Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias (PREVENT VT)

• ClinicalTrials.gov Identifier: NCT01013714
• Recruitment Status: Recruiting
• First Posted: November 16, 2009
• Last Update Posted: January 10, 2023
• Sponsor: University of California, Los Angeles
• Collaborators: Vanderbilt University; Oregon Health and Science University
• Information provided by (Responsible Party): Marmar Vaseghi, University of California, Los Angeles

Study Description

Brief Summary:

The purpose of this research study is to examine the effect of cardiac sympathetic denervation (CSD) surgery on life threatening abnormal heart rhythms called ventricular tachycardia or ventricular fibrillation that can lead to sudden cardiac death. Subjects will be asked to participate in this research study if they have recurrent ventricular tachycardia (at least one ICD shock for ventricular tachycardia) and have undergone at least one catheter ablation procedure or have ventricular tachycardia or fibrillation that is not ablatable. The goal of this study is to determine whether cardiac sympathetic denervation can prevent these abnormal heart rhythms from occurring and therefore, prevent, ICD shocks which are not only painful, but have been shown to reduce quality of life and/or lead to depression, particularly in the period immediately after the shock.

Condition or disease	Intervention/treatment	Phase
Sudden Cardiac Death; Ventricular Tachycardia; Ventricular Fibrillation; Cardiomyopathy	Procedure: Cardiac Sympathetic Denervation (CSD); Drug: Routine Care	Phase 3

Detailed Description:

The purpose of this study is to determine if bilateral cardiac sympathetic denervation (CSD) in addition to routine care is more effective than routine care for the treatment of ventricular tachycardia or fibrillation in patients with implantable cardioverter defibrillators (ICDs) who continue to have episodes of VT despite drug therapy and when appropriate, at least one catheter ablation procedure.

The CSD procedure involves removal of part of the cervical stellate ganglia and thoracic ganglia of level 2 to 4. These ganglia house the left and right sided nerves that feed the heart and have been implicated in the occurrence of fast abnormal rhythms that cause defibrillator shocks and sudden death. Stimulation of these nerves has been shown to increase the incidence of sudden death and fast abnormal heart rhythms that lead to internal defibrillator shocks called ventricular tachycardia/ventricular fibrillation. Removal of the ganglia of these nerves in animal and human studies has been shown to decrease the incidence of life threatening abnormal rhythms and sudden death.The procedure takes less than 45 minutes on each side and can be performed endoscopically.

We are inviting patients to participate in this clinical trial who have undergone at least one catheter ablation procedure for ventricular tachycardia but have continued to experience recurrent arrhythmias (ICD shocks) or who have a type of ventricular tachycardia or fibrillation that can not be treated with catheter ablation procedures. Patients will be randomized in a 1:1 fashion to either routine care + cardiac sympathetic denervation (CSD) or routine care without cardiac sympathetic denervation. We are asking 40 individuals (approximate age range 18-80 years) who continue to experience ICD shocks to participate in this research study but only half these individual will be randomized to cardiac sympathetic denervation (CSD) surgery.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prophylactic Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias (PREVENT VT)
• Actual Study Start Date: July 26, 2021
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Routine Care + Cardiac Sympathetic Denervation (CSD); Patients in this arm receive routine care and undergo cardiac sympathetic denervation. The procedure must be scheduled to occur within one month of randomization. Follow-up Visits; Follow up at 4 weeks after optimization of medical therapy and surgery; All patients are followed at the ICD clinic at 7 months or as needed.; Information regarding ICD therapy and arrhythmias will be obtained from ICD interrogations at the follow up visits.; Monthly phone calls will be used to determine for interval events, including presence of side-effects. VT Ablation is permitted in both arms for ICD shock after optimization.	Procedure: Cardiac Sympathetic Denervation (CSD); Cardiac sympathetic denervation is performed using an endoscopic procedure called VATS (video-assisted thoracoscopic sympathectomy). The surgeon removes the lower half of the stellate ganglia in addition to the thoracic ganglia of T2 - T4 on both the right and left side. The VATS procedure provides a minimally invasive endoscopic approach that is safe and effective. The procedure can be completed in less than 45 minutes on each side.; Drug: Routine Care; Anti-arrhythmic medications are continued for the duration of the study unless discontinued or adjusted to due to drug toxicity, intolerance, or ICD shock. All anti-arrhythmic medications (whether in the routine care or surgical arm) can be adjusted at the discretion of the treating physician.
Placebo Comparator: Routine Care; Patients in this arm remain on prescribed drug regimen and will not undergo CSD. Follow-up Visits; Medical follow up at 4 weeks after optimization of medical therapy.; All patients are followed at the ICD clinic at 7 months or as needed.; Information regarding ICD therapy and arrhythmias will be obtained from ICD interrogations at the follow up visits.; Monthly phone calls will be used to determine for interval events, including presence of side-effects. VT Ablation is permitted in both arms for ICD shock after optimization.	Drug: Routine Care; Anti-arrhythmic medications are continued for the duration of the study unless discontinued or adjusted to due to drug toxicity, intolerance, or ICD shock. All anti-arrhythmic medications (whether in the routine care or surgical arm) can be adjusted at the discretion of the treating physician.

