Atrial Fibrillation
Conditions
Keywords
Baseline (pre-atenolol), Post-atenolol
Brief summary
Atrial fibrillation (AF), the most common sustained heart rhythm disorder, is becoming increasingly prevalent in the Western world. The number of people with AF in the United States is projected to roughly double by the year 2050, to an estimated 6-12 million. For many patients with AF, rate control with atrioventricular (AV) node blockers is a widely accepted therapeutic strategy. These agents control heart rate, thus preventing symptoms and systolic heart failure associated with tachycardia due to a rapid ventricular response to AF. Beta-blockers are widely accepted as first line agents for rate control in AF, especially when patients have concomitant hypertension (HTN), coronary artery disease, cardiomyopathies, or heart failure (HF). As a class, beta-blockers are among the most commonly prescribed cardiovascular medications. Among patients with AF treated with beta-blockers, the heart rate (HR) response varies substantially. Sometimes, adequate rate control can be achieved by titration of the beta-blocker dose; but frequently, additional AV nodal blockers and/or digoxin are necessary. In some cases, adequate rate control cannot be achieved even with the simultaneous use of multiple AV nodal blockers, necessitating mechanical ablation of the AV node and permanent pacemaker implantation. Patient-specific variables that influence the response to beta-blockers include comorbid conditions, weight, age, and level of physical activity. Ethnic differences in the response to beta-blockers for the treatment of HTN and HF are well-described. However, the contribution of genetic variants to beta-blocker efficacy in AF is unknown. We propose to study whether the ADRB1 Gly389Asp SNP reduces response to beta-blockade in subjects with permanent AF.
Interventions
DRUGAtenolol
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be at least 18 years of age. * Subjects must have a history of persistent AF currently treated with a rate control strategy. * Subjects should be willing to give written, informed consent. * Subjects must be willing and able to participate in the exercise protocol.
Exclusion criteria
* New York Heart Association Class III or IV heart failure. * A history of heart failure induced by tachy-arrhythmia. * A history of coronary artery disease and the presence of at least one of the following: * Canadian Class III or IV angina. * Recent myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention within 6 months. * Severe renal or hepatic impairment. * Subjects who have a clinically significant allergy/intolerance to atenolol, including a history of beta-blocker induced bronchospasm. * Females who are pregnant or nursing. * History of severe AV node dysfunction/pacemaker dependence. * Subjects who have a systolic blood pressure \< 90 mm Hg or resting Ventricular Rate \<50 or \>120 per minute on the day of the study. * Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise | after 5minutes of exercise | After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol. |
| Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise | after 10 amd 15 minutes of exercise | After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants all participants | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 70.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 38 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise
After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.
Time frame: after 10 amd 15 minutes of exercise
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Atenolol: Ancestral Alleles | Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise | After 10 minutes | -11 beats per minute |
| Atenolol: Ancestral Alleles | Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise | After 15 minutes | -25.5 beats per minute |
| Atenolol: Variant Carriers | Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise | After 15 minutes | -35.2 beats per minute |
| Atenolol: Variant Carriers | Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise | After 10 minutes | -19.7 beats per minute |
Primary
Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise
After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.
Time frame: after 5minutes of exercise
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atenolol: Ancestral Alleles | Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise | -10 beats per minute |
| Atenolol: Variant Carriers | Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise | -13 beats per minute |