Advances in Our Clinical Understanding of Autonomic Regulation Therapy Using Vagal Nerve Stimulation in Patients Living With Heart Failure

Figures

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  FIGURE 1. Organization and Function of Autonomic Nervous System for Neuromodulation and Cardiac Control. DRG = Dorsal root ganglia, a group of cell bodies responsible for the transmission of sensory messages from receptors such as thermoreceptors, nociceptors, proprioceptors, and chemoreceptors, to the central nervous system. ICN = intracardiac network, a “little brain” of the heart comprising intracardiac ganglia and interconnecting neurons making adjustments of the cardiac mechanical and electrical activity comprising intracardiac ganglia and interconnecting neurons. From Hanna H, Shivkumar K, and Ardell J. Card Fail Review 2018; 4: 92–98, with permission.

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  FIGURE 2. VNS system to deliver ART. Adapted from Anand IS, et al. ESC Heart Fail 2020 with permission.

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  FIGURE 3. VNS intensity encompasses a combination of pulse amplitude (current), pulse frequency, pulse duration, and duty cycle. Adapted from Anand IS, et al. Int J Neurol Neurother 2019 with permission.

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  FIGURE 4. Mechanisms of action of ART and GDMT. Figure adapted from Konstam MA, et al. Circ Heart Fail 2019 with permission. Additional information is provided in Supplementary Appendix S1, S2

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  FIGURE 5. Stimulation frequencies used for VNS and associated changes from baseline in symptomatic and functional outcomes in the treatment arms of ANTHEM-HF, INOVATE-HF, and NECTAR-HF. △ = difference; % = percent; bpm = beats per minute; Hz = Hertz; m = meters; ms = milliseconds; other abbreviations as in the text. p-values are two-sided and are based on two-sample t-tests. From Inand AS, et al. ESC Heart Fail 2020; 7: 76–84, with permission.

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  FIGURE 6. ANTHEM-HFrEF Pivotal Study Design. CVD = Cardiovascular death. HFH = Heart failure hospitalization. Mo = months. N = number. PMA = Pre-Market Application. sPMA = supplementary Pre- Market Application. Dotted lines represent serial interim analyses as appropriate. Other abbreviations as in text. From Konstam MA, et al. Circ Heart Fail 2019; 12: e005879, with permission.