker-Axon S, Schilling R, Honarbakhsh S, Papageorgiou N, Creta A, Ahluwalia N, Hunter R, Finlay M. Subclavian Ansae Stimulation on Cardiac Hemodynamics and Electrophysiology in Atrial Fibrillation: A Target for Sympathetic Neuromodulation. JACC Clin Electrophysiol 2024:S2405-500X(24)00931-9. [PMID: 39797853 DOI: 10.1016/j.jacep.2024.10.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/23/2024] [Accepted: 10/21/2024] [Indexed: 01/13/2025]
Abstract
BACKGROUND The sympathetic autonomic nervous system plays a major role in arrhythmia development and maintenance. Historical preclinical studies describe preferential increases in cardiac sympathetic tone upon selective stimulation of the subclavian ansae (SA), a nerve cord encircling the subclavian artery. OBJECTIVES This study sought to define, for the first time, the functional anatomy and physiology of the SA in humans using a percutaneous approach. METHODS The authors prospectively recruited patients undergoing catheter ablation for paroxysmal atrial fibrillation (AF) under general anesthesia. SA stimulation (SAS) was performed on the left and/or the right (L/SAS and/or R/SAS, respectively) within the subclavian artery using an ablation catheter introduced via a femoral arterial sheath. Stimulation involved up to 70 V, 10 Hz, and a 2- to 4-millisecond pulse width for 15 to 30 seconds. Invasive blood pressure (BP), heart rate, and electrophysiological parameters were recorded. A positive response was a ≥10% increase in BP or heart rate from baseline. RESULTS Seventeen patients (median age 60 years [quartile 1-quartile 3: 58-67 years];11 male subjects; paroxysmal AF duration 24 months [quartile 1-quartile 3: 10-60 months) underwent the stimulation protocol before their clinical AF ablation procedure. A positive hemodynamic response was observed in 11 patients; of these, arrhythmia was inducible in 5 patients. The median sinus cycle length decreased after stimulation, and there was a larger decrease with R/SAS (L/SAS 1,008 milliseconds to 926 milliseconds [P = 0.037] vs R/SAS 1,029.5 milliseconds to 917 milliseconds [P = 0.005]). Both L/SAS and R/SAS led to a notable increase in median systolic BP (L/SAS 81 mm Hg to 128 mm Hg [P = 0.005] vs R/SAS 85 mm Hg to 104 mm Hg [P = 0.007]) and a similar trend in diastolic BP. In addition, there was a demonstrable decrease in interatrial conduction time and increase in P-wave dispersion. CONCLUSIONS This study represents the first successful application of selective SAS in humans. The SA is a potentially important site for targeted autonomic neuromodulation therapy.
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Affiliation(s)
- Vijayabharathy Kanthasamy
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Richard Ang
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
| | | | - Sandip Vyas
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
| | | | - Richard Schilling
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Shohreh Honarbakhsh
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | | | - Antonio Creta
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Nikhil Ahluwalia
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Ross Hunter
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Malcolm Finlay
- St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
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Vrabec T, Bender S, Chan SA, Cha S, Haridas S, Hanna P, Ajijola OA, Shivkumar K, Smith C, Ardell JL. Bioelectronic block of stellate ganglia mitigates pacing-induced heterogeneous release of catecholamine and neuropeptide Y in the infarcted pig heart. J Physiol 2024. [PMID: 39557601 DOI: 10.1113/jp286924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/23/2024] [Indexed: 11/20/2024] Open
Abstract
The sympathetic nervous system modulates cardiac contractile and electrophysiological function and contributes to adverse remodelling following myocardial infarction (MI). Axonal modulation therapy (AMT), directed at the sympathetic chain, blocks efferent sympathetic outflow to the heart and is a strategy to transiently and controllably mitigate chronic MI-associated sympatho-excitation. In porcine models, we evaluated scalable AMT, directed at the paravertebral chain, in blocking reflex-mediated pacing-induced sympatho-excitation post-MI. The level of sympatho-excitation was assessed by dynamic interstitial measurement of noradrenaline (NA) and neuropeptide Y (NPY). In anaesthetized normal (n = 5) and age-matched pigs 6 weeks post-MI induction (n = 10), we electrically stimulated the right sympathetic chain and determined levels of direct current block applied at the T1-T2 level sufficient to reduce the evoked changes in heart rate and/or contractility by 25-75%. Reflex-mediated neural release of NA and NPY into the interstitial space during programmed pacing (PP) was assessed using fast-scanning cyclic voltammetry and capacitive immunoprobes. Normal animals demonstrated homogeneous NA and NPY release profiles during PP. In contrast, for MI animals PP evoked differential NA and NPY release in remote and MI border zones of the left ventricle. Right-sided AMT mitigated NA and NPY pacing-induced release in the remote left ventricle with a positive correlation to increasing AMT levels. Pacing-induced NA and NPY release in the MI border zone was not mitigated by AMT. Differential effects of AMT on NA and NPY may underlie the anti-arrhythmic effects of partial stellate ganglion block in the setting of chronic MI. KEY POINTS: Programmed cardiac pacing evokes homogeneous noradrenaline (NA) and neuropeptide Y (NPY) release in equivalent areas (e.g. medial and lateral aspects) of the normal left ventricle. Programmed cardiac pacing evokes differential NA and NPY release in remote and border zones of the infarcted left ventricle. Axonal modulation therapy (AMT), using a graded direct current block applied to the stellate ganglia, can proportionally modulate cardiac sympathetic reflexes. Unilateral AMT mitigates NA and NPY release in remote left ventricular tissue, with release negatively correlated to increasing AMT levels. Heterogeneities in NA and NPY between the border and remote tissues are reduced by progressive AMT.
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Affiliation(s)
- Tina Vrabec
- Department of Physical Medicine & Rehabilitation, MetroHealth Medical Center, Cleveland, OH, USA
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Shane Bender
- Department of Physical Medicine & Rehabilitation, MetroHealth Medical Center, Cleveland, OH, USA
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Shyue-An Chan
- Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
| | - Steven Cha
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
| | - Sahil Haridas
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
| | - Peter Hanna
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
| | - Olujimi A Ajijola
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
| | - Kalyanam Shivkumar
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
| | - Corey Smith
- Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
| | - Jeffrey L Ardell
- David Geffen School of Medicine, University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, Los Angeles, CA, USA
- UCLA Neurocardiology Research Program of Excellence, Los Angeles, CA, USA
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Herring N, Ajijola OA, Foreman RD, Gourine AV, Green AL, Osborn J, Paterson DJ, Paton JFR, Ripplinger CM, Smith C, Vrabec TL, Wang HJ, Zucker IH, Ardell JL. Neurocardiology: translational advancements and potential. J Physiol 2024. [PMID: 39340173 DOI: 10.1113/jp284740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 09/03/2024] [Indexed: 09/30/2024] Open
Abstract
In our original white paper published in the The Journal of Physiology in 2016, we set out our knowledge of the structural and functional organization of cardiac autonomic control, how it remodels during disease, and approaches to exploit such knowledge for autonomic regulation therapy. The aim of this update is to build on this original blueprint, highlighting the significant progress which has been made in the field since and major challenges and opportunities that exist with regard to translation. Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding emerges of where and how to target in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), vagus nerve, brainstem, and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical, and molecular) such that closed-loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes.
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Affiliation(s)
- N Herring
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
| | - O A Ajijola
- UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine, Los Angeles, CA, USA
| | - R D Foreman
- Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - A V Gourine
- Centre for Cardiovascular and Metabolic Neuroscience, University College London, London, UK
| | - A L Green
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - J Osborn
- Department of Surgery, University of Minnesota, Minneapolis, MN, USA
| | - D J Paterson
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
| | - J F R Paton
- Manaaki Manawa - The Centre for Heart Research, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - C M Ripplinger
- Department of Pharmacology, University of California Davis, Davis, CA, USA
| | - C Smith
- Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
| | - T L Vrabec
- Department of Physical Medicine and Rehabilitation, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - H J Wang
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - I H Zucker
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - J L Ardell
- UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine, Los Angeles, CA, USA
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Lei Q, Jiang Z, Shao Y, Liu X, Li X. Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation. Front Cardiovasc Med 2024; 11:1453127. [PMID: 39328238 PMCID: PMC11424448 DOI: 10.3389/fcvm.2024.1453127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 08/29/2024] [Indexed: 09/28/2024] Open
Abstract
Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.
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Affiliation(s)
- Qiulian Lei
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zefei Jiang
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yu Shao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xinghong Liu
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiaoping Li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Tokcan M, Federspiel J, Lauder L, Hohl M, Al Ghorani H, Kulenthiran S, Bettink S, Böhm M, Scheller B, Tschernig T, Mahfoud F. Characterisation and distribution of human coronary artery innervation. EUROINTERVENTION 2024; 20:e1107-e1117. [PMID: 39219360 PMCID: PMC11352544 DOI: 10.4244/eij-d-24-00167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 06/04/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches. AIMS This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries. METHODS Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres. RESULTS A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 μm [31-73], middle 38 μm [26-58], distal 31 μm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 μm [31-81]), followed by the LAD (42 μm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005). CONCLUSIONS Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.
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Affiliation(s)
- Mert Tokcan
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
| | - Jan Federspiel
- Institute of Legal Medicine, Saarland University, Faculty of Medicine, Homburg, Germany
| | - Lucas Lauder
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
- Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, Basel, Switzerland
| | - Mathias Hohl
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
| | - Hussam Al Ghorani
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
| | - Saarraaken Kulenthiran
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
| | - Stephanie Bettink
- Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland
| | - Michael Böhm
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
| | - Bruno Scheller
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
- Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland
| | - Thomas Tschernig
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, Basel, Switzerland
| | - Felix Mahfoud
- Klinik für Innere Medizin III - Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center and Saarland University, Homburg, Germany
- Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, Basel, Switzerland
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Lemery R. Historical Perspective of the Cardiac Autonomic Nervous System. Card Electrophysiol Clin 2024; 16:219-227. [PMID: 39084715 DOI: 10.1016/j.ccep.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
The contemporary history of the cardiac autonomic nervous system includes early descriptions of neuroanatomy in the 19th century, followed by an understanding of the physiologic determinants of neurocardiology in the 20th century. Neurology and cardiology preceded the arrival of clinical cardiac electrophysiology, a specialized field in medicine devoted to the diagnosis and treatment of cardiac arrhythmias. The rapid growth in pharmacology, ablation, pacing and defibrillation, associated with significant technological breakthroughs, have resulted in new opportunities for neuromodulation in the 21st century. Small changes in autonomic tone can potentially provide important therapeutic benefits for patients with cardiac and arrhythmia disorders.
