View from the Field: ASNC/IANC Fellowship Awardee Describes Winning Research Project

On Friday, Sept. 25, during the ASNC2020 Presidents' Session, ASNC will recognize Sanjay Divakaran, MD, recipient of this year's ASNC/Institute for the Advancement of Nuclear Cardiology (IANC) Research Fellowship Award. Dr. Divakaran will receive a $50,000 grant to support his project, “Skeletal Muscle Perfusion and Energetics in Patients with Symptomatic Peripheral Artery Disease.”

Connect with Sanjay Divakaran, MD,
on Twitter at @SanjayDivakaran.

Dr. Divakaran is an associate physician in the Division of Cardiovascular Medicine and the Cardiovascular Imaging Program at Brigham and Women's Hospital. He joined ASNC in 2016 and is a member of the Education Committee and Social Media Task Force. Earlier this year, he was among seven early-career members selected for ASNC's 2020 Leadership Development Program.
Now, Dr. Divakaran joins a growing number of early-career investigators whose work has earned ASNC's support. Past awardees include Krishna Patel, MD, MSc, of Saint Luke's Mid America Heart Institute/University of Missouri-Kansas City, and Senthil Selvaraj, MD, of the Hospital of the University of Pennsylvania; both are presenting at ASNC2020.
ASNC Past President Raymond Russell III, MD, PhD, MASNC, who will present the award, has noted that Dr. Divakaran's project will address PAD, “a serious disease associated with high rates of morbidity and mortality.” In a conversation with ASNC, Dr. Divakaran explained why the PAD focus is important for improving outcomes for both PAD and CAD patients, described the imaging techniques he'll be using, and thanked his mentors. Here's our conversation:
ASNC: Dr. Divakaran, congratulations on proposing the winning research project for this year's 2020 IANC Research Fellowship Award. Your IANC-funded research will help further the specialty's understanding of how PAD patients' affected limbs respond to exercise. This is a timely project considering, first, the new research suggesting that revascularization may not be superior to supervised exercise for at least some PAD patients and, second, that CMS has recently begun covering supervised exercise therapy. Would you talk briefly about the primary question your project will address and why it is important now?
SD:  Thanks very much! I am honored to receive this award and am incredibly grateful to ASNC and IANC for supporting this work. Intermittent claudication from PAD is independently associated with increased risk of cardiovascular mortality and decreased quality of life, but its pathophysiology remains poorly understood. Because of this, we currently have an inability to individualize treatment for patients with PAD.
During the ASNC/IANC Award Year, we will use two novel imaging biomarkers (perfusion/metabolic positron emission tomography and 31P magnetic resonance spectroscopy) at rest and post-exercise to investigate the contributions of skeletal muscle oxygen delivery and oxygen utilization to the pathophysiology of intermittent claudication and patient symptoms. Deep phenotyping of patients with intermittent claudication from PAD using these techniques has the potential to lead to individualized therapy, improved risk stratification, and the discovery of novel therapeutic targets.
ASNC: Your study will employ a novel imaging technique called 11C-acetate PET. Why this imaging technique to test your hypotheses? Could it reveal things that other imaging techniques cannot?
SD: PET imaging with 11C-acetate is a powerful tool to study both muscle perfusion and oxygen utilization. Acetate is rapidly converted to acetyl-coenzyme A (acetyl-CoA) after it is taken up by muscle. Acetyl-CoA is then metabolized through the tricarboxylic acid (TCA) cycle. Since there is tight coupling between the TCA cycle and oxidative phosphorylation, muscle turnover of 11C-acetate reflects overall flux in the TCA cycle and therefore overall oxygen consumption. 11C-acetate PET is, therefore, unique in that we can use it to capture both oxygen delivery (perfusion) and oxygen consumption (metabolism) data. By studying skeletal muscle perfusion and metabolism pre- and post-exercise, we hope to better understand the relative contributions of both to claudication symptoms.
ASNC: This project has relevance for the 200 million people who have PAD. Many of these patients also have coronary artery disease, correct? When you think about possible impact, is the intersection of the two diseases important for this project?
SD: This is an extremely important point – thank you for bringing it up. In the recently published VOYAGER-PAD study (led by one of my mentors, Marc P. Bonaca, MD, MPH), of the 6,564 patients with PAD who had undergone peripheral revascularization studied in the trial, 31.5 percent had concomitant symptomatic coronary artery disease (CAD).
Additionally, PAD is a strong predictor of adverse cardiovascular events, including CAD-related events such as myocardial infarction and coronary revascularization. Understanding why claudication happens and why it is associated with adverse cardiovascular events will be crucial to improving both limb and coronary outcomes in patients with PAD.
ASNC: How do you envision your work – either with this project or the work that could follow from it – impacting the care of cardiovascular patients?
SD: Our hope is that if we can better understand what is causing claudication at the individual limb and patient level, we can individualize management and treatment approaches. For example, if we find that a particular patient has abnormalities in both skeletal muscle perfusion and oxygen utilization, but the abnormalities in perfusion are more pronounced, then maybe that patient should be referred for revascularization for refractory symptoms. If a different patient also has abnormalities in both but the abnormalities in metabolism are more pronounced, then maybe this second patient should be referred for a supervised exercise therapy program as initial therapy to improve skeletal muscle oxygen utilization.
ASNC: Good luck with your project. ASNC is looking forward to your results presentation next year at ASNC2021. Any final words before we let you get to work?
SD: Thank you! I want to thank ASNC/IANC again for the support. I also want to thank the patients with PAD we have and will work with. They have been generous with their time and have been as dedicated to learning more about the pathophysiology of PAD as I have. Finally, I'd like to thank our entire research team and my mentors, Marcelo F. Di Carli, MD, MASNC, Marc P. Bonaca, MD, MPH, Alexander P. Lin, PhD, and Mark W. Feinberg, MD, for their support and encouragement. I am looking forward to sharing what we find at ASNC2021!

The ASNC2020 Presidents' Session will convene at 8:45 AM (EDT) on Friday, Sept. 25. The session will include a welcome from ASNC2020 Program Chair Terrence D. Ruddy, MD, MASNC; addresses by ASNC President Sharmila Dorbala, MD, FASNC, ASNC President-elect Randall C. Thompson, MD, FASNC, and ACC President Athena Poppas, MD; as well as recognition of the ASNC Distinguished Service, Journal of Nuclear Cardiology, and ASNC/IANC awardees.

For more information about the ASNC/IANC Research Fellowship Award, visit Awards.