Safety and Efficacy of Cardiac Sympathetic Denervation for Ventricular Arrhythmias: An Updated Review and Meta-Analysis

Safety and Efficacy of Cardiac Sympathetic Denervation for Ventricular Arrhythmias: An Updated Review and Meta-Analysis | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Safety and Efficacy of Cardiac Sympathetic Denervation for Ventricular Arrhythmias: An Updated Review and Meta-Analysis View ORCID Profile Daniel B. Hanna , Ahmadreza Karimianpour , Nicole Mamprejew , Chris Fiechter , Dhiran Verghese , Juan Sierra , Viviana Navas , Dinesh Sharma doi: https://doi.org/10.1101/2024.08.09.24311768 Daniel B. Hanna a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Daniel B. Hanna For correspondence: danielhannamd{at}gmail.com Ahmadreza Karimianpour b Piedmont Heart of Buckhead , Piedmont, Georgia DO Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nicole Mamprejew a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chris Fiechter a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dhiran Verghese a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Juan Sierra a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Viviana Navas a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dinesh Sharma a Rooney Heart Institute , Naples, Florida MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Introduction The role of sympathetic nervous system in the initiation and continuation of ventricular tachyarrhythmias (VTA) is well established. However, whether CSD reduces implantable cardioverter defibrillator (ICD) shocks and recurrent VTA is still uncertain. Objective To explore long-term arrhythmic outcomes, safety, and efficacy of CSD by measuring event rates of recurrent VTA and ICD shocks after CSD. Methods A comprehensive literature search was performed at Medline and Embase until March 2023. Our primary outcome was event rate of ICD shocks and VTA. Analyses were conducted using Comprehensive Meta-Analysis software. Results Initial search yielded 1,324 scientific studies with a total of 15 studies fitting our inclusion criteria. ICD shocks at 1 year post CSD revealed an event rate of 69.8% (95% CI, 56.4% – 80.4% with 50% heterogeneity) (I 2 statistic)). ICD shocks at 6 months had an event rate of 59.1% (95% CI 46.9% - 70.4%, 47 I 2 ). Freedom of VTA 1 year post CSD revealed an event rate of 64.3% (95% CI, 42.3% - 81.5%, 26% I 2 ). Freedom from VTA at 6 months revealed an event rate of of 62.3% (95% CI, 51.2% - 72.2%, 40% I 2 ). Reported mortality due to VTA was subdivided into short-term (0-30 days), intermediate-term (31-364 days) and long-term (32-364 days). The event rate for the short-term tertile was 8.9% (95% CI, 5.0% - 15.4%, 0% I 2 ), medium-term was 5.3% (95% CI, 2.4% - 11.3%, 0% I 2 ) and long-term 5.2% (95% CI, 2.4% - 10.9%, 0% I 2 ). Conclusion CSD seems to be promising as an acceptable treatment strategy for recurrent VTA refractory to traditional pharmacological or ablation therapy. Introduction The annual incidence of sudden cardiac death (SCD) ranges from 180,000–300,000 in the United States (US) and 4,250,000 worldwide. 1 Moreover, 25% of all deaths is due to SCD in the form of ventricular tachycardia arrhythmias (VTA) 2 . In patients protected from SCD with an implantable cardioverter defibrillator (ICD), recurrent VTA and ICD therapies increases mortality 2 . The autonomic nervous system (ANS) is a key component in the development of recurrent VTA. The interplay between sympathetic and parasympathetic inputs exert profound effects on cardiac electrophysiology and predispose individuals to the development and worsening of arrhythmias, notably VTA. 3 Increased sympathetic tone augments automaticity and alters myocardial conduction properties 3 . These