# Impact of Aortic Wall Inflammation and Stiffness on Thoracic Aortic Growth in Marfan Syndrome

> **NIH NIH K23** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $151,740

## Abstract

PROJECT SUMMARY/ABSTRACT
Thoracic aortic aneurysms (TAAs) predispose patients to sudden death due to aortic rupture or
dissection. Despite advances in surgical management and medical treatment, nearly 40% of patients
die before reaching a hospital – highlighting the importance of more effective risk stratification to
prevent sudden death. Current risk stratification is based on noninvasive imaging to regularly assess
aortic size, the criterion used to guide timing of prophylactic surgical repair. However, we know that
size alone does not fully capture the underlying causes of TAA complications. For example, among
patients with genetically-mediated TAAs (the leading cause of TAAs), up to 60% of dissections occur in
aortic segments with diameters below the conventional threshold for surgery. Until we identify new risk
factors for aortic instability, patients will continue to suffer life-threatening complications not predicted
by aortic size alone. This knowledge gap will be addressed in the applicant's proposal.
In his career development proposal, based on his robust pilot data, the applicant hypothesizes that
increased aortic wall inflammation and abnormal aortic biomechanics lead to faster aortic growth, a
metric for aortic instability. The detection of these pathological processes is not possible with the
currently used anatomic-based imaging approaches, but rather requires application of molecular and
functional imaging techniques, such as positron emission tomography (PET) and magnetic resonance
imaging (MRI). To establish the impact of inflammation on aortic growth, he innovatively proposes to
use inflammatory radiotracers to detect aortic wall inflammation as a high-risk marker. He then
proposes to study the impact of aortic stiffness, a validated biomechanical parameter, as another high-
risk marker that results in rapid aortic growth. Finally, he proposes to evaluate whether stiffness and
inflammation are inter-related, and whether the combination improves prediction of aortic growth. This
novel study approach takes advantage of an institutional infrastructure that includes state-of-the-art
hybrid PET-MR scanner that allow for simultaneous assessment of aortic anatomy and function. In
addition, he will leverage the strength of his institution as a leading recruitment site for the NIH/NHLBI-
sponsored GenTAC registry, and recruit participants with Marfan Syndrome, a prototype TAA disorder.
The completion of the proposed project will help us understand the association between inflammation
and biomechanics with aortic instability. The findings from this proposal have the potential to accelerate
diagnosis, refine prognosis, and guide optimal treatment to prevent aortic complications. These findings
may lead to a paradigm-shift in our approach to TAA monitoring and change in existing management
guidelines with resultant reduction in mortality.

## Key facts

- **NIH application ID:** 9952414
- **Project number:** 5K23HL138299-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** PARMANAND SINGH
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,740
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952414

## Citation

> US National Institutes of Health, RePORTER application 9952414, Impact of Aortic Wall Inflammation and Stiffness on Thoracic Aortic Growth in Marfan Syndrome (5K23HL138299-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9952414. Licensed CC0.

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