Atrial Fibrillation | Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

Atrial Fibrillation research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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 VR <50 or >120 per minute on the day of the study. - Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Atrial Fibrillation

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.


Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

AtenololPatients will undergo a standardized, graded exercise protocol before ank after receiving a dose of oral atenolol.

Study Status


Start Date: January 2013

Completed Date: September 2016

Phase: N/A

Type: Interventional


Primary Outcome: Ventricular rate response during exercise.

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator:

Lead Sponsor: Vanderbilt University


More information:

European Heart Rhythm Association; Heart Rhythm Society, Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. Erratum in: J Am Coll Cardiol. 2007 Aug 7;50(6):562..

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