Duke Anesthesiology’s Kamrouz Ghadimi, MD, has been awarded the 2020 International Anesthesia Research Society (IARS) Mentored Research Award ($175,000, two-year grant) to study “Right Ventricular Metabolic Dysregulation after Surgery for Heart Failure.”
Perioperative right heart failure (RHF) is the leading cause of death within 30 days of left ventricular assist device and heart transplant operations. The objective of Ghadimi’s research is to identify cardiometabolic pathways that underlie early RHF after these operations due to changes in right ventricular (RV) afterload and heterogeneity in response to inhaled pulmonary vasodilators (iPVD). Supported by preliminary metabolomic analyses, the central hypothesis posits that RV-pulmonary arterial (PA) coupling is optimized in the responder phenotype, which signals efficient fatty acid oxidation in RV myocardium. Study aims include 1) quantifying differences in key metabolites using targeted mass spectrometry in serial plasma and RV myocardial samples to determine cardiometabolic pathways, including dysregulated fatty acid oxidation, that underlie early RHF and heterogeneity in response to iPVD, and 2) identifying baseline biomarkers reflecting fatty acid oxidation defects that are associated with RV-PA coupling status, iPVD response phenotypes, and early RHF development to create an integrated clinical-molecular model for outcome prediction in critically-ill patients.
The foundation for this mentored research training grant is embedded in the INSPIRE-FLO clinical trial that Ghadimi has led since 2017 and the biospecimen repository that derived from trial patients undergoing advanced heart failure surgery, such as left ventricular assist device insertion and heart transplantation. As part of this award, Ghadimi and his research team plan to enroll patients undergoing routine cardiac operations by utilizing the vast resources available through Duke Anesthesiology’s Clinical Research Unit. As a member of the Shah laboratory at the Duke Molecular Physiology Institute, Ghadimi is being mentored by laboratory principal investigator (PI) and associate dean of genomics, Dr. Svati Shah, to accomplish the aims of this investigation and to acquire the necessary experiential training to become an independent clinical and translational investigator. As a previous recipient of the NIH T32 award (sponsored by the National Institutes of General Medical Sciences, PI: David Warner, MD), Ghadimi will obtain a Master in Health Science (MHSc) from the NIH-Duke Clinical Research Training Program and pursue additional coursework in precision medicine during this award.
“Receiving this grant is the next step in achieving my long-term goal of using translational methods to identify molecular pathways of right heart failure that will lead to potential novel therapeutic strategies and biomarker discovery for personalized patient care,” says Ghadimi, associate professor of anesthesiology and critical care. “With a large sense of gratitude, being named an award recipient has helped validate (1) the countless hours of hard work and sacrifice that were required to mature this project with my group of mentors and advisors, (2) the time my research team and I have utilized to coordinate multiple resources at Duke that are essential for proper acquisition and storage of biospecimens associated with our parent clinical trial, INSPIRE-FLO, and (3) the importance of ongoing professional development through enrollment in formal research training.”