Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

Conditions:Atrial Fibrillation
Therapuetic Areas:Cardiology / Vascular Diseases
Age Range:18 - Any
Start Date:January 2013
End Date:June 2016

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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, using a candidate gene approach, the effect of genetic variants on heart rate
response to beta-blockade in patients with AF.

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

- 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

- 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 VR <50 or >120 per
minute on the day of the study.

- Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.
We found this trial at
1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
Principal Investigator: Dawood Darbar, M.D.
Phone: 615-936-1713
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
Nashville, TN
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