Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias

Vaseghi, Marmar; Barwad, Parag; Corrales, Federico J. Malavassi; Tandri, Harikrishna; Mathuria, Nilesh; Shah, Rushil; Sorg, Julie M.; Gima, Jean; Mandal, Kaushik; Morales, Luis C. Sàenz; Lokhandwala, Yash; Shivkumar, Kalyanam

doi:10.1016/j.jacc.2017.04.035

Cited by 276 publications

(203 citation statements)

References 45 publications

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“…91 In a study of 121 patients from five international sites with structural heart disease and recurrent VT, CSD decreased sustained VT and ICD shock recurrence and approximately one-third of patients no longer took antiarrhythmic medications on follow up. 92 The observed benefit in these high-risk patients supports the need for prospective randomized clinical trials to better characterize the impact of this therapy.…”

Section: Blockade Of Sympathetic Neurotransmissionmentioning

confidence: 97%

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Wu¹,

Vaseghi²

2020

Pacing Clinical Electrophis

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Ventricular arrhythmias (VA) can range in presentation from asymptomatic to cardiac arrest and sudden cardiac death (SCD). Sustained ventricular tachycardias/ventricular fibrillation (VT/VF) are a common cause of SCD in the setting of myocardial infarction (MI) and heart failure. A particularly arrhythmogenic cardiac syncytia in these conditions can be attributed to both sympathetic activation and parasympathetic dysfunction, while appropriate neuromodulation has the potential to reduce occurrence of VT/VF. In this review, we outline the components of the autonomic nervous system that play an important role in normal cardiac electrophysiology and function. In addition, we discuss changes that occur in the setting of cardiac disease including adverse neural remodeling and neurohormonal activation which significantly contribute to propensity for VT/VF. Finally, we review neuromodulation strategies to mitigate VT/VF which predominantly rely on increasing parasympathetic drive and blockade of sympathetic neurotransmission.

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Section: Blockade Of Sympathetic Neurotransmissionmentioning

confidence: 97%

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Wu¹,

Vaseghi²

2020

Pacing Clinical Electrophis

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“…53 In a recent multicenter registry that included 121 patients with structural heart disease who underwent left or bilateral CSD for refractory VT or ES, bilateral CSD was associated with a two-fold risk reduction of the combined event of sustained VT/ICD shock recurrence, death, and/or heart transplant as compared with in patients who underwent a left side-only procedure. 54 …”

Section: Sympathetic Denervationmentioning

confidence: 99%

Electrical Storm in Patients with Implantable Cardioverter-defibrillators: A Practical Overview

Muser

Liang

2017

J Innov Cardiac Rhythm Manage

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ABSTRACT. Electrical storm (ES) is an increasingly common medical emergency characterized by clustered episodes of sustained ventricular arrhythmias (VAs) that lead to repeated appropriate implantable cardioverter-defibrillator (ICD) therapies. A diagnosis of ES can be made with the occurrence of three or more sustained episodes of VAs, or of three or more appropriate ICD therapies within 24 hours in patients with implanted devices. ES is associated with poor outcomes in patients with structural heart disease, particularly those with severe left ventricular dysfunction. In large clinical trials involving patients with ICDs for primary and secondary prevention, ES appears to be a predictor of cardiac death, with notably higher rates of mortality soon after the event. ES management is challenging and requires special medical attention with accurate patient risk stratification and a multidisciplinary approach that includes the use of pharmacologic therapies such as antiarrhythmic drugs (AADs) and interventional approaches like catheter ablation, surgical ablation, or sympathetic neuromodulation. Initial management involves determining and addressing the underlying ischemia, any electrolyte imbalances, and/or other causative factors. Hemodynamic support needs to be considered in high-risk patients with unstable VAs or those with severe comorbidities such as low left ventricular ejection fraction, advanced New York Heart Association class, and/or chronic pulmonary disease. Following the acute phase of ES, treatment should shift towards maximizing therapeutic efforts to address heart failure, performing revascularization, and preventing subsequent VAs. In the present manuscript, we offer an overview of the most relevant clinical aspects of ES with regard to novel therapeutic strategies.

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“…4 In this study we provide the first single cell RNA sequencing (scRNAseq) analysis of stellate ganglia neurons and use this to guide a detailed biophysical characterisation in an animal model of prehypertension 10 , with validation in human stellate ganglia tissue. We highlight several important ion channels as putative targets for pharmacological intervention to reduce cardiac sympathetic neuron firing rate, rather than resorting to irreversible surgery with its associated complications (such as pneumothorax and Horner's syndrome 11 ).…”

Section: Introductionmentioning

confidence: 99%

Novel target identification using single cell sequencing and electrophysiology of cardiac sympathetic neurons in disease

Davis

Herring

Paterson

2019

Preprint

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Word Count: 4421 (Limit: 5000) Methods word count: 2047 (Limit: 3000) Abstract (150 words)The activity of cardiac sympathetic nerves from the stellate ganglia is increased in many cardiovascular diseases contributing to the pathophysiology. However, the mechanisms underlying this are unknown. Moreover, clinical studies show their surgical removal is an effective treatment, despite the biophysical properties of these neurons being largely unstudied. We demonstrate that stellate ganglia neurons from prehypertensive spontaneously hypertensive rats are hyperactive and describe in detail their electrophysiological phenotype guided by single cell RNA-sequencing, molecular biology, perforated patch-clamp and computational modelling to uncover the underlying mechanism.The expression of key transcripts is confirmed in human stellate ganglia. We demonstrate the contribution of a plethora of ion channels to stellate ganglia neuronal firing, and show that hyperexcitability is curbed by M-current activators, non-selective sodium current blockers or inhibition of Nav1.1-1.3, Nav1.6 or INaP. These findings have important implications for target discovery to reduce cardiac sympathetic neuron activity pharmacologically without resorting to surgery.

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Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias

Abstract: CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure.

Cited by 276 publications

References 45 publications

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Electrical Storm in Patients with Implantable Cardioverter-defibrillators: A Practical Overview

Novel target identification using single cell sequencing and electrophysiology of cardiac sympathetic neurons in disease

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