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Affiliation(s)
- Robert Lemery
- Cardiology and Medical History, 835 René-Lévesque E, Montréal, Québec, Canada, H2L 4V5.
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Sarkar A, Ajijola OA. Pathophysiologic Mechanisms in Cardiac Autonomic Nervous System and Arrhythmias. Card Electrophysiol Clin 2024; 16:261-269. [PMID: 39084719 DOI: 10.1016/j.ccep.2023.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
The autonomic nervous system, including the central nervous system and the cardiac plexus, maintains cardiac physiology. In diseased states, autonomic changes through neuronal remodeling generate electrical mechanisms of arrhythmia such as triggered activity or increased automaticity. This article will focus on the pathophysiological mechanisms of arrhythmia to highlight the role of the autonomic nervous system in disease and the related therapeutic interventions.
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Affiliation(s)
- Abdullah Sarkar
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research program of Excellence, Los Angeles, CA, USA
| | - Olujimi A Ajijola
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research program of Excellence, Los Angeles, CA, USA.
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Kuwabara Y, Wong B, Mahajan A, Salavatian S. Pharmacologic, Surgical, and Device-Based Cardiac Neuromodulation. Card Electrophysiol Clin 2024; 16:315-324. [PMID: 39084724 DOI: 10.1016/j.ccep.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases.
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Affiliation(s)
- Yuki Kuwabara
- Department of Anesthesiology and Perioperative Medicine of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
| | - Benjamin Wong
- Department of Anesthesiology and Perioperative Medicine of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aman Mahajan
- Department of Anesthesiology and Perioperative Medicine of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
| | - Siamak Salavatian
- Department of Anesthesiology and Perioperative Medicine of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA.
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Do DH, Shivkumar K. Idiopathic Ventricular Fibrillation: Truly Idiopathic or Are We Missing Occult Pathology? JACC Clin Electrophysiol 2024; 10:1995-1997. [PMID: 39066780 DOI: 10.1016/j.jacep.2024.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 06/11/2024] [Indexed: 07/30/2024]
Affiliation(s)
- Duc H Do
- UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine at UCLA, Los Angeles, Los Angeles, California, USA.
| | - Kalyanam Shivkumar
- UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine at UCLA, Los Angeles, Los Angeles, California, USA
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11
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Hu H, Li Q, Wang J, Cheng Y, Zhao J, Hu C, Yin X, Wu Y, Sang R, Jiang H, Sun Y, Wang S. Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury. Acta Biomater 2024:S1742-7061(24)00445-8. [PMID: 39122136 DOI: 10.1016/j.actbio.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 07/30/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024]
Abstract
Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.
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Affiliation(s)
- Haoyuan Hu
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Qian Li
- National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, China
| | - Jiale Wang
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Ye Cheng
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Jiahui Zhao
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Changhao Hu
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Xinyue Yin
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yuzhe Wu
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Ruiqi Sang
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China.
| | - Yao Sun
- National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, China.
| | - Songyun Wang
- Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan, China.
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12
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Balão J, Sepúlveda D, Borges A, Fonseca C, Rodrigues SS. Combined Stellate Ganglion Blockade and Epidural Thoracic Anesthesia for the Management of Ventricular Storm: A Case Report. Ann Card Anaesth 2024; 27:253-255. [PMID: 38963362 PMCID: PMC11315240 DOI: 10.4103/aca.aca_177_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 11/30/2023] [Accepted: 12/25/2023] [Indexed: 07/05/2024] Open
Abstract
ABSTRACT The term "ventricular storm (VS)" is defined as the occurrence of two or more separate episodes of ventricular tachycardia or fibrillation (VT/VF) or three or more appropriate discharges of an implantable cardioverter defibrillator for VT/VF during a 24-h period. A patient in his early 40s was observed in the emergency department of our hospital and was admitted to the cardiac intensive care unit due to multiple episodes of VT. This led to the need for deep sedation with orotracheal intubation and mechanical ventilation. Intravenous lidocaine treatment was started; however, the patient had a recurrence of the episodes of VT. We decided to combine stellate ganglion block with epidural thoracic anesthesia. After the sympathetic block, there was no recurrence of the arrhythmic episodes. The patient was then transferred for ablation treatment. We demonstrated the efficacy of both techniques in managing a patient with multiple episodes of ventricular storm.
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Affiliation(s)
- João Balão
- Department of Anesthesiology, Hospital Senhora da Oliveira, Guimarães, Portugal
| | - Daniela Sepúlveda
- Department of Anesthesiology, Hospital Senhora da Oliveira, Guimarães, Portugal
| | - Alexandra Borges
- Department of Anesthesiology, Hospital Senhora da Oliveira, Guimarães, Portugal
| | - Cristiana Fonseca
- Department of Anesthesiology, Hospital Senhora da Oliveira, Guimarães, Portugal
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13
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Li M, Sorensen M, Johnson MA, Ingram SL, Andresen MC, Habecker BA. Hypertension increases sympathetic neuron activity by enhancing intraganglionic cholinergic collateral connections. J Physiol 2024:10.1113/JP286601. [PMID: 39031543 PMCID: PMC11662085 DOI: 10.1113/jp286601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 06/06/2024] [Indexed: 07/22/2024] Open
Abstract
Autonomic dysregulation, including sympathetic hyperactivity, is a common feature of hypertension (HT) and other cardiovascular diseases. The CNS plays a role in driving chronic sympathetic activation in disease, but several lines of evidence suggest that neuroplasticity in the periphery may also contribute. The potential contribution of postganglionic sympathetic neurons to sustained sympathetic hyperactivity is not well understood. We recently discovered that noradrenergic sympathetic neurons in the stellate ganglion (SG) have excitatory cholinergic collateral connections to other neurons within the ganglion. We hypothesize that remodelling of these neurons and increased cholinergic collateral transmission contributes to sustained sympathetic hyperactivity in cardiovascular diseases, including HT. To test that hypothesis, we examined the activity of sympathetic neurons in isolated SG under control conditions and after 1 week of HT induced by peripheral angiotensin II infusion, using whole-cell patch clamp recordings. Despite the absence of central inputs, we observed elevated spontaneous activity and synaptic transmission in sympathetic SG neurons from hypertensive mice that required generation of action potentials. Genetically disrupting cholinergic transmission in noradrenergic neurons decreased basal neuronal activity and prevented angiotensin II-mediated enhancement of activity. Similar changes in activity, driven by increased collateral transmission, were identified in cardiac projecting neurons and neurons projecting to brown adipose tissue. These changes were not driven by altered A-type K+ currents. This suggests that HT stimulates increased activity throughout the intraganglionic network of collateral connections, contributing to the sustained sympathetic hyperactivity characteristic in cardiovascular disease. KEY POINTS: Sympathetic neurons in ganglia isolated from angiotensin II-treated hypertensive mice are more active than neurons from control mice despite the absence of central activation. The enhanced activity is the result of a ganglionic network of cholinergic collaterals, rather than altered intrinsic excitability. Increased neuronal activity was observed in both cardiac neurons and brown adipose tissue-projecting neurons, which are not involved in cardiovascular homeostasis.
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Affiliation(s)
- Minghua Li
- Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, United States of America, 97239
| | - Michelle Sorensen
- Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, United States of America, 97239
| | - Morgan A. Johnson
- Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, United States of America, 97239
| | - Susan L. Ingram
- Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045
| | - Michael C. Andresen
- Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, United States of America, 97239
| | - Beth A. Habecker
- Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, United States of America, 97239
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14
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Jacinto S, Reis J, Martins Oliveira M. Management of life-threatening ventricular arrhythmias: What is going on with autonomic neuromodulation. Rev Port Cardiol 2024; 43:357-359. [PMID: 38336221 DOI: 10.1016/j.repc.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 11/09/2023] [Indexed: 02/12/2024] Open
Affiliation(s)
- Sofia Jacinto
- Cardiology Department, Santa Marta Hospital, CHULC, Lisbon, Portugal.
| | - João Reis
- Cardiology Department, Santa Marta Hospital, CHULC, Lisbon, Portugal
| | - Mário Martins Oliveira
- Cardiology Department, Santa Marta Hospital, CHULC, Lisbon, Portugal; Faculty of Medicine of Lisbon, CCUL, Lisbon, Portugal
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15
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Zhang H, Wang Y, Wu Y, Luo Z, Zhong M, Hong Z, Wang D. Intrathecal Anesthesia Prevents Ventricular Arrhythmias in Rats with Myocardial Ischemia/Reperfusion. Pharmacology 2024; 109:253-265. [PMID: 38648737 DOI: 10.1159/000538997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 04/05/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Ventricular arrhythmia is commonly provoked by acute cardiac ischemia through sympathetic exaggeration and is often resistant to anti-arrhythmic therapies. Thoracic epidural anesthesia has been reported to terminate fatal ventricular arrhythmia; however, its underlying mechanism is unknown. METHODS Rats were randomly divided into four groups: sham, sham plus bupivacaine, ischemia/reperfusion (IR), and IR plus bupivacaine groups. Bupivacaine (1 mg/mL, 0.05 mL/100 g body weight) was injected intrathecally into the L5-L6 intervertebral space prior to establishing a myocardial IR rat model. Thereafter, cardiac arrhythmia, cardiac function, myocardial injury, and electrical activities of the heart and spinal cord were evaluated. RESULTS Intrathecal bupivacaine inhibited spinal neural activity, improved heart rate variability, reduced ventricular arrhythmia score, and ameliorated cardiac dysfunction in IR rats. Furthermore, intrathecal bupivacaine attenuated cardiac injury and myocardial apoptosis and regulated cardiomyocyte autophagy and connexin-43 distribution during myocardial IR. CONCLUSION Our results indicate that intrathecal bupivacaine blunts spinal neural activity to prevent cardiac arrhythmia and dysfunction induced by IR and that this anti-arrhythmic activity may be associated with regulation of autonomic balance, myocardial apoptosis and autophagy, and cardiac gap junction function.
