Anisiia Doytchinova

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram

BACKGROUND Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.

Estimating Sympathetic Tone by Recording Subcutaneous Nerve Activity in Ambulatory Dogs

We tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to estimate the sympathetic tone.

Subcutaneous nerve activity and spontaneous ventricular arrhythmias in ambulatory dogs

BACKGROUND Stellate ganglion nerve activity (SGNA) is important in ventricular arrhythmogenesis. However, because thoracotomy is needed to access the stellate ganglion, it is difficult to use SGNA for risk stratification. OBJECTIVE The purpose of this study was to test the hypothesis that subcutaneous nerve activity (SCNA) in canines can be used to estimate SGNA and predict ventricular arrhythmia. METHODS We implanted radiotransmitters to continuously monitor left stellate ganglion and subcutaneous electrical activities in 7 ambulatory dogs with myocardial infarction, complete heart block, and nerve growth factor infusion to the left stellate ganglion. RESULTS Spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in each dog. SCNA preceded a combined 61 episodes of VT and VF, 61 frequent bigeminy or couplets, and 61 premature ventricular contractions within 15 seconds in 70%, 59%, and 61% of arrhythmias, respectively. Similar incidence of 75%, 69%, and 62% was noted for SGNA. Progressive increase in SCNA [48.9 (95% confidence interval [CI] 39.3-58.5) vs 61.8 (95% CI 45.9-77.6) vs 75.1 (95% CI 57.5-92.7) mV-s] and SGNA [48.6 (95% CI 40.9-56.3) vs 58.5 (95% CI 47.5-69.4) vs 69.0 (95% CI 53.8-84.2) mV-s] integrated over 20-second intervals was demonstrated 60 seconds, 40 seconds, and 20 seconds before VT/VF (P <.05), respectively. The Pearson correlation coefficient for integrated SCNA and SGNA was 0.73 ± 0.18 (P <.0001 for all dogs, n = 5). Both SCNA and SGNA exhibited circadian variation. CONCLUSION SCNA can be used as an estimate of SGNA to predict susceptibility to VT and VF in a canine model of ventricular arrhythmia and sudden cardiac death.

Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs

BACKGROUND Stellate ganglion nerve activity (SGNA) is important in cardiac arrhythmogenesis. However, direct recording of SGNA requires access to the thoracic cavity. Skin of upper thorax is innervated by sympathetic nerve fibers originating from the stellate ganglia and is easily accessible. OBJECTIVE The purpose of this study was to test the hypothesis that thoracic skin nerve activity (SKNA) can be used to estimate SGNA. METHODS We recorded SGNA and SKNAs using surface electrocardiogram leads in 5 anesthetized and 4 ambulatory dogs. Apamin injected into the right stellate ganglion abruptly increased both right SGNA and SKNA in 5 anesthetized dogs. We integrated nerve activities and averaged heart rate in each 1-minure window over 10 minutes. We implanted a radiotransmitter to record left SGNA in 4 ambulatory dogs (2 normal, 1 with myocardial infarction, 1 with intermittent rapid atrial pacing). After 2 weeks of recovery, we simultaneously recorded the SKNA and left SGNA continuously for 30 minutes when the dogs were ambulatory. RESULTS There was a positive correlation [average r = 0.877, 95% confidence interval (CI) 0.732-1.000, P <.05 for each dog] between integrated skin nerve activity (iSKNA) and SGNA (iSGNA) and between iSKNA and heart rate (average r = 0.837, 95% CI 0.752-0.923, P <.05). Similar to that found in the anesthetized dogs, there was a positive correlation (average r = 0.746, 95% CI 0.527-0.964, P <.05) between iSKNA and iSGNA and between iSKNA and heart rate (average r = 0.706, 95% CI 0.484-0.927, P <.05). CONCLUSION SKNAs can be used to estimate SGNA in dogs.

Cervical Vagal Nerve Stimulation Activates the Stellate Ganglion in Ambulatory Dogs

Background and Objectives Recent studies showed that, in addition to parasympathetic nerves, cervical vagal nerves contained significant sympathetic nerves. We hypothesized that cervical vagal nerve stimulation (VNS) may capture the sympathetic nerves within the vagal nerve and activate the stellate ganglion. Materials and Methods We recorded left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA), and subcutaneous electrocardiogram in seven dogs during left cervical VNS with 30 seconds on-time and 30 seconds off time. We then compared the SGNA between VNS on and off times. Results Cervical VNS at moderate (0.75 mA) output induced large SGNA, elevated heart rate (HR), and reduced HR variability, suggesting sympathetic activation. Further increase of the VNS output to >1.5 mA increased SGNA but did not significantly increase the HR, suggesting simultaneous sympathetic and parasympathetic activation. The differences of integrated SGNA and integrated VNA between VNS on and off times (ΔSGNA) increased progressively from 5.2 mV-s {95% confidence interval (CI): 1.25-9.06, p=0.018, n=7} at 1.0 mA to 13.7 mV-s (CI: 5.97-21.43, p=0.005, n=7) at 1.5 mA. The difference in HR (ΔHR, bpm) between on and off times was 5.8 bpm (CI: 0.28-11.29, p=0.042, n=7) at 1.0 mA and 5.3 bpm (CI 1.92 to 12.61, p=0.122, n=7) at 1.5 mA. Conclusion Intermittent cervical VNS may selectively capture the sympathetic components of the vagal nerve and excite the stellate ganglion at moderate output. Increasing the output may result in simultaneously sympathetic and parasympathetic capture.

