The Fellows: A Closer Look

Duke University
SFRN Heart Failure Fellow, 2016-2017

The high global mortality rate in heart failure patients is alarming to Abhinav Sharma, MD.

That’s why the American Heart Association Heart Failure Strategically Focused Research Network at Duke University appealed to him. He focuses on diabetes and heart failure patients, and how advances in digital health and technology can improve understanding and therapies.

As a fellow, Dr. Sharma said the SFRN allowed him to lead several projects and to be part of a bigger series of collaborations that extended beyond his time at Duke.

“It certainly has opened up many years of collaboration and many years of opportunities to work with my mentors and to really network amongst a lot of the other sites,” said Dr. Sharma, now an assistant professor in the Department of Medicine, Divisions of Cardiology and Experimental Medicine at McGill University in Montreal, Quebec, Canada.

At Duke, Dr. Sharma worked on population and digital health care studies. He helped design the digital program, learned about site management and wrote the methods paper.

Several hundred people recruited from outpatient clinics wore devices and were monitored using an app to gauge physical activity and medication adherence and to prompt them to move more. They were also followed when intervention efforts were withdrawn to see if those behaviors persisted. The Duke studies also focused on the safety and efficacy of anti-hypoglycemic drugs that many of the patients used.

“My hope was that I would be involved in a project that actually has real-world benefits and real-world applicability — and, certainly, the digital health project has a very specific real-world impact, because if we show that it’s beneficial, then it can be scaled and made available to a lot of people,” Dr. Sharma said.

Many experiences with the SFRN have translated to his major research interest at McGill: digital health in diabetes and heart failure. Investing in the future of medicine and training well-rounded researchers is a hallmark of the SFRN system.

“It really gives fellows and early-career researchers an opportunity to take ownership of a project that can build the foundation of their career,” he said. “I think there are certainly a lot of avenues to explore. And to conduct a project that’s funded, and to see it through from beginning to end, I think that’s a really powerful part of the SFRN.” The emphasis on collaboration and mentorship is also key.

“With every AHA meeting, when we would connect around the SFRN and hear what everyone was doing around the different sites, it sparked so much discussion and opportunity for new research and collaboration,” said Dr. Sharma, who also won an AHA Get With The Guidelines Award.

University of Colorado Denver
SFRN Heart Failure Fellow, 2016-2017

The American Heart Association’s Heart Failure Strategically Focused Research Network was a perfect fit for Khadijah Breathett, MD.

While a fellow at the University of Colorado Denver Center, Dr. Breathett explored how to improve medication-based therapy for patients with heart failure — matching her interest in racial and ethnic disparities in health care.

As a fellow in the Heart Failure SFRN, she focused on population studies and assessed hospitalization information on thousands of patients across the U.S. She looked at whether race impacted cardiologists’ care for patients, particularly among the sickest requiring an ICU stay for heart failure. “We found that, unfortunately, it did,” she said, along with other factors such as hospital size and location and comorbidities.

“Consistently, there was the same finding where, if you were a black patient, you were less likely to receive care by a cardiologist than if you were a white patient. If you were a black male patient, you were the least likely of all the different groups to receive care by a cardiologist”, she said.

Dr. Breathett, who participated in weekly Colorado Cardiovascular Outcomes meetings, said her role in the Center and the information shared with colleagues across the Network helped develop her career. She is an advanced heart failure and transplant cardiologist, physician scientist and assistant professor of medicine at the University of Arizona College of Medicine – Tucson.

She has received an NHLBI grant, known as a K Award, to explore the best ways to address racial disparities in health care. And in 2019, the National Minority Quality Forum selected Breathett as one of the 40 Under 40 Leaders in Minority Health. Dr. Breathett is also an AHA Oversight Advisory Committee member, giving her insight into the benefits of SFRNs and similar projects from multiple sides.

She said the AHA welcomed her, providing focus areas — disparities and equity in cardiovascular care — that she cared about. “They provided the opportunity to serve and lead in ways that can change clinical care and lead to better health care delivery.”

“And I’d say, as a long-term member, I am happy to see how the AHA has continued to stand behind its mission to seek cardiovascular health equity for all groups.”

Massachusetts General Hospital
SFRN Heart Failure Fellow, 2017-2019

Dr. Haobo Li was completing his Ph.D. in Hong Kong when he heard about the American Heart Association Heart Failure Strategically Focused Research Network.

