Original-clinicalGeneticLeft cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery
Introduction
Congenital long QT syndrome (LQTS) affects 1 in 2,500 people and was first described clinically in 1957 by Jervell and Lange-Nielsen.1, 2 The trademark dysrhythmia underlying LQTS is torsades de pointes (TdP), a potentially lethal polymorphic ventricular arrhythmia.3 The genetic understanding of LQTS has been advanced by the discovery of 12 LQTS susceptibility genes, which encode complex proteins that regulate sodium, potassium, and calcium ion flux across cardiac membranes to control ventricular repolarization.3 Mutations in potassium channel genes KCNQ1 (LQT1) and KCNH2 (LQT2) as well as the sodium channel gene SCN5A gene account for approximately 75% of patients with clinically definite LQTS and compose over 95% of genetically identifiable LQTS.4, 5, 6, 7
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal-dominant heritable arrhythmia syndrome first described in 1975.8 Patients with CPVT characteristically present with exertional syncope or sudden death.9 The 2 main genetic subtypes of CPVT are type 1 CPVT (CPVT1), caused by mutations in the RYR2-encoded cardiac ryanodine receptor/calcium release channel, and the rarer type 2 CPVT (CPVT2), caused by mutations in the CASQ2-encoded calsequestrin protein.9, 10, 11, 12 Patients with CPVT typically have a normal resting 12-lead electrocardiogram (ECG), but can have ventricular ectopy on exercise or catecholamine stress testing. Untreated, patients with CPVT have a risk of lethality as high as 30% to 50% by age 40.13, 14
The mainstay of medical therapy for both LQTS and CPVT patients is beta-blocker pharmacotherapy.14, 15 Moss et al15 showed a significant reduction in cardiac events in LQTS probands and affected patients and in affected family members during a 5-year period while on beta-blockers. In that same study, however, the investigators reported that symptomatic QT prolongation resulting in sudden death continues to occur on beta-blocker therapy. Implantable cardioverter defibrillators (ICDs) offer a more aggressive and effective sudden cardiac death counterattack strategy for LQTS and CPVT patients who present with aborted cardiac arrest (ACA), remain symptomatic despite beta-blocker therapy, or are intolerant of their medication.14, 16 Although arguably the most definitive means of sudden death prevention, ICDs are associated with significant comorbidities including device-related malfunction and recalls, infections, inappropriate therapies, and psychological sequelae.16
There has been renewed consideration of left cardiac sympathetic denervation (LCSD) originally described by Moss17 in 1971, in part because of the therapeutic and comorbidity gap between daily medications and an ICD, and in part because of LQTS specialists increasingly understanding and embracing its anti-fibrillatory potential. LCSD is known to raise the threshold for ventricular fibrillation18 and reduce the arrhythmias associated with acute myocardial ischemia in animal models19, 20 without reducing heart rate or impairing myocardial contractility.21 A significant protective effect of LCSD among high-risk patients with LQTS was shown by Schwartz et al,22 who reported the outcome of LCSD in 147 LQTS patients. Almost half of the study cohort had a history of prior aborted cardiac arrest, and 75% of the patients had cardiac events despite beta-blocker therapy before LCSD. Surgically, LCSD involved resection of the lower half of the left stellate ganglion and the left-sided sympathetic chain at the level of T2, T3, and T4 (Figure 1A). Postoperatively, there was a >90% reduction in the frequency of cardiac events. Recently, LCSD has been used as an effective treatment option for patients with CPVT.23 Herein, we describe our single-institution experience in performing video-assisted thoracic surgery (VATS)-LCSD for patients with either LQTS or CPVT.
Section snippets
Case review
In this institutional review board–approved study, we identified all patients who had undergone LCSD surgery at our institution between November 1, 2005, and November 1, 2008. Patients were identified through Mayo Clinic's LQTS/CPVT clinic electronic medical records. A detailed retrospective review of the electronic medical record was performed, specifically looking at demographic variables, genotype, specific mutation (if available), indications for surgery, available follow-up, surgical
Technique
All patients underwent their procedures by a single surgeon (C.M.). Each patient was placed on the operating table with their right side down. After anesthetic induction, the right bronchus was selectively intubated and the left lung collapsed. The selective intubation allows for adequate visualization of the posterior mediastinum without using prone positioning or hemithorax CO2 insufflation, which can irritate the pleura. Three small mid-axillary incisions were made in the left chest wall in
Results
Among the 450 patients with clinically and/or genetically established LQTS/CPVT who have been seen in our LQTS Clinic since July 2000, 20 patients (8 female, mean age 9.1 ± 9.7 years, range 2 months to 42 years, average QTc 518 ± 70 ms, range 430 to 687 ms) have had LCSD performed at our institution (Table 1, Table 2). An open thoracotomy approach was used in the first 2 patients, whereas VATS was used in the subsequent 18 patients. The 20 patients included 16 with autosomal dominant LQTS (12
Discussion
In the setting of beta-blocker breakthroughs, intolerance to pharmacotherapy, and history of appropriate ICD therapies, LCSD should be considered as a viable treatment option for patients with a sudden-death-predisposing channelopathy such as LQTS or CPVT. Herein, we report a series of 20 genotypically and phenotypically diverse patients who have undergone LCSD at a single institution, 18 via VATS, without any perioperative complications and significant, albeit not universal, short-term
Conclusion
Videoscopic denervation surgery, in addition to traditional LCSD, offers a safe and effective treatment option for the personalized medicine required for infants, children, and adults with LQTS/CPVT, particularly for those with medically refractory arrhythmias, medication intolerance, or a history of appropriate ICD therapies. Additional studies are needed to further define the role and indications for videoscopic denervation surgery and to assess quality of life related to the various
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2023, Cardiac Electrophysiology ClinicsPersonalized Care in Long QT Syndrome: Better Management, More Sports, and Fewer Devices
2023, Cardiac Electrophysiology ClinicsCatheter Ablation of Ventricular Fibrillation
2022, Cardiac Electrophysiology ClinicsCitation Excerpt :Initially, an open surgical approach was used via a supraclavicular access or thoracotomy.83 Subsequently, a less invasive approach using video assisted thoracic surgery was adopted.84 During this procedure, the lower half of the stellate ganglion is removed along with the thoracic ganglia T2 to T4 and its rami communicantes.
Dr. Ackerman's research program was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program, the Dr. Scholl Foundation, the CJ Foundation for SIDS, Hannah Wernke Memorial Foundation, an Established Investigator Award from the American Heart Association, and the National Institutes of Health (HD42569).
Dr. Ackerman is a consultant for PGxHealth, Medtronic, and Pfizer.