# A Controlled Septal Ablation for Inoperable Hypertrophic Cardiomyopathy

> **NIH NIH R15** · UNIVERSITY OF TEXAS ARLINGTON · 2022 · $433,120

## Abstract

Project Summary
Hypertrophic cardiomyopathy (HCM) is a genetic disease that results in abnormal thickening of ventricular heart
muscle, particularly the septum, causing left ventricular outflow tract (LVOT) obstruction. When medication alone
is not sufficient to relieve symptoms, the current gold standard, septal myectomy, is performed to surgically
remove excess muscle with an open heart surgery. Unfortunately, many patients are poor surgical candidates
and require less invasive treatment options. In these cases, cardiologists treat the patients with a minimally
invasive catheterization technique called alcohol septal ablation (ASA), in which 1-4 mL of pure alcohol is injected
into the septum via a septal perforator (artery) to destroy part of the septal muscle by triggering necrosis.
However, the diffusive nature of pure alcohol causes dangerous uncontrollable necrosis and a very high
complication profile for a minimally invasive technique. Risky complications of ASA, with a periprocedural
mortality rate of ~2%, include atrioventricular block, ventricular fibrillation/tachycardia, and complete heart block
due to lack of control of alcohol localization and indiscriminate tissue destruction. To answer the unmet clinical
need, recently cyanoacrylate (super glue) was investigated as a replacement for pure alcohol but experienced
challenges in efficacy and long-term safety. To overcome those limitations, our goal is to design a novel ablation
system to replace the pure alcohol in ASA and achieve a controllable, localized septal tissue shrinkage and
hence a safer ablation. Based on our preliminary data, we hypothesize that the delivery of a collagenase-coated,
doxorubicin-loaded, degradable nanoparticles (NPs) will allow for localized doxorubicin-induced destruction of
the hypertrophic cardiomyocytes, and this single dosage delivery will lead to regression of the overgrown HCM
septal tissue. Doxorubicin was recently found to be responsible for the clearance of unwanted hypertrophic
cardiac tissue, and the proposed single dosage delivery can avoid cardiac toxicity often caused by repeat
exposure. Three aims will thus be pursued to better understand HCM septal tissue and develop this novel
treatment approach: (1) Determine the biomechanical and microstructural abnormalities of human HCM septal
tissues and develop a biomimicking in vitro 3D HCM model; (2) Develop a collagenase-coated, doxorubicin-
loaded, biodegradable nanoparticle ablation system and optimize the ablation system using the in vitro 3D HCM
model; (3) Validate the safety and efficacy of the newly developed ablation system in an HCM mouse model.
The proposed research paves a new avenue to improve the safety and efficacy of septal ablation in inoperable
HCM patients. The impacts are (i) the innovative concept and design of a controllable, localized ablation to
replace the unpredictable, diffusive pure alcohol ablation, and (ii) the promising translational potential. This AREA
project will a...

## Key facts

- **NIH application ID:** 10514872
- **Project number:** 1R15HL159599-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS ARLINGTON
- **Principal Investigator:** Jun Liao
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $433,120
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514872

## Citation

> US National Institutes of Health, RePORTER application 10514872, A Controlled Septal Ablation for Inoperable Hypertrophic Cardiomyopathy (1R15HL159599-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10514872. Licensed CC0.

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