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MESH Headings
- Animals
- Bupivacaine/administration & dosage
- Myocardial Reperfusion Injury/prevention & control
- Male
- Rats, Sprague-Dawley
- Arrhythmias, Cardiac/prevention & control
- Arrhythmias, Cardiac/etiology
- Rats
- Injections, Spinal
- Anesthetics, Local/pharmacology
- Anesthetics, Local/administration & dosage
- Anesthesia, Spinal
- Connexin 43/metabolism
- Apoptosis/drug effects
- Heart Rate/drug effects
- Autophagy/drug effects
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Anti-Arrhythmia Agents/administration & dosage
- Anti-Arrhythmia Agents/pharmacology
- Disease Models, Animal
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Affiliation(s)
- Huabin Zhang
- Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China
| | - Yue Wang
- Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China
| | - Yong Wu
- Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China
- Department of Geriatrics, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China
| | - Zhongxu Luo
- Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China
| | - Ming Zhong
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, China
| | - Zongyuan Hong
- School of Pharmacy, Wannan Medical College, Wuhu, China
| | - Deguo Wang
- Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, China
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16
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Batnyam U, Vlassakov KV, Halawa A, Seligson E, Chen L, Redouane B, Janfaza D, Tedrow UB. Safety and Efficacy of Ultrasound-Guided Sympathetic Blockade by Proximal Intercostal Block in Electrical Storm Patients. JACC Clin Electrophysiol 2024; 10:734-746. [PMID: 38300210 DOI: 10.1016/j.jacep.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 12/01/2023] [Accepted: 12/05/2023] [Indexed: 02/02/2024]
Abstract
BACKGROUND Electrical storm (ES) patients who fail standard therapies have a high mortality rate. Previous studies report effective management of ES with bedside, ultrasound-guided percutaneous stellate ganglion block (SGB). We report our experience with sympathetic blockade administered via a novel alternative approach: proximal intercostal block (PICB). Compared with SGB, this technique targets an area typically free of other catheters and support devices, and may pose less strict requirements for anticoagulation interruption, along with lower risk of focal neurological side effects. OBJECTIVES The authors sought to describe the safety and efficacy of PICB in patients with refractory ES. METHODS We reviewed our institutional data on ES patients who underwent PICB between January 2018 and February 2023 to analyze procedural safety and short- and long-term outcomes. RESULTS A total of 15 consecutive patients with ES underwent PICB during this period. Of those, 11 patients (73.3%) were maintained on PICB alone, and 4 patients (26.6%) were maintained on combined block with SGB and PICB. Overall, 72.7% patients who were maintained on PICB alone and 77.8% patients who were maintained on bilateral PICB had excellent arrhythmia suppression. After PICB, implantable cardioverter-defibrillator therapies were significantly reduced (P < 0.05), with 93.3% of patients receiving PICB having no implantable cardioverter-defibrillator shock until discharge or heart transplant. Anticoagulation was continued in all patients and there were no procedure-related complications. Apart from mild transient neurological symptoms seen in 3 patients, no significant neurological or hemodynamic sequelae were observed. CONCLUSIONS In patients with refractory ES, continuous PICB provided safe and effective sympathetic block (77.8% ventricular arrhythmia suppression), achievable without interruption of anticoagulation, and without significant side effects.
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Affiliation(s)
- Uyanga Batnyam
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kamen V Vlassakov
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Ahmad Halawa
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Erica Seligson
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Liting Chen
- Department of Anesthesiology, Northwestern Memorial Hospital, Feinberg School of Medicine, Chicago, Illinois, USA
| | - Brahim Redouane
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - David Janfaza
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Usha B Tedrow
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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17
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Krokhaleva Y, Vaseghi M. Weathering the Storm With Intercostal Blockade: Repurposing an Old Approach for a Novel Application. JACC Clin Electrophysiol 2024; 10:747-749. [PMID: 38658063 DOI: 10.1016/j.jacep.2024.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 01/16/2024] [Accepted: 02/08/2024] [Indexed: 04/26/2024]
Affiliation(s)
| | - Marmar Vaseghi
- UCLA Cardiac Arrhythmia Center, Los Angeles, California, USA.
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18
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Yoneda Z, Kanagasundram AN. Neuraxial Modulation for Refractory Ventricular Arrhythmias. JACC Clin Electrophysiol 2024; 10:759-761. [PMID: 38520439 DOI: 10.1016/j.jacep.2024.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 01/26/2024] [Indexed: 03/25/2024]
Affiliation(s)
- Zachary Yoneda
- Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Arvindh N Kanagasundram
- Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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19
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Lenarczyk R, Zeppenfeld K, Tfelt-Hansen J, Heinzel FR, Deneke T, Ene E, Meyer C, Wilde A, Arbelo E, Jędrzejczyk-Patej E, Sabbag A, Stühlinger M, di Biase L, Vaseghi M, Ziv O, Bautista-Vargas WF, Kumar S, Namboodiri N, Henz BD, Montero-Cabezas J, Dagres N. Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society. Europace 2024; 26:euae049. [PMID: 38584423 PMCID: PMC10999775 DOI: 10.1093/europace/euae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 02/07/2024] [Indexed: 04/09/2024] Open
Abstract
Electrical storm (ES) is a state of electrical instability, manifesting as recurrent ventricular arrhythmias (VAs) over a short period of time (three or more episodes of sustained VA within 24 h, separated by at least 5 min, requiring termination by an intervention). The clinical presentation can vary, but ES is usually a cardiac emergency. Electrical storm mainly affects patients with structural or primary electrical heart disease, often with an implantable cardioverter-defibrillator (ICD). Management of ES requires a multi-faceted approach and the involvement of multi-disciplinary teams, but despite advanced treatment and often invasive procedures, it is associated with high morbidity and mortality. With an ageing population, longer survival of heart failure patients, and an increasing number of patients with ICD, the incidence of ES is expected to increase. This European Heart Rhythm Association clinical consensus statement focuses on pathophysiology, clinical presentation, diagnostic evaluation, and acute and long-term management of patients presenting with ES or clustered VA.
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Affiliation(s)
- Radosław Lenarczyk
- Medical University of Silesia, Division of Medical Sciences, Department of Cardiology and Electrotherapy, Silesian Center for Heart Diseases, Skłodowskiej-Curie 9, 41-800 Zabrze, Poland
| | - Katja Zeppenfeld
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jacob Tfelt-Hansen
- The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- The Department of Forensic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Frank R Heinzel
- Cardiology, Angiology, Intensive Care, Städtisches Klinikum Dresden Campus Friedrichstadt, Dresden, Germany
| | - Thomas Deneke
- Clinic for Interventional Electrophysiology, Heart Center RHÖN-KLINIKUM Campus Bad Neustadt, Bad Neustadt an der Saale, Germany
- Clinic for Electrophysiology, Klinikum Nuernberg, University Hospital of the Paracelsus Medical University, Nuernberg, Germany
| | - Elena Ene
- Clinic for Interventional Electrophysiology, Heart Center RHÖN-KLINIKUM Campus Bad Neustadt, Bad Neustadt an der Saale, Germany
| | - Christian Meyer
- Division of Cardiology/Angiology/Intensive Care, EVK Düsseldorf, Teaching Hospital University of Düsseldorf, Düsseldorf, Germany
| | - Arthur Wilde
- Department of Cardiology, Amsterdam UMC University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Heart Failure and arrhythmias, Amsterdam, the Netherlands
| | - Elena Arbelo
- Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; IDIBAPS, Institut d'Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
| | - Ewa Jędrzejczyk-Patej
- Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Centre for Heart Diseases, Zabrze, Poland
| | - Avi Sabbag
- The Davidai Center for Rhythm Disturbances and Pacing, Chaim Sheba Medical Center, Tel Hashomer, Israel
- School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Markus Stühlinger
- Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Luigi di Biase
- Albert Einstein College of Medicine at Montefiore Hospital, New York, NY, USA
| | - Marmar Vaseghi
- UCLA Cardiac Arrythmia Center, Division of Cardiology, Department of Medicine, University of California, Los Angeles, CA, USA
| | - Ohad Ziv
- Case Western Reserve University, Cleveland, OH, USA
- The MetroHealth System Campus, Cleveland, OH, USA
| | | | - Saurabh Kumar
- Department of Cardiology, Westmead Hospital, Westmead Applied Research Centre, University of Sydney, Sydney, Australia
| | | | - Benhur Davi Henz
- Instituto Brasilia de Arritmias-Hospital do Coração do Brasil-Rede Dor São Luiz, Brasilia, Brazil
| | - Jose Montero-Cabezas
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
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20
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Dusi V, Angelini F, Baldi E, Toscano A, Gravinese C, Frea S, Compagnoni S, Morena A, Saglietto A, Balzani E, Giunta M, Costamagna A, Rinaldi M, Trompeo AC, Rordorf R, Anselmino M, Savastano S, De Ferrari GM. Continuous stellate ganglion block for ventricular arrhythmias: case series, systematic review, and differences from thoracic epidural anaesthesia. Europace 2024; 26:euae074. [PMID: 38531027 PMCID: PMC11020261 DOI: 10.1093/europace/euae074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 03/18/2024] [Indexed: 03/28/2024] Open
Abstract
AIMS Percutaneous stellate ganglion block (PSGB) through single-bolus injection and thoracic epidural anaesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). However, data on continuous PSGB (C-PSGB) are scant. The aim of this study is to report our dual-centre experience with C-PSGB and to perform a systematic review on C-PSGB and TEA. METHODS AND RESULTS Consecutive patients receiving C-PSGB at two centres were enrolled. The systematic literature review follows the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Our case series (26 patients, 88% male, 60 ± 16 years, all with advanced structural heart disease, left ventricular ejection fraction 23 ± 11%, 32 C-PSGBs performed, with a median duration of 3 days) shows that C-PSGB is feasible and safe and leads to complete VAs suppression in 59% and to overall clinical benefit in 94% of cases. Overall, 61 patients received 68 C-PSGBs and 22 TEA, with complete VA suppression in 63% of C-PSGBs (61% of patients). Most TEA procedures (55%) were performed on intubated patients, as opposed to 28% of C-PSGBs (P = 0.02); 63% of cases were on full anticoagulation at C-PSGB, none at TEA (P < 0.001). Ropivacaine and lidocaine were the most used drugs for C-PSGB, and the available data support a starting dose of 12 and 100 mg/h, respectively. No major complications occurred, yet TEA discontinuation rate due to side effects was higher than C-PSGB (18 vs. 1%, P = 0.01). CONCLUSION Continuous PSGB seems feasible, safe, and effective for the acute management of refractory VAs. The antiarrhythmic effect may be accomplished with less concerns for concomitant anticoagulation compared with TEA and with a lower side-effect related discontinuation rate.
