Postoperative Atrial Fibrillation Suppression By Nerve Stimulation

Low Level Transcutaneous Electrical Vagus Nerve Stimulation To Suppress Atrial Fibrillation

The current study will evaluate the potential of stimulating the R.auricularis of the vagus nerve located at the Fossa triangularis to ameliorate or suppress AF in the study Population!

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: DUCEST Neurostimulator V Group A; Device: DUCEST Neurostimulator V Group B

Detailed Description

Scientific Background Nearly 30% of patients undergoing coronary artery bypass grafting (CABG), 40% of patients undergoing valvular heart surgery and over 50% of patients with combined coronary and valvular procedures develop atrial fibrillation (AF).

Postoperative AF occurs mostly due to conditions like chronic kidney diseases, emergency surgery, age >75 years, cardiopulmonary bypass time >180 min and due to lacking postoperative application of aldosterone- and beta-blockers.

An overview of pre- intra- and postoperative risks for AF is listed in

Table 1: Pre-, intra-, postoperative risks for AF.

Preoperative High age Male gender Previous cardiac surgery Valvular heart disease Chronic lung disease Chronic renal failure Leſt atrium enlargement Leſt ventricular hypertrophy Withdrawal of beta-blocker medication History of AF Hypertension Obesity Diabetes Metabolic Syndrome

Intraoperative Endotracheal tube insertion Intraoperative IABP Leſt ventricular venting Aortic cross-clamp time Extracorporeal circulation Myocardial ischemia Venous cannulation Damage to the atrium Excess inotropic requirements Acute volume change

Postoperative Return to intensive care unit Ventilation longer than 24 hours Volume overload Pneumonia Electrolyte imbalances Imbalance of auton. nervous system Atrial extrasystole Increased postop adrenergic status Increased aſterload Inflammation Hypotension

Several theories describe the emergence of AF like "multiple-wavelet re-entry", "focal mechanism" and "mother rotor" but the exact underlying mechanisms are still not well understood.

Prevention and treatment of postoperative AF are managed with conservative medication therapies including e.g. beta-blockers and other clinical interventions include radio frequency catheter ablation, cardioversion and occlusion of the left atrial appendage.

A novel approach for suppression of AF utilizing low-level transcutaneous electrical vagus nerve stimulation has been described recently in the Journal of the American College of Cardiology. The newly developed "DUCEST Neurostimulator V" device (manufactured by Biegler Medizinelektronik GmbH Mauerbach, Austria) offers similar action as in. This Neurostimulator device is designed to emit small direct current electrical pulses (0-1,2mA) to stimulate the R.auricularis of the vagus nerve located at the Fossa triangularis. The target population are patients with de-novo postoperative AF. The stimulation is achieved with the attachment of two needle- electrodes and connection of the electrodes to the Neurostimulator.

Following the stimulation of the vagus nerve positive effects were already achieved in chronical wound healing, peripheral artery occlusive disease (PAOD), Claudicatio intermittens (CI) and chronic pain patients.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• De-novo postoperative AF
• CABG or aortic valve replacement
• Age of 18-80 years
• Willing and able to understand, sign and date the informed consent form that has been approved by the institutional review board

Exclusion Criteria:

• Pacemaker or ICD
• Impaired EF < 30%
• Patients with acute myocardial infarction within the past 14 days
• Pregnant or lactating patients
• Any condition that, in the judgement of the investigator, would place the patient at undue risk
• Any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study
• Treatment and/or an uncompleted follow-up treatment of any investigational therapy within 6 months before procedure and intent to participate in any other investigational drug or cell therapy study during the follow-up period of this study
• Active participation in other Research therapy for cardiovascular repair/regeneration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DUCEST Neurostimulator V Group A	Device: DUCEST Neurostimulator V Group A; The DUCEST Neurostimulator V needle-electrodes are applied post-operatively to stimulate the R.auricularis of the vagus nerve located at the Fossa triangularis. Connecting the needle-electrode cables to the Neurostimulator V activates the device. (The stimulation intensity can be adjusted from 0,05mA to 1,2mA, default value is 0,4mA). The starting stimulation intensity will be adjusted to 1mA and takes place at 1Hz continuously for 40 minutes, followed by a 20 minute break. The built-in 3V battery lasts for approx. 14 days. After 7 days the electrodes are replaced and applied to the other ear of the patient. A plaster with a plastic mounting clip is attached on the shoulder of the patient. The Neurostimulator is connected to the mounting clip. After 14 days or at hospital discharge of the patient, the device is unmounted and the needle-electrodes are removed.
Sham Comparator: DUCEST Neurostimulator V Group B	Device: DUCEST Neurostimulator V Group B; The DUCEST Neurostimulator V needle-electrodes are applied post-operatively at the Fossa triangularis. Connecting the needle-electrode cables to the Neurostimulator V activates only the signal lamp but not the device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Atrial Fibrillation events in routine ECG and continous HOLTER ECG for the length of the hospital stay.	Patients are randomized to a treatment or a sham group. The corresponding device is prepared by a third person according to the double-blind setting for the surgeon. The DUCEST Neurostimulator V needle-electrodes are applied post-operatively to stimulate the R.auricularis of the vagus nerve located at the Fossa triangularis. Connecting the needle-electrode cables to the Neurostimulator V activates the device. (The stimulation intensity can be adjusted from 0,05mA to 1,2mA, default value is 0,4mA). The starting stimulation intensity will be adjusted to 1mA and takes place at 1Hz continuously for 40 minutes, followed by a 20 minute break. After 7 days the electrodes are replaced and applied to the other ear of the patient. A plaster with a plastic mounting clip is attached on the shoulder of the patient. The Neurostimulator is connected to the mounting clip. After 14 days or at hospital discharge of the patient, the device is unmounted and the needle-electrodes are removed.	07-14 days post operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of postoperative inflammation markes, using plasma values of CRP, TNF-alpha, IL-6, and IL-10	Inflammation markers will be assessed via laboratory blood sample testing at day 0 (at device attachment), +2 and +7 days post device attachment. CRP, TNF-alpha, IL-6, and IL-10 will be will be measured.	07-14 days post operative

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Alfred Kocher, MD, Surgeon

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): March 1, 2018
• Study Completion (Anticipated): May 31, 2018

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 1 KlinPruefplanProtocol6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No