Improving outcomes for heart disease patients was the focus of studies by Jae Hyung Cho, MD, PhD, and Lily K. Stern, MD, who in May won the 2021 Cedars-Sinai Clinical Fellows Award for Excellence in Research.

"This award aims to foster clinical and translational research, enrich knowledge and encourage the development of our clinical fellows as investigators," said Mariko Ishimori, MD, assistant professor of Medicine, Committee Chair for the Clinical Fellows Research Award Programand associate director of the Cedars-Sinai site of the UCLA Clinical and Translational Science Institute.

She noted that despite the challenges posed by the COVID-19 pandemic, which led to cancellation of the annual award last year, many high-quality abstracts were submitted for review, from which four finalists were chosen.

At the May 11 virtual event, the finalists presented their work to a panel of judges, who later announced the two winners.

Cho's presentation focused on heart failure with preserved ejection fraction, which Cho said accounts for about half of diagnosed heart failure cases. More than 6 million U.S. adults have heart failure, which occurs when the heart cannot pump enough blood, according to the U.S. Centers For Disease Control and Prevention.

Death rates are high for heart failure with preserved ejection fraction—just 25% survival after five years. There are no treatments available that increase life expectancy for people diagnosed with this type of heart failure, Cho said.

Inflammation is thought to be behind disease progression, so Cho and fellow investigators treated laboratory rats with heart failure with preserved ejection fraction by using tiny particles called exosomes that were isolated from human cardiac progenitor cells, which regulate inflammation.

The results showed that these exosomes:

• Preserved diastolic function
• Improved exercise capacity
• Reduced development of abnormal electrical signals in the heart
• Reduced systemic inflammation
• Decreased ventricular fibrosis, a buildup of inflexible fiber-like tissue in the heart's ventricular chamber

Noting that exosomes are stable, durable and easy to store compared with cells, Cho called the results, if confirmed in humans, "very promising for next-generation therapeutics."

Cho's mentors were Eduardo Marbán, MD, PhD, professor of Medicine, Mark Siegel Family Foundation Distinguished Chair and executive director of the Smidt Heart Institute; and Eugenio Cingolani, MD, assistant professor of Cardiology and director of Preclinical Research and the Cardiogenetics Program at the Smidt Heart Institute.

Reflecting on how his work and outlook have been affected by the tumult of the past year, Cho said: "I am a physician-scientist and have always believed in science. But when COVID-19 appeared and our society was shut down, it made me question the power of our science. One year later, however, our fellow scientists developed vaccines, and we have the ability to control these tiny viruses. I am excited when I dream of carrying out research that will change the world for my children."

Stern, a second-year cardiology fellow, presented her recent research on the impact of the 2018 revision of the United Network's donor heart allocation system. The allocation system is a protocol that determines who among many ill patients will first receive life-saving heart transplantation surgery.

The revised allocation system was intended to better prioritize transplantation of the sickest patients listed for heart transplantation and thereby reduce mortality while they wait for transplant. However, by transplanting the sickest patients on the wait list, there was concern there would be worse morbidity and mortality post-transplant.

Under the mentorship of Michelle Kittleson, MD, PhD , professor of Medicine, Stern and fellow investigators performed a single-center retrospective study at Cedars-Sinai's high-volume heart transplant center involving 169 adult patients. They were divided into two groups: those who underwent first-time, single-organ heart transplantation under the old allocation system and those who underwent transplants after the system changed.

Stern said analysis of the data showed that under the new donor allocation system, patients who underwent heart transplantation were higher risk with greater rates of mechanical circulatory support requirements, and they waited a shorter amount of time on the wait list prior to transplant. The study further confirmed that there was no significant difference in mortality between those transplanted in the year after the allocation system change as compared to those transplanted in the year before the allocation system change despite transplantation of a sicker population of patients.

Stern said that the findings indicate that with careful patient selection, the revised allocation system may optimize wait list and post-transplant outcomes for patients needing heart transplant surgery.

Stern also reflected on the past year, saying: "It was amazing to see researchers come together to rapidly chip away at important questions to provide guidance for clinicians on the front line. This year has given me a deeper appreciation for people who have and continue to devote their time to research, which is the glue that holds our clinical practice together. This year emphasized to me how community, as well as acts of kindness and compassion, can fill our tanks, even when we are running on empty."

Ishimori concurred, saying: "I want to commend the hard work and resilience of all of our applicants, who adapted to the difficult circumstances of the past year to continue to conduct high-quality research, regardless of the challenges that they may have faced."

Each winner received a $3,000 cash prize funded by the Burns and Allen Research Institute at Cedars-Sinai and the Cedars-Sinai site of the UCLA Clinical and Translational Science Institute.

The two other finalists were Stephanie Wu, MD, who presented work on long-term outcomes for women with ischemic heart disease, and Neal Yuan, MD, who discussed the efficacy of remote cardiology clinic visits in the COVID-19 era.