Clinical trial NCT04239144: Sympathetic Denervation by Video-assisted Thoracoscopy in Control of Cardiac Arrhythmias in Patients With Chagas Disease
Official title: Role of Sympathetic Denervation by Video-assisted Thoracoscopy in Control of Cardiac Arrhythmias in Patients With Chagas Disease - Pilot Study Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chagas Cardiomyopathy
Ventricular Arrythmia
Keywords: Ventricular Tachycardia,
Chagas Disease
Catheter Ablation
Bilateral Sympathectomy
Cardiac Sympathetic Denervation
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Biosense Webster, Inc.
First posted: 2020-01-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this pilot study, the investigators will select 45 patients with Chagas cardiomyopathy with ICD who presented at least four ICD therapies in the prior six months. These patients will be randomly assigned to three groups, 15 patients in medical therapy group, 15 in catheter ablation and 15 in bilateral sympathectomy. The objective of this study is to evaluate the efficacy of the bilateral sympathectomy in the reduction of ventricular tachycardia in patients with Chagas cardiomyopathy.
Primary purpose: TREATMENT

Brief summary: Ventricular tachycardia (VT) is the main cause of sudden death in patients with structural heart diseases. The use of ICD (implantable cardio-defibrillator) could prevent sudden death, however, the occurrence of repetitive shock decreases significantly the quality of life and could increase the mortality rate. Chagas disease in our environment is the most common heart disease and often associated with the occurrence appropriate ICD therapies.

The chronic treatment of VT aims to prevent recurrences with the use of antiarrhythmic drugs and catheter ablation, but in many cases, these treatments are insufficient to control the VT. Cardiac Sympathetic Denervation by bilateral sympathectomy has been described as an alternative treatment of VT refractory to medical treatment and radiofrequency ablation, especially in patients with channelopathies. This treatment could have a role in patients with structural heart disease.

The objective of this study is to evaluate the efficacy of the bilateral sympathectomy in the reduction of ventricular tachycardia in patients with Chagas cardiomyopathy. In this pilot study, the investigators will select 45 patients with Chagas cardiomyopathy with ICD who presented at least four ICD therapies in the prior six months. These patients will be randomly assigned to three groups, 15 patients in medical therapy group, 15 in catheter ablation and 15 in bilateral sympathectomy.

Detailed description: OBJECTIVE

Primary

• Evaluate the efficacy of bilateral sympathectomy in the reduction of VT episodes in patients with Chagas cardiomyopathy.

Secondary

* To compare the efficacy of bilateral sympathectomy against VT ablation and against optimal medical therapy.
* To evaluate the density of ventricular premature beats 24-hour Holter and monitor the events recorded by the ICD and the impact of the treatment performed.
* To evaluate the length of the hospital stay according to the type of intervention.
* To evaluate the rate of clinical complications according to the type of intervention.
* To evaluate the impact of treatment on left ventricular function.

Follow up

Outcomes Assessment in six months and one year

* Recurrence rate of appropriate therapies;
* Density of ventricular ectopies;
* Complication rates per type of intervention;
* Number of in-hospital days per type of intervention;
* Assessment of LV function;

METHODS

This is a pilot, single-centre, open-label, randomized trial in patients with Chagas disease and multiple appropriate ICD therapies. This study consists of three groups: (1) medical treatment, (2) catheter ablation and (3) bilateral sympathectomy, being included 15 patients in each group.

Inclusion Criteria:

* Patients with Chagas Disease Cardiomyopathy having an ICD
* At least four appropriate ICD therapies in the past six months, documented by device interrogation or medical records;
* Use of amiodarone and beta blockers in an optimized fashion;
* Life expectancy of more than one year
* Conditions for following the plan of clinical follow-up of the study.

Exclusion criteria:

* Presence of an absolute contraindication to receive any of the possible treatments of the study;
* Pregnant Woman;
* Less than 18 years-old;
* Renal insufficiency with creatinine \>2.5 mg/dL (221 umol/L);
* Mobile thrombus in the left ventricle;
* Left Ventricle Ejection fraction \< 10%;
* Unstable angina;
* Severe aortic stenosis
* Primary severe mitral insufficiency;
* New York Heart Association (NYHA) functional class IV;
* Previous cardiac surgery or scheduled.

