Child-onset systemic lupus erythematosus (SLE) confers a 20-fold higher standardized mortality rate and greater potential for cumulative tissue damage compared to adult-onset disease, yet there is a paucity of data on cardiac outcomes in this population. Acute cardiac manifestations, including myopericarditis and endocarditis, and subclinical cardiac disease, such as diastolic dysfunction and valvular insufficiency, have been recognized in adults with SLE. Long-term, SLE is associated with an increased risk of heart failure, with the highest relative risks observed in young adults with SLE compared to the general population. The risk factors for cardiac involvement at acute or chronic stages of disease are poorly understood in child-onset SLE. As a result, it is unclear whether routine or selective monitoring is warranted. Therefore, the objectives of this proposal are to utilize a large administrative database to identify risk factors for cardiac inflammation in youth with SLE, estimate the contribution of acute cardiac manifestations to subsequent heart failure, and utilize retrospective echocardiographic data in a large inception cohort of asymptomatic children with SLE to ascertain potential subclinical precursors to heart failure. Specifically, this research proposal aims to 1) estimate the incidence of and patient characteristics associated with acute cardiac manifestations in youth with SLE; 2) determine whether a history of acute cardiac manifestations of SLE is an independent risk factor for subsequent heart failure during younger adulthood; and 3) compare echocardiographic signs of diastolic impairment, a potential precursor to cardiac damage, among asymptomatic youth with new-onset SLE to healthy controls. This study will estimate the burden of clinical and subclinical cardiac disease in youth with SLE, and identify potential risk factors to determine which SLE patients, if any, warrant routine cardiac testing. This study will be the largest study of cardiac outcomes in children and adolescents with SLE to date, and will be a first step toward developing guidelines for screening and long-term monitoring to reduce the risk of heart failure and other cardiovascular outcomes in this high-risk population. Completion of the project will provide the applicant with experience and preliminary data necessary to apply for future mentored grants to study targeted cardiovascular prevention and intervention strategies.

Public Health Relevance

The proposed research seeks to improve the long-term cardiovascular health of youth with systemic lupus erythematosus (SLE) by understanding the impact and risk factors for injury to the heart over the course of disease. Understanding the unique characteristics of cardiac disease in youth with SLE is critical for the future development of monitoring and treatment strategies to promptly identify cardiac disease and prevent long-term cardiovascular complications. !

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL142176-01
Application #
9539298
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Purkiser, Kevin
Project Start
2018-07-01
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104