Researching Cardiac Amyloidosis: First ASNC/Pfizer Young Investigator Awardee Describes Her Project

Today's ASNC2020 “Amyloidosis – Best Practices” session will begin with the presentation of the first ASNC/Pfizer Young Investigator in Cardiac Amyloidosis Research Fellowship Award to Vasvi Singh, MD. She will receive $50,000 in grant support for her project, “Screening for Early ATTR Cardiac Amyloidosis by 99mTc-PYP SPECT/CT in Older Adults With HFpEF and Sarcopenia.” 

Connect with Vasvi Singh, MD, 
on Twitter at @SinghVasvi.

Dr. Singh is the Amyloidosis Research Fellow in the Division of Nuclear Medicine and Molecular Imaging and the Department of Radiology at Brigham and Women's Hospital and Harvard Medical School in Boston. An active member of ASNC since 2016, Dr. Singh won ASNC's Clinical Young Investigator Award in 2018. She is a member of ASNC's Quality Steering Committee and chairs the ASNC FIT Workgroup. She also has participated in ASNC educational programs, including case presentations at prior Scientific Sessions and the Cardiac PET Workshop. During the COVID-19 shutdown, she was a presenter at the ASNC Nuclear Cardiology Virtual Elective.
Before today's presentation, Dr. Singh spoke with ASNC about her research as well as her goals for working with ASNC in the future. Here's our conversation: 

ASNC: Congratulations for being selected as the first recipient of the ASNC/Pfizer Young Investigator in Cardiac Amyloidosis Research Fellowship Award. Your project will evaluate the potential of screening for sarcopenia to achieve earlier identification and treatment of patients with cardiac amyloidosis. Catching the condition early is important because the current treatment – tafamidis – isn't as effective once the amyloidosis burden is advanced, correct? Why focus on sarcopenia? Why might it be a better screening mechanism than what clinicians are relying on today?  

VS: Yes, that is correct. Tafamidis, a recent therapeutic breakthrough, has improved survival, alleviated symptoms, and reduced HF hospitalizations from transthyretin cardiac amyloidosis. However, it is ineffective in about one-third of patients; advanced HF from high ATTR amyloid burden is a probable cause of lack of response. Therefore, as you said, early identification of ATTR-CA is critical to improve clinical outcomes; and, without this capability, we are unable to fully harness the recent therapeutic breakthroughs to alleviate HFpEF from ATTR-CA.
Also, currently, patients referred for PYP-SPECT based on clinical suspicion of ATTR-CA are primarily diagnosed in the advanced stages, when treatment is less effective or ineffective. For this reason, improved screening approaches to select HFpEF patients for diagnostic PYP scans are necessary. One possible approach is suggested by the fact that musculoskeletal manifestations, including carpal tunnel syndrome and lumbar spinal stenosis, are associated with ATTR amyloidosis. Sarcopenia, a related condition that can be identified by body-composition analysis on CT images, is emerging as a novel pathophysiological and risk marker of HFpEF and other aging disorders. In addition to HF, ATTR deposition in the gastrointestinal tract is known to impact nutritional status and, consequently, muscle mass. If ATTR amyloidosis is, indeed, a common pathophysiological link between sarcopenia and HFpEF, then screening for PYP-SPECT on the basis of presence of sarcopenia may be an effective strategy.   

ASNC: In your proposal, you wrote that you expect quantitative PYP SPECT/CT with a novel CZT-based 360-degree scanner will be capable of identifying early ATTR-CA. Why this imaging technique?

VS: Current visual or semi-quantitative approaches to PYP scan interpretation, while adequate for diagnosis, are inadequate for identification of early ATTR-CA.  Recent advances in SPECT instrumentation and reconstruction, with effective corrections for attenuation and scatter, as well as resolution recovery, have substantially improved accuracy, leading to an increased interest in absolute quantitation by SPECT.
Newer solid-state detector-based systems are promising for quantitation, as they offer improved spatial and energy resolution. Some have 360-degree geometry, eliminating the need for detector rotation and improving sensitivity. The state-of-the-art imaging lab at Brigham and Women's Hospital is equipped with the country's first CZT-based 360-degree scanner, and we expect that quantitative PYP SPECT/CT using this novel latest generation scanner will be capable of identifying early ATTR-CA.
ASNC: This project builds on earlier studies you have been involved in and may lay the groundwork for a larger, longitudinal study. Would you speak to your longer-term research goals? How might the answers you uncover impact patient care? 
VS: This proposal has the potential to substantially increase identification of ATTR-CA in older adults with HFpEF who may benefit from novel ATTR therapies. A quantitative PYP metric for early ATTR-CA will be developed for the first time and validated against ECV. This may enable PYP imaging to not only diagnose advanced ATTR-CA but also diagnose early ATTR-CA and response to therapy. This highly innovative proposal evaluates a machine-learning-based CT-based body composition metric, a previously unexplored screening tool for ATTR-CA. The results of this study will pave the way for improved screening strategies and prevention strategies for heart failure from ATTR-CA (e.g., diet, exercise). We hope to generate preliminary data to support a large multicenter/cross-sectional study of sarcopenia in ATTR-CA.
ASNC: This isn't the first time you have been recognized on the ASNC stage. How have your 2018 Young Investigator Award (YIA) and participation in ASNC initiatives, such as this year's Nuclear Cardiology Virtual Elective, helped to advance your career? Are there other ASNC opportunities you are eyeing? 
VS: Thanks for the question. ASNC, as an educational society, has provided me with distinctive opportunities to showcase personal research interests to the best in the field, which promotes future collaborations. Winning the 2018 YIA award offered a young aspiring cardiovascular researcher like me the chance to engage an audience that comprises the world's leading cardiovascular professionals in interactive discussions and receive global appreciation.
I have been an active participant in several ASNC activities since my initial general cardiology fellowship years, and they have definitely had a very encouraging impact on my early-career development as an academic imaging cardiologist.
Since you asked, another ASNC opportunity that I am “eyeing” is the ASNC Leadership Development Program. If I am accepted, it will give me a wonderful opportunity to satisfy personal aspirations of making a difference in the field of nuclear cardiology and the ability to truly follow my heart!
ASNC: Good luck with your project. ASNC is looking forward to your results presentation at ASNC2021. Is there anything else you would like to share before getting to work on your project? 
VS: Thank you! This interview cannot be complete without thanking ASNC for this distinctive scholastic opportunity and acknowledging the unparalleled mentorship of Dr. Sharmila Dorbala. Despite a busy schedule, Dr. Dorbala is always generous with time and guidance for her mentees, and I am grateful to be one. I often find that her passion kick-starts my own assessment of where I want my professional journey to take me. I'm confident I'll continue to gather important experiences from such avenues and hope to continue to be a part of the ASNC family for the rest of my professional career.

The ASNC2020 session "Amyloidosis – Best Practices" will convene today, Sept. 25, at 3:25 AM (EDT). The session will be moderated by Donna M. Polk, MD, MPH, FASNC, and also will include presentations by Frederick L. Ruberg, MD, Jamieson Bourque, MD, FASNC, Omar F. Abouezzeddine, MDCM, and Dr. Dorbala. 

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