# Integrated Proteomic and Metabolomic Determinants of Left Atrial Dysfunction

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $671,254

## Abstract

PROJECT SUMMARY
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are prevalent cardiovascular
syndromes of aging that frequently co-exist. Unfortunately, clinical outcomes are worse among individuals with
comorbid HFpEF and AF compared with either syndrome in isolation. Although AF and HFpEF share several
common clinical risk factors, such risk factors lack the pathway-specific granularity that is essential toward
identifying therapeutic targets for prevention and treatment. Over the last 6 years, our group has identified
reduced left atrial (LA) mechanics as a shared upstream phenotype that predates both AF and HFpEF. Recently,
we have demonstrated that LA functional reserve (i.e., change in LA function after intravascular volume
challenge) is uniquely linked to subclinical HFpEF syndromes. Despite consistent associations between LA
dysfunction and cardiometabolic risk factors, how these risk factors promote LA dysfunction remains elusive.
The advent of high-throughput circulating metabolite profiling and protein quantification has presented a unique
opportunity to define metabolic pathways driving LA dysfunction to illuminate its pathobiology. We have
previously defined a distinct proteomic signature of LA dysfunction in prevalent HFpEF. Similarly, select
metabolites have been associated with LA dysfunction, AF, and HFpEF. Despite these early findings, several
questions remain: 1) are these molecular biomarkers of LA dysfunction simply a consequence of prevalent
AF/HFpEF?; 2) what is the proteomic and metabolomic signature of sensitive measures of LA function at rest
and after hemodynamic provocation?; and 3) do these associations exist in ethnically diverse populations at high
joint AF and HFpEF risk? The overall goal of the proposal is to elucidate key metabolic pathways linked to LA
dysfunction to determine the shared biology of AF and HFpEF among individuals at risk. Our study will leverage
multimodality measures of LA function at rest and after hemodynamic provocation in participants of the Multi-
Ethnic Study of Atherosclerosis (MESA). In Aim 1, we will determine proteomic associations of LA dysfunction,
incident AF, and incident HFpEF using targeted and untargeted approaches. We will validate our findings in the
Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, Coronary Artery Risk
Development in Young Adults Study (CARDIA), and the HeartShare study. In Aim 2, we will determine the
metabolomic signature of LA dysfunction and its association with incident AF and HFpEF in MESA, and validate
findings in CARDIA, Framingham Heart Study (FHS), a cohort of hospitalized patients who have undergone
cardiopulmonary exercise testing, and the HeartShare study. In Aim 3, we will perform integrative analyses of
the metabolome and proteome and its relationship with LA dysfunction, incident AF, and HFpEF. We will
determine associations of genetic variation of the most highly loaded pr...

## Key facts

- **NIH application ID:** 10803985
- **Project number:** 1R01HL167986-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ravi Bharat Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,254
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803985

## Citation

> US National Institutes of Health, RePORTER application 10803985, Integrated Proteomic and Metabolomic Determinants of Left Atrial Dysfunction (1R01HL167986-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803985. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*