# Multi-Omic Markers of Cardiac Function and Structure within the Pressure Overloaded Heart

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $665,495

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposed study is motivated by the public health importance of aortic stenosis (AS), a common form of
valvular heart disease that is associated with substantial morbidity and mortality. Once symptomatic, survival is
a dismal 50% at 1-year if left untreated. Clinical symptoms develop once cardiac compensatory mechanisms
fail, indicating the need for aortic valve replacement (AVR), but because AS primarily affects the elderly,
symptoms are often incorrectly attributed to comorbid conditions, advanced age, or both—resulting in delayed
treatment. While most patients that eventually undergo AVR experience improvements in symptoms and
survival, nearly half of patients die within the first year after AVR or fail to reap the symptom and health status
improvements for which they underwent AVR. Our research suggests that irreversible cardiac remodeling and
injury related to delayed treatment contribute to these poor clinical outcomes, highlighting the unmet need for
objective and sensitive measures to inform clinical decisions regarding the timing of AVR. Our long-term goal is
to develop and implement an omics-based precision medicine approach for identifying patients with severe AS
at-risk for irreversible cardiac remodeling and injury who would benefit from earlier AVR, and our central
hypothesis is that multi-omic signatures reflective of dimensions of cardiac structure and function will identify
irreversible cardiac remodeling and therefore predict the clinical response to AVR. Our prior work and
preliminary studies provide strong support for our hypothesis and demonstrate that our experienced
multidisciplinary team is uniquely qualified to complete the proposed study. We have identified metabolomic
signatures that relate strongly to measures of cardiac function and structure and predict mortality after AVR,
and also proteomic signatures relating to cardiac function that differentiate severe AS and associate with
mortality. Within this proposal, we adopt a longitudinal systems biology approach that leverages the latest in
proteomic and metabolomic (multi-omic) sciences to: discover, test, and cross-validate multi-omic signatures of
cardiac function and structure in patients with severe AS (Aim 1); characterize longitudinal multi-omic
signatures and associations with changes in cardiac structure and function after AVR (Aim 2); and evaluate the
accuracy with which multi-omic signatures predict response to AVR (Aim 3). Our approach will enable us to
identify multi-omic signatures of irreversible cardiac remodeling and injury in patients with severe AS. These
data will support the development of new precision medicine-based strategies for identifying patients who
would benefit from earlier clinical intervention in an effort to reduce mortality and maximize health after AVR.

## Key facts

- **NIH application ID:** 10127697
- **Project number:** 5R01HL151838-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Sammy Elmariah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $665,495
- **Award type:** 5
- **Project period:** 2020-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127697

## Citation

> US National Institutes of Health, RePORTER application 10127697, Multi-Omic Markers of Cardiac Function and Structure within the Pressure Overloaded Heart (5R01HL151838-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10127697. Licensed CC0.

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