Tamara Norwich (candidate) is an Assistant Professor at the University of California, Los Angeles. The candidate's long-term career goal is to be a clinician-investigator, focusing research in the area of heart failure (HF). Although the candidate has had experience and success with observational research in the HF field, her goal is to acquire the experience and skills to successfully and independently conduct prospective, experimental studies / translational research. UCLA is an ideal institution to commence a career in clinical cardiovascular investigation;the candidate will have the benefit of formal instruction through the Masters in Clinical Research Program via UCLA's Department of Biomathematics while working with excellent, dedicated mentors on a clinical study to investigate mechanisms of a potential new therapy for HF. The candidate's recent research suggests that HMG-Coenzyme A (statin) therapy is associated with improved survival in both ischemic and non-ischemic HF. Thus, the candidate is interested in investigating statins'potentially beneficial mechanisms of action in HF. The current project will study statins'effects on: 1) sympathetic nervous system activation 2) myocardial remodeling and 3) systemic inflammation. Fifty patients with systolic, non-ischemic HF will be randomized in a double-blinded fashion to 3 months of atorvastatin 10mg QD (25 subjects) vs matching placebo QD (25 subjects). The following exams will be performed both pre- and post- treatment phase: 1) sympathetic microneurography, for direct quantification of changes in sympathetic nerve activity, 2) cardiac imaging (echocardiography and MRI in a subset without pacemakers/defibrillators) to track changes in cardiac structure and function, and 3) peripheral blood analysis for candidate chemokines. Additional investigation will include studying effect of statins on cardiac biomarkers, arrhythmias, heart rate variability, and quality of life and global clinical assessment. Relevance: HF affects over 5 million people in the U.S., and only 50% survive at 5 years. The cholesterol- lowering drugs known as statins may improve the hearts'pumping function, as well as improve symptoms and survival HF, even in the absence of coronary artery disease. This study will investigate how statins may potentially benefit patients with HF, and thus may ultimately contribute to discovering new strategies to treat HF.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL085097-04
Application #
7867861
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Program Officer
Scott, Jane
Project Start
2007-08-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$108,000
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Loh, John C; Creaser, Julie; Rourke, Darlene A et al. (2013) Temporal trends in treatment and outcomes for advanced heart failure with reduced ejection fraction from 1993-2010: findings from a university referral center. Circ Heart Fail 6:411-9
Clark, Adrienne L; Chyu, Jennifer; Horwich, Tamara B (2012) The obesity paradox in men versus women with systolic heart failure. Am J Cardiol 110:77-82
Tomova, G Sofia; Nimbal, Vani; Horwich, Tamara B (2012) Relation between hemoglobin a(1c) and outcomes in heart failure patients with and without diabetes mellitus. Am J Cardiol 109:1767-73
Bui, Anh L; Horwich, Tamara B; Fonarow, Gregg C (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8:30-41
Horwich, Tamara B; Middlekauff, Holly R; Maclellan, W Robb et al. (2011) Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial. J Card Fail 17:879-86
Horwich, Tamara B; Fonarow, Gregg C (2010) Glucose, obesity, metabolic syndrome, and diabetes relevance to incidence of heart failure. J Am Coll Cardiol 55:283-93
Shah, Digish D; Fonarow, Gregg C; Horwich, Tamara B (2010) Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes. J Card Fail 16:200-6
Cheng, Richard K; Horwich, Tamara B; Fonarow, Gregg C (2008) Relation of systolic blood pressure to survival in both ischemic and nonischemic systolic heart failure. Am J Cardiol 102:1698-705
Horwich, Tamara B; Kalantar-Zadeh, Kamyar; MacLellan, Robb W et al. (2008) Albumin levels predict survival in patients with systolic heart failure. Am Heart J 155:883-9
Horwich, Tamara B; Hernandez, Adrian F; Dai, David et al. (2008) Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. Am Heart J 156:1170-6

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