Elsevier

Heart Rhythm

Volume 17, Issue 10, October 2020, Pages 1639-1645
Heart Rhythm

Clinical
Left cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome

https://doi.org/10.1016/j.hrthm.2020.03.023Get rights and content

Background

Although left cardiac sympathetic denervation (LCSD) is an effective antiarrhythmic therapy for patients with long QT syndrome (LQTS), direct evidence of reduced sympathetic activity after LCSD in humans is limited.

Objective

The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD.

Methods

We prospectively enrolled 17 patients with LQTS who underwent LCSD between 2017 and 2019. SKNA recordings from the left arm (L-SKNA) and chest (C-SKNA) leads were performed before and after LCSD. Mean SKNA, burst activity, and nonburst activity of L-SKNA and C-SKNA were analyzed.

Results

The mean patient age was 21 ± 9 years (8 men 47%). The longest baseline corrected QT value was 497 ± 55 ms at rest and 531 ± 38 ms on exercise stress testing. Five patients (29.4%) had previous LQTS-triggered cardiac events including syncope, documented torsades de pointes, and ventricular fibrillation. In the 24 hours after LCSD, mean L-SKNA decreased from 1.25 ± 0.64 to 0.85 ± 0.33 μV (P = .005) and mean C-SKNA from 1.36 ± 0.67 to 1.05 ± 0.49 μV (P = .11). The frequency of episodes of SKNA bursts recorded from the left-arm lead (2.87 ± 1.61 bursts per minute vs 1.13 ± 0.99 bursts per minute; P < .001) and mean L-SKNA during burst (1.82 ± 0.79 μV vs 1.15 ± 0.44 μV; P < .001) and nonburst (1.09 ± 0.60 μV vs 0.75 ± 0.32 μV; P = .03) periods significantly decreased after LCSD, while the frequency of episodes of SKNA bursts recorded from the chest lead (P = .57) and mean C-SKNA during burst (P = .44) and nonburst (P = .10) periods did not change significantly. No arrhythmic events were documented after 11.9 months (range 3.0–22.2 months) of follow-up.

Conclusion

LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA.

Introduction

Long QT syndrome (LQTS) comprises a heterogeneous group of potentially life-threatening cardiac channelopathies that are associated with malignant ventricular tachyarrhythmia. LQTS is characterized by abnormally delayed cardiac repolarization and an increased likelihood of palpitations, syncope, and even arrhythmic sudden death. On electrocardiography (ECG), patients with LQTS have increased QTc values (QT interval corrected for the heart rate). There are 3 main types of LQTS—LQT1, LQT2, and LQT3—which correspond to the first 3 identified LQTS-causing genes (KCNQ1, KCNH2, and SCN5A) and their associated protein products. Currently, at least 15 different ion channel genes have been associated with LQTS.1

The aim of management of LQTS is to prevent arrhythmic sudden death. Previous studies showed that the cardiac sympathetic nervous system has an important role in triggering lethal ventricular arrhythmia.2,3 Pharmaceutical intervention (ie, β-blockers), an implantable cardioverter-defibrillator (ICD) implantation, and left cardiac sympathetic denervation (LCSD) are recommended approaches to reduce sudden death events.3,4 LCSD is used to treat patients who have breakthrough cardiac events or who are intolerant to β-blockers.4 Previous studies have suggested that LCSD has an antifibrillatory effect in LQTS, resulting from decreased localized sympathetic chain release of norepinephrine in the absence of postdenervation supersensitivity.5,6 However, to our knowledge, no studies have reported the effects of direct measurements of LCSD on sympathetic activity. Recent studies have shown that recording skin sympathetic nerve activity (SKNA) can noninvasively determine cardiac sympathetic efferent activity in various conditons.7, 8, 9 Therefore, we aimed to study SKNA in patients with LQTS who underwent LSCD. We hypothesized that (1) LSCD reduces peripheral sympathetic activity as measured by SKNA and (2) reduced sympathetic activity is associated with less recurrence of syncope and ventricular arrhythmic events.

Section snippets

Study population

The Mayo Clinic Institutional Review Board approved this prospective study designed to enroll patients with LQTS who were undergoing LCSD. All patients had given written informed consent to participate in the study. After fasting for >3 hours in a quiet morning setting, all patients had SKNA recording performed within 24 hours before and 24–48 hours after LCSD in the sitting or supine position (to minimize the effect of immediate postoperative pain). The SKNA was recorded at 3–6 months

Baseline patient characteristics

Seventeen patients with LQTS who underwent LCSD between December 26, 2017, and July 12, 2019, were enrolled. The baseline demographic and clinical characteristics of the 17 study patients are summarized in Table 1. There were 8 men (47%). The mean patient age was 21 ± 9 years. At baseline, the longest QTc value was 497 ± 55 ms at rest and 531 ± 38 ms on exercise stress testing. Eleven patients (65%) had a prolonged QTc value both at rest and on exercise stress testing, and the other 6 patients

Main findings

The main findings of the present study were as follows: (1) LCSD reduced L-SKNA in patients with LQTS; (2) SKNA burst firing, including frequency and mean L-SKNA during bursts, was consistently inhibited immediately after LCSD and at 3-month follow-up in every patient; and (3) sympathetic bursts did not affect QTc values before and after LCSD.

LCSD reduces sympathetic activity in LQTS

The sympathetic nervous system has a pivotal role in the development of lethal ventricular arrhythmia in patients with LQTS.5,6 At least 1 episode of

Conclusion

LCSD is an effective therapeutic option for patients with LQTS. LCSD provided an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA, with a concomitant effect of patients being free of ventricular arrhythmia. SKNA may be a useful tool for determining the effect of sympathetic inhibition in medical and nonpharmacological therapies for patients at high risk of sudden death.

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  • Cited by (0)

    This work was supported by the National Institutes of Health, United States. (NIH R01HL 134864), a research award of the Department of Cardiovascular Medicine, Mayo Clinic (Rochester, MN), and the Windland Smith Rice Comprehensive Sudden Cardiac Death Program, Mayo Clinic (Rochester, MN).

    Dr Ackerman is a consultant for Audentes Therapeutics, Biotronik, Boston Scientific, Daiichi Sankyo, Gilead Sciences, Invitae, Medtronic, MyoKardia, and St. Jude Medical. Dr Ackerman and Mayo Clinic have an equity/royalty relationship with AliveCor, Blue Ox Health and StemoniX but without remuneration thus far. The rest of the authors report no conflicts of interest.

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