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Affiliation(s)
- Veronica Dusi
- Cardiology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Filippo Angelini
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Enrico Baldi
- Arrhythmia and Electrophysiology Unit, Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Antonio Toscano
- Department of Anaesthesia, Critical Care and Emergency, ‘Città della Salute e della Scienza’ Hospital, Torino, Italy
| | - Carol Gravinese
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Simone Frea
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Sara Compagnoni
- Department of Molecular Medicine, Section of Cardiology, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy
| | - Arianna Morena
- Cardiology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Andrea Saglietto
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Eleonora Balzani
- Department of Surgical Sciences, University of Turin, Torino, Italy
| | - Matteo Giunta
- Department of Anaesthesia, Critical Care and Emergency, ‘Città della Salute e della Scienza’ Hospital, Torino, Italy
| | - Andrea Costamagna
- Department of Anaesthesia, Critical Care and Emergency, ‘Città della Salute e della Scienza’ Hospital, Torino, Italy
| | - Mauro Rinaldi
- Department of Surgical Sciences, University of Turin, Torino, Italy
- Department of Cardiovascular and Thoracic Surgery, ‘Città della Salute e della Scienza’ Hospital, Torino, Italy
| | - Anna Chiara Trompeo
- Department of Anaesthesia, Critical Care and Emergency, ‘Città della Salute e della Scienza’ Hospital, Torino, Italy
| | - Roberto Rordorf
- Arrhythmia and Electrophysiology Unit, Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Matteo Anselmino
- Cardiology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
| | - Simone Savastano
- Arrhythmia and Electrophysiology Unit, Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Gaetano Maria De Ferrari
- Cardiology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
- Division of Cardiology, Cardiovascular and Thoracic Department, ‘Città della Salute e della Scienza’ Hospital, Corso Bramante 88/90, 10126 Torino, Italy
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21
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Malik V, Shivkumar K. Stellate ganglion blockade for the management of ventricular arrhythmia storm. Eur Heart J 2024; 45:834-836. [PMID: 38366239 PMCID: PMC10919926 DOI: 10.1093/eurheartj/ehae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/18/2024] Open
Affiliation(s)
- Varun Malik
- Cardiac Arrhythmia Center, University of California, Los Angeles (UCLA), 100 UCLA Medical Plaza, Suite 660, Los Angeles, CA 90095, USA
- Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
| | - Kalyanam Shivkumar
- Cardiac Arrhythmia Center, University of California, Los Angeles (UCLA), 100 UCLA Medical Plaza, Suite 660, Los Angeles, CA 90095, USA
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22
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Donahue JK, Chrispin J, Ajijola OA. Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar. Circ Res 2024; 134:328-342. [PMID: 38300981 PMCID: PMC10836816 DOI: 10.1161/circresaha.123.321553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.
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Affiliation(s)
| | | | - Olujimi A. Ajijola
- UCLA Cardiac Arrhythmia Center, David Geffen School of Medicine at UCLA, Los Angeles, CA USA
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23
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Trohman RG. Etiologies, Mechanisms, Management, and Outcomes of Electrical Storm. J Intensive Care Med 2024; 39:99-117. [PMID: 37731333 DOI: 10.1177/08850666231192050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2023]
Abstract
Electrical storm (ES) is characterized by three or more discrete sustained ventricular tachyarrhythmia episodes occurring within a limited time frame (generally ≤ 24 h) or an incessant ventricular tachyarrhythmia lasting > 12 h. In patients with an implantable cardioverterdefibrillator (ICD), ES is defined as three or more appropriate device therapies, separated from each other by at least 5 min, which occur within a 24-h period. ES may constitute a medical emergency, depending on the number arrhythmic episodes, their duration, the type, and the cycle length of the ventricular arrhythmias, as well as the underlying ventricular function. This narrative review was facilitated by a search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1999 and 2023. ES was searched using the terms mechanisms, genetics, channelopathies, management, pharmacological therapy, sedation, neuraxial modulation, cardiac sympathetic denervation, ICDs, and structural heart disease. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. This manuscript examines the current strategies available to treat ES and compares pharmacological and invasive treatment strategies to diminish ES recurrence, morbidity, and mortality.
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Affiliation(s)
- Richard G Trohman
- Section of Electrophysiology, Division of Cardiology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
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24
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Meter M, Borovac JA. A Refractory Electrical Storm after Acute Myocardial Infarction: The Role of Temporary Ventricular Overdrive Pacing as a Bridge to ICD Implantation. PATHOPHYSIOLOGY 2024; 31:44-51. [PMID: 38251048 PMCID: PMC10801483 DOI: 10.3390/pathophysiology31010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 01/23/2024] Open
Abstract
An electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 h. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1-V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On day 8 of hospitalization, the patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.
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Affiliation(s)
- Mijo Meter
- Cardiovascular Diseases Department, University Hospital of Split (KBC Split), Spinciceva 1, 21000 Split, Croatia;
| | - Josip Andelo Borovac
- Cardiovascular Diseases Department, University Hospital of Split (KBC Split), Spinciceva 1, 21000 Split, Croatia;
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia
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25
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López-Millán Infantes JM, Coca-Gamito C, Cámara-Faraig A, Díaz-Infante E, García-Rubira JC. Stellate ganglion block for the management of electrical storm: An observational study. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2024; 71:1-7. [PMID: 37666452 DOI: 10.1016/j.redare.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 01/11/2023] [Indexed: 09/06/2023]
Abstract
INTRODUCTION Electrical storm is a life-threatening emergency with a high mortality rate. When acute conventional treatment is ineffective, stellate ganglion block can help control arrhythmia by providing a visceral cervicothoracic sympathetic block. The objective of this study is to assess the effectiveness and safety of stellate ganglion block in the management of refractory arrhythmic storm. METHOD Follow-up of a cohort of patients with refractory electrical storm that met the criteria for performing stellate ganglion block. The block was ultrasound-guided at C6 using local anaesthetic and a steroid - left unilateral first, bilateral if no response, followed by fluoroscopy-guided radiofrequency ablation at C7 if there was a favourable response but subsequent relapse. RESULTS Seven patients were included. The in-hospital mortality rate was 14.29%. Four patients received unilateral and 3 bilateral stellate ganglion block. Six were ablated and 1 received an implantable cardioverter-defibrillator. Electrical storm was controlled temporarily beyond the effect of the local anaesthetic in all patients. Three patients underwent radiofrequency ablation and 2 underwent surgical thoracic sympathectomy. The only side effect was Horner's syndrome, which was observed in all cases after administering a stellate ganglion block with local anaesthetic. Two patients died after discharge and 4 are alive at the time of writing, 3 of them have not been re-admitted for ventricular events for more than 2 years. CONCLUSION Ultrasound-guided stellate ganglion block is an effective and safe complement to standard cardiological treatment of refractory electrical storm.
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Affiliation(s)
- J M López-Millán Infantes
- Department of Anaesthesiology, Critical Care and Pain Medicine, Virgen Macarena University Hospital, Seville, Spain.
| | - C Coca-Gamito
- Department of Anaesthesiology, Critical Care and Pain Medicine, Virgen Macarena University Hospital, Seville, Spain
| | - A Cámara-Faraig
- Department of Anaesthesiology, Critical Care and Pain Medicine, Virgen Macarena University Hospital, Seville, Spain
| | - E Díaz-Infante
- Department of Cardiology, Arrhythmia Unit, Virgen Macarena University Hospital, Seville, Spain
| | - J C García-Rubira
- Department of Cardiology, Coronary Unit, Virgen Macarena University Hospital, Seville, Spain
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26
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Salamon RJ, Halbe P, Kasberg W, Bae J, Audhya A, Mahmoud AI. Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration. iScience 2023; 26:107709. [PMID: 37674983 PMCID: PMC10477065 DOI: 10.1016/j.isci.2023.107709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 07/25/2023] [Accepted: 08/23/2023] [Indexed: 09/08/2023] Open
Abstract
Sympathetic innervation influences homeostasis, repair, and pathology in the cardiac ventricles; in contrast, parasympathetic innervation is considered to have minimal contribution and influence in the ventricles. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling to define cardiac nerve architecture during development, disease, and regeneration. Our approach reveals that parasympathetic nerves extensively innervate the cardiac ventricles. Furthermore, we identify that parasympathetic and sympathetic axons develop synchronously and are bundled throughout the ventricles. We further investigate cardiac nerve remodeling in the regenerative neonatal and the non-regenerative postnatal mouse heart. Our results show that the regenerating myocardium undergoes a unique process of physiological reinnervation, where proper nerve distribution and architecture is reestablished, in stark contrast to the non-regenerating heart. Mechanistically, we demonstrate that physiological reinnervation during regeneration is dependent on collateral artery formation. Our results reveal clinically significant insights into cardiac nerve plasticity which can identify new therapies for cardiac disease.
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Affiliation(s)
- Rebecca J. Salamon
- Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Poorva Halbe
- Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - William Kasberg
- Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Jiyoung Bae
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA
| | - Anjon Audhya
- Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Ahmed I. Mahmoud
- Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
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27
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Zhang L, Guo F, Xu S, Deng Q, Xie M, Sun J, Kwok RTK, Lam JWY, Deng H, Jiang H, Yu L, Tang BZ. AIEgen-Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023:e2304620. [PMID: 37532257 DOI: 10.1002/adma.202304620] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/14/2023] [Indexed: 08/04/2023]
Abstract
The engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF are reported, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuroinflammation peri-SG microenvironment, which is favorable for inhibiting ischemia-induced VAs. In vivo studies have confirmed that BTDBETA-COF-mediated LHT enhances thermogenesis and browning-related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri-SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA-COF-mediated LHT in ameliorating the neuroinflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. The work on AIE COF-based hyperthermia agent for VAs inhibition provides a new avenue for mitigating cardiac sympathetic nerve hyperactivity.
