Heart failure (HF) with preserved ejection fraction is a cardiovascular disorder with significant public health impact without a single disease-modifying treatment available to improve outcomes. HF imposes fatigue, reduced aerobic capacity, and multiple hospitalizations with 50% mortality risk within 5 years of diagnosis. Metabolic syndrome (MetS), a hyperendemic comorbidity, is a strong risk factor for HF development and highly prevalent in HF with preserved ejection fraction (HFpEF). Recognized as a progressive disorder, HF can be categorized into 4 stages (A, B, C, or D) with Stages A and B representing preclinical phases (i.e. they confer elevated risk of HF without the overt clinical syndrome of HF). Diastolic dysfunction, an often asymptomatic cardiac abnormality, is a significant precursor to HFpEF development and is representative of Stage B HF (structural heart disease without signs or symptoms of HF). The focus of this K application is to perform comprehensive cardiac phenotyping of MetS individuals to allow for the early detection of Stage B HF. We will leverage the Boston University METabolic Heart Disease Study (BUMETS) to: 1) compare the differences in biomarkers between obese, MetS+/Stage B-, and MetS+/Stage B+ individuals using both targeted and untargeted biomarker approaches; 2) study the effect of MetS on left atrial mechanics using echocardiographic strain imaging; 3) study the effect of provocation via passive leg raises and exercise (using cardiopulmonary exercise testing) on left atrial mechanics to unmask latent cardiac abnormalities and to provide insight about which MetS individuals may be more prone to develop HFpEF. Via these aims, we will develop a cardiac phenotypic strategy in MetS individuals for the detection of Stage B HF to help direct and test early therapeutic strategies for HF prevention. Via her mentorship team, career development training plan, and research objectives proposed in this application, the primary investigator hopes to achieve independence as a clinician-investigator in HF.
|Program type||Fellow-to-Faculty Transition Award|
|Effective start/end date||07/01/2017 → 06/30/2022|