Noninvasive Neuromodulation to Reserve Diastolic Dysfunction

Study Overview
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Brief Summary
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This is a 2x2 cross over pilot study using low level transcutaneous vagus nerve stimulation (LLTS) to reverse diastolic dysfunction in patients with diastolic dysfunction. All patients will receive 2 separate, 1-hour sequences, at least 1 day apart, of active and sham LLTS, but the sequence will be randomized. Patients will be randomly assigned (1:1) to active/sham or sham/active LLTS. LLTS will be performed using a transcutaneous electrical nerve stimulation (TENS) device with electrodes attached to the tragus of the ear, which is innervated by auricular branch of the vagus nerve. Echocardiography will be performed after 30 minutes of LLTS or sham stimulation to assess diastolic function. Five-minute ECGs will be obtained for HRV analysis every 15 minutes of stimulation (total of 4 recordings).

Official Title
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Noninvasive Neuromodulation to Reserve Diastolic Dysfunction

Conditions
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Heart Failure, Diastolic

Intervention / Treatment
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* Device: transcutaneous vagus nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients older than 18 year old Evidence of diastolic dysfunction on echocardiogram within 24 months of study enrollment Exclusion Criteria: Left ventricular dysfunction (Left ventricular ejection fraction <40%) Significant valvular disorder (i.e., prosthetic valve or hemodynamically relevant valvular diseases) Recent (<6 months) stroke or myocardial infarction Severe heart failure (NYHA class III or IV) Recurrent vaso-vagal syncopal episodes Unilateral or bilateral vagotomy Pregnancy or breast feeding Sick sinus syndrome (without a pacemaker), 2nd or 3rd degree AV block, bifascicular block or prolonged (PR>300ms) 1st degree AV block

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sham stimulation first<br>Sham stimulation delivered at the earlobe (devoid of vagal innervation) is given on first session. Transcutaneous vagus nerve stimulation delivered at the tragus (vagal innervation) is given on second session. | Device: transcutaneous vagus nerve stimulation<br>* All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized<br>|
| Active Comparator: Active stimulation first<br>Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. | Device: transcutaneous vagus nerve stimulation<br>* All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiographic Markers of Diastolic Dysfunction | Global longitudinal strain | after 1 hour of stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Variability Measures | low frequency to high frequency ratio. This is a measure of sympathovagal balance. A lower value reflects a more favorable balance between sympathetic and parasympathetic (vagal) tone. | after 1 hour of stimulation |