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Affiliation(s)
- Liang Zhang
- Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
- Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Key Laboratory of Biomedical Polymers-Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Luojiashan, Wuhan, 430072, China
| | - Fuding Guo
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Saiting Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Qiang Deng
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Mengjie Xie
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Jianwei Sun
- Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China
| | - Ryan T K Kwok
- Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China
| | - Jacky W Y Lam
- Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China
| | - Hexiang Deng
- Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Key Laboratory of Biomedical Polymers-Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Luojiashan, Wuhan, 430072, China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Lilei Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China
| | - Ben Zhong Tang
- Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China
- Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, China
- Center for Aggregation-Induced Emission, South China University of Technology, Guangzhou, 510640, China
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28
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van Weperen VYH, Ripplinger CM, Vaseghi M. Autonomic control of ventricular function in health and disease: current state of the art. Clin Auton Res 2023; 33:491-517. [PMID: 37166736 PMCID: PMC10173946 DOI: 10.1007/s10286-023-00948-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 04/20/2023] [Indexed: 05/12/2023]
Abstract
PURPOSE Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure. METHODS Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized. RESULTS A harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain. CONCLUSIONS Although our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging.
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Affiliation(s)
- Valerie Y H van Weperen
- Division of Cardiology, Department of Medicine, UCLA Cardiac Arrythmia Center, University of California, 100 Medical Plaza, Suite 660, Los Angeles, CA, 90095, USA
| | | | - Marmar Vaseghi
- Division of Cardiology, Department of Medicine, UCLA Cardiac Arrythmia Center, University of California, 100 Medical Plaza, Suite 660, Los Angeles, CA, 90095, USA.
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29
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Salavatian S, Kuwabara Y, Wong B, Fritz JR, Howard-Quijano K, Foreman RD, Armour JA, Ardell JL, Mahajan A. Spinal neuromodulation mitigates myocardial ischemia-induced sympathoexcitation by suppressing the intermediolateral nucleus hyperactivity and spinal neural synchrony. Front Neurosci 2023; 17:1180294. [PMID: 37332861 PMCID: PMC10272539 DOI: 10.3389/fnins.2023.1180294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/16/2023] [Indexed: 06/20/2023] Open
Abstract
Introduction Myocardial ischemia disrupts the cardio-spinal neural network that controls the cardiac sympathetic preganglionic neurons, leading to sympathoexcitation and ventricular tachyarrhythmias (VTs). Spinal cord stimulation (SCS) is capable of suppressing the sympathoexcitation caused by myocardial ischemia. However, how SCS modulates the spinal neural network is not fully known. Methods In this pre-clinical study, we investigated the impact of SCS on the spinal neural network in mitigating myocardial ischemia-induced sympathoexcitation and arrhythmogenicity. Ten Yorkshire pigs with left circumflex coronary artery (LCX) occlusion-induced chronic myocardial infarction (MI) were anesthetized and underwent laminectomy and a sternotomy at 4-5 weeks post-MI. The activation recovery interval (ARI) and dispersion of repolarization (DOR) were analyzed to evaluate the extent of sympathoexcitation and arrhythmogenicity during the left anterior descending coronary artery (LAD) ischemia. Extracellular in vivo and in situ spinal dorsal horn (DH) and intermediolateral column (IML) neural recordings were performed using a multichannel microelectrode array inserted at the T2-T3 segment of the spinal cord. SCS was performed for 30 min at 1 kHz, 0.03 ms, 90% motor threshold. LAD ischemia was induced pre- and 1 min post-SCS to investigate how SCS modulates spinal neural network processing of myocardial ischemia. DH and IML neural interactions, including neuronal synchrony as well as cardiac sympathoexcitation and arrhythmogenicity markers were evaluated during myocardial ischemia pre- vs. post-SCS. Results ARI shortening in the ischemic region and global DOR augmentation due to LAD ischemia was mitigated by SCS. Neural firing response of ischemia-sensitive neurons during LAD ischemia and reperfusion was blunted by SCS. Further, SCS showed a similar effect in suppressing the firing response of IML and DH neurons during LAD ischemia. SCS exhibited a similar suppressive impact on the mechanical, nociceptive and multimodal ischemia sensitive neurons. The LAD ischemia and reperfusion-induced augmentation in neuronal synchrony between DH-DH and DH-IML pairs of neurons were mitigated by the SCS. Discussion These results suggest that SCS is decreasing the sympathoexcitation and arrhythmogenicity by suppressing the interactions between the spinal DH and IML neurons and activity of IML preganglionic sympathetic neurons.
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Affiliation(s)
- Siamak Salavatian
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Division of Cardiology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Yuki Kuwabara
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Benjamin Wong
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Jonathan R. Fritz
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Kimberly Howard-Quijano
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Robert D. Foreman
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - J. Andrew Armour
- Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Jeffrey L. Ardell
- Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Aman Mahajan
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
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30
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McCabe MD, Cervantes R, Kewcharoen J, Sran J, Garg J. Quelling the Storm: A Review of the Management of Electrical Storm. J Cardiothorac Vasc Anesth 2023:S1053-0770(23)00338-5. [PMID: 37296026 DOI: 10.1053/j.jvca.2023.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/17/2023] [Indexed: 06/12/2023]
Abstract
Heightened sympathetic input to the myocardium potentiates cardiac electrical instability and may herald an electrical storm. An electrical storm is characterized by 3 or more episodes of ventricular tachycardia, ventricular fibrillation, or appropriate internal cardiac defibrillator shocks within 24 hours. Management of electrical storms is resource-intensive and inevitably requires careful coordination between multiple subspecialties. Anesthesiologists have an important role in acute, subacute, and long-term management. Identifying the phase of an electrical storm and understanding the characteristics of each morphology may help the anesthesiologist anticipate the management approach. In the acute phase, management of an electrical storm is aimed at providing advanced cardiac life support and identifying reversible causes. After initial stabilization, subacute management focuses on dampening the sympathetic surge with sedation, thoracic epidural, or stellate ganglion blockade. Definitive long-term management with surgical sympathectomy or catheter ablation also may be warranted. Our objective is to provide an overview of electrical storms and the anesthesiologist's role in management.
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Affiliation(s)
- Melissa D McCabe
- Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California.
| | - Richard Cervantes
- Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California
| | - Jakrin Kewcharoen
- Cardiac Arrhythmia Service, Loma Linda University School of Medicine, Loma Linda, California
| | - Jasmine Sran
- Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California
| | - Jalaj Garg
- Cardiac Arrhythmia Service, Loma Linda University School of Medicine, Loma Linda, California
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31
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Hori K, Tsujikawa S, Egami M, Waki S, Watanabe R, Hino H, Matsuura T, Mori T. Thoracic epidural analgesia prolongs postoperative QT interval on electrocardiogram in major non-cardiac surgery: a randomized comparison and a prospective cohort analysis. Front Pharmacol 2023; 14:936242. [PMID: 37274100 PMCID: PMC10235468 DOI: 10.3389/fphar.2023.936242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 05/09/2023] [Indexed: 06/06/2023] Open
Abstract
Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study. Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3 ml/h of 0.25% epidural levobupivacaine (7.5 mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5 ml/h epidural levobupivacaine (12.5 mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry. Results: The median postoperative corrected QT interval interval with 3 ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23 ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164 ng/ml with 3 ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5 ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166 ng/ml with 5 ml/h, the correlation coefficient of which showed no significant correlation. Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine. Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center.
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Affiliation(s)
- Kotaro Hori
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Shogo Tsujikawa
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Mika Egami
- Central Laboratory, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Sayaka Waki
- Department of Anesthesiology, Osaka Rosai Hospital, Osaka, Japan
| | - Ryota Watanabe
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hideki Hino
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Tadashi Matsuura
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Takashi Mori
- Department of Anesthesiology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Chung WH, Lin YN, Wu MY, Chang KC. Sympathetic Modulation in Cardiac Arrhythmias: Where We Stand and Where We Go. J Pers Med 2023; 13:786. [PMID: 37240956 PMCID: PMC10221179 DOI: 10.3390/jpm13050786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 04/27/2023] [Accepted: 04/29/2023] [Indexed: 05/28/2023] Open
Abstract
The nuance of autonomic cardiac control has been studied for more than 400 years, yet little is understood. This review aimed to provide a comprehensive overview of the current understanding, clinical implications, and ongoing studies of cardiac sympathetic modulation and its anti-ventricular arrhythmias' therapeutic potential. Molecular-level studies and clinical studies were reviewed to elucidate the gaps in knowledge and the possible future directions for these strategies to be translated into the clinical setting. Imbalanced sympathoexcitation and parasympathetic withdrawal destabilize cardiac electrophysiology and confer the development of ventricular arrhythmias. Therefore, the current strategy for rebalancing the autonomic system includes attenuating sympathoexcitation and increasing vagal tone. Multilevel targets of the cardiac neuraxis exist, and some have emerged as promising antiarrhythmic strategies. These interventions include pharmacological blockade, permanent cardiac sympathetic denervation, temporal cardiac sympathetic denervation, etc. The gold standard approach, however, has not been known. Although neuromodulatory strategies have been shown to be highly effective in several acute animal studies with very promising results, the individual and interspecies variation between human autonomic systems limits the progress in this young field. There is, however, still much room to refine the current neuromodulation therapy to meet the unmet need for life-threatening ventricular arrhythmias.