findings have prompted investigation of sympathetic modulation strategies as a means to manage refractory ventricular arrhythmias. Cardiac sympathetic denervation (CSD) has emerged as a promising intervention. The primary objective is to reduce sympathetic tone and thus arrhythmia burden to help improve long-term mortality and quality of life. This method was originally explored to address VTA in inherited channelopathies such as catecholaminergic polymorphic ventricular tachycardia, however, CSD appears to be a potentially viable treatment option for patients with VTA in the setting of structural heart disease. 4 , 5 CSD has demonstrated efficacy in reducing VTA storm refractory to conventional antiarrhythmic drug therapy and catheter ablation, which highlights its potential as a therapeutic strategy in patients hospitalized with VTA storm. 6 The utility of CSD extends beyond ischemic cardiomyopathies and may also prove useful in treatment of multimorphology VTA in nonischemic cardiomyopathies (NICM) and where multifocal premature ventricular contractions present a significant challenge to standard catheter ablation techniques. 7 In these cases, CSD may be an effective alternative for arrhythmia control and symptom management. There is limited data regarding the long-term efficacy and safety of CSD in patients. Specific to HF, further investigation is warranted to determine the broader positive or negative physiologic effects other than suppressing arrhythmias. 8 Thus, the aim of this contemporary systematic review and meta-analysis is to provide updated insights into the safety and efficacy of CSD regarding patients with structural heart disease suffering from recurrent VTA. Methods A comprehensive literature search was performed at Medline and Embase from inception until March 2023. The search terms “Sympathectomy” OR “Cardiac sympathetic denervation” OR “Refractory ventricular tachycardia” OR “Cardiac Denervation” OR “Electrical storm” OR “Ventricular arrhythmia,” were used. A total of four investigators agreed on the final study selection and independently searched the complete database. The inclusion criteria included any study which reported the short- or long-term outcomes of CSD in the management of VTA if a) age group was >18 years of age b) mortality was reported c) there was an occurrence of VTA or electrical storm, or d) follow-up data for at least 1 month. Individual case reports were not included. Data obtained included study design, follow-up duration, number of patients, baseline demographics, comorbidities, type of ventricular arrhythmia, type of cardiomyopathy, and our primary and secondary outcomes. This was compiled through PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( Figure 1 ). Download figure Open in new tab Figure 1. PRISMA Analysis Statistical analysis Statistical analysis was conducted using a single-arm-meta-analysis model using CMA software (Comprehensive Meta-Analysis Version 4.0) with a random-effects model to calculate overall event rate. Study heterogeneity was evaluated with Cochran’s Q and I2 index. Results The initial search yielded 1,324 scientific studies, compiled in PRISMA for inclusion, exclusion and analysis as shown in Figure 1 . After the removal of duplicates, 1272 underwent title and abstract review as primary survey which excluded 1,210 studies. The remaining 62 studies underwent full-text review and 38 were excluded due to a lack of reporting outcomes of interests, overlap of patients or insufficient data. This yielded 15 studies with a total of 373 patients that met inclusion our criteria 9 – 22 . Using the Newcastle-Ottawa quality assessment form, thirteen were identified as good quality while two were of fair quality. Baseline characteristics