Alcohol, Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Alcohol, Electrophysiologic properties of the atria, Randomized Clinical Study
Brief summary
Atrial fibrillation (AF) is the most common sustained arrhythmia in the United States and it has been associated with ethanol use. Understanding how ethanol affects the electrical properties of the heart and induces AF has important public health implications. The objective of this research is to investigate the mechanistic relationship between ethanol and atrial fibrillation in humans by performing a placebo controlled study looking at the electrical properties of the heart in patients receiving intravenous ethanol or placebo. The investigators hypothesize that ethanol increases the susceptibility of human myocardium to atrial fibrillation through electrophysiologic changes in the atrial myocardium in the acute setting.
Detailed description
The purpose of this study is to look for changes in the electrical properties of heart that may be caused by ethanol (commonly referred to as alcohol) and specifically how ethanol may trigger episodes of the most common abnormal heart rhythm, atrial fibrillation (AF). This study will demonstrate the mechanism of ethanol induced atrial fibrillation and clarify the health effects of one of the worlds' most popular drugs (ethanol). With this understanding, physicians may be able to better identify those patients most at risk for ethanol induced AF and target public health campaigns towards this vulnerable population. Patients in this study will undergo an electrophysiologic study both prior to and after receiving either an ethanol or placebo infusion. This electrophysiology study will measure AF inducibility (the primary outcome), left and right atrial conduction times, and the atrial effective refractory period in multiple locations (AERP). The changes in the conduction times and AERPs (before and after study drug infusion) will be recorded as secondary outcomes. About 100 people will participate in this study. 50 people will be randomized to receive intravenous ethanol, and 50 people will be randomized to receive an intravenous placebo. The placebo will be in the form of 0.45% saline solution (half normal saline) and the alcohol will be in the form of 6% volume/volume ethanol in 0.45% saline solution.
Interventions
DRUGPlacebo
The placebo with be 0.45% saline solution (half normal saline).
DRUGEthanol
6% volume/volume ethanol in 0.45% saline solution.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 21-80 with paroxysmal atrial fibrillation (AF), supraventricular tachycardia, or undifferentiated palpitations who are to undergo either an elective ablation procedure (for AF, atrial flutter, atria tachycardia, atrial ventricular nodal reentrant tachycardia (AVNRT), or atrial ventricular reentrant tachycardia (AVRT)) or a diagnostic electrophysiology study in order to diagnose and treat their clinical arrhythmia at the University of California, San Francisco (UCSF) will be eligible for enrollment.
Exclusion criteria
* Patients will be excluded if they are not in normal sinus rhythm (i.e. in AF, atrial tachycardia, atrial flutter, or incessant AVNRT/AVRT) at the time of onset of the procedure, any history of substance abuse or alcoholism as determined by history, AUDIT questionnaire, or chart review, left ventricular ejection fraction \<50%, inability to give informed consent, liver dysfunction (elevated aspartate aminotransferase , alanine aminotransferase, total bilirubin, or alkaline phosphatase \>2x normal), clinical evidence of liver disease (enlarged liver, caput medusa, spider angiomas, or other signs of liver disease on exam), or pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Atrial Fibrillation Induction | This will be measured after study drug (ethanol or placebo) infusion. The measurement will be performed within 1 hour of the infusion. | Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Conduction Time | This will be assessed during the experimental study from the Conduction Times that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion. | The atrial conduction time will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in Conduction Time |
| Change in Atrial Effective Refractory Period (AERP) | This will be assessed during the experimental study from the AERPs that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion. | The AERP will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in AERP |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded.
Placebo: The placebo with be 0.45% saline solution (half normal saline). | 50 |
| Ethanol Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded.
Ethanol: 6% volume/volume ethanol in 0.45% saline solution. | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Placebo | Ethanol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 16 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 34 Participants | 62 Participants |
| Age, Continuous | 61.14 years STANDARD_DEVIATION 13.08 | 58.78 years STANDARD_DEVIATION 11.27 | 60.51 years STANDARD_DEVIATION 10.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 48 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 45 Participants | 44 Participants | 89 Participants |
| Region of Enrollment United States | 50 participants | 50 participants | 100 participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 38 Participants | 36 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 1 / 50 | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 | 1 / 50 |
Outcome results
Primary
Number of Participants With Atrial Fibrillation Induction
Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome.
Time frame: This will be measured after study drug (ethanol or placebo) infusion. The measurement will be performed within 1 hour of the infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Atrial Fibrillation Induction | 22 Participants |
| Ethanol | Number of Participants With Atrial Fibrillation Induction | 24 Participants |
Secondary
Change in Atrial Effective Refractory Period (AERP)
The AERP will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in AERP
Time frame: This will be assessed during the experimental study from the AERPs that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change in Atrial Effective Refractory Period (AERP) | 1.59 ms |
| Ethanol | Change in Atrial Effective Refractory Period (AERP) | -3.35 ms |
Secondary
Change in Conduction Time
The atrial conduction time will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in Conduction Time
Time frame: This will be assessed during the experimental study from the Conduction Times that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change in Conduction Time | Paroximal coronary sinus (CSp) to high right atrium (hRA) | 0.67 ms |
| Placebo | Change in Conduction Time | CSp to Left upper pulmonary vein (LUPV) | 3.50 ms |
| Placebo | Change in Conduction Time | Distal coronary sinus (CSd) to CSp | 0 ms |
| Placebo | Change in Conduction Time | hRA to His bundle (His) | -0.50 ms |
| Placebo | Change in Conduction Time | hRA to low right atrium (lRA) | 0.50 ms |
| Placebo | Change in Conduction Time | LUPV to right upper pulmonary vein (RUPV) | 3.67 ms |
| Placebo | Change in Conduction Time | RUPV to CSd | 1 ms |
| Placebo | Change in Conduction Time | RUPV to His | 0.33 ms |
| Ethanol | Change in Conduction Time | RUPV to His | 4.33 ms |
| Ethanol | Change in Conduction Time | Paroximal coronary sinus (CSp) to high right atrium (hRA) | 0.33 ms |
| Ethanol | Change in Conduction Time | hRA to low right atrium (lRA) | 0.50 ms |
| Ethanol | Change in Conduction Time | CSp to Left upper pulmonary vein (LUPV) | 2.88 ms |
| Ethanol | Change in Conduction Time | RUPV to CSd | 2.33 ms |
| Ethanol | Change in Conduction Time | Distal coronary sinus (CSd) to CSp | 0.33 ms |
| Ethanol | Change in Conduction Time | LUPV to right upper pulmonary vein (RUPV) | 3.33 ms |
| Ethanol | Change in Conduction Time | hRA to His bundle (His) | -2.00 ms |