Auricular Vagus Stimulation and STEMI

Study Overview
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Brief Summary
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At the moment, the invasive strategy for the infarct-associated coronary artery in patients with ST-segment elevation myocardial infarction (STEMI) necessary to save the myocardium and reduce the size of the necrosis zone remains the leading one. However, despite the high efficiency of providing medical care to patients with acute coronary syndrome (ACS), there remains a high mortality and disability of this group of patients. In this regard, the search for new drug and non-drug strategies for the treatment of patients with ACS is actively continuing. Over the past decade, it has been shown that transcutaneous vagus nerve stimulation (TENS) has a cardioprotective effect both in chronic heart failure and in coronary heart disease, improves cardiac function, prevents reperfusion injury, weakens myocardial remodeling, increases the effectiveness of defibrillation and reduces the size of a heart attack. One of the methods of noninvasive stimulation of the afferent fibers of the vagus nerve is percutaneous electrical stimulation of the auricular branch of the vagus nerve. However, further studies are needed to determine whether stimulation of the tragus can improve the long-term clinical outcome in this cohort of patients.

Detailed Description
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ACS is a combined concept for such life-threatening conditions as acute myocardial infarction (AMI) and unstable angina, which are exacerbations of coronary heart disease. However, despite the high effectiveness of the invasive treatment strategy, there remains a high mortality and disability of this group of patients. One of the reasons for this problem is reperfusion injury of the myocardium during revascularization, since reperfusion itself causes myocardial damage, known as Myocardial Ischemia Reperfusion Injury (MIRI). Every year, new data from experimental studies and small clinical trials appear, confirming the concept that MIRI makes a big contribution to the final size of a heart attack and cardiac myocardial function. Currently, there is no specific treatment aimed at MIRI in patients with STEMI. Thus, new treatment methods are needed that can reduce MIRI in revascularized patients. In the course of small clinical studies, it was shown that against the background of vagus nerve stimulation, a significant decrease in heart rate occurs, inflammatory processes and cellular apoptosis are suppressed, left ventricular remodeling decreases and myocardial contractile function improves. Also, a significant decrease in MIRI is demonstrated with percutaneous stimulation of the vagus nerve in the acute period of myocardial infarction. The data of the first clinical trial with VNS in patients with STEMI were published in 2017 (doi:10.1016/j.jcin.2017.04.036). This experimental study increases the likelihood that this noninvasive therapy can be used to treat patients with STEMI who are undergoing primary percutaneous coronary intervention (PCI). New studies are needed to prove the safety and effectiveness of vagus nerve stimulation in patients with STEMI.

Official Title
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Auricular Vagus Stimulation and ST-Segment Elevation Myocardial Infarction

Conditions
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Vagus Nerve Stimulation, Acute Coronary Syndrome, Ischemia Reperfusion Injury

Intervention / Treatment
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* Device: TENS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with STEMI who have signed an informed voluntary consent to participate in the study; primary myocardial infarction; treatment in the first 12 hours from the onset of pain syndrome; primary PCI. Exclusion Criteria: acute heart failure III-IV; bradyarrhythmias; atrial fibrillation/flutter at the time of switching on; Thrombolytic therapy at the prehospital stage; a history of myocardial infarction; PCI/coronary artery bypass grafting (CABG) in the anamnesis.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization of active stimulation vs. sham stimulation
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active TENS<br>It will be performed attached to the tragus of the left ear. | Device: TENS<br>* TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.<br>|
| Sham Comparator: Sham TENS<br>It will be performed attached to the earlobe of the left ear. | Device: TENS<br>* TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital mortality | The number of patients who died in the hospital. | From date of randomization until the date of death from any cause, assessed up to 14 days. | 
| 30-day mortality | The number of patients who died within 30 days from the development of myocardial infarction. | From date of randomization until the date of death from any cause, assessed up to 30 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with non-lethal events. | The main hospital non-lethal events (Pulmonary edema, Cardiogenic shock, Cardiac arrhythmias: Atrial fibrillation, Ventricular tachycardia/fibrillation, Accelerated idioventricular rhythm/Atrioventricular block II, III). | From the date of randomization to the date of any of the listed events, assessed up to 14 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auricular stimulation, auricular vagus nerve stimulation, transcutaneous vagus nerve stimulation (TENS), vagus nerve stimulation (VNS), acute coronary syndrome, myocardial ischemia reperfusion injury, ST-segment elevation myocardial infarction, coronary heart disease, acute myocardial infarction, mortality, atrial fibrillation