of the included studies are listed in Table 1 . View this table: View inline View popup Table 1: Baseline Characteristics of all studies Our final 15 studies yielded a total of 373 patients with a mean age of 55 ± 5.3 years with 72% ± 24% being male and a mean follow-up of 477.8 ± 317.7 months. Average left ventricular ejection fraction (EF) amongst all studies was found to be 30.5% ± 9.2% with the most common type of heart failure being ischemic cardiomyopathy with a prevalence of 31%. Demographic of patients can be found in Table 2 . The most common type of ventricular arrhythmia was monomorphic VT (17%) ( Table 3 ). Of the 15 studies, 14 included surgical complications. We found that both neuropathic pain and hypotension was the most common complications with an incidence of 20.5% ( Figure 2 ). Of the total 373 patients 79% (n=291) underwent bilateral, 21% (n=77) left sided, and 0.5% (n=2) right sided CSD. All of the patients underwent CSD using video-assisted thoracoscopic surgery (VATS). Download figure Open in new tab Figure 2. Post surgical complications. View this table: View inline View popup Download powerpoint Table 2. Demographics & Medical History CKD = chronic kidney disease; PVD = peripheral vascular disease; COPD = chronic obstructive pulmonary disease; CAD = coronary artery disease. View this table: View inline View popup Download powerpoint Table 3. Types of VTA and HF. NICM = non-ischemic cardiomyopathy. Changes in ICD Shocks post-surgery A total of 11 studies reported freedom from ICD shocks at 1 year post CSD yielding a pooled event rate of 69.8% (95% CI, 56.4% – 80.4%, 57% heterogeneity) (I 2 statistic). A total of 13 studies reported freedom from ICD shocks at 6 months which yielded a pooled event rate of 59.1% (95% CI, 46.9% - 70.4%, 47% I 2 ) ( Figures 3 &4). Download figure Open in new tab Figure 3. Forest plot event rate of ICD shocks 1 year post CSD where B indicates a ≥ 75% freedom of ICD shocks. Download figure Open in new tab Figure 4. Forest plot showing event rate of ICD shocks at 6 months post CSD where B indicates a ≥ 75% freedom of ICD shocks. Changes in VTA post-surgery A total of 9 studies reported freedom from VTA 1 year post CSD with a pooled event rate of 64.3% (95% CI, 42.3% - 81.5%, 26% I 2 ). There were 11 studies that reported freedom from VTA at 6 months with a pooled event rate of 62.3% (95% CI, 51.2% - 72.2%, 40% I 2 ) ( Figures 5 &). Download figure Open in new tab Figure 5. Forest plot of event rate of recurrent ventricular arrhythmias 1 year post CSD where B indicates a ≥ 75% freedom of ICD shocks. Download figure Open in new tab Figure 6. Forest plot of event rate of recurrent ventricular arrhythmias 6 months post CSD where B indicates freedom of ICD shocks ≥75%. Temporal Mortality of CSD Reported mortality due to VTA was subdivided into short-term (0-30 days), intermediate-term (31-364 days) and long-term (>364 days). The pooled event rate of mortality for short-term tertile was 8.9% (95% CI, 5.0% - 15.4%, 0% I 2 ), medium term was 5.3% (95% CI, 2.4% - 11.3%, 0% I 2 ) and long-term 5.2% (95% CI, 2.4% - 10.9%, 0% I 2 ) ( Figures 7 - 9 ). Download figure Open in new tab Figure 7. Forrest plot for short term mortality of CSD where A = mortality event rate < 25%. Download figure Open in new tab Figure 8. Forrest plot for medium term mortality of CSD where A = mortality event rate < 25%. Download figure Open in new tab Figure 9. Forrest plot for long term mortality of CSD where A = mortality event rate < 25%. Changes in ablation post-surgery A total of 11 studies provided the percentage of patients that underwent ablation pre and post CSD. On average, 69% of patients underwent cardiac ablation prior to CSD vs. only 15% after CSD (p<0.0003 CI 33.2 80.1). Discussion This contemporary meta-analysis reports the largest series of adult patients suffering from recurrent VTA with structural heart disease who underwent left or bilateral CSD for VTA refractory to antiarrhythmic therapy and/or catheter ablation. Two similar previous meta-analyses have covered this topic. 