Crescendo Skin Sympathetic Nerve Activity and Ventricular Arrhythmia

We recently reported a new method (neuECG) to simultaneously record electrocardiogram (ECG) and skin sympathetic nerve activity (SKNA) in humans [(1)][1]. There was a significant association between SKNA and paroxysmal atrial tachyarrhythmias [(2)][2]. While our preliminary study showed that

Recording sympathetic nerve activity from the skin

Sympathetic tone is important in cardiac arrhythmogenesis; however, methods to estimate sympathetic tone are either invasive or require proper sinus node function that may be abnormal in disease states. Because of the direct and extensive connections among various nerve structures, it is possible for the sympathetic nerves in the various structures to activate simultaneously. Therefore, we hypothesized that nerve activity can be recorded from the skin and it can be used to estimate the cardiac sympathetic tone. Preclinical studies in canines demonstrated that nerve activity is detectable using conventional ECG electrodes and can be used to estimate cardiac sympathetic tone. Subsequent clinical studies further supported this concept. In addition to studying the autonomic mechanisms of cardiac arrhythmia, these new methods may have broad application in studying both cardiac and non-cardiac diseases.

123I-meta-Iodobenzylguanidine Imaging in Patients with Cardiac Resynchronization Therapy: Results are Intriguing, but Unknowns Remain

Excess sympathetic activation and subsequent decrease in neuronal reuptake of norepinephrine due to receptor downregulation are important in the pathogenesis of congestive heart failure. I-meta-iodobenzylguanidine (mIBG) scintigraphy has emerged as a method to measure cardiac sympathetic activity because I-mIBG shares the same biological properties as norepinephrine, but is not metabolized by the body. Impaired sympathetic integrity is manifested by low cardiac I-mIBG uptake relative to the mediastinal background, resulting in a low heart-to-mediastinal ratio (HMR). The comparison between early and delayed HMR is quantified by the washout rate, with high rates corresponding to increased sympathetic activity. I-mIBG imaging was first shown to have an important prognostic value in patients with heart failure in the early 1990s. Since then, a number of studies have confirmed that late HMR is an independent predictor of cardiac events both as a dichotomous and a continuous variable. Tamaki et al. have also demonstrated that abnormal I-mIBG washout rate serves an independent predictor for sudden cardiac death. Models have further incorporated late HMR and clinical variables to predict 2and 5-year mortality, with a recent study validating the 2-year risk model in those with heart failure at low and intermediate cardiac risk. Despite the current level of evidence, clinical use of I-mIBG scintigraphy has remained limited, potentially because I-mIBG activity can be affected by imaging and processing conditions, raising the need for protocol standardization. With the advent of cadmium-zinc-telluride cameras, data have demonstrated that despite a good agreement between transaxial and planar HMR, the absolute HMR values obtained using a multi-pinhole cadmium-zinc-telluride camera were lower than those using conventional planar imaging. However, Bateman et al. have shown that HMR of ImIBG is highly reproducible when subjects are imaged on the same camera. In addition, the specific HMR thresholds for various patient populations and outcomes have remained sub-optimally defined in clinical studies. In light of these considerations, efforts have been made to specifically focus on the subset of heart failure patients eligible for cardiac resynchronization therapy (CRT). Research has suggested that CRT is associated with improved washout rate and HMR. A study of 30 patients by Nishioka et al. demonstrated that late ImIBG HMR can independently predict response to resynchronization with an optimal cutoff value of 1.36, yielding a sensitivity of 75% and specificity of 71%. More recent data also highlight an association between global longitudinal strain improvement and increase in late HMR in patients with CRT. However, the number of patients included in these studies was relatively small and they did not assess the presence of left bundle branch block (LBBB) as a variable. In this issue of the Journal, Moreira et al. studied 121 patients with severe systolic dysfunction and primarily non-ischemic cardiomyopathy, also included in the BETTER-HF trial, who underwent CRT. Fifty-five patients also had I-mIBG scintigraphy performed 6 months after implant placement. The mean follow-up Reprint requests: Myron C. Gerson, MD, Division of Cardiovascular Health and Disease, University of Cincinnati Medical Center, Cincinnati, OH; myron.gerson@uc.edu J Nucl Cardiol 2020;27:291–3. 1071-3581/

Erratum: Evaluation of the genetic basis of familial aggregation of pacemaker implantation by a large next generation sequencing panel (PLoS ONE (2016) 11:1 (e0147455) DOI:10.1371/journal.pone.0147455)

34.00 Copyright 2018 American Society of Nuclear Cardiology.

Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy

1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States of America, 2 Krannert Institute of Cardiology, Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America, 3 Center for Computational Biology and Bioinformatics, Indiana University Purdue University Indianapolis, Indianapolis, IN, United States of America, 4 Baruch Padeh Medical Center, Poriya MP Lower Galilee, Israel, 5 Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel