Calming the Nervous Heart: Autonomic Therapies in Heart Failure

Hanna, Peter; Shivkumar, Kalyanam; Ardell, Jeffrey L.

doi:10.15420/cfr.2018.20.2

Cited by 41 publications

(33 citation statements)

References 88 publications

(77 reference statements)

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“…19 The methodologies used for VNS in ANTHEM-HF, INOVATE-HF, and NECTAR-HF differed considerably in their neurologic targets, technology platforms, the mode and delivery of VNS for ART, and the responses in heart rate and heart rate variability that occurred in association with VNS. 10,20,21 INOVATE-HF was a multinational, randomized, controlled study of high amplitude, low-frequency VNS plus GDMT vs. GDMT alone in 707 patients with chronic HF, NYHA 3 symptoms, and ejection fraction ≤ 40%. VNS delivery aimed preferentially at peripheral neural targets using closed-loop, lowfrequency, asymmetric pulses and was not associated with any long-term change in mean heart rate or heart rate variability.…”

Section: Discussionmentioning

confidence: 99%

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM‐HF, INOVATE‐HF, and NECTAR‐HF

et al. 2020

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Aims Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM‐HF), increase of vagal tone in heart failure (INOVATE‐HF), and neural cardiac therapy for heart failure (NECTAR‐HF) for hypothesis generation. Methods and results Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson's chi‐square test, differences in mean values using Student's unpaired t‐test, and differences in changes of mean values using two‐sample t‐tests. Guideline‐directed medical therapy recommendations were similar across studies. Fewer patients were in New York Heart Association 3, and baseline heart rate (HR) was higher in ANTHEM‐HF. In INOVATE‐HF, VNS was aimed at peripheral neural targets, using closed‐loop delivery that required synchronization of VNS to R‐wave sensing by an intracardiac lead. Pulse frequency was low (1–2 Hz) because of a timing schedule allowing ≤3 pulses of VNS following at most 25% of detected R waves. NECTAR‐HF and ANTHEM‐HF used open‐loop VNS delivery (i.e. independent of any external signal) aimed at both central and peripheral targets. In NECTAR‐HF, VNS delivery at 20 Hz caused off‐target effects that limited VNS up‐titration in a majority of patients. In ANTHEM‐HF, VNS delivery at 10 Hz allowed up‐titration until changes in HR dynamics were confirmed. Six months after VNS titration, significant improvements in both HR and HR variability occurred only in ANTHEM‐HF. When ANTHEM‐HF and NECTAR‐HF were compared, greater improvements from baseline were observed in ANTHEM‐HF in standard deviation in normal‐to‐normal R‐R intervals (94 ± 26 to 111 ± 50 vs. 146 ± 48 to 130 ± 52 ms; P < 0.001), left ventricular ejection fraction (32 ± 7 to 37 ± 0.4 vs. 31 ± 6 to 33 ± 6; P < 0.05), and Minnesota Living with Heart Failure mean score (40 ± 14 to 21 ± 10 vs. 44 ± 22 to 36 ± 21; P < 0.002). When compared with INOVATE‐HF, greater improvement in 6‐min walk distance was observed in ANTHEM‐HF (287 ± 66 to 346 ± 78 vs. 304 ± 111 to 334 ± 111 m; P < 0.04). Conclusions In this post‐hoc analysis, differences in patient demographics were seen and may have caused the differential responses in symptoms and function observed in association with VNS. Major differences in technology platforms, neural targets, VNS delivery, and HR and HR variability responses could have also potentially played a very important role. Further study is underway in a randomized controlled trial with these considerations in mind.

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Section: Discussionmentioning

confidence: 99%

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM‐HF, INOVATE‐HF, and NECTAR‐HF

et al. 2020

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“…Both the progression of heart failure and the potential for sudden cardiac death are associated with excessive sympathocardiac excitation ( 9 , 11 ) with resultant elevated interstitial cardiac NE ( 4 ). Heterogeneous and high levels of sympathetic output to the heart are major risk factors for morbidity and mortality ( 9 , 11 , 14 ). Although direct nerve recordings of sympathetic firing provide an index of neuronal activity ( 15 ), measurement of catecholamine levels directly within the heart would provide the most relevant measure of neurotransmitter-receptor interactions, especially when evaluating autonomic tone or assessing regional NE release.…”

Section: Discussionmentioning

confidence: 99%

Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart

Chan

Vaseghi

Kluge

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload. NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.

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“…Moreover, ACh also exerts direct antiinflammatory and antiapoptotic effects at cardiac level through purinergic pathways [147]. With disease associated withdrawal of parasympathetic tone, the antiadrenergic, anti-inflammatory, and antiapoptotic protective effects mediated by parasympathetic activity are lost [148]. As such, autonomic dysregulation spanning from the peripheral to the central level is now recognized as fundamental contributor to the progression of cardiac pathology.…”

Section: Neuraxial Transduction Of Cardiac Pathologymentioning

confidence: 99%

Brain-Heart Afferent-Efferent Traffic

Dusi¹,

Ardell²

2020

Brain and Heart Dynamics

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The understanding of cardiac neuronal control has dramatically evolved in the last 50 years, both from an anatomical and a functional point of view. Cardiac neuronal control is mediated via a series of reflex control networks involving somata in the (i) intrinsic cardiac ganglia (heart), (ii) intrathoracic extracardiac ganglia (stellate, middle cervical), (iii) superior cervical ganglia, (iv) spinal cord, (v) brainstem, and (vi) higher centers. Each of these processing centers contains afferent, efferent, and local circuit neurons, which interact locally and in an interdependent fashion with the other levels

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Calming the Nervous Heart: Autonomic Therapies in Heart Failure

Cited by 41 publications

References 88 publications

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM‐HF, INOVATE‐HF, and NECTAR‐HF

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM‐HF, INOVATE‐HF, and NECTAR‐HF

Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart

Brain-Heart Afferent-Efferent Traffic

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