23 , 24 This meta-analysis differs from previous analyses done by Shah et al. and Murtaza et al. by including 3 new studies, only including adults, and reports on incidence of mortality after CSD. Utilization of CSD was first used in 1961 by Estes et al. in a patient with valvular heart disease and later in 1971 Moss and McDonald in a women experiencing recurrent episodes of ventricular fibrillation due to idiopathic LQTS. 25 , 26 The use of CSD was later used by Wilde et al, Collura et al, and De Ferrari et al, in patients with polymorphic ventricular tachycardia. 27 – 29 In 1981 Schwartz and Stone verified that left stellectomy applies a noteworthy protective effect in reducing ventricular fibrillation in dogs with myocardial ischemia. 30 This was eventually expounded further by Schwartz and Vanoli and Schwartz et al by revealing the autonomic mechanism in stellectomys. 31 , 32 This eventually led to a clinical trial which revealed the usefulness of surgical and pharmacological antiadrenergic interventions in lowering mortality in patients who are at high risk for sudden cardiac death. 33 Bourke et al then reported the first reduction of VTA in patients with ischemic cardiomyopathy or non-ischemic cardiomyopathy after left-sided CSD. 34 Lately, CSD has gained importance as a reasonable substitute in patients with refractory VTA. This meta-analysis demonstrates that patients who undergo CSD benefit from significant VTA and ICD shock reduction by more than 60% at both 6-month and 1-year intervals. This is consistent with prior meta-analyses by Murtaza et al., which reported a pooled rate of freedom from VTA at 60% but with a mean follow-up time of 10 months. 23 Additionally, this is the first meta-analysis that reports mortality from VTA after CSD to be less than 6% in the short-, medium-, and long-term intervals. Most of the studies selected patients for CSD who had failed traditional therapy with antiarrhythmic medications and previous cardiac ablations and were still suffering from VTA and VT storms. Most patients underwent multiple failed catheter ablations prior to CSD ( Table 1 ). VT storm was defined as 3 episodes of VTA within 24 hours. Definition of VTA recurrence was based on data from ICD interrogations (any sustained VTA: ventricular fibrillation, monomorphic or polymorphic ventricular tachycardia) or 12-lead ECGs in case of documented sustained VTs below ICD detection. Multiple studies have shown that patients with cardiac ischemia, inherited arrhythmias, and heart failure predisposes them to have sympathetic activation which in return can cause or worsen VTA. 35 , 36 Currently, CSD is a class I recommendation for long QT syndromes and catecholaminergic polymorphic ventricular tachycardia in the 2017 AHA/ACC/HRS guideline in the management of VTA refractory to maximum tolerated beta-adrenergic blockade. 37 However, much of this evidence is from pediatric studies and patients under the age of 18 years. As previously reported in a combined assessment of the association between VTA burden and mortality, patients who received 1 shock had a fourfold increased risk of death and patients with ≥ 2 shocks had an eightfold increase in death, compared with patients who received no ICD shocks. 