He jumped at the chance to participate because of its unique and exciting three-part configuration. His first postdoctoral fellowship in the U.S. would allow him to collaborate with researchers from basic, clinical, and population science disciplines. In the basic science study at Massachusetts General Hospital, Dr. Li and his colleagues focused on animal models to investigate the role of micro-RNA in cardiac hypertrophy, the thickening of the cardiac muscle.

The aim was to determine how long non-coding RNAs factor into both cardiac hypertrophy in response to exercise and disease. Physiological cardiac hypertrophy is a healthy response to exercise and can protect against stress. Pathological hypertrophy occurs in disease and often precedes heart failure.

Dr. Li and his colleagues explored why different types of hypertrophies can affect the heart and how each is influenced by different molecules and micro-RNAs.

Sharing clinical sample data with the University of Colorado Center in Denver and others helped him and his colleagues look for similarities or trends between basic and clinical studies.

“It’s good to collaborate with different centers to increase the number and diversity of samples you can have, which can strengthen your findings and make them more generalizable,” he said.

“We can share information to not only give us the chance to learn from different people, but it can also provide the opportunity to expand your network.” Dr. Li, now an instructor in medicine at the Cardiovascular Research Center, Massachusetts General Hospital/Harvard Medical School, said his current work is an extension of his research with the Heart Failure SFRN.

“We’re looking in more detail at this long noncoding RNA that we identified from the SFRN project that we would like to explore further for cardiovascular disease and heart failure,” said Dr. Li, who also received an AHA Career Development Award based on his research and an AHA Abstract Travel Award in 2019.

University of Utah
SFRN Heart Failure Fellow, 2017-2019

Dr. Yuan Zhang’s interest in cardiovascular research was piqued at an early age. She was about 12 years old when both her grandparents in China died of heart attacks, but their doctors couldn’t give concrete answers for the causes.

She turned that interest to her undergraduate studies at the University of Beijing and Ph.D. work at Peking Medical College, where she focused on the intricacies of heart disease and cardiovascular disease related to mitochondrial dysfunction.

Heart failure is particularly important to research, given the high cost, lack of effective treatments and high death rates, says Dr. Zhang. As soon as she heard about the Heart Failure Strategically Focused Research Network at the University of Utah Center, she was interested in the SFRN fellowship.

“The networking and the collaboration are impressive not only because we have the collaborations in the same institution, but also we exchange the studies’ progress and we got some suggestions” from other centers, Dr. Zhang said.

She said it was helpful to meet with other fellows and field their questions. “Some questions might be tough, but at least, for this network, discussing questions in small groups” helped her “understand it better and find my future direction.”

In the University of Utah’s basic science project, Dr. Zhang investigated how glucose and pyruvate, a byproduct of glucose metabolization, affects heart failure in mice and how an altered diet could prevent or reverse negative effects.

The project involved deleting MPC, or the mitochondrial pyruvate carrier, in adult mice and embryos. When researchers deleted the protein, the heart failed — a finding with possible serious implications for heart failure in people.

Dr. Zhang was shocked at how effective — and fast — dietary changes were in mice who had already exhibited enlarged and failing hearts. “MPC is important for the heart to continue beating and using glucose efficiently,” she said. “We tried to rescue the failing heart by providing it another substrate. So, we tried to feed the mice with a ketogenic diet.”

Success, even at late stages of heart failure, was “pretty dramatic” and “outside of my expectations,” she said. Some mice model hearts returned to normal within two months.

“From the beginning, I felt like there might be some beneficial effect,” Dr. Zhang said. “The mice may live longer on this because we are providing it with other substrates it can use. But I was surprised to see, wow, they just came back to normal.” Further research must be conducted to delve deeper into the phenomenon and the translatable consequences for human patients.

Dr. Zhang is already doing that at the University of Iowa, where she is an instructor in the Roy J. and Lucille A. Carver College of Medicine. She has also applied for an AHA Career Development Award. Her findings and experience in the SFRN have further fueled her determination to learn more about heart failure, especially the roles of other “interesting molecules” identified in the basic study. “There are more questions coming out, so it’s not like the end,” she said. “It’s a milestone to keep working on.”