# Towards Personalized Prosthetic Graft Replacement for Genetically Triggered Thoracic Aortic Aneurysms

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $691,821

## Abstract

PROJECT SUMMARY / ABSTRACT
For patients with thoracic aortic aneurysms (TAA), replacement of the ascending aorta with a current standard
of care prosthetic graft (polyethylene terephthalate) eliminates risk for dissection in graft-replaced regions and
can thus be lifesaving. Nevertheless, accumulating evidence reveals that proximal aortic grafting can increase
risk for downstream dissection, which is also life-threatening: Risk is greatest in patients with genetically triggered
TAA, who undergo graft replacement at lower thresholds, higher frequency, and younger age - after which risk
for dissection in graft-replaced regions is eliminated but possibility of distal complications increases. Up to two
thirds of dissections in genetic TAA patients occur in the distal (arch or descending) aorta. We have also shown
that over half of distal dissections with genetic TAA occur after graft surgery; proximal grafting has been linked
to a >2-fold increase in risk for dissection independent of aortic size. Our clinical observations are consistent
with experimental data: In pre-clinical and computational models, the dramatic increase in proximal aortic stiff-
ness with grafting induces hemodynamic changes that exacerbate distal stiffening. Aortic stiffness is increased
with genetic TAA - it is also known that mechanical loading forces drive adverse aortic remodeling. There is thus
a critical need to identify markers of distal aortic disease progression after proximal grafting, with focus on altered
hemodynamic loading in relation to graft characteristics (stiffness, length, enclosed volume). Our central hypoth-
esis is that loss of proximal aortic compliance due to stiff prosthetic grafts induces adverse distal aortic remod-
eling (driven by increased wall and wall shear stress) and predicts adverse prognosis. We also posit that adoption
of grafts, for which compliance is tailored to compensate for patient-specific aortic stiffness, will attenuate ad-
verse distal aortic remodeling. This will be tested in genetic TAA patients undergoing prosthetic graft replace-
ment, via Aims integrated towards the goal of testing if graft implantation produces progressive increments in
adverse remodeling (Aim 1A), identifying (native aortic and graft) features most responsible for adverse remod-
eling (1B), testing if these features are modifiable via a new class of tailored grafts (Aim 2), and exploring if widely
generalizable surrogates of graft-induced remodeling and native aortic stiffness predict clinical events (Aim 3).
To do so, cardiac MRI will be integrated with computational modeling of fluid structure interactions and vascular
remodeling - informed by material property testing of resected aortic tissue and simulations of tailored grafts for
which compliance can be paired to patient-specific aortic features. Our team provides complementary expertise
in cardiac imaging, aortic surgery, genetic TAA, computational modeling, and graft design - and a track record
of pro...

## Key facts

- **NIH application ID:** 10878897
- **Project number:** 5R01HL170570-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Mario FL Gaudino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $691,821
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878897

## Citation

> US National Institutes of Health, RePORTER application 10878897, Towards Personalized Prosthetic Graft Replacement for Genetically Triggered Thoracic Aortic Aneurysms (5R01HL170570-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10878897. Licensed CC0.

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