Heart failure (HF) is a major public health problem: it affects >6 million people in the U.S., it is the #1 cause of hospitalization and readmission in older adults, and 5-year survival after HF hospitalization is a dismal 35%, regardless of underlying ejection fraction (EF). These statistics highlight the urgent need for prevention of HF and better understanding of how and why HF develops in high-risk individuals. However, a critical limitation of prior population-based studies is the ascertainment of incident HF based on hospitalizations for HF and/or signs of overt volume overload. Many older individuals may suffer from early HF: breathlessness, fatigue, and exercise intolerance (without overt volume overload) due to underlying cardiac structure/function abnormalities, typically with a preserved EF (i.e. early HFpEF). Thus, the current epidemiology of HF is most likely missing a major form of prevalent HF. In this ancillary study of the Multi-Ethnic Study of Atherosclerosis (MESA, Year-15 Exam, n=3500), we will define early HF in a contemporary, multi-ethnic, elderly cohort; we will utilize cutting- edge indices of cardiac mechanics and ventricular-arterial interactions, including Lagrangian strain and time- varying pressure-stress analyses; and we will perform novel phenomics analyses to better characterize the interplay of risk factors and cardiac structure/function abnormalities (i.e., multi-dimensional phenotypic signatures) as they relate to early and overt HF.
The aims of our study are to: (1) determine the prevalence of early HF using a combination of validated symptom surveys, 6-minute walk test, NTproBNP, and echocardiography, with validation using cardiopulmonary exercise testing (CPEX); (2) better understand the pathophysiology of early HF, particularly HFpEF; and (3) delineate the key phenotypic signatures associated with early and overt HF. The proposed exam will include anthropometry, blood pressure, symptom surveys, functional status (6-minute walk test), physical activity, laboratory measures (NTproBNP, fasting glucose, renal function), and comprehensive echocardiography (with tissue Doppler and speckle-tracking at rest and during physiologic maneuvers) in all participants. In sub-samples we will also measure arterial tonometry, novel biomarkers, and fitness (CPEX). We will utilize the wealth of data collected during the 5 prior MESA exams to perform longitudinal analyses (including latent class trajectory and statistical learning analyses) to determine the extent to which risk factors are associated with early HF, particularly early HFpEF. By the end of our 4-year study, we will accomplish the following key goals, each of which will have a lasting impact on the field of HF: (1) we will establish the prevalence of early HF in the community; (2) we will have a standardized method for the screening/diagnosis of early HFpEF, validated by CPEX, and readily applicable to the clinical setting; (3) we will define novel mechanisms by which risk factors, alone and in combination, relate to abnormalities in cardiac mechanics and ventricular-arterial coupling in the general population; and (4) we will have defined phenotypic signatures of HF development that will inform future clinical trials for HF prevention and treatment.

Public Health Relevance

Heart failure is a common, expensive, and deadly health problem, especially among the elderly. Unfortunately, once overt heart failure develops it is difficult to treat and results in poor outcomes. Therefore it is critical to determine the relationhip between risk factors and abnormalities in heart structure and function that lead to early forms of heart failure. This project aims to: (1) determine how common early heart failure is in the population; (2) better understand the mechanisms of early heart failure by studying the heart and blood vessels using imaging and laboratory tests; and (3) use 'big data' techniques to harness the wealth of quantitative data we have collected to determine individuals at highest risk for the development of early heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL127028-01
Application #
8864355
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Olson, Jean
Project Start
2015-08-01
Project End
2019-06-30
Budget Start
2015-08-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Subramanya, Vinita; Zhao, Di; Ouyang, Pamela et al. (2018) Sex hormone levels and change in left ventricular structure among men and post-menopausal women: The Multi-Ethnic Study of Atherosclerosis (MESA). Maturitas 108:37-44
Subramanya, Vinita; Ambale-Venkatesh, Bharath; Ohyama, Yoshiaki et al. (2018) Relation of Sex Hormone Levels With Prevalent and 10-Year Change in Aortic Distensibility Assessed by MRI: The Multi-Ethnic Study of Atherosclerosis. Am J Hypertens 31:774-783
Zhao, Di; Guallar, Eliseo; Ouyang, Pamela et al. (2018) Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. J Am Coll Cardiol 71:2555-2566
Steffen, Brian T; Duprez, Daniel; Bertoni, Alain G et al. (2018) Lp(a) [Lipoprotein(a)]-Related Risk of Heart Failure Is Evident in Whites but Not in Other Racial/Ethnic Groups. Arterioscler Thromb Vasc Biol 38:2498-2504
Tampakakis, Emmanouil; Shah, Sanjiv J; Borlaug, Barry A et al. (2018) Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart Disease. Circ Heart Fail 11:e004436
Butler, Javed; Kalogeropoulos, Andreas P; Anstrom, Kevin J et al. (2018) Diastolic Dysfunction in Individuals With Human Immunodeficiency Virus Infection: Literature Review, Rationale and Design of the Characterizing Heart Function on Antiretroviral Therapy (CHART) Study. J Card Fail 24:255-265
Burns, Jacob A; Sanchez, Cynthia; Beussink, Lauren et al. (2018) Lack of Association Between Anemia and Intrinsic Left Ventricular Diastolic Function or Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction. Am J Cardiol 122:1359-1365
Polsinelli, Vincenzo B; Shah, Sanjiv J (2017) Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine. Expert Opin Pharmacother 18:399-409
Freed, Benjamin H; Shah, Sanjiv J (2017) Stepping Out of the Left Ventricle's Shadow: Time to Focus on the Left Atrium in Heart Failure With Preserved Ejection Fraction. Circ Cardiovasc Imaging 10:
Luo, Yuan; Ahmad, Faraz S; Shah, Sanjiv J (2017) Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction. J Cardiovasc Transl Res 10:305-312

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