37 , 38 This favorably translates benefit in this review as CSD lowers rate of ICD shocks. This review also found that the mean number of ICD shocks decreased by 40% when comparing a 1-year pre-CSD to 1 year post CSD. Unfortunately, only 6 studies reported this data and with high degree of heterogeneity, making statistical analysis unfruitful. However, when evaluating the burden of ablation, there was an overwhelming decrease in the percentage of patients requiring repeat ablation post CSD. This is encouraging and might suggest that patients might be demonstrating a better quality of life while exhibiting a reduction in overall symptoms. Moreover, this review finds that post operative mortality is slightly higher in the first 30 days. The association is unclear, but may be due to comorbidities, end-organ failure in setting of electrical storm, surgical technique, or failure to respond to sympathectomy due to incomplete denervation. Incomplete denervation is linked to the nerve of Kuntz; collateral nerves that bypass the sympathetic trunk form the second to the first intercostal nerve. 23 Marhold et al. found that detecting the nerve of Kunts was more frequent during open techniques compared to thoracoscopic approach, a technique that is most used in CSD. Failure of complete denervation may result in perpetuation of electrical storm and clinical demise. In evaluating studies that included both bilateral and unilateral procedures, surgical approach was generally started on the left side followed by the right. Our analysis showed that 79% of our studies conducted bilateral surgical approaches. This was similar to the previous analysis done which found 82% of patients that underwent bilateral carotid sympathetic denervation (BCSD). 24 Patients who had unilateral CSD and still exhibited VTA, underwent repeat denervation of the opposite sympathetic chain. In these subsets of patients, we found that their response to BCSD was sustained with little no recurrence of VTA or ICD shocks. Our review found that neuropathic pain and hypotension were the two most common complications with an incidence of 20.5% ± 8.3%. This was similar from previous meta-analysis by Chihara et al. and Shah et al. in which both studies found pneumothorax to be the most common complication. Hypotensive episodes were limited to immediate postoperative period and all patients were successfully weaned off vasopressor medications. Since the procedure involved sympathetic denervation, Horner’s syndrome was a major concern in many of the studies. However, we found that 17% of patients experienced the complication. The lower complication rate might be explained by how surgical technology has advanced with the use of 3-dimensional cameras, and wristed instruments to help with better visualization of the nerve during VATS. Although this series and others have demonstrated the benefit and risks of CSD in a retrospective observational way, there is quite a paucity of high-quality randomized trial data for this therapy for patients with refractory VTA. It is still unclear as to the appropriate timing to pursue CSD over other traditional standards of care which include further escalation of antiarrhythmic agents, catheter ablation, and cardiac transplantation. Furthermore, the safety of this procedure is still concerning, given that complication rates are high, the long-term implications of chronotropic incompetence after CSD in patients who ultimately undergo cardiac transplantation are unknown. An ongoing randomized clinical trial “Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias (PREVENT VT)” may answer some of these questions. 