# The Road to Destination Therapy: Developing a Durable Ambulatory Mechanical Cardiopulmonary Support for Pulmonary Hypertension

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $771,563

## Abstract

Project Abstract
Pulmonary hypertension (PH), which causes right ventricular failure (RVF), is a life-threatening disease with
limited long-term treatment options and a 5-year survival rate of only 50% despite advances in medical therapy,
which temporarily ameliorate it. Lung transplant is the only definitive treatment; however, PH patients can acutely
deteriorate and become ineligible for transplant. It is difficult to predict and intervene prior to RVF due to the
limited physiologic understanding about end-stage PH and also because patients with severe PH do not tolerate
exercise testing that would otherwise better predict their prognosis. Mechanical cardiopulmonary support (MCS)
technology, notably extracorporeal membrane oxygenation (ECMO), is used sometimes to rescue patients with
PH-RVF and has occasionally served as a bridge to lung transplant. However, it is a limited intervention because
of its many technological shortcomings: its complexity of operation, poor durability and biocompatibility, and
bulky size that limits patient mobility and ambulatory use. Moreover, ECMO does not address the specific
physiologic and metabolic deficits incurred by end-stage PH patients, which change drastically between rest and
exercise states and remain poorly characterized. Due to the ethical challenges and barriers of studying severe
PH in clinical subjects, our team proposes to use a large animal model to address this challenging disease. We
will use our group’s high-fidelity large animal model of PH-RVF that utilizes progressive pulmonary artery banding
approach in sheep subjects. Our prior work with this animal model has demonstrated that the sheep subjects
accurately recapitulate the clinical pathophysiology of PH that spans across multiple organ systems. Using our
established expertise with this animal model, we will first reveal the exercise limitations associated with this
severe disease, and use this physiologic understanding to develop a more durable, wearable MCS that can
support patients with end-stage PH-RVF. Under Aim 1, the PH-RVF sheep subjects will undergo treadmill
exercise testing to characterize the longitudinal changes in cardiopulmonary reserve, metabolism, and exercise
tolerance during disease progression. Under Aim 2, the PH-RVF sheep will receive 14 days of MCS to address
the specific physiologic and metabolic deficits that were characterized under Aim 1. The novel portable MCS
system consists of low-resistance, low-profile, highly biocompatible gas exchangers coupled with a ventricular
assist device pump. The mode of attachment will be varied between two optimized configurations (right atrium-
left atrium, RA-LA, and right atrium-aorta, RA-Ao) that were narrowed down in our team’s previous investigation,
R01HL140231. During 14 days of wearable device support, RV and device function will be studied under
conditions of dynamic exercise induced stress using multi-scale analysis to assess the impact on RV recovery
and end-organ func...

## Key facts

- **NIH application ID:** 10781192
- **Project number:** 1R01HL171577-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Matthew Dominic Bacchetta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $771,563
- **Award type:** 1
- **Project period:** 2024-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10781192

## Citation

> US National Institutes of Health, RePORTER application 10781192, The Road to Destination Therapy: Developing a Durable Ambulatory Mechanical Cardiopulmonary Support for Pulmonary Hypertension (1R01HL171577-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10781192. Licensed CC0.

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