Outcome Measures

Primary Outcome Measures :

1. Time to ICD shock, death, or cardiac transplantation [ Time Frame: 7 months ]
   To compare the time to first occurrence of appropriate ICD shock, death or cardiac transplantation in CSD+routine care vs. routine care groups.

Secondary Outcome Measures :

1. Number of ICD shocks [ Time Frame: 7 months ]
   To compare the number of ICD shocks in patients with Routine Care + CSD to Routine Care.
2. Number of appropriate ICD therapies (including ATPs ) and sustained VT below ICD detection [ Time Frame: 7 months ]
   To compare the number of appropriate ICD therapies and VT episodes below ICD detection in patients with Routine Care + CSD to Routine Care.
3. Serious adverse events [ Time Frame: 7 months ]
   To assess the occurrence of serious adverse events in patients treated with Routine Care + CSD and Routine Care.
4. Number and etiology of hospitalizations [ Time Frame: 7 months ]
   Number and etiology of hospitalization will be compared in the control vs. intervention group.
5. Number of deaths or cardiac transplantations [ Time Frame: 7 months ]
   Number of deaths or cardiac transplantation in both arms of the study will be compared.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA

1. Appropriate ICD shock for VT after at least one catheter ablation of VT procedure, OR appropriate ICD shock for VT and underwent electrophysiology study/ablation procedure where the procedure was not successful (i.e. determined that VT comes from an inaccessible location or VT was not inducible and could not be targeted or continued to have inducible VT at the end of the procedure) OR appropriate ICD shock for VT and not a candidate for VT ablation (i.e. patients with presence polymorphic VT or ventricular fibrillation, LV thrombus)).
2. Presence of structural heart disease as defined as EF ≤ 50% or presence of ventricular scar as detected by imaging modalities or electroanatomic mapping, hypertrophic cardiomyopathy, cardiac sarcoidosis, or arrhythmogenic right ventricular cardiomyopathy.
3. Patient is taking at least one anti-arrhythmic drug or has documented intolerance or toxicity to at least one anti-arrhythmic drug.
4. 18 years of age or older at time of enrollment
5. Able and willing to comply with all pre- and follow-up testing and requirements.
6. Provision of signed informed consent and stated willingness to comply with all study procedures for duration of the study.

EXCLUSION CRITERIA

1. Active ongoing cardiac ischemia as assessed by: ECG, cardiac enzymes, symptoms, coronary angiography with evidence of significant epicardial coronary stenosis (>70%), or stress testing. (Note: positive troponin assay due to ICD shocks is not an exclusion criterion).
2. Any medical or non-medical condition likely to prevent completion of trial.
3. Contraindication to cardiac sympathetic denervation (i.e. unlikely to tolerate general anesthesia, single-lung ventilation, severe pulmonary disease, or severe pulmonary hypertension) or previous cardiac sympathetic denervation procedure.
4. Left ventricular assist device or status post orthotopic heart transplantation
5. Severe thrombocytopenia (platelets < 50,000) or Coagulopathy (INR > 2.0) that is not due to medications or a reversible cause.
6. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal).
7. Unable or unwilling to comply with protocol requirements.
8. NYHA class IV heart failure symptoms.
9. Known channelopathy such as long QT syndrome and catecholaminergic polymorphic VT.
10. Clinical VT rate < 150 bpm

Contacts and Locations

Contacts

Contact: Marmar Vaseghi, MD, PhD; 310-206-2235; mvaseghi@mednet.ucla.edu

Locations

United States, California

UCLA Health; Recruiting

Los Angeles, California, United States, 90095

Contact: Marmar M Vaseghi, MD, PhD 310-206-2235 mvaseghi@mednet.ucla.edu

Principal Investigator: Marmar Vaseghi, MD, PhD

Sub-Investigator: Kalyanam Shivkumar, MD, PhD

United States, Oregon

OHSU; Recruiting

Portland, Oregon, United States, 97239

Contact: Saket Sanghai, MD sanghai@ohsu.edu

United States, Tennessee

Vanderbilt University; Recruiting

Nashville, Tennessee, United States, 37235

Contact: Arvindh Kanagasundram, MD arvindh.n.kanagasundram@vanderbilt.edu

Sponsors and Collaborators

University of California, Los Angeles

Vanderbilt University

Oregon Health and Science University

Investigators

• Principal Investigator: Marmar Vaseghi, MD, PhD; University of California, Los Angeles

More Information

Publications:

Mahajan A, Moore J, Cesario DA, Shivkumar K. Use of thoracic epidural anesthesia for management of electrical storm: a case report. Heart Rhythm. 2005 Dec;2(12):1359-62. doi: 10.1016/j.hrthm.2005.09.004. No abstract available.

