# Inter-ventricular decoupling is an overlooked contributor to right ventricular myocardial stress and dysfunction in pediatric pulmonary hypertension

> **NIH NIH K25** · UNIVERSITY OF COLORADO DENVER · 2021 · $120,960

## Abstract

Project Summary
 Pediatric pulmonary arterial hypertension (PAH) is a degenerative disease that
can ultimately lead to right heart failure. Lately, proposed clinical techniques for
assessing disease progression and risk stratification have utilized the relative safety of,
and abundant information available in, Cardiac MR (CMR) images. These techniques
allow for direct functional and morphological measurements, and can be used to
perform patient-specific computational simulations that can predict the biomechanical
state of the heart under different scenarios. Tagged MRI is a relatively new technique
that can also reveal strain and local ventricular twisting. This project will combine MR
imaging (with and without tissue tagging) and computational modeling in pediatric PH
patients, and tissue gene expression in rats, to completely phenotype right ventricular
dysfunction in pediatric pulmonary hypertension and improve our understanding of the
biomechanical/biochemical progression of the disease.
 Right ventricular (RV) dysfunction is commonly attributed to pressure or volume
overload, but direct contribution of the left ventricle (LV) is usually overlooked. However,
multiple previous studies have shown that the RV is relying on the mechanical energy
transfer from LV contraction for up to 80% of its pumping performance. The initial
dysfunction of a single ventricle can trigger a remodeling response in the neighboring
ventricle, which would further contribute to the dysfunction of the former. Therefore,
changes to LV twisting-rate seen in PAH is likely both the cause and effect of ultimate
RV dysfunction. The objective of this study is to: (1) provide definitive evidence that
LV torsion-rate is decreased in pediatric PAH, which is associated with a decrease in
RV contractility; (2) investigate, using computational modeling, if restoring LV torsion-
rate would improve RV function and consequently establish LV torsion-rate as the
biomechanical cause for declining RV function; and (3) identify differentially expressed
genes in the blood and myocardium of a PH rat model. The successful completion of
these objectives will: (1) lead to novel prognostic markers and a better understanding of
the cardio-pulmonary pathophysiology associated with PAH; (2) provide career
development training for animal modeling, genomic analysis, and bioinformatics; and (3)
generate preliminary data for a future NIH R01 application to study the link between
functional RV-LV decompensation and changes in gene expression.

## Key facts

- **NIH application ID:** 10246380
- **Project number:** 5K25HL133481-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Vitaly Kheyfets
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $120,960
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246380

## Citation

> US National Institutes of Health, RePORTER application 10246380, Inter-ventricular decoupling is an overlooked contributor to right ventricular myocardial stress and dysfunction in pediatric pulmonary hypertension (5K25HL133481-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246380. Licensed CC0.

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