Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

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.

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.