The patients will be recruited consecutively in the outpatient clinic of Cardiac Pacing Unit, or in outpatient clinic of Arrhythmias Clinical Unit or in the Emergency Clinical Unit.

Group 1 - Medical Treatment: patients allocated to this group will receive amiodarone reimpregnation, incremental dose of beta-blocker and if possible ICD reprogramming.

Group 2 - Catheter ablation: patients allocated to this group will undergo epicardial and endocardial catheter ablation with the use of an irrigated contact sensor tip catheter. Voltage electroanatomical mapping using Carto System will be performed in all cases and if hemodynamically stable VT is induced, activation mapping will also be performed. The aim of the ablation is to eliminate the clinical VT additionally to substrate modification. The result of ablation will be defined as (1) complete success (all VTs non-inducible); (2) partial success (clinical VT non inducible, but other morphologies still inducible) and (3) failure (clinical VT still inducible).

Group 3 - Bilateral sympathectomy - bilateral sympathectomy will be performed using video assisted thoracoscopy using the Ethicon Ultracision device. The denervation consists of lower 1/3 stellate ganglion and T3- T4 thoracic interspinal space videothoracoscopic cutting, isolating the whole sympathetic chain between these two points using ultracision device on the nerve branches. The cephalic portion of the stellate ganglion will be preserved to avoid Horner's syndrome and the electrocautery use will also be avoided for the same reason. Hemodynamic and echocardiographic behaviors will be continuously monitored during these surgical maneuvers. After the application, 10 ml of 0.25% bupivacaine solution will be injected along the site of the pleural dissection for postoperative analgesia. The lung will be reinflated under direct vision and a small tube will be inserted to remove the air through the upper incision, which will be removed at the end of the operation if possible. The two port sites will be closed primarily with absorbable stitches.

The study conformed to the principles outlined in the Declaration of Helsinki and was approved by the ethics committee and institutional review board of our hospital. All patients will provide written informed consent before randomization.

Eligibility criteria: Inclusion Criteria:

* Patients with Chagas Disease Cardiomyopathy having an ICD
* At least four appropriate ICD therapies in the past six months, documented by device interrogation or medical records;
* Use of amiodarone and beta blockers in an optimized fashion;
* Life expectancy of more than one year
* Conditions for following the plan of clinical follow-up of the study.

Exclusion criteria:

* Presence of an absolute contraindication to receive any of the possible treatments of the study;
* Pregnant Woman;
* Less than 18 years-old;
* Renal insufficiency with creatinine \>2.5 mg/dL (221 umol/L);
* Mobile thrombus in the left ventricle;
* Left Ventricle Ejection fraction \< 10%;
* Unstable angina;
* Severe aortic stenosis
* Primary severe mitral insufficiency;
* New York Heart Association (NYHA) functional class IV;
* Previous cardiac surgery or scheduled.

Primary outcomes:
measure: Time to Ventricular Tachycardia Recurrence
timeFrame: 12 months
measure: Burden of Ventricular Tachycardia Recurrence
timeFrame: 12 months
Secondary outcomes:
measure: Ventricular Tachycardia Recurrence Following Sympathectomy Compared to Catheter Ablation.
timeFrame: 12 months
measure: Mortality and Transplant Rate
timeFrame: 12 months
measure: Ventricular Ectopic Beats Density
timeFrame: 12 months
measure: Length of Hospital Stay
timeFrame: 12 months
measure: Rate of Complications Following Intervention
timeFrame: 12 months
measure: Impact on Left Ventricular Ejection Fraction
timeFrame: 12 months
measure: Autonomic Measures
timeFrame: 12 months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Study officials:
affiliation: Instituto do Coração Faculdade de Medicina da USP - (INCOR-FMUSP)
name: Paulo M Pego Fernandes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto do Coração Faculdade de Medicina da USP - (INCOR-FMUSP)
name: Rodrigo M Kulchetscki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto do Coração Faculdade de Medicina da USP - (INCOR-FMUSP)
name: Maurício I Scanavacca, MD, PhD
role: STUDY_DIRECTOR
References: