Probing Regional Metabolism During Exercise through Coronary Sinus Sampling

/ABSTRACT Despite advances in our management of patients with heart failure with reduced ejection fraction (HFrEF), substantial residual morbidity and mortality continues to plague the contemporary treatment era. A hallmark feature of HF remains reduced exercise capacity, which is associated with substantially reduced quality of life. A growing appreciation for interventions that alter metabolism to improve HF pathobiology has accumulated in recent years. Through his K23 application, Dr. Selvaraj is currently investigating the role of therapeutic ketosis to modify exercise capacity in HFrEF. Noting both cardiovascular and peripheral limitations to exercise observed in HFrEF, techniques to dissect regional metabolic changes are pivotal to understanding metabolic modulation as a treatment principle. To decipher local metabolic changes, arteriovenous sampling is a powerful technique which measures metabolic gradients across muscle beds. For example, coupled with arterial access, catheters in the coronary sinus and femoral vein can be used to calculate fuel uptake and secretion in the heart and legs, respectively. This feasibility study through an R03 mechanism seeks to implement arteriovenous sampling of the heart and leg to determine changes in metabolite utilization during submaximal (constant-intensity) exercise. This collaborative team will leverage interventional cardiologists and electrophysiologists (who routinely access the coronary sinus during clinically indicated procedures) to perform blood sampling among patients referred to the cardiac catheterization laboratory at Duke University Hospital, a high-volume center for diagnostic catheterization. Aim 1 will assess the feasibility of coronary sinus sampling in 10 patients during low/moderate constant-intensity exercise. Aim 2 will determine time-dependent metabolite trajectories after the cessation of exercise from the coronary sinus. Dr. Selvaraj, an early career investigator and Assistant Professor at Duke University, has a long-term goal of becoming an independently funded cardiovascular researcher with a focus on cardiovascular metabolic interventions in HF and using deep phenotyping techniques to define pathways of benefit. Achievement of these aims will position Dr. Selvaraj to investigate regional metabolism with metabolic interventions. Furthermore, the technique can be leveraged for other ‘omic platform analysis to comprehensively assess myocardial and skeletal muscle biology during exercise. Project Number: 1R03HL180898-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Senthil Selvaraj | Institution: DUKE UNIVERSITY, DURHAM, NC | Award Amount: $242,250 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZHL1 CSR-Y (M1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03HL18089801