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ARRA Investments in Atrial Fibrillation (AFib)

Public Health Burden
AFib is an irregular heart rhythm manifested by symptoms ranging from palpitations to heart failure.  It doubles the risk of death, accounts for 15-20 percent of all strokes, and has been estimated to cost $6.4 billion annually in the United States.  AFib affects an estimated 2.2 million people in the United States, a number that is expected to double by 2020.  The prevalence of AFib increases with age and is now estimated to affect about 6 percent of Americans who are 65 years of age and older.

Because AFib often goes unrecognized until a catastrophic event occurs, its prevalence is difficult to determine and individuals who need treatment tend not to be identified.  Several ARRA grants are seeking to improve the ability to identify at-risk patients.  They include studies to:
  • Identify genetic variations that cause AFib through genome-wide association studies.1,2

  • Examine a wide array of risk factors and biomarkers in a unique cohort that includes a large proportion of understudied minorities.3
  • Analyze pooled data from several large cohorts to refine and validate a recently published Framingham Heart Study AFib risk prediction model in order to improve the assessment of AFib by primary care physicians in diverse populations.4
  • Use the existing NIH-funded Cardiovascular Research Network to develop and test a risk stratification tool for AFib and its thromboembolic (stroke) complications in 10,000 adults who are in a health care system that uses advanced electronic medical records.5
Basic Research
Complete fundamental understanding is lacking about what initiates AFib in individual patients or why AFib progresses from rare episodes to a permanent irregular rhythm in many, but not all, patients.  Basic understanding of the mechanisms that determine the initiation and propagation of AFib will be advanced through ARRA grants by:
  • Studying the molecular mechanisms of ion channels and regulatory receptors and how they change in aging or diseased hearts.6,7

  • Examining the role of autonomic nerve regulation in areas known to initiate AFib, such as the pulmonary veins and posterior left atrium.8,9

  • Developing patient-specific computer models using high resolution electrophysiologic and anatomical data to study the complexity of arrhythmia associated with AFib initiation and propagation.10
  • Establishing the infrastructure to collect and distribute human cardiac tissue that would otherwise be discarded after clinically indicated cardiac surgery.  This will allow electrophysiologists to test mechanistic hypotheses, derived from animal models, in viable human tissues.11
Current therapeutic strategies include medical control of heart rate and rhythm, antithrombotic treatment for stroke prevention, and the use of surgical procedures to remove tissue associated with AFib initiation and propagation.  Other than the use of anticoagulants to avoid strokes that may result from AFib, no treatments have been proven to eliminate risk due to AFib.  Medical heart rate control leaves patients with an abnormal rhythm that affects quality of life and perceived well-being.  Antiarrhythmic medications have a high incidence of “proarrhythmic” effects, which can cause more deadly arrhythmias. Percutaneous ablation procedures, though increasingly used, have not been shown to be better than medical therapy, and they are costly and entail a small risk of very serious complications.  In addition, newly recognized risk factors for AFib might offer new ways to treat and prevent AFib.  Some ARRA-funded clinical studies will address the need for improved therapy by:
  • Developing new three-dimensional imaging tools for increasing the safety and efficacy of percutaneous procedures.12
  • Developing and evaluating a real-time, magnetic resonance imaging-guided surgical ablation procedure that uses a minimally invasive, catheter-based radio frequency approach.13
  • Testing whether specific treatment with a new continuous positive airway pressure method called adaptive servo-ventilation can diminish the incidence of AFib in patients who have sleep apnea.14,15
  • Testing  the ability of fish oil to protect against cognitive decline by decreasing the postoperative incidence of AFib in patients undergoing cardiac surgery.16

  1. 3R01HL090620-01A1S1 -- Genetics of Atrial Fibrillation -- Chung, Mina Kay (OH)
  2. 2R01HL068986-05A2 -- Atrial Fibrillation: Incidence, Risk Factors, and Genetics -- Heckbert, Susan (WA)
  3. 1RC1HL099452-01 -- Epidemiologic Study of Risk Factors and Biomarkers of Atrial Fibrillation -- Alonso, Alvaro (MN)
  4. 1RC1HL101056-01 -- Risk Prediction of Atrial Fibrillation: Clinical, Biological and Genetic Markers -- Benjamin, Emelia J (MA)
  5. 1RC2HL101589-01 -- Contemporary Treatment and Outcomes for Atrial Fibrillation in Clinical Practice -- Go, Alan S (CA)
  6. 2R01HL067840-05A2 -- Molecular Basis for KV Channel Heterogeneity in the Heart -- Tseng, Gea-Ny (VA)
  7. 3R01HL089598-02S1 -- Camkii Regulation of Cardiac Ryanodine Receptors in Atrial Fibrillation -- Wehrens, Xander (TX)
  8. 3R01HL071140-06S1 -- Autonomic Nerve Activity and Paroxysmal Atrial Fibrillation -- Chen, Peng-Sheng (IN)
  9. 1R21HL088304-01A1 -- Disruption of Autonomic Pathways in Left Atrium by Inhibition of G Proteins -- Kadish, Alan H (IL)
  10. 3R01HL083359-01A1S1 --The Dynamics of Human Atrial Fibrillation -- Narayan, Sanjiv M (CA)
  11. 1RC1HL099789-01 --UCSF Living Heart Resource -- Olgin, Jeffrey E (CA)
  12. 1R01HL087917-01A2 -- C-Arm CT for Guidance of Cardiac Interventions -- Fahrig, Rebecca (CA)
  13. 3R01HL086975-02S1 --Real-Time MRI-Guided RF Ablation of Cardiac Tachyarrhythmias -- Unal, Orhan (WI)
  14. 1RC1HL099534-01 --Treatment of Sleep Disordered Breathing in Atrial Fibrillation -- Caples, Sean Michael (MN)
  15. 1RC2HL101417-01 -- Phase II Trial of Sleep Apnea Treatment to Reduce Cardiovascular Morbidity -- Redline, Susan S (OH)
  16. 1RC2HL101816-01 --Ancillary: Inflammation/Oxidation, Omega-3’s & Post-Op Afib & Cognitive Decline -- Mozaffarian, Dariush (MA)

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