Cardiac Arrhythmia
Conditions
Keywords
Oxytocin, Arrhythmia
Brief summary
In this pilot study the investigators will perform a double-blind randomized trial of intranasal oxytocin on measures of cardiac refractoriness, among individuals who are undergoing clinically indicated catheter ablation procedures for paroxysmal atrial fibrillation. The investigators seek to enroll 20 patients for this study, for the purpose of estimating effect sizes for a larger future study.
Detailed description
Despite widespread advances in the treatment of coronary artery disease and the growing use of automated external defibrillators and implantable cardioverter-defibrillators (ICDs) to treat ventricular arrhythmias, sudden cardiac death (SCD) due to ventricular arrhythmia remains a major public health problem. National estimates of SCD or out-of- hospital cardiac arrest range from 400,000 to 450,000 events annually. Although cardiac mortality rates have declined over time, the proportion of cardiac deaths that are sudden has increased during a time when major advances in device therapy for the prevention and treatment of SCD have taken place. This unfavorable trend is a consequence of the inability to accurately identify those who will die suddenly from a lethal ventricular arrhythmia and to disseminate effective preventive strategies for populations at risk. Observational evidence has indicated that depression is associated with risk of SCD, both in patients with coronary artery disease as well as in individuals without heart disease. In patients with ICDs, depressive symptoms are associated with increased risk of shocks for ventricular arrhythmia, suggesting that ventricular arrhythmia is more common in depressed individuals. A leading candidate mechanism that may account for the association between depression and ventricular arrhythmia involves cardiac autonomic dysfunction; for instance, multiple studies have shown that depressed individuals have abnormal heart rate variability. Recent evidence has emerged about the potential importance of oxytocin in the cardiovascular response to stress and depression. Oxytocin is a 9-amino acid peptide that is produced in the hypothalamus and released into the central nervous system and the bloodstream. Oxytocin has both hormone and neurotransmitter function, and affects targets including the hypothalamus, amygdala, hippocampus, brainstem, heart, uterus, and regions of the spinal cord that regulate the autonomic nervous system. Polymorphisms of the oxytocin receptor have been associated with improved cardiovascular responses to laboratory stress in humans. Exogenous administration of intravenous oxytocin in a prairie vole model of isolation has been shown to protect against the heart rate response to social isolation and to improve heart rate variability. In addition, intranasal oxytocin administered to humans augments both sympathetic and parasympathetic modulation of the heart rate. Initial studies of intravenous oxytocin demonstrated direct effects on cardiac arrhythmias in animal models, even including termination of ventricular fibrillation, suggestive of a quinidine-like action on myocardial excitability. However, administration of intravenous oxytocin in women after delivery has been associated with abnormalities in cardiac repolarization and even with induced ventricular arrhythmia. Therefore, although there is reason to believe that administration of exogenous oxytocin may affect the probability of arrhythmia, the direction of this impact is unclear.
Interventions
DRUGOxytocin
Intranasal dose of 20 IU oxytocin
OTHERSaline
Intranasal dose of saline
Sponsors
William Whang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Males and females older than 18 and younger than 85 years of age * Undergoing catheter ablation for paroxysmal atrial fibrillation * Presenting in sinus rhythm at the time of their procedure
Exclusion criteria
* Left ventricular ejection fraction \<0.40 * Paced rhythm \>50 percent of the time by device interrogation if a pacemaker is present
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Electrophysiology Measure of AH Interval | Baseline and 30 min | First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour. |
| Change in Electrophysiology Measure of HV Interval | Baseline and 30 min | First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour. |
| Change in Electrophysiology Measure of Right Ventricular Refractory Period | Baseline and 30 min | First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Patients will be administered an intranasal dose of the study drug, 20 IU oxytocin. Repeat electrophysiologic measurements will be assessed at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, we will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'preablation' period normally takes 45 minutes to one hour.
Oxytocin: Intranasal dose of 20 IU oxytocin | 6 |
| Saline Patients will be administered an intranasal dose of saline. Repeat electrophysiologic measurements will be assessed at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, we will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'preablation' period normally takes 45 minutes to one hour.
Saline: Intranasal dose of saline | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Oxytocin | Saline | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 15.5 | 68.1 years STANDARD_DEVIATION 3.7 | 66.0 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change in Electrophysiology Measure of AH Interval
First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.
Time frame: Baseline and 30 min
Population: Only 3 out of 6 were evaluable for the Oxytocin group. Only 2 out of 6 were evaluable for the Saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Electrophysiology Measure of AH Interval | 12.7 milliseconds | Standard Deviation 11.2 |
| Saline | Change in Electrophysiology Measure of AH Interval | -1.5 milliseconds | Standard Deviation 13.4 |
Primary
Change in Electrophysiology Measure of HV Interval
First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.
Time frame: Baseline and 30 min
Population: Only 4 out of 6 were evaluable for the Oxytocin group. Only 5 out of 6 were evaluable for the Saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Electrophysiology Measure of HV Interval | 3.0 milliseconds | Standard Deviation 9.2 |
| Saline | Change in Electrophysiology Measure of HV Interval | 1.0 milliseconds | Standard Deviation 6 |
Primary
Change in Electrophysiology Measure of Right Ventricular Refractory Period
First measured at time zero, then at 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.
Time frame: Baseline and 30 min
Population: Only 4 out of 6 were evaluable for the Oxytocin group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Electrophysiology Measure of Right Ventricular Refractory Period | -30 milliseconds | Standard Deviation 62.2 |
| Saline | Change in Electrophysiology Measure of Right Ventricular Refractory Period | 5 milliseconds | Standard Deviation 24.3 |