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 #
5K24HL105780-02
Application #
8204448
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
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
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
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Weng, Lu-Chen; Preis, Sarah R; Hulme, Olivia L et al. (2018) Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation. Circulation 137:1027-1038
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Turcot, Valérie (see original citation for additional authors) (2018) Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 50:26-41
Choi, Seung Hoan; Weng, Lu-Chen; Roselli, Carolina et al. (2018) Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation. JAMA 320:2354-2364
Khurshid, Shaan; Choi, Seung Hoan; Weng, Lu-Chen et al. (2018) Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 11:e006273
Hu, Ray; Morley, Michael P; Brandimarto, Jeffrey et al. (2018) Genetic Reduction in Left Ventricular Protein Kinase C-? and Adverse Ventricular Remodeling in Human Subjects. Circ Genom Precis Med 11:e001901
Roselli, Carolina; Chaffin, Mark D; Weng, Lu-Chen et al. (2018) Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet 50:1225-1233
Staerk, Laila; Wang, Biqi; Preis, Sarah R et al. (2018) Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study. BMJ 361:k1453

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