# Interplay of Myocardial Fibrosis and Cardiac TTR Amyloid in Age Related Cardiac Remodeling in MESA-Multi-Ethnic Study of Atherosclerosis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $1,461,844

## Abstract

Project Summary:
Myocardial fibrosis is characterized by the accumulation of extracellular matrix in the myocardium
and has been identified as one of the main determinants of age related cardiac remodeling. This
can manifest as either increased diffuse interstitial fibrosis or focal fibrosis as a scar and lead to
cardiac dysfunction. Cardiac transthyretin amyloidosis characterized by infiltration of the
myocardium by misfolded transthyretin protein, on the other hand, has emerged as an important
cause of accelerated remodeling leading to heart failure and CVD, and predisposing to frailty and
dementia. Importantly, novel FDA approved therapies (tafamidis, inotersen) may allow treatment
of cardiac amyloidosis highlighting the need for early detection. We expect this study to establish
the pivotal importance of quantifying fibrosis and amyloidosis at the population level to facilitate
clinical detection and orient the development of novel strategies to prevent heart failure, atrial
fibrillation and complications of CVD in older adults. Therefore, our specific aims are: Aim 1a)
determine the cross-sectional associations of presence as well as extent of amyloidosis measured
by Tc-PYP, with extent of myocardial fibrosis measured by MRI T1 mapping at MESA Exam 7.
1b) determine cross-sectional associations of presence and extent of amyloidosis as well as
fibrosis, with magnitude of cardiac remodeling defined as structural and functional alterations of
the left and right heart chambers by cine MRI at MESA Exam 7.1c) construct prediction models
for presence as well as for extent of both cardiac amyloidosis and progressive fibrosis at Exam 7,
by combining risk factor exposure and subclinical disease trajectories based on phenotypes
obtained from all MESA Exams (1-6) prior to Exam 7. In Aim 2a) we will compare the magnitude
of ECV change between MESA Exams 5 and 7 in the absence versus presence, as well as extent
of amyloidosis measured at Exam 7. 2b) compare the magnitude of 12-14 year changes in 4
chamber cardiac remodeling attributed to amyloidosis versus those attributed to progressive
fibrosis. 2c) construct longitudinal predictive models of 12-14 year change in ECV attributed to
amyloidosis versus ECV changes attributed to progressive fibrosis, using all phenotypic variables
obtained from MESA Exams 1 through 5. We propose to use data acquired during 2010-2012 in
800 individuals (400 men and 400 women) as part of the MESA 5 exam. As part of this proposal,
all participants will undergo a repeat MRI exam and Tc-99m-PYP at Exam 7. This study leverages
the already acquired MESA phenotypic data to predict amyloidosis and malignant progressive
fibrosis leading to adverse remodeling, CVD, frailty and dementia.

## Key facts

- **NIH application ID:** 10467374
- **Project number:** 1R01HL159987-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Sharmila Dorbala
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,461,844
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467374

## Citation

> US National Institutes of Health, RePORTER application 10467374, Interplay of Myocardial Fibrosis and Cardiac TTR Amyloid in Age Related Cardiac Remodeling in MESA-Multi-Ethnic Study of Atherosclerosis (1R01HL159987-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467374. Licensed CC0.

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