# Precision Medicine for Dilated Cardiomyopathy—Novel Assessment of Cardiac Mechanics via Speckle Tracking Echocardiography to Identify Early Phenotypes

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $392,992

## Abstract

PROJECT SUMMARY
Dilated cardiomyopathy of unknown cause (DCM), a major public health problem affecting more than a million
people in the U.S., is usually diagnosed late in its course with overt heart failure or sudden death. Recent
preliminary evidence indicates that most DCM has an underlying genetic basis; this hypothesis is being tested
in the DCM Precision Medicine Study, the parent study of this ancillary application, which is conducting family
based enrollment of 1300 DCM patients (probands) and 2600 of their relatives at 26 centers. In the parent study,
the echocardiographic (echo) data currently collected on case report forms are only those necessary to confirm
or detect left ventricular enlargement or systolic dysfunction. Genetic analysis is also conducted in probands to
identify relevant variants (pathogenic, likely pathogenic, or uncertain significance) in DCM-related genes, but
cascade testing in relatives is limited to pathogenic and likely pathogenic variants that would change clinical
management. While these echocardiographic and genetic data are sufficient to achieve the aims of the parent
study, collection of additional data exceeding the scope of the parent study is essential to test the central
hypothesis of this ancillary study: that DCM-related abnormalities in cardiac mechanics are (1) present in
individuals genetically at risk for DCM prior to development of left ventricular systolic dysfunction and dilation
and (2) reflect the level of genetic risk. In particular, we propose centrally collecting digital echo data currently
stored at sites and analyzing these data at an echo core lab using speckle-tracking echocardiography (STE),
which is capable of detecting subtle abnormalities in cardiac mechanics. We also propose additional cascade
testing for variants of uncertain significance (VUSs) in first-degree relatives (FDRs); VUSs have been found in
46% of probands with completed adjudications thus far, but their implications for genetic risk in FDRs are
currently uncertain. Using these data, we will (1) examine how STE-derived strain measurements vary with the
level of genetic risk using a two-fold approach. First, we will (a) compare these measurements between
genetically at-risk FDRs with varying levels of measured genetic risk (i.e., severity and number of mutations in
DCM-related genes identified via testing) and normal population controls. Second, we will (b) conduct a family-
based analysis to determine the relative contributions of these measured and other unmeasured genetic factors
to variation in these measurements. We will also (2) determine the effect of physiologic stress (exercise) on
cardiac mechanics in 200 unaffected FDRs who have uncertain genetic risk (carriers of familial VUSs or FDRs
of probands with negative genetic testing) compared to matched controls. This study, if successful, will lead to
novel understanding of how varying levels of genetic risk, and especially VUSs, associate with abnormalities of
c...

## Key facts

- **NIH application ID:** 10436899
- **Project number:** 5R01HL149423-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** RAY E. HERSHBERGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,992
- **Award type:** 5
- **Project period:** 2019-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436899

## Citation

> US National Institutes of Health, RePORTER application 10436899, Precision Medicine for Dilated Cardiomyopathy—Novel Assessment of Cardiac Mechanics via Speckle Tracking Echocardiography to Identify Early Phenotypes (5R01HL149423-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10436899. Licensed CC0.

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