38 Conclusion In patients with electrical storm and refractory VTA, CSD is a feasible adjunctive therapy to reduce the burden of VTA and ICD shocks once traditional therapies such as antiarrhythmic drug escalation and catheter ablation have been exhausted. The CSD procedure has some risk of complication and morbidity/mortality that needs further investigation. Limitations This systematic review and meta-analysis suffers from limitations and biases of retrospective data collection and analysis. Moreover, meta-analyses have inherent quality issues due to heterogeneity of the data across included studies, poor quality data, selection biases, and large standard errors. There were also no control studies included in this systematic review. Finally, conclusions regarding the efficacy of CSD in comparison to anti-arrhythmic therapy was not possible. Data Availability All data generated or analyzed during this study are included in this published article and its supplementary information files. The datasets generated and analyzed during the current study are available to open access. Acknowledgements None Footnotes Financial support: None Disclosures: None Conflict of Interest: None Abbreviations VTA Ventricular Tachyarrhythmias CSD Cardiac sympathetic denervation HF heart failure EF Ejection Fraction ICD Implanted Cardiac Defibrillator References 1. ↵ Srinivasan NT , Schilling RJ. Sudden cardiac death and arrhythmias . Arrhythm Electrophysiol Rev . 2018 ; 7 ( 2 ): 111 – 117 . doi: 10.15420/aer.2018:15 : OpenUrl CrossRef 2. ↵ Samuel M , Elsokkari I , Sapp JL . Ventricular tachycardia burden and mortality: Association or causality? . Can J Cardiol . 2022 ; 38 ( 4 ): 454 – 464 . doi: 10.1016/j.cjca.2022.01.016 OpenUrl CrossRef 3. ↵ Manolis AA , Manolis TA , Apostolopoulos EJ , Apostolaki NE , Melita H , Manolis AS . The role of the autonomic nervous system in cardiac arrhythmias: The neuro-cardiac axis, more foe than friend? Trends Cardiovasc Med . 2021 ; 31 ( 5 ): 290 – 302 . doi: 10.1016/j.tcm.2020.04.011 OpenUrl CrossRef 4. ↵ Vaseghi M , Barwad P , Malavassi Corrales FJ , et al. Cardiac sympathetic denervation for refractory ventricular arrhythmias . J Am Coll Cardiol . 2017 ; 69 ( 25 ): 3070 – 3080 . doi: 10.1016/j.jacc.2017.04.035 OpenUrl FREE Full Text 5. ↵ Witt CM , Bolona L , Kinney MO , et al. Denervation of the extrinsic cardiac sympathetic nervous system as a treatment modality for arrhythmia . Europace . 2017 ; 19 ( 7 ): 1075 – 1083 . doi: 10.1093/europace/eux011 OpenUrl CrossRef 6. ↵ Vaseghi M , Gima J , Kanaan C , et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up . Heart Rhythm . 2014 ; 11 ( 3 ): 360 – 366 . doi: 10.1016/j.hrthm.2013.11.028 OpenUrl CrossRef PubMed 7. ↵ Ahmed A , Charate R , Bawa D , et al. Bilateral cardiac sympathetic denervation for refractory multifocal premature ventricular contractions in patients with nonischemic cardiomyopathy . JACC Clin Electrophysiol . 2024 ; 10 ( 1 ): 31 – 39 . doi: 10.1016/j.jacep.2023.09.014 OpenUrl CrossRef 8. ↵ Grassi G , Seravalle G , Dell’Oro R , Facchini A , Ilardo V , Mancia G . Sympathetic and baroreflex function in hypertensive or heart failure patients with ventricular arrhythmias . J Hypertens . 2004 ; 22 ( 9 ): 1747 – 1753 . doi: 10.1097/00004872-200409000-00019 OpenUrl CrossRef PubMed Web of Science 9. ↵ Barwad P , Sinkar K , Bachani N , et al. Long-term clinical outcomes of cardiac sympathetic denervation in patients with refractory ventricular arrhythmias . J Cardiovasc Electrophysiol . 2021 ; 32 ( 4 ): 1065 – 1074 . doi: 10.1111/jce.14947 OpenUrl CrossRef 10. Cai C , Dai MY , Tian Y , et al. Electrophysiologic effects and outcomes of sympatholysis in patients with recurrent ventricular arrhythmia and structural heart disease . J Cardiovasc Electrophysiol . 2019 ; 30 ( 9 ): 1499 – 1507 . doi: 10.1111/jce.14030 OpenUrl CrossRef 11. Cardona-Guarache R , Padala SK , Velazco-Davila L , et al. Stellate ganglion blockade and bilateral cardiac sympathetic denervation in patients with life-threatening ventricular arrhythmias . J Cardiovasc Electrophysiol . 