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Affiliation(s)
- Wei-Hsin Chung
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- UCLA Cardiac Arrhythmia Center, Ronald Reagan UCLA Medical Center, Los Angeles, CA 90024, USA
| | - Yen-Nien Lin
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- School of Medicine, China Medical University, Taichung 404333, Taiwan
| | - Mei-Yao Wu
- School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404333, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Kuan-Cheng Chang
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- School of Medicine, China Medical University, Taichung 404333, Taiwan
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Howard-Quijano K, Kuwabara Y, Yamaguchi T, Roman K, Salavatian S, Taylor B, Mahajan A. GABAergic Signaling during Spinal Cord Stimulation Reduces Cardiac Arrhythmias in a Porcine Model. Anesthesiology 2023; 138:372-387. [PMID: 36724342 PMCID: PMC9998372 DOI: 10.1097/aln.0000000000004516] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Neuraxial modulation, including spinal cord stimulation, reduces cardiac sympathoexcitation and ventricular arrhythmogenesis. There is an incomplete understanding of the molecular mechanisms through which spinal cord stimulation modulates cardiospinal neural pathways. The authors hypothesize that spinal cord stimulation reduces myocardial ischemia-reperfusion-induced sympathetic excitation and ventricular arrhythmias through γ-aminobutyric acid (GABA)-mediated pathways in the thoracic spinal cord. METHODS Yorkshire pigs were randomized to control (n = 11), ischemia-reperfusion (n = 16), ischemia-reperfusion plus spinal cord stimulation (n = 17), ischemia-reperfusion plus spinal cord stimulation plus γ-aminobutyric acid type A (GABAA) or γ-aminobutyric acid type B (GABAB) receptor antagonist (GABAA, n = 8; GABAB, n = 8), and ischemia-reperfusion plus GABA transaminase inhibitor (GABAculine, n = 8). A four-pole spinal cord stimulation lead was placed epidurally (T1 to T4). GABA modulating pharmacologic agents were administered intrathecally. Spinal cord stimulation at 50 Hz was applied 30 min before ischemia. A 56-electrode epicardial mesh was used for high-resolution electrophysiologic recordings, including activation recovery intervals and ventricular arrhythmia scores. Immunohistochemistry and Western blots were performed to measure GABA receptor expression in the thoracic spinal cord. RESULTS Cardiac ischemia led to myocardial sympathoexcitation with reduction in activation recovery interval (mean ± SD, -42 ± 11%), which was attenuated by spinal cord stimulation (-21 ± 17%, P = 0.001). GABAA and GABAB receptor antagonists abolished spinal cord stimulation attenuation of sympathoexcitation (GABAA, -9.7 ± 9.7%, P = 0.043 vs. ischemia-reperfusion plus spinal cord stimulation; GABAB, -13 ± 14%, P = 0.012 vs. ischemia-reperfusion plus spinal cord stimulation), while GABAculine alone caused a therapeutic effect similar to spinal cord stimulation (-4.1 ± 3.7%, P = 0.038 vs. ischemia-reperfusion). The ventricular arrhythmia score supported these findings. Spinal cord stimulation during ischemia-reperfusion increased GABAA receptor expression with no change in GABAB receptor expression. CONCLUSIONS Thoracic spinal cord stimulation reduces ischemia-reperfusion-induced sympathoexcitation and ventricular arrhythmias through activation of GABA signaling pathways. These data support the hypothesis that spinal cord stimulation-induced release of GABA activates inhibitory interneurons to decrease primary afferent signaling from superficial dorsal horn to sympathetic output neurons in the intermediolateral nucleus. EDITOR’S PERSPECTIVE
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Affiliation(s)
- Kimberly Howard-Quijano
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center. 200 Lothrop St, Pittsburgh, PA 15213, United States
| | - Yuki Kuwabara
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
| | - Tomoki Yamaguchi
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
| | - Kenny Roman
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
| | - Siamak Salavatian
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
| | - Bradley Taylor
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
| | - Aman Mahajan
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh. A-1305 Scaife Hall, 3550 Terrace Street Pittsburgh, PA 15261, United States
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center. 200 Lothrop St, Pittsburgh, PA 15213, United States
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Zhou L, Zhang Y, Cao G, Zhang C, Zheng C, Meng G, Lai Y, Zhou Z, Liu Z, Liu Z, Guo F, Dong X, Liang Z, Wang Y, Guo S, Zhou X, Jiang H, Yu L. Wireless Self-Powered Optogenetic System for Long-Term Cardiac Neuromodulation to Improve Post-MI Cardiac Remodeling and Malignant Arrhythmia. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2205551. [PMID: 36698262 PMCID: PMC10037959 DOI: 10.1002/advs.202205551] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 12/02/2022] [Indexed: 06/17/2023]
Abstract
Autonomic imbalance is an important characteristic of patients after myocardial infarction (MI) and adversely contributes to post-MI cardiac remodeling and ventricular arrhythmias (VAs). A previous study proved that optogenetic modulation could precisely inhibit cardiac sympathetic hyperactivity and prevent acute ischemia-induced VAs. Here, a wireless self-powered optogenetic modulation system is introduced, which achieves long-term precise cardiac neuromodulation in ambulatory canines. The wireless self-powered optical system based on a triboelectric nanogenerator is powered by energy harvested from body motion and realized the effective optical illumination that is required for optogenetic neuromodulation (ON). It is further demonstrated that long-term ON significantly mitigates MI-induced sympathetic remodeling and hyperactivity, and improves a variety of clinically relevant outcomes such as improves ventricular dysfunction, reduces infarct size, increases electrophysiological stability, and reduces susceptibility to VAs. These novel insights suggest that wireless ON holds translational potential for the clinical treatment of arrhythmia and other cardiovascular diseases related to sympathetic hyperactivity. Moreover, this innovative self-powered optical system may provide an opportunity to develop implantable/wearable and self-controllable devices for long-term optogenetic therapy.
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Affiliation(s)
- Liping Zhou
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Yuanzheng Zhang
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
- Hubei Yangtze Memory LaboratoriesKey Laboratory of Artificial Micro, and Nano‐structures of Ministry of EducationSchool of Physics and TechnologyWuhan UniversityWuhan430072P. R. China
| | - Gang Cao
- Biomedical CenterCollege of Veterinary MedicineHuazhong Agricultural UniversityWuhan430072P. R. China
| | - Chi Zhang
- Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan430072P. R. China
| | - Chen Zheng
- Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan430072P. R. China
| | - Guannan Meng
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Yanqiu Lai
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Zhen Zhou
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Zhihao Liu
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Zihan Liu
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Fuding Guo
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Xin Dong
- Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan430072P. R. China
| | - Zhizhuo Liang
- Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan430072P. R. China
| | - Yueyi Wang
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Shishang Guo
- Hubei Yangtze Memory LaboratoriesKey Laboratory of Artificial Micro, and Nano‐structures of Ministry of EducationSchool of Physics and TechnologyWuhan UniversityWuhan430072P. R. China
| | - Xiaoya Zhou
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Hong Jiang
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
| | - Lilei Yu
- Department of CardiologyRenmin Hospital of Wuhan UniversityHubei Key Laboratory of Autonomic Nervous System ModulationCardiac Autonomic Nervous System Research Center of Wuhan UniversityTaikang Center for Life and Medical SciencesWuhan UniversityCardiovascular Research InstituteWuhan UniversityHubei Key Laboratory of CardiologyWuhan430060P. R. China
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Guarracini F, Bonvicini E, Zanon S, Martin M, Casagranda G, Mochen M, Coser A, Quintarelli S, Branzoli S, Mazzone P, Bonmassari R, Marini M. Emergency Management of Electrical Storm: A Practical Overview. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:405. [PMID: 36837606 PMCID: PMC9963509 DOI: 10.3390/medicina59020405] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 02/08/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023]
Abstract
Electrical storm is a medical emergency characterized by ventricular arrythmia recurrence that can lead to hemodynamic instability. The incidence of this clinical condition is rising, mainly in implantable cardioverter defibrillator patients, and its prognosis is often poor. Early acknowledgment, management and treatment have a key role in reducing mortality in the acute phase and improving the quality of life of these patients. In an emergency setting, several measures can be employed. Anti-arrhythmic drugs, based on the underlying disease, are often the first step to control the arrhythmic burden; besides that, new therapeutic strategies have been developed with high efficacy, such as deep sedation, early catheter ablation, neuraxial modulation and mechanical hemodynamic support. The aim of this review is to provide practical indications for the management of electrical storm in acute settings.
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Affiliation(s)
| | - Eleonora Bonvicini
- Department of Cardiology, S. Chiara Hospital, 38122 Trento, Italy
- Department of Cardiology, University of Verona, 37126 Verona, Italy
| | - Sofia Zanon
- Department of Cardiology, University of Verona, 37126 Verona, Italy
| | - Marta Martin
- Department of Cardiology, S. Chiara Hospital, 38122 Trento, Italy
| | | | - Marianna Mochen
- Department of Radiology, Santa Chiara Hospital, 38122 Trento, Italy
| | - Alessio Coser
- Department of Cardiology, S. Chiara Hospital, 38122 Trento, Italy
| | | | - Stefano Branzoli
- Cardiac Surgery Unit, Santa Chiara Hospital, 38122 Trento, Italy
- Department of Cardiac Surgery, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, 1090 Brussels, Belgium
| | - Patrizio Mazzone
- Cardiothoracovascular Department, Electrophysiology Unit, Niguarda Hospital, 20162 Milan, Italy
| | | | - Massimiliano Marini
- Department of Cardiology, S. Chiara Hospital, 38122 Trento, Italy
- Heart Rhythm Management Centre, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, 1090 Brussel, Belgium
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Elia A, Fossati S. Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer's disease. Front Physiol 2023; 14:1060666. [PMID: 36798942 PMCID: PMC9926972 DOI: 10.3389/fphys.2023.1060666] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 01/19/2023] [Indexed: 01/31/2023] Open
Abstract
The heart is a functional syncytium controlled by a delicate and sophisticated balance ensured by the tight coordination of its several cell subpopulations. Accordingly, cardiomyocytes together with the surrounding microenvironment participate in the heart tissue homeostasis. In the right atrium, the sinoatrial nodal cells regulate the cardiac impulse propagation through cardiomyocytes, thus ensuring the maintenance of the electric network in the heart tissue. Notably, the central nervous system (CNS) modulates the cardiac rhythm through the two limbs of the autonomic nervous system (ANS): the parasympathetic and sympathetic compartments. The autonomic nervous system exerts non-voluntary effects on different peripheral organs. The main neuromodulator of the Sympathetic Nervous System (SNS) is norepinephrine, while the principal neurotransmitter of the Parasympathetic Nervous System (PNS) is acetylcholine. Through these two main neurohormones, the ANS can gradually regulate cardiac, vascular, visceral, and glandular functions by turning on one of its two branches (adrenergic and/or cholinergic), which exert opposite effects on targeted organs. Besides these neuromodulators, the cardiac nervous system is ruled by specific neuropeptides (neurotrophic factors) that help to preserve innervation homeostasis through the myocardial layers (from epicardium to endocardium). Interestingly, the dysregulation of this neuro-signaling pathway may expose the cardiac tissue to severe disorders of different etiology and nature. Specifically, a maladaptive remodeling of the cardiac nervous system may culminate in a progressive loss of neurotrophins, thus leading to severe myocardial denervation, as observed in different cardiometabolic and neurodegenerative diseases (myocardial infarction, heart failure, Alzheimer's disease). This review analyzes the current knowledge on the pathophysiological processes involved in cardiac nervous system impairment from the perspectives of both cardiac disorders and a widely diffused and devastating neurodegenerative disorder, Alzheimer's disease, proposing a relationship between neurodegeneration, loss of neurotrophic factors, and cardiac nervous system impairment. This overview is conducive to a more comprehensive understanding of the process of cardiac neuro-signaling dysfunction, while bringing to light potential therapeutic scenarios to correct or delay the adverse cardiovascular remodeling, thus improving the cardiac prognosis and quality of life in patients with heart or neurodegenerative disorders.