Stephenson EA, Berul CI. Electrophysiological interventions for inherited arrhythmia syndromes. Circulation. 2007 Aug 28;116(9):1062-80. doi: 10.1161/CIRCULATIONAHA.106.655779. No abstract available.

Nademanee K, Taylor R, Bailey WE, Rieders DE, Kosar EM. Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy. Circulation. 2000 Aug 15;102(7):742-7. doi: 10.1161/01.cir.102.7.742.

Tygesen H, Wettervik C, Claes G, Drott C, Emanuelsson H, Solem J, Lomsky M, Radberg G, Wennerblom B. Long-term effect of endoscopic transthoracic sympathicotomy on heart rate variability and QT dispersion in severe angina pectoris. Int J Cardiol. 1999 Aug 31;70(3):283-92. doi: 10.1016/s0167-5273(99)00101-1.

Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, Bloise R, De Ferrari GM, Klersy C, Moss AJ, Zareba W, Robinson JL, Hall WJ, Brink PA, Toivonen L, Epstein AE, Li C, Hu D. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation. 2004 Apr 20;109(15):1826-33. doi: 10.1161/01.CIR.0000125523.14403.1E. Epub 2004 Mar 29.

Li J, Wang L, Wang J. Video-assisted thoracoscopic sympathectomy for congenital long QT syndromes. Pacing Clin Electrophysiol. 2003 Apr;26(4 Pt 1):870-3. doi: 10.1046/j.1460-9592.2003.t01-1-00152.x.

Ouriel K, Moss AJ. Long QT syndrome: an indication for cervicothoracic sympathectomy. Cardiovasc Surg. 1995 Oct;3(5):475-8. doi: 10.1016/0967-2109(95)94444-2.

Lobato EB, Kern KB, Paige GB, Brown M, Sulek CA. Differential effects of right versus left stellate ganglion block on left ventricular function in humans: an echocardiographic analysis. J Clin Anesth. 2000 Jun;12(4):315-8. doi: 10.1016/s0952-8180(00)00158-6.

Schlack W, Dinter W. Haemodynamic effects of a left stellate ganglion block in ASA I patients. An echocardiographic study. Eur J Anaesthesiol. 2000 Feb;17(2):79-84. doi: 10.1046/j.1365-2346.2000.00606.x.

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.

Ajijola OA, Vaseghi M, Mahajan A, Shivkumar K. Bilateral cardiac sympathetic denervation: why, who and when? Expert Rev Cardiovasc Ther. 2012 Aug;10(8):947-9. doi: 10.1586/erc.12.93. No abstract available.

Johnson JP, Ahn SS, Choi WC, Masciopinto JE, Kim KD, Filler AG, Desalles AA. Thoracoscopic sympathectomy: techniques and outcomes. Neurosurg Focus. 1998 Feb 15;4(2):e4. doi: 10.3171/foc.1998.4.2.7.

Vaseghi M, Gima J, Kanaan C, Ajijola OA, Marmureanu A, Mahajan A, Shivkumar K. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm. 2014 Mar;11(3):360-6. doi: 10.1016/j.hrthm.2013.11.028. Epub 2013 Nov 28.

Vaseghi M, Barwad P, Malavassi Corrales FJ, Tandri H, Mathuria N, Shah R, Sorg JM, Gima J, Mandal K, Saenz Morales LC, Lokhandwala Y, Shivkumar K. Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. J Am Coll Cardiol. 2017 Jun 27;69(25):3070-3080. doi: 10.1016/j.jacc.2017.04.035. Erratum In: J Am Coll Cardiol. 2017 Aug 8;70(6):811.

• Responsible Party: Marmar Vaseghi, Associate Professor of Medicine/Cardiology, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01013714
• Other Study ID Numbers: UCLA09-07-100-01
• First Posted: November 16, 2009
• Last Update Posted: January 10, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Deidentified data will be shared with other investigators upon request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: 3 years

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marmar Vaseghi, University of California, Los Angeles:

Sudden cardiac death; Ventricular tachycardia; Ventricular fibrillation; Cardiomyopathy; Internal cardiac defibrillator shocks; Internal cardiac defibrillator therapies

Additional relevant MeSH terms:

Cardiomyopathies; Tachycardia; Tachycardia, Ventricular; Death, Sudden, Cardiac; Ventricular Fibrillation; Death; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Arrest; Death, Sudden