2017 ; 28 ( 8 ): 903 – 908 . doi: 10.1111/jce.13249 OpenUrl CrossRef 12. Juhos P , Janik M , Hatala R , et al. Bilateral thoracoscopic cardiac sympathetic denervation in patients with refractory ventricular tachyarrhythmias nonresponsive to other treatment . Bratisl Lek Listy . 2022 ; 123 ( 7 ): 528 – 532 . doi: 10.4149/BLL_2022_091 OpenUrl CrossRef 13. König S , Schröter T , Borger MA , et al. Outcomes following cardiac sympathetic denervation in patients with structural heart disease and refractory ventricular arrhythmia . Europace . 2022 ; 24 ( 11 ): 1800 – 1808 . doi: 10.1093/europace/euac078 OpenUrl CrossRef 14. Krause EM , Appelbaum J , Naselsky W , et al. Limited left thoracoscopic sympathectomy effectively silences refractory electrical storm . Ann Thorac Surg . 2022 ; 113 ( 1 ): 217 – 223 . doi: 10.1016/j.athoracsur.2021.01.039 OpenUrl CrossRef 15. Lee ACH , Tung R , Ferguson MK . Thoracoscopic sympathectomy decreases disease burden in patients with medically refractory ventricular arrhythmias . Interact Cardiovasc Thorac Surg . 2022 ; 34 ( 5 ): 783 – 790 . doi: 10.1093/icvts/ivab372 OpenUrl CrossRef 16. Melinosky K , Leng A , Johnson CR , et al. Outcomes comparison of robot-assisted and video-assisted thoracoscopic cardiac sympathetic denervation . Innovations . 2023 ; 18 ( 6 ): 512 – 518 . doi: 10.1177/15569845231210282 OpenUrl CrossRef 17. Miki Y , Yoshimura S , Sasaki T , et al. Bilateral cardiac sympathetic denervation for treatment-resistant ventricular arrhythmias in heart failure patients with a reduced ejection fraction . Int Heart J . 2022 ; 63 ( 4 ): 692 – 699 . doi: 10.1536/ihj.21-601 OpenUrl CrossRef 18. Prabhu MA , Prasad SB , Abhilash SP , Thajudeen A , R BK , Namboodiri N . Left sympathetic cardiac denervation in managing electrical storm: Acute outcome and long term follow up . J Interv Card Electrophysiol . 2016 ; 47 ( 3 ): 285 – 292 . doi: 10.1007/s10840-016-0153-2 OpenUrl CrossRef 19. Richardson T , Lugo R , Saavedra P , et al. Cardiac sympathectomy for the management of ventricular arrhythmias refractory to catheter ablation . Heart Rhythm . 2018 ; 15 ( 1 ): 56 – 62 . doi: 10.1016/j.hrthm.2017.09.006 OpenUrl CrossRef 20. Vaseghi M , Barwad P , Malavassi Corrales FJ , et al. Cardiac sympathetic denervation for refractory ventricular arrhythmias . J Am Coll Cardiol . 2017 ; 69 ( 25 ): 3070 – 3080 . doi: 10.1016/j.jacc.2017.04.035 OpenUrl FREE Full Text 21. Velásquez M , Fernández L , Leib CS , Orozco V , Pava F , Perafan P . Cardiac sympathetic denervation for conventional treatment refractory arrhythmias . Arch Cardiol Mex . 2019 ; 89 ( 3 ): 211 – 215 . doi: 10.24875/ACM.M19000052 OpenUrl CrossRef 22. ↵ Yalin K , Liosis S , Palade E , et al. Cardiac sympathetic denervation in patients with nonischemic cardiomyopathy and refractory ventricular arrhythmias: a single-center experience . Clin ResCardiol . 2021 ; 110 ( 1 ): 21 – 28 . doi: 10.1007/s00392-020-01643-8 OpenUrl CrossRef 23. ↵ Murtaza G , Sharma SP , Akella K , et al. Role of cardiac sympathetic denervation in ventricular tachycardia: A meta-analysis . Pacing Clin Electrophysiol . 2020 ; 43 ( 8 ): 828 – 837 . doi: 10.1111/pace.13968 OpenUrl CrossRef 24. ↵ Shah R , Assis F , Alugubelli N , Okada DR , Cardoso R , Shivkumar K , Tandri H . Cardiac sympathetic denervation for refractory ventricular arrhythmias in patients with structural heart disease: A systematic review . Heart Rhythm . 2019 Oct ; 16 ( 10 ): 1499 – 1505 . doi: 10.1016/j.hrthm.2019.06.018 . Epub 2019 Jun 2. PMID: 31252084 . OpenUrl CrossRef PubMed 25. ↵ Estes EH Jr . , Izlar HL Jr . . Recurrent ventricular tachycardia. A case successfully treated by bilateral cardiac sympathectomy . Am J Med . 