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Sharma S, Littman R, Tompkins J, Arneson D, Contreras J, Dajani AH, Ang K, Tsanhani A, Sun X, Jay PY, Herzog H, Yang X, Ajijola OA. Tiered Sympathetic Control of Cardiac Function Revealed by Viral Tracing and Single Cell Transcriptome Profiling. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.18.524575. [PMID: 36711942 PMCID: PMC9882306 DOI: 10.1101/2023.01.18.524575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) Npy-expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.
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Salamon RJ, Halbe P, Kasberg W, Bae J, Audhya A, Mahmoud AI. Defining Cardiac Nerve Architecture During Development, Disease, and Regeneration. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2022.12.31.522405. [PMID: 36711742 PMCID: PMC9881855 DOI: 10.1101/2022.12.31.522405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Cardiac nerves regulate neonatal mouse heart regeneration and are susceptible to pathological remodeling following adult injury. Understanding cardiac nerve remodeling can lead to new strategies to promote cardiac repair. Our current understanding of cardiac nerve architecture has been limited to two-dimensional analysis. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling tools to define cardiac nerve architecture and neurovascular association during development, disease, and regeneration. Our results demonstrate that cardiac nerves sequentially associate with coronary veins and arteries during development. Remarkably, our results reveal that parasympathetic nerves densely innervate the ventricles. Furthermore, parasympathetic and sympathetic nerves develop synchronously and are intertwined throughout the ventricles. Importantly, the regenerating myocardium reestablishes physiological innervation, in stark contrast to the non-regenerating heart. Mechanistically, reinnervation during regeneration is dependent on collateral artery formation. Our results reveal how defining cardiac nerve remodeling during homeostasis, disease, and regeneration can identify new therapies for cardiac disease.
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Sridharan A, Bradfield JS, Shivkumar K, Ajijola OA. Autonomic nervous system and arrhythmias in structural heart disease. Auton Neurosci 2022; 243:103037. [DOI: 10.1016/j.autneu.2022.103037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/21/2022] [Accepted: 09/21/2022] [Indexed: 11/28/2022]
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Cardiac Sympathetic Denervation for the Management of Ventricular Arrhythmias. J Interv Card Electrophysiol 2022; 65:813-826. [PMID: 35397706 DOI: 10.1007/s10840-022-01211-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 03/29/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND The autonomic nervous system contributes to the pathogenesis of ventricular arrhythmias (VA). Though anti-arrhythmic drug therapy and catheter ablation are the mainstay of management of VAs, success may be limited in patients with more refractory arrhythmias. Sympathetic modulation is increasingly recognized as a valuable adjunct tool for managing VAs in patients with structural heart disease and inherited arrhythmias. RESULTS In this review, we explore the role of the sympathetic nervous system and rationale for cardiac sympathetic denervation (CSD) in VAs and provide a disease-focused review of the utility of CSD for patients both with and without structural heart disease. CONCLUSIONS We conclude that CSD is a reasonable therapeutic option for patients with VA, both with and without structural heart disease. Though not curative, many studies have demonstrated a significant reduction in the burden of VAs for the majority of patients undergoing the procedure. However, in patients with unilateral CSD and subsequent VA recurrence, complete bilateral CSD may provide long-lasting reprieve from VA.
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Zhang S, Wang M, Jiao L, Liu C, Chen H, Zhou L, Wang Y, Wang Y, Liu Z, Liu Z, Zhou Y, Zhou H, Xu X, Li Z, Liu Z, Yu Z, Nie L, Yu L, Jiang H. Ultrasound-guided injection of botulinum toxin type A blocks cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic myocardial infarction. Heart Rhythm 2022; 19:2095-2104. [PMID: 35948203 DOI: 10.1016/j.hrthm.2022.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/20/2022] [Accepted: 08/01/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Strategies to improve various cardiovascular diseases by blocking cardiac sympathetic ganglion have been increasingly available currently. Botulinum toxin type A (BTA), a typical neurotoxin, has been shown to block neural transmission in a safe and long-lasting manner. OBJECTIVE The aim of the present preclinical study was to assess the efficacy of BTA microinjection to alleviate cardiac remodeling after chronic myocardial infarction (MI) by blocking cardiac sympathetic ganglion in a canine model. METHODS Beagles were randomly divided into a control group (saline microinjection with sham surgery), an MI group (saline microinjection with MI), and an MI + BTA group (BTA microinjection with MI). Ultrasound-guided percutaneous BTA or saline injection into the left stellate ganglion (LSG) was performed followed by MI induction via left anterior descending artery occlusion (LADO) or sham surgery. After 30 days, electrocardiography, Doppler echocardiography, LSG function, neural activity, and ventricular electrophysiological detection were performed in all experimental dogs. At the end, LSG and ventricular tissues were collected for further detection. RESULTS BTA treatment significantly inhibited LSG function and neural activity and improved heart rate variability. Additionally, BTA application alleviated ventricular remodeling, ameliorated cardiac function, and prevented ventricular arrhythmias after 30-day chronic LADO-induced MI. CONCLUSION Ultrasound-guided percutaneous microinjection of BTA can block cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic LADO-induced MI. Ultrasound-guided BTA microinjection has potential for clinical application as a novel cardiac sympathetic ganglion blockade strategy for MI.
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Affiliation(s)
- Song Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Meng Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Liying Jiao
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Chengzhe Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Huaqiang Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Liping Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yueyi Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yuhong Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zhihao Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zihan Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yuyang Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Huixin Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Xiao Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zeyan Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zhihao Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zhongyang Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Liqing Nie
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Lilei Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China.
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China
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42
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Ponde VC, Bosenberg AT, Lokhandwala YY, Nagdev T, Puri K. Diagnostic and therapeutic application of thoracic epidural in a child with intractable cardiac arrhythmias: A case report. Paediatr Anaesth 2022; 32:1073-1075. [PMID: 35656894 DOI: 10.1111/pan.14503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/17/2022] [Accepted: 05/29/2022] [Indexed: 12/01/2022]
Abstract
A 3-year-old boy presented with episodes of uneasiness and transient loss of consciousness. Atrial tachyarrhythmias with rapid ventricular rate was diagnosed and initially unsuccessfully treated with oral antiarrhythmic drugs. Subsequent Holter monitoring revealed ventricular arrhythmias. Despite pharmacologic treatment, he needed numerous cardioversions. Surgical sympathectomy was planned. Initially, sympathectomy was achieved using a continuous high thoracic epidural block and was performed to ascertain the efficacy of the thoracic sympathectomy. This successfully reduced the ventricular arrhythmias and the need for antiarrhythmic agents. The epidural infusion was also used for pain relief following the subsequent surgical sympathectomy.
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Affiliation(s)
| | | | | | | | - Kriti Puri
- Kovai Medical Center Hospital, Coimbatore, India
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43
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Miki Y, Yoshimura S, Sasaki T, Takizawa R, Kimura K, Haraguchi Y, Sasaki W, Kishi S, Nakatani Y, Kaseno K, Goto K, Take Y, Nakamura K, Niwamae N, Kamiyoshihara M, Naito S. Bilateral Cardiac Sympathetic Denervation for Treatment-Resistant Ventricular Arrhythmias in Heart Failure Patients with a Reduced Ejection Fraction. Int Heart J 2022; 63:692-699. [PMID: 35908853 DOI: 10.1536/ihj.21-601] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The sympathetic nervous system plays an important role in life-threatening ventricular arrhythmias (VAs). Bilateral cardiac sympathetic denervation (BCSD) is performed for refractory VAs. We sought to assess our institutional experience with BCSD in managing treatment-resistant monomorphic ventricular tachycardia (MMVT) in heart failure patients with a reduced ejection fraction (HFrEF).Four patients with HFrEF (EF 30.0 ± 8.2%, New York Heart Association [NYHA] class IV 1) underwent BCSD for MMVT (VT storm 3, repetitive VT requiring implantable cardioverter defibrillator [ICD] therapy 1) refractory to antiarrhythmic drugs, catheter ablation and ICD therapy. BCSD was effective for suppressing VT in 3 patients for whom deep sedation was effective for suppressing VT. One patient remained alive after 14 months of follow-up without episodes of VT. One patient died of acute myocardial infarction before discharge and 1 patient died from unknown cause at 3 days post-discharge. In contrast, BCSD was completely ineffective for suppressing VT in a patient with NYHA class IV for whom deep sedation and stellate ganglion block were ineffective. This patient died on the 10th post-CSD day, despite left ventricular assist device implantation. In all cases, BCSD was successfully performed without procedure-related complications.Despite the limited number of cases, our results showed that BCSD in patients with HFrEF suppressed refractory MMVT in acute-phase except for a patient with NYHA class IV; however, the prognoses were not good. BCSD may be a treatment option at an earlier stage of NYHA and a bridge to orthotopic heart transplantation, even if BCSD is effective for suppressing VAs.
