# Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $1,102,200

## Abstract

Project Abstract
 Heart failure (HF) with preserved ejection fraction (HFpEF) is a major public health concern that
disproportionately affects the elderly and currently has no effective therapy. Accumulating evidence suggests
that myocardial deposition of misfolded transthyretin proteins (ATTR) increases with age and is responsible for
13-18% of HFpEF in late life. ATTR cardiac amyloidosis (CA) is one of the most-deadly forms of HF with a median
survival of 25-41 months. The diagnosis of ATTR-CA has commonly been delayed, often by several years, because
of the need for invasive endocardial biopsy for diagnosis and lack of urgency due to limited therapeutic options.
This has changed recently. ATTR CA can now be diagnosed non-invasively using 99mtechnetium pyrophosphate
(99mTc-PYP) imaging, and recent therapeutic breakthroughs (e.g., tafamidis, inotersen, patisiran) have improved
survival, alleviated symptoms, and reduced HF hospitalizations. However, lack of knowledge regarding the early
changes in cardiac structure, function, and circulating biomarkers that reflect myocardial ATTR deposition, and
their prognostic relevance in elderly persons free of HF are key barriers to effectively harnessing recent
diagnostic and therapeutic breakthroughs to treat and prevent this important cause of HFpEF. Over the past 8
years, we have been building a unique database detailing longitudinal changes in cardiac structure and function
over 5 years in >4,000 elderly participants (age 70-95 years) in the largely biracial Atherosclerosis Risk in
Communities (ARIC) cohort study. We now aim to leverage this rich resource, in addition to serial clinical and
circulating biomarker data over 25 years, to define the prevalence, predictors, and prognostic importance of
incidentally detected late-life cardiac ATTR deposits. We will perform 99mTc-PYP SPECT imaging in 900 ARIC
participants with either prevalent HFpEF (n=300) or asymptomatic cardiac remodeling/dysfunction (n=600).
Our specific aims are to: 1) Define antecedent alterations in cardiac structure, function, and circulating
biomarkers that discriminate late-life HFpEF with compared to without ATTR-CA. ; 2) Determine the predictors
and prognostic relevance of ATTR-CA in elderly persons without HF but with cardiac remodeling/dysfunction;
and 3) Define the extent to which novel candidate proteins and protein networks in mid- and late-life predict
ATTR-CA in late-life. At the completion of this project, we will have defined the cardiac changes that antecede
and predict HF from ATTR-CA, established the prognostic importance of asymptomatic ATTR-CA in late life,
and identified novel circulating biomarkers of ATTR-CA. These findings will facilitate identification of persons
at high risk to screen for ATTR-CA to facilitate HF treatment and, possibly, prevention. The results of these
studies are likely to identify novel therapeutic targets to transform the management of ATTR-CA.

## Key facts

- **NIH application ID:** 10333349
- **Project number:** 5R01HL150342-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sharmila Dorbala
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,102,200
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333349

## Citation

> US National Institutes of Health, RePORTER application 10333349, Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life (5R01HL150342-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10333349. Licensed CC0.

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