ClinicalLeft cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome
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.
References (28)
- et al.
Management of patients with long QT syndrome
J Arrhythm
(2017) - et al.
Characterization of skin sympathetic nerve activity in patients with cardiomyopathy and ventricular arrhythmia
Heart Rhythm
(2019) - et al.
Recording sympathetic nerve activity from the skin
Trends Cardiovasc Med
(2017) - et al.
Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram
Heart Rhythm
(2017) - et al.
Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery
Heart Rhythm
(2009) - et al.
Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period
Heart Rhythm
(2017) - et al.
Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation
Heart Rhythm
(2017) - et al.
Skin sympathetic nerve activity and ventricular rate control during atrial fibrillation
Heart Rhythm
(2020) - et al.
Crescendo skin sympathetic nerve activity and ventricular arrhythmia
J Am Coll Cardiol
(2017) - et al.
Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy
Heart Rhythm
(2017)
Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces ventricular rate during sustained atrial fibrillation in ambulatory dogs
Heart Rhythm
Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome
Mayo Clin Proc
Sex and genotype in long QT syndrome risk stratification
JAMA Cardiol
Role of the autonomic nervous system in modulating cardiac arrhythmias
Circ Res
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.