Atrial fibrillation (AF) is the most common arrhythmia and affects over 2 million Americans, a number that is expected to rise to between 6 and 12 million by 2050. AF is a major public health burden as it is associated with a five-fold increased stroke risk, doubling in dementia risk, tripling in heart failure risk, and nearly two-fold increase in mortality. Many risk factors for AF have been identified, including advancing age, male sex, hypertension, heart failure, obesity and family history. Despite the profound socioeconomic costs of AF, our understanding of the fundamental mechanisms for the arrhythmia remains limited. The central goal of the candidate's research is to identify novel genes and pathways for AF. The candidate is a cardiac electrophysiologist with a bench to bedside research focus on AF. He has developed a cohort of patients with lone AF, leads an international consortium of investigators studying the genetics of AF, and performs laboratory work on the mechanisms of AF. Despite the success that the candidate has had in developing an arrhythmia research program, his current clinical commitments are limiting his exposure to the increasing number of fellows that he is mentoring. Therefore, the specific aims of this application are to provide the candidate long-term support to enable a reduction in his clinical commitments, and thus expand the training of mentees interested in pursuing patient-oriented arrhythmia research. Research mentees will have a rich diversity of opportunities to participate in patient-oriented research through the MGH AF study, the CHARGE-AF Consortium, and the candidate's own translational laboratory work. The fellow's research activities will be complemented by the extensive educational resources available at Massachusetts General Hospital and Harvard University. Ultimately, if funded, this application will contribute to the development of new clinical investigators in arrhythmia research and will catalyze understanding of this common and morbid arrhythmia.

Public Health Relevance

Atrial fibrillation, a common, irregular heart rhythm, increases the risk of stroke and death. Despite affecting over 2 million Americans, relatively little is known about the underlying mechanisms that lead to atrial fibrillation. The goal of this application is to support Dr. Patrick T. Ellinor's efforts to train new investigators in clinical research methods in order to learn more about the pathogenesis of this common arrhythmia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL105780-03
Application #
8387040
Study Section
Special Emphasis Panel (ZHL1-CSR-X (O1))
Program Officer
Carlson, Drew E
Project Start
2010-12-03
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$127,330
Indirect Cost
$9,432
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Christophersen, Ingrid E; Magnani, Jared W; Yin, Xiaoyan et al. (2017) Fifteen Genetic Loci Associated With the Electrocardiographic P Wave. Circ Cardiovasc Genet 10:
Lubitz, Steven A; Yin, Xiaoyan; McManus, David D et al. (2017) Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study. Stroke 48:490-492
Christophersen, Ingrid E; Rienstra, Michiel; Roselli, Carolina et al. (2017) Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat Genet 49:946-952
Rosenberg, Michael A; Lubitz, Steven A; Lin, Honghuang et al. (2017) Validation of Polygenic Scores for QT Interval in Clinical Populations. Circ Cardiovasc Genet 10:
Tucker, Nathan R; Dolmatova, Elena V; Lin, Honghuang et al. (2017) Diminished PRRX1 Expression Is Associated With Increased Risk of Atrial Fibrillation and Shortening of the Cardiac Action Potential. Circ Cardiovasc Genet 10:
Hucker, William J; Hanley, Alan; Ellinor, Patrick T (2017) Improving Atrial Fibrillation Therapy: Is There a Gene for That? J Am Coll Cardiol 69:2088-2095
Lin, Honghuang; Yin, Xiaoyan; Xie, Zhijun et al. (2017) Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study. Sci Rep 7:40377
Hulsmans, Maarten; Clauss, Sebastian; Xiao, Ling et al. (2017) Macrophages Facilitate Electrical Conduction in the Heart. Cell 169:510-522.e20
Chatterjee, Neal A; Giulianini, Franco; Geelhoed, Bastiaan et al. (2017) Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization. Circulation 135:741-754
Khurshid, Shaan; Weng, Lu-Chen; Hulme, Olivia L et al. (2017) Factors Associated with Anticoagulation Delay Following New-Onset Atrial Fibrillation. Am J Cardiol 120:1316-1321

Showing the most recent 10 out of 93 publications