SFRN Centers: Heart Failure

Center Director: Michael Felker, M.D.

The Heart Failure Strategically Focused Research Network Center at Duke University focused on the link between diabetes and heart failure and whether diabetes drugs could treat the latter.

“There has been increasing recognition that there’s an interaction between patients with heart failure and the presence or absence of diabetes that affects heart failure patients’ outcomes — and also their response to therapy,” said Michael Felker, M.D., Center Director at Duke.

Dr. Felker and his team explored how mitochondria and muscle cells interact, use glucose and metabolize similar “substrates,” or fuel for the body. Researchers in the basic, clinical and population studies investigated tissue from patients with both conditions, monitoring how physical activity could improve the health of sedentary patients and researching the effects of different patterns of drug therapy.

One class of drugs was “OK” for diabetes, but “an extremely effective heart failure medication, whether or not you have diabetes,” Dr. Felker said.

“The link between diabetes and heart failure has gathered momentum within the medical community since Duke began its SFRN — but merits much more attention in light of the prevalence and relatively limited knowledge of heart failure,” Dr. Felker said.

“There has been a lot of progress on research into heart failure, but I think it’s only going to need to be more and more,” he said. “A key thing is: How do we get people using the right treatments in the most effective way consistently?”

“We still know there’s a big gap between what we know is out there, best therapy and what’s actually happening in the real world.” He added that programs and organizations such as the SFRN and AHA are fundamental to fueling research and enhancing scientific developments.

“AHA is both an advocacy organization — funds research, does public health awareness campaigns — and it has physician members, volunteer members, patients,” he said. “It really brings together in one organization a lot of the different stakeholders for cardiovascular health.”

Center Director: Peter Buttrick, M.D.

The goals of the SFRN aligned well with the expertise of many scientists at UCD, according to Peter Buttrick, M.D., Center Director.

“We liked the idea of bridging the gap between basic and population science,” he said. “We try to think very broadly and translationally, so it was consistent with our general approach to scientific discovery. We were blessed in having experts in heart failure in all three domains.”

Researchers looked at cellular mechanisms affecting heart function, drug therapies and genetic links, focusing on whether certain genes or “families of genes” could be manipulated or blocked to prevent heart dysfunction or heart failure.

Researchers also looked “for small molecules that were novel that would influence expression and binding of these particular domains and would, by extension, influence the expression of families of genes,” Dr. Buttrick said.

Like Duke, UCD researched new medications and discovered several drugs that seemed promising in preventing heart failure in animal models.

“We were trying to identify gaps in therapy, which is to say our current therapy’s not perfect,” Dr. Buttrick said. “We know a lot about how to treat heart failure, but there are a large number of patients who don’t do very well. We thought there were biological pathways that could be exploited to develop therapeutic agents.

Center Director: Anthony Rosenzweig, M.D.

Anthony Rosenzweig, M.D., Center Director and Chief of Cardiology of the Corrigan Minehan Heart Center at Massachusetts General Hospital, called heart failure the “cancer of cardiology.” MGH focused on finding molecular clues for curing it.

Much of the research focused on the role and possible use of RNA molecules. While scientists know those molecules create proteins, MGH also explored the function of RNA that didn’t.

“It turns out RNA does an enormous number of things,” Dr. Rosenzweig said. “They control whole genetic programs. We were focused on studying that kind of molecule and understanding how it might be used in both clinical and basic research to work on heart failure.”

We showed RNA in the blood could be a biomarker for developing heart trouble and identified RNA pathways that could potentially regenerate heart muscle.

MGH studied blood from a diverse group of patients using large-scale sequencing techniques, in addition to looking at patients who had recovered from heart failure and their traits.

The basic study also focused on molecular effects on the heart in small animal models and “found a couple of molecules that could prevent or even restore function,” said Dr. Rosenzweig, adding the team looked to apply the findings to larger animals and human cells.

Most therapies for heart failure “slow the decline and mitigate the disease but don’t really reverse or repair the damage that’s occurred in the heart — so it’s a huge unmet clinical need,” he said. “What this program did was bring together a lot of people interested and focused on this.”

As a physician scientist, Dr. Rosenzweig said the SFRN provided unique opportunities for medical advancements, teaching and collaboration.

“I think most of us who have a foot in the clinical world and a foot in the research world recognize that for us to come up with new therapies and approaches that improve the kind of care we can deliver for our patients, it takes collaboration across these disciplines from people who do very fundamental discovery to people who do clinical studies and population science,” he said.

“One of the things I think is unique about the SFRN program is this explicit mandate to bring in people who really address each of those areas to work together in a collaborative way within a center in the hope of making transformative discoveries and moving them forward.”

Center Director: Craig Selzman, M.D.

SFRN researchers at the University of Utah focused on discovering “why bad hearts get good,” said Craig Selzman, M.D., Center Director.

“A lot of people spend a lot of time figuring out why a good heart becomes a bad heart,” said Dr. Selzman, noting that his team attempted to do the opposite and looked at why some patients may recover without a transplant.

“When you have a really bad heart, there’s a discreet population of patients, when supported with devices, in which the heart muscle recovers its function and we can actually remove the devices and avoid a heart transplant altogether,” he said. “So, we have been curious for over a decade to study this population.”

The SFRN “really resonated with what we were trying to do locally at the University of Utah,” Dr. Selzman said. “It was a good opportunity for us internally to try to unify our message and our efforts. The bonus was that we were going to get to hang out with a few other centers that were like minded, with the glue being the AHA.”

The Utah team reviewed thousands of patients’ histories in addition to investigating biological and metabolic factors. In mice, researchers studied the impact of genetic deletions and whether manipulations could aid heart recovery. In humans, they also tried to devise a scoring system to indicate heart problems for clinicians that could be widely adopted and almost considered as another “vital sign”.

It helped that other centers worked on related topics.

“Having four centers actually was a nice number; it wasn’t too small, but it wasn’t so big that things got lost,” Dr. Selzman said. “Over the course of the project period, everybody had a good feeling about what the others were doing. And then it allowed the natural integration of ideas.”

“I think it was a brave, courageous move by the American Heart Association, and obviously the concept’s working.”