Project Details
Description
PROJECT SUMMARY/ABSTRACT
Duchenne and Becker muscular dystrophy (DMD/BMD) are devastating diseases with no cure resulting in loss
of ambulation, respiratory failure, cardiomyopathy, and premature death. Dystrophin associated
cardiomyopathy (defined here as CM) is the leading cause of death in DMD/BMD, and an under-studied
concern in DMD and BMD mutation carriers (MDC). CM progression is variable and poorly described in the
current era. There are no blood or imaging biomarkers that can predict the pace of progression or the risk of
early mortality. More importantly, there are no established cardiac outcome measures. Novel, targeted
therapeutics are necessary to treat CM, but these significant knowledge gaps make clinical trials challenging. A
better understanding of DMD/BMD/MDC cardiovascular disease progression and the identification of surrogate
outcome measures are critical for the field to advance. To address these obstacles, we propose to leverage
the Duchenne muscular dystrophy cardiac care consortium (DMDCCC). Created with grants from the NHLBI
and the FDA, this consortium consists of eight high-volume sites with similar DMD/BMD/MDC cardiovascular
treatment and diagnostic protocols, including surveillance CMR imaging every 1-2 years. This proposal will
create a comprehensive prospective registry of DMD/BMD/MDC patients with meticulously collected clinical
data and cardiac magnetic resonance (CMR) images; we anticipate enrollment of 950 patients with over 4000
CMR studies. This cohort will be used to better define the progression of CM and to determine associations
with mortality. The central hypothesis of our proposal is that integrated statistical modeling based on advanced
imaging can improve prediction of CM progression and mortality. Aim 1 will create a comprehensive cohort of
DMD/BMD/MDC patients and model the progression of CM. Aim 2 will determine cardiovascular measures that
are associated with CM mortality or rapid progression using novel, data-driven, personalized machine learning
models. Aim 3 will create a portal for DMD/BMD/MDC centers to determine patient risk. This multi-PI proposal
leverages expertise in clinical care, cardiac imaging, biomedical engineering, complex image analysis, and
neural networks. To our knowledge, this study will create the largest cohort of DMD/BMD/MDC patients with
CMR images, allowing for a better understanding of CM progression and identifying biomarkers that associate
with poor outcomes. The resulting risk portal will provide clinicians all over the world with a method to assess
their patient’s risk in real time, allowing intensification of therapy for those deemed high risk. By building on
prior productive collaborations, particularly that of the DMDCCC, this proposal will expand our understanding of
CM, improving clinical care and future cardiac-specific therapeutic trials.
Status | Active |
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Effective start/end date | 01/23/24 → 12/31/24 |
Funding
- National Heart, Lung, and Blood Institute: $838,348.00
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