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Kheyfets receives ENTELLIGENCE Young Investigator Program grant award

Vitaly Kheyfets, PhD, Assistant Research Professor in the Department of Bioengineering has received an ENTELLIGENCE Young Investigator Program grant for his research titled, Inter-ventricular decoupling is an overlooked contributor to right ventricular myocardial stress and dysfunction in pediatric pulmonary hypertension. 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 compute mechanical stress. 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), computational modeling, and blood biochemical analysis 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 twisting-rate is decreased in pediatric PAH, which is associated with a decrease in RV contractility; (2) investigate, using computational modeling, if restoring LV twisting-rate would improve RV function; (3) test how restoring LV twisting-rate would impact myocardial stress; and (4) identify imaging and biochemical markers that correlate with LV twisting-rate and are indicative of myocardial stress. 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, which would improve our ability to tailor clinical intervention to patient-specific etiology and regularly evaluate therapeutic efficacy; and (2) provide preliminary data for a future studies to investigate the link between functional RV-LV decompensation and changes in gene expression.




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