Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

Zannad, Faı̈ez; Ferrari, Gaetano M. De; Tuinenburg, Anton E.; Wright, David J.; Brugada, Josép; Butter, Christian; Klein, Helmut U.; Stolen, Craig M.; Meyer, Scott; Steín, Kenneth M.; Ramuzat, A.; Schubert, Bernd; Daum, Doug; Neužil, Petr; Botman, Cornelis J.; Castel, María Ángeles; D’Onofrio, Antonio; Solomon, Scott D.; Wold, Nicholas; Ruble, Stephen B.

doi:10.1093/eurheartj/ehu345

Cited by 319 publications

(241 citation statements)

References 30 publications

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“…Nevertheless, the study did show an improvement in quality of life measures and NYHA classification (Zannad et al, 2015). A subsequent international multi-centre clinical trial using VNS on heart failure patients to assess whether VNS increases the time to first event defined by all-cause mortality or unplanned heart failure hospitalization was discontinued due to a statistical futility in this primary efficacy endpoint (Gold et al, 2016).…”

Section: Anatomy Of the Auricular Branch Of The Vagus Nervementioning

confidence: 99%

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

Murray

Atkinson

Mahadi

et al. 2016

Autonomic Neuroscience

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The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve.

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Section: Anatomy Of the Auricular Branch Of The Vagus Nervementioning

confidence: 99%

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

Murray

Atkinson

Mahadi

et al. 2016

Autonomic Neuroscience

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“…It failed to demonstrate an improvement in LV end-systolic diameter, the primary endpoint, in 6 months' time. 37 However, it did show that VNS was safe and able to significantly improve the quality of life.…”

Section: Clinical Trialsmentioning

confidence: 98%

Interventional and Device-Based Autonomic Modulation in Heart Failure

Shen¹,

Zipes²

2015

Heart Failure Clinics

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Abstract/SummaryHeart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapy has sought to restore autonomic balance by neuromodulation.Results of preclinical animal studies and early clinical trials have demonstrated its safety and efficacy in heart failure. In this review article, we will discuss specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy and renal sympathetic nerve denervation. Key Points (3-5)• Heart failure (HF) is a disease categorized by sympathetic hyperactivity, parasympathetic withdrawal and impaired baroreflex control of sympathetic activation.• Several measures of autonomic modulation either by implanted devices or interventions seek to restore the autonomic balance in HF and improve outcomes. These measures include spinal cord stimulation, vagus nerve 3 stimulation, baroreceptor activation therapy and renal sympathetic nerve denervation.• Preclinical work and the majority of early clinical trials demonstrate the benefits of these modalities in HF. Additional larger, well-designed, outcome-based clinical trials are warranted to verify the results and determine whether these evolving, innovative neuromodulation approaches can be recommended to the growing population of HF patients.4

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“…According to recent data from the CDC (Health United States Report, 2016) 23.4% of all-cause mortality is attributed to heart disease. Recent trials involving bioelectronic medicine have yielded equivocal results [23][24][25]. These are likely due to sub-optimum applications of the therapy [22] based on an incomplete appreciation of control system component interdependencies.…”

Section: Concept 3: Neuromodulation-based Therapies Impact Multiple Lmentioning

confidence: 99%

Foundational Concepts for Cardiac Neuromodulation

Ardell

Shivkumar

2017

Bioelectron. Med.

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" It is only through an improved mechanistic understanding of structure/function that rationale neuromodulation-based therapies of cardiac control will advance. The twofold objectives are: do no harm and develop a better understanding of the nuances governing structure/function of the cardiac control hierarchy; and, develop therapies that account for the biological complexity of the system. " Heart disease remains the primary cause of morbidity and mortality in the world with its impact cutting across all segments of the population [1]. The field of neurocardiology incorporates all aspects of cardiology with important elements of autonomic neuroscience to define cellular physiology/pathophysiology [2]. The fundamental premise of neurocardiology is that it is the dynamic interactions between autonomic control and the heart that ultimately determines how closed-loop control of cardiac function evolves in response to cardiovascular stressors including those leading to cardiac disease [2]. In the worst case scenario, imbalances in autonomic control coupled with regional variations in cardiac electrical/mechanical function set the stage for arrhythmias leading to sudden cardiac death or heart failure [3][4][5]. Through a mechanistic understanding of neurohumoral-cardiac processes, a rationale for therapies designed to maintain cardiovascular homeostasis [6] can be defined. Neuromodulation is at the forefront of novel therapies that are establishing new frontiers for effective treatments of cardiac disease. A conceptual framework for bioelectronic medicine, as related to cardiac disease, is presented via three key concepts of neurocardiology. Concept 1: neural control of cardiac function involves a multitier hierarchy of interdependent reflexesCardiac control depends on interactions between intrathoracic and central aspects of the cardiac nervous system. Peripheral neural networks for cardiac control include intrinsic cardiac and extracardiac-intrathoracic (e.g., stellate and middle cervical) ganglia. These ganglia contain all the necessary neural machinery for reflex control of the heart (afferent, efferent and local circuit interneurons for information processing) [2].Centrally located neural networks involved in cardiac control include elements of the spinal cord, brainstem and higher centers up to and including the insular cortex [7][8][9]. These top-down contributions to control involve projections from preganglionic soma located in the brainstem (parasympathetic) and spinal cord (sympathetic) toward the heart with both regions (nucleus Ambiguus and intermediolateral cell column) impacted by interconnections with brainstem (e.g., nucleus tractus solitaries) and higher centers (e.g., hypothalamus, limbic system). Bottom-and middle-level cardio-centric contributions to control include intrathoracic ganglia (intrinsic cardiac and stellate/middle cervical) receiving cardiac-related afferent projections and central neurons (spinal cord and brainstem) receiving cardiovascular-related afferent inputs via primary sensory...

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Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

Cited by 319 publications

References 30 publications

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

Interventional and Device-Based Autonomic Modulation in Heart Failure

Foundational Concepts for Cardiac Neuromodulation

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