# SCAN-MP (Screening for Cardiac Amyloidosiswith Nuclear imaging in Minority Populations)

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $1,429,986

## Abstract

Heart failure with preserved ejection fraction (HFpEF) disproportionately afflicts older Black and Hispanic
Americans. ATTR cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded
transthyretin protein (TTR or prealbumin) and is classified by the genetics of TTR into wild-type (ATTRwt) or
mutant (ATTRm). ATTR CA, irrespective of genotype, is an age-dependent, often unrecognized, mechanism
underlying HFpEF. While ATTRm CA results from point mutations that promote TTR misfolding and amyloid
aggregation, factors that contribute to ATTRwt CA are not well defined. While previously thought to be
untreatable, promising therapies in late-stage clinical trials will likely be most effective if administered early in
disease course. Only a small proportion of individuals with wild-type TTR will develop ATTRwt CA,
overwhelmingly reported in Caucasian males beyond age 60 years. However, as an autosomal protein, allele
distribution is not sex specific. For ATTRm, a substitution of isoleucine for valine (V122I) is the most frequent
TTR mutation in the US, observed exclusively in Black Americans with an allele frequency of 3.4%. But there
are no data regarding the prevalence of ATTRwt CA in African Americans and no data for ATTR CA
prevalence, irrespective of genotype, in the Hispanic population. One of the reasons for the knowledge deficit
is the challenge of diagnosis. Endomyocardial biopsy, while nearly 100% sensitive and specific, is impractical
as a screening test and genotyping alone of patients is insufficient to identify ATTR CA because wild-type
patients develop disease. We have developed a highly accurate technique for ATTR CA identification using
Tc99m-pyrophosphate (PYP) imaging that avoids the need for biopsy. Tc99m-PYP myocardial uptake can occur
before echocardiographic or clinical changes, suggesting enhanced sensitivity. While studies using the
technique have suggested that 10-15% of elderly hospitalized patients with HF may have ATTR CA, Tc99m-
PYP has not been applied broadly in HF patients as a means to facilitate early diagnosis. In addition, we have
also reported both a point-of-care diagnostic tool that utilizes a novel biomarker, retinol binding protein 4
(RBP4), and an assay to measure TTR stability. We hypothesize that a significant proportion of HF in elderly
Blacks and Hispanics is caused ATTR CA. We propose to leverage our methodologies to establish the
prevalence of ATTR CA and explore the relationship between RBP4 concentration and TTR stability in a
prospective cohort study of elderly Black and Hispanic Americans with HF. Aim 1 will determine the
prevalence and clinical progression of ATTR CA relative to genotype, clarify sex distribution, and calibrate the
aforementioned point-of-care diagnostic tool. Aim 2 will explore the relationships between RBP4
concentration in serum and urine, TTR stability, and genotype in ATTR CA. Successful completion of these
Aims will inform understanding of ATTR CA pathogenesis a...

## Key facts

- **NIH application ID:** 10133718
- **Project number:** 5R01HL139671-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MATHEW S MAURER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,429,986
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133718

## Citation

> US National Institutes of Health, RePORTER application 10133718, SCAN-MP (Screening for Cardiac Amyloidosiswith Nuclear imaging in Minority Populations) (5R01HL139671-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133718. Licensed CC0.

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