1961 ; 31 : 493 – 497 . doi: 10.1016/0002-9343(61)90132-2 OpenUrl CrossRef PubMed Web of Science 26. ↵ Moss AJ , McDonald J . Unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome . N Engl J Med . 1971 ; 285 ( 16 ): 903 – 904 . doi: 10.1056/NEJM197110142851607 OpenUrl CrossRef PubMed Web of Science 27. ↵ Wilde AA , Bhuiyan ZA , Crotti L , et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia . N Engl J Med . 2008 ; 358 ( 19 ): 2024 – 2029 . doi: 10.1056/NEJMoa0708006 OpenUrl CrossRef PubMed Web of Science 28. Collura CA , Johnson JN , Moir C , Ackerman MJ . Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery . Heart Rhythm . 2009 ; 6 ( 6 ): 752 – 759 . doi: 10.1016/j.hrthm.2009.03.024 OpenUrl CrossRef PubMed Web of Science 29. ↵ De Ferrari GM , Dusi V , Spazzolini C , et al. Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation . Circulation . 2015 ; 131 ( 25 ): 2185 – 2193 . doi: 10.1161/CIRCULATIONAHA.115.015731 OpenUrl Abstract / FREE Full Text 30. ↵ Schwartz PJ , Stone HL . Left stellectomy in the prevention of ventricular fibrillation caused by acute myocardial ischemia in conscious dogs with anterior myocardial infarction . Circulation . 1980 ; 62 ( 6 ): 1256 – 1265 . doi: 10.1161/01.cir.62.6.1256 OpenUrl Abstract / FREE Full Text 31. ↵ Schwartz PJ , Vanoli E . Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs . J Cardiovasc Pharmacol . 1981 ; 3 ( 6 ): 1251 – 1259 . doi: 10.1097/00005344-198111000-00012 OpenUrl CrossRef PubMed Web of Science 32. ↵ Schwartz PJ , Vanoli E , Zaza A , Zuanetti G . The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity . Am Heart J . 1985 ; 109 ( 5 Pt 1): 937 - 948 . doi: 10.1016/0002-8703(85)90233-9 OpenUrl CrossRef PubMed Web of Science 33. ↵ Schwartz PJ , Motolese M , Pollavini G , et al. Prevention of Sudden Cardiac Death After a First Myocardial Infarction by Pharmacologic or Surgical Antiadrenergic Interventions . Journal of Cardiovascular Electrophysiology . 1992 ; 3 ( 1 ): 2 – 16 . doi: 10.1111/j.1540-8167.1992.tb01090.x OpenUrl CrossRef Web of Science 34. ↵ Bourke T , Vaseghi M , Michowitz Y , Sankhla V , Shah M , Swapna N , Boyle NG , Mahajan A , Narasimhan C , Lokhandwala Y , Shivkumar K . Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation . Circulation . 2010 Jun 1; 121 ( 21 ): 2255 – 62 . doi: 10.1161/CIRCULATIONAHA.109.929703 . Epub 2010 May 17. PMID: 20479150 ; PMCID: PMC2896716 . OpenUrl Abstract / FREE Full Text 35. ↵ Shen MJ , Zipes DP . Role of the autonomic nervous system in modulating cardiac arrhythmias . Circ Res . 2014 ; 114 ( 6 ): 1004 – 1021 . doi: 10.1161/CIRCRESAHA.113.302549 OpenUrl Abstract / FREE Full Text 36. ↵ Lukas A , Antzelevitch C . Differences in the electrophysiological response of canine ventricular epicardium and endocardium to ischemia. Role of the transient outward current . Circulation . 1993 ; 88 ( 6 ): 2903 – 2915 . doi: 10.1161/01.cir.88.6.2903 OpenUrl Abstract / FREE Full Text 37. ↵ Al-Khatib SM , Stevenson WG , Ackerman MJ , et al. 2017 AHA/ACC/HRS Guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society . Circulation . 2018 ; 138 ( 13 ): e210 - e271 . doi: 10.1161/CIR.0000000000000548 OpenUrl CrossRef 38. ↵ Poole JE , Johnson GW , Hellkamp AS , et al. Prognostic importance of defibrillator shocks in patients with heart failure . N Engl J Med . 2008 ; 359 ( 10 ): 1009 – 1017 . doi: 10.1056/NEJMoa071098 OpenUrl CrossRef PubMed Web of Science 39. Cardiac Sympathetic Denervation for Prevention of ventricular tachyarrhythmias - Full text view - ClinicalTrials.gov . https://classic.clinicaltrials.gov/ct2/show/NCT01013714 View the discussion thread. Back to top Previous Next Posted August 10, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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