Heart Failure, Diastolic
Conditions
Brief summary
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).
Interventions
DEVICEtranscutaneous vagus nerve stimulation
All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients older than 18 year old 2. Evidence of diastolic dysfunction on echocardiogram within 24 months of study enrollment
Exclusion criteria
1. Left ventricular dysfunction (Left ventricular ejection fraction \<40%) 2. Significant valvular disorder (i.e., prosthetic valve or hemodynamically relevant valvular diseases) 3. Recent (\<6 months) stroke or myocardial infarction 4. Severe heart failure (NYHA class III or IV) 5. Recurrent vaso-vagal syncopal episodes 6. Unilateral or bilateral vagotomy 7. Pregnancy or breast feeding 8. Sick sinus syndrome (without a pacemaker), 2nd or 3rd degree AV block, bifascicular block or prolonged (PR\>300ms) 1st degree AV block
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Echocardiographic Markers of Diastolic Dysfunction | after 1 hour of stimulation | Global longitudinal strain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Variability Measures | after 1 hour of stimulation | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 68.2 years STANDARD_DEVIATION 11.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Echocardiographic Markers of Diastolic Dysfunction
Global longitudinal strain
Time frame: after 1 hour of stimulation
Population: All patients received both active and sham transcutaneous vagus nerve stimulation, with the order being randomized. The comparison is between active and sham stimulation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Stimulation | Echocardiographic Markers of Diastolic Dysfunction | -21.2 percent | Standard Deviation 3 |
| Active Stimulation | Echocardiographic Markers of Diastolic Dysfunction | -23.0 percent | Standard Deviation 2.8 |
Secondary
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.
Time frame: after 1 hour of stimulation
Population: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized. The comparison is between active and sham stimulation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Stimulation | Heart Rate Variability Measures | 3.1 ratio | Standard Deviation 0.4 |
| Active Stimulation | Heart Rate Variability Measures | 1.8 ratio | Standard Deviation 0.4 |