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Affiliation(s)
- Yuko Miki
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | | | - Takehito Sasaki
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Ryoya Takizawa
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Kohki Kimura
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | | | - Wataru Sasaki
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Shohei Kishi
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Yosuke Nakatani
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Kenichi Kaseno
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Koji Goto
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Yutaka Take
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Kohki Nakamura
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
| | - Nogiku Niwamae
- Department of Cardiovascular Medicine, Japanese Red Cross Maebashi Hospital
| | | | - Shigeto Naito
- Division of Cardiology, Gunma Prefectural Cardiovascular Center
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44
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König S, Schröter T, Borger MA, Bertagnolli L, Nedios S, Darma A, Hindricks G, Arya A, Dinov B. Outcomes following cardiac sympathetic denervation in patients with structural heart disease and refractory ventricular arrhythmia. Europace 2022; 24:1800-1808. [DOI: 10.1093/europace/euac078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/02/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Aim
Cardiac sympathetic denervation (CSD) has been introduced as a bailout therapy in patients with structural heart disease and refractory ventricular arrhythmias (VAs), but available data are scarce. Purpose of this study was to estimate immediate results, complications, and mid-term outcomes of CSD following recurrent VA after catheter ablation.
Methods and results
Adult patients who underwent CSD in the Heart Center Leipzig from March 2017 to February 2021 were retrospectively analysed. Follow-up (FU) was executed via implantable cardioverter defibrillator (ICD) interrogation, telephone interviews, and reviewing medical records. Twenty-one patients (age 63.7 ± 14.4 years, all men, 71.4% non-ischaemic cardiomyopathy, left ventricular ejection fraction 31.6 ± 12.6%) received CSD via video-assisted thoracoscopic surgery (90.5% bilateral, 9.5% left-sided only). Indication for CSD was monomorphic ventricular tachycardia in 76.2% and ventricular fibrillation in 23.8 with 71.4% of patients presenting with electrical storm before index hospitalization. Procedure-related major complications occurred in 9.5% of patients. In-hospital adverse events not related to surgery were common (28.6%) and two patients died during the index hospital stay. During FU (mean duration 9.1 ± 6.5 months), five more patients died. Of the remaining patients, 38.5 and 76.9% were free from any VA or ICD shocks, respectively.
Conclusions
The CSD showed additional moderate efficacy to suppress VAs, when performed as a bailout therapy after previously unsuccessful catheter ablation. At 9 months, it was associated with freedom of ICD shocks in two-thirds of patients. In a population with many comorbidities, the rate of CSD-related complications was acceptable, although there was an overall high risk of procedure unrelated adverse events and death.
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Affiliation(s)
- Sebastian König
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
- Leipzig Heart Institute , Leipzig , Germany
| | - Thomas Schröter
- Heart Center Leipzig at University of Leipzig, Department of Cardiac Surgery , Leipzig , Germany
| | - Michael A Borger
- Heart Center Leipzig at University of Leipzig, Department of Cardiac Surgery , Leipzig , Germany
| | - Livio Bertagnolli
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
| | - Sotirios Nedios
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
| | - Angeliki Darma
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
| | - Gerhard Hindricks
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
- Leipzig Heart Institute , Leipzig , Germany
| | - Arash Arya
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
| | - Borislav Dinov
- Department of Electrophysiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, Leipzig 04289 , Germany
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45
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Zhou Z, Liu C, Xu S, Wang J, Guo F, Duan S, Deng Q, Sun J, Yu F, Zhou Y, Wang M, Wang Y, Zhou L, Jiang H, Yu L. Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model. Basic Res Cardiol 2022; 117:34. [PMID: 35819552 DOI: 10.1007/s00395-022-00939-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 06/03/2022] [Accepted: 06/09/2022] [Indexed: 01/31/2023]
Abstract
The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.
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Affiliation(s)
- Zhen Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Chengzhe Liu
- Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Saiting Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Jun Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Fuding Guo
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Shoupeng Duan
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Qiang Deng
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Ji Sun
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Fu Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Yuyang Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Meng Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Yueyi Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Liping Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China. .,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China. .,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. .,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China. .,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China.
| | - Lilei Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China. .,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China. .,Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. .,Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China. .,Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China.
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46
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Tanabe S, Nakano Y, Suzuki Y, Amano T. Successful use of stellate ganglion phototherapy in refractory ventricular tachycardia in a patient with cardiac sarcoidosis. BMJ Case Rep 2022; 15:15/7/e249183. [PMID: 35863858 PMCID: PMC9310165 DOI: 10.1136/bcr-2022-249183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Ventricular arrhythmias are a life-threatening factor in cardiac sarcoidosis (CS), posing a significant therapeutic challenge. Stellate ganglion phototherapy (SGP), a non-invasive procedure for modification of the sympathetic nervous system, is an effective treatment for refractory ventricular tachycardia (RVT). However, there are limited data on the efficacy of SGP for RVT in patients with CS. In our case report, we found that SGP was effective for treating RVT in a patient with CS. We present the case of a man in his 60s with multiple cardioversions of implantable cardioverter defibrillator for ventricular tachycardia. The patient was administered prednisolone for the management of CS, which subsequently led to an increase in anti-tachycardia pacing for ventricular tachycardias. We introduced SGP to suppress RVT and anti-tachycardia pacing decreased from 371 to 25 events. Thus, SGP could be a feasible option for the management of RVT in patients with CS.
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47
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Lee ACH, Tung R, Ferguson MK. Thoracoscopic sympathectomy decreases disease burden in patients with medically refractory ventricular arrhythmias. Interact Cardiovasc Thorac Surg 2022; 34:783-790. [PMID: 35015855 PMCID: PMC9070511 DOI: 10.1093/icvts/ivab372] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 11/22/2021] [Accepted: 12/08/2021] [Indexed: 11/13/2022] Open
Abstract
Abstract
OBJECTIVES
Thoracic sympathectomy has been shown to be effective in reducing implantable cardioverter-defibrillator (ICD) shocks and ventricular tachycardia recurrence in patients with channelopathies, but the evidence supporting its use for refractory ventricular arrhythmias in patients without channelopathies is limited. This is a single-centre cohort study of bilateral R1–R4 thoracoscopic sympathectomy for medically refractory ventricular arrhythmias.
METHODS
Clinical information was examined for all bilateral thoracoscopic R1–R4 sympathectomies for ventricular arrhythmias at our institution from 2016 through 2020.
RESULTS
Thirteen patients underwent bilateral thoracoscopic R1–R4 sympathectomy. All patients had prior ICD implant. Patients had a recent history of multiple ICD discharges (12/13), catheter ablation (10/13) and cardiac arrest (3/13). Ten patients were urgently operated on following transfer to our centre for sustained ventricular tachycardia. Seven patients had ventricular tachycardia ablations preoperatively during the same admission. Five patients were in intensive care immediately preoperatively, with 3 requiring mechanical ventilation. Three patients suffered in-hospital mortality. Kaplan–Meier analysis estimated 73% overall survival at 24-month follow-up. Among the 10 patients who survived to discharge, all were alive at a median follow-up of 8.7 months (interquartile range 0.6–26.7 months). Six of 10 patients had no further ICD discharges. Kaplan–Meier analysis estimated 27% ICD shock-free survival at 24 months follow-up for all patients. Three of 10 patients had additional ablations, while 2 patients underwent cardiac transplantation.
CONCLUSIONS
Bilateral thoracoscopic sympathectomy is an effective option for patients with life-threatening ventricular arrhythmia refractory to pharmacotherapy and catheter ablation.
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Affiliation(s)
- Andy Chao Hsuan Lee
- Section of Thoracic Surgery, Department of Surgery, The University of Chicago, Chicago, IL, USA
| | - Roderick Tung
- Division of Cardiology, Department of Internal Medicine, University of Arizona, Phoenix, AZ, USA
| | - Mark K Ferguson
- Section of Thoracic Surgery, Department of Surgery, The University of Chicago, Chicago, IL, USA
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48
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Structural and function organization of intrathoracic extracardiac autonomic projections to the porcine heart: implications for targeted neuromodulation therapy. Heart Rhythm 2022; 19:975-983. [DOI: 10.1016/j.hrthm.2022.01.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 01/20/2022] [Accepted: 01/28/2022] [Indexed: 12/30/2022]
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49
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Hadaya J, Buckley U, Gurel NZ, Chan CA, Swid MA, Bhadra N, Vrabec TL, Hoang JD, Smith C, Shivkumar K, Ardell JL. Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control. Am J Physiol Heart Circ Physiol 2022; 322:H105-H115. [PMID: 34860595 PMCID: PMC8714250 DOI: 10.1152/ajpheart.00568.2021] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart and maybe a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n = 14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r = 0.83-0.96, effect size d = 1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.NEW & NOTEWORTHY Autonomic imbalance and excess sympathetic activity have been implicated in the pathogenesis of cardiovascular disease and are targets for existing medical therapy. Neuromodulation may allow for control of sympathetic projections to the heart in an on-demand and reversible manner. This study provides proof-of-concept evidence that axonal modulation therapy (AMT) blocks sympathoexcitation by defining scalability, sustainability, and memory properties of AMT. Moreover, AMT directly reduces release of myocardial norepinephrine, a mediator of arrhythmias and heart failure.
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Affiliation(s)
- Joseph Hadaya
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California,2UCLA Molecular, Cellular and Integrative Physiology
Program, Los Angeles, California
| | - Una Buckley
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Nil Z. Gurel
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Christopher A. Chan
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Mohammed A. Swid
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Niloy Bhadra
- 3Department of Physical Medicine and Rehabilitation, MetroHealth Medical Center, Cleveland, Ohio,4Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio
| | - Tina L. Vrabec
- 3Department of Physical Medicine and Rehabilitation, MetroHealth Medical Center, Cleveland, Ohio,4Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio
| | - Jonathan D. Hoang
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California,2UCLA Molecular, Cellular and Integrative Physiology
Program, Los Angeles, California
| | - Corey Smith
- 5Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio
| | - Kalyanam Shivkumar
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California,2UCLA Molecular, Cellular and Integrative Physiology
Program, Los Angeles, California
| | - Jeffrey L. Ardell
- 1Cardiac Arrhythmia Center and Neurocardiology Research Program of
Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California,2UCLA Molecular, Cellular and Integrative Physiology
Program, Los Angeles, California
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Stress-related dysautonomias and neurocardiology-based treatment approaches. Auton Neurosci 2022; 239:102944. [DOI: 10.1016/j.autneu.2022.102944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 10/13/2021] [Accepted: 01/16/2022] [Indexed: 11/21/2022]
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