# Clinical benefits and mechanism of action of angiotensin-II receptor blocker on Cardiovascular remodeling in patients with repaired coarctation of aorta

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $652,072

## Abstract

PROJECT SUMMARY/ABSTRACT
The median survival in adults with repaired coarctation of aorta (COA) is ~55 years, and more that 50% of
deaths are due to end-stage heart failure and sudden cardiac death from left ventricular (LV) systolic/diastolic
dysfunction. LV dysfunction results from chronic pressure overload from hypertension, which in turn leads to
LV remodeling (increased fibrosis and stiffness, and impaired relaxation). LV dysfunction has been observed in
COA patients with borderline hypertension or stage 1 hypertension (B/S1) (blood pressure 120-139/80-89
mmHg), even though the severity of hypertension in these patients is considered significant enough to warrant
antihypertensive therapy based on the current guidelines. Additionally, COA patients with B/S1 hypertension
have impaired aerobic capacity and exhibit hypertensive response to exercise, both of which are associated
with cardiovascular adverse events The pathophysiologic mechanisms responsible for LV remodeling and
abnormal hemodynamic response to exercise in this subset of COA patients are not well understood but are
postulated to be due to increased aortic stiffness. We recently demonstrated that a 2-week course of
angiotensin-II receptor blocker (ARB) improved aortic stiffness, coronary flow reserve (CFR), cardiac output
reserve and vasodilatory reserve (VDR) during exercise. However, it is unknown whether these hemodynamic
changes will lead to LV reserve remodeling (decreased fibrosis and stiffness, and improved relaxation) and
improved aerobic capacity during long-term therapy. Our long-term goal is to prevent early cardiovascular
death in COA patients, by identifying and modifying the pathophysiologic mechanisms leading to LV
dysfunction and vascular complications in this population. Our overall objective for this application is to
determine whether ARB might promote LV reserve remodeling and improve aerobic capacity, and to delineate
the mechanisms of response to ARB. Our central hypothesis is that ARB will promote LV reserve remodeling
and improve aerobic capacity by improving CFR and VDR.
This hypothesis will be tested by pursuing two specific aims: (1) Determine whether ARB promotes LV reverse
remodeling in patients with repaired COA and B/S1 hypertension and delineate the mechanisms of response to
ARB; (2) Determine whether ARB improves aerobic capacity and delineate the mechanisms of response to
ARB. We will randomize 80 subjects 1:1 to ARB (losartan 50 mg) or placebo for 52 weeks. These subjects will
undergo multi-domain assessment of cardiovascular structure and function at baseline and after 52 weeks of
therapy. This proposal is innovative because it will novel magnetic resonance imaging techniques to assess
cardiovascular response to ARB in patients with repaired COA. The results will be significant because it will
enable the development of novel management paradigms for prevention of LV dysfunction and cardiovascular
death in this population.

## Key facts

- **NIH application ID:** 10914234
- **Project number:** 5R01HL162830-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Alexander Egbe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $652,072
- **Award type:** 5
- **Project period:** 2023-08-25 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914234

## Citation

> US National Institutes of Health, RePORTER application 10914234, Clinical benefits and mechanism of action of angiotensin-II receptor blocker on Cardiovascular remodeling in patients with repaired coarctation of aorta (5R01HL162830-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10914234. Licensed CC0.

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