Transcutaneous Vagal Nerve Stimulation to Prevent Tachyarrhythmias in Patients Early Following Myocardial Infarction

Study Overview
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Brief Summary
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Among patients early following ST-segment (ST) elevation myocardial infarction, transcutaneous vagus nerve stimulation is associated with a reduce of the burden of premature ventricular contractions in the first 40 days post-myocardial infarction (MI). The above hypothesis will be tested with a randomized, prospective, parallel, single-blind clinical trial. The expected study duration is approximately 12 months from the time the first subject is enrolled (planned for June 2023) to the time of study's termination date (December 2024). Patient enrollment is planned to take place at two major centers in Greece. The researchers will obtain approval by the institutional review board (IRB).

Official Title
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Transcutaneous Vagal Nerve Stimulation to Prevent Tachyarrhythmias in Patients Early Following Myocardial Infarction: A Randomized Clinical Trial

Conditions
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Myocardial Infarction, Tachyarrhythmia

Intervention / Treatment
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* Device: Parasym device (active, current (mA) < discomfort threshold)
* Device: Parasym device (sham, current (mA) = 0)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥18 years ST-elevation myocardial infarction which is treated with a primary percutaneous coronary intervention Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule Exclusion Criteria: A patient will be excluded from the study if one or more of all the following criteria are present: < 3 months after prior ablation Patients on amiodarone Patients with known thyroid issues, on renal-dialysis Life expectancy of < 12 months Complex congenital heart disease Cardiogenic shock Women who are pregnant (as evidenced by pregnancy test if pre-menopausal) Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia Symptomatic sinus bradycardia or sinus node dysfunction at baseline without an implantable pacemaker Complete heart block or trifascicular block without an implantable pacemaker Recurrent vasovagal syncope Pre-existing implantable cardioverter-defibrillator (ICD) Secondary prevention indication for an ICD (i.e. sustained ventricular arrhythmias occurring more than 48 hours after qualifying myocardial infarction (patients with ventricular arrhythmias occurring ≤48 hours of myocardial infarction, or with non-sustained ventricular tachycardia at any time, are not excluded)) On the heart transplant list Recurrent unstable angina despite revascularisation (defined as ongoing chest pain or ischemic symptoms at rest or with minimal exertion despite adequate treatment with anti-anginal medications) Congestive heart failure New York Heart Association class IV, defined as shortness of breath at rest, which is refractory to medical treatment (not responding to treatment)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Transcutaneous Vagal Nerve Stimulation<br> | Device: Parasym device (active, current (mA) < discomfort threshold)<br>* Active transcutaneous Vagal Nerve Stimulation (tVNS) (Parasym device, Parasym Health, Inc, London, UK) will be performed with a clip attached to the ear at 20 hertz (Hz), 250 microseconds (ms) at a current just below discomfort threshold for 30 minutes twice a day, starting on post-MI day 0. Stimulation will continue until 7 days post-MI or discharge.<br>|
| Sham Comparator: Sham Transcutaneous Vagal Nerve Stimulation<br> | Device: Parasym device (sham, current (mA) = 0)<br>* Parasym device will be attached to the ear twice a day, turned on but current set to 0 milliamp (mA), starting on post-MI day 0. Stimulation will continue until 7 days post-MI or discharge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Ventricular tachycardia burden | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate their number of Premature ventricular contractions (PVCs) and number of Non-Sustain Ventricular Tachycardias (NSVT). | 1, 7 and 40 days follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Heart Rate Variability | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Heart Rate Variability | 1, 7 and 40 days follow-up | 
| Change of Heart Rate Turbulence | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Heart Rate Turbulence | 1, 7 and 40 days follow-up | 
| Change of Deceleration Capacity (DC) | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Deceleration Capacity | 1, 7 and 40 days follow-up | 
| Change of Echocardiographic strain | Patients will undergo echocardiography at 1, 7 and 40 days to assess Myocardial substrate lesions and Post-infraction fibrosis | 1, 7 and 40 days follow-up | 
| Change of Left Ventricle Ejection Fraction (LVEF) | Patients will undergo echocardiography at 1, 7 and 40 days to assess Left Ventricle Ejection Fraction | 1, 7 and 40 days follow-up | 
| Change of Signal Averaged ECG | Patients will undergo a 12-lead electrocardiogram at 1, 7 and 40 days | 1, 7 and 40 days follow-up | 
| Change of T Wave alternans and equal indexes derived from holter monitoring | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days | 1, 7 and 40 days follow-up | 
| Change of QT duration | Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days | 1, 7 and 40 days follow-up | 
| Pain assessment | Pain scores will be assessed on postoperative days 0-7 using the visual analog score (Scale 0-10). Zero for no pain and ten being the worst pain experienced. They will be obtained and recorded into the medical record by the nurse monitoring the subject as part of standard care | 7 days follow-up | 
| Number of participants with adverse effects | Number of participants with pruritus, flush, pain at the stimulation site | 7 days follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcutaneous vagal nerve stimulation