Women of the Heart – Aligning Research from Bench to Bedside

By Eric Swedlund –

With a new director at the helm, the University of Arizona’s Sarver Heart Center is moving forward on an expanded research mission – aiming to increase clinical trials and translate molecular and genetic discoveries into innovative therapies.

Dr. Nancy K. Sweitzer, who took the reins on March 1, is the first woman to lead the Sarver Heart Center, which was founded as the University Heart Center in 1986.

Only about 15 percent of cardiologists nationwide are women – which makes the Sarver Heart Center stand out – with Sweitzer, co-director Carol Gregorio and renowned researchers like Dr. Jil Tardiff.

“The concentration of female leadership here is incredible and very unusual in medicine. It makes for a very vibrant atmosphere and it was definitely attractive to me looking at this position,” Sweitzer said.

“The fact that we have women here in prominent roles will certainly help us draw other exceptional women to Arizona. It creates a culture where women see role models and thus are attracted to stay in that environment and, over time, are groomed for leadership themselves.”

The Sarver Heart Center membership includes more than 30 women physicians and scientists among its 170 members – women who are conducting clinical and basic science research focusing on heart disease, stroke, diabetes, nutrition and exercise.

Sweitzer takes over for Dr. Gordon Ewy, who was recruited to join the fledgling College of Medicine in 1968 as one of the founding fathers in cardiology. He took over as director of the University Heart Center in 1991 and led an era of fundraising that gathered donations from the Sarver family and many others, leading to 13 endowed chairs.

Perpetual sources of funding
The endowments create dedicated, perpetual sources of funding that allow for strategic, prestigious hires – like Tardiff, an expert in hypertrophic cardiomyopathy, one of the most frequent causes of sudden cardiac death. Tardiff, a dual M.D. and Ph.D., was recruited away from the Albert Einstein College of Medicine in New York to serve as the first Steven M. Gootter Endowed Chair for the Prevention and Treatment of Sudden Cardiac Death.

“I’ve looked at a number of chief of cardiology jobs around the country and as chief of cardiology, like the chairman of anything these days, you’re expected to do more with less. Doctors are working harder and often making less, and research is very hard now because the NIH (National Institutes of Health) budget is so poor,” Sweitzer said.

“But the unique thing about the Sarver Heart Center was the philanthropic aspect and the tremendous involvement of the donor community in maintaining heart disease research – even in these lean times. The intensity and dedication of that group – and the support the faculty feel – made it a very attractive opportunity. That extra dimension that exists here is really rare and really special to Tucson.”

Sweitzer, like Tardiff, is a dual M.D. and Ph.D. She said several particular strengths of the Sarver Center drew her in – including the UA’s storied history in heart transplants and the development of the artificial heart, the world-renowned muscle biology group, a growing bioinformatics effort, and collaborations not only with other medical colleges, but with main-campus researchers in engineering and optics.

Enormous opportunities for collaboration
“I am a very collaborative person, a very multidisciplinary person,” she said. “I’ve increasingly become the bridging person. My own research has expanded in a way that involves collaboration with radiology. I’ve done collaborative work with the School of Nursing in Wisconsin, and I’m starting to build those bridges with the College of Nursing here.

“I’ve done collaborative work with engineers and obviously that’s attractive at the University of Arizona. Cardiology is very attractive to engineers. We do a lot of electrical and mechanical research. You can usually get biomedical engineers excited about it and they add an exciting and innovative dimension to the work.”

Sweitzer said the UA’s heart muscle cell biology group is probably the best in the world – but hasn’t been able to fully translate that work into human disease models until recently.
“So there’s an enormous opportunity there for collaboration that will be truly translational and impact care of patients with heart disease,” she said.

Gregorio, who served as interim director of the Sarver Center after Ewy’s July 2013 retirement and chaired the search committee that selected Sweitzer, directs the Molecular Cardiovascular Research Program and is the Luxford/Schoolcraft Endowed Professor of Cardiovascular Disease Research.

Research at the molecular level
A specialist in how proteins in the heart’s cells control contractions of the muscle, Gregorio is an integral part of the translational research – which aims to align research from “bench to bedside,” solving questions on a continuum from molecules in the basic laboratory to individual patients.

“One thing that is relatively unique as far as our mission and our focus is to get clinical and basic researchers to collaborate more,” Gregorio said. “That’s a general direction that’s very important. With NIH funding now, they emphasize this translational focus. It’s really hard to be good at everything, but we have an amazing amount on both sides.”

Gregorio’s research, combined with the collaborative efforts of other world-class scientists and physicians at the Sarver Heart Center, works to build a greater understanding of the development of the heart at the level of individual molecules, so that mutations that cause disease can be identified at their very beginning.

“What we try to do is figure out why disease occurs, how a mutation goes from a protein alteration to the clinical problem – and we’re making huge progress on understanding what goes wrong,” Gregorio said. “That will allow us and others to design screening, therapy and hopefully repair for heart disease. That will have huge impacts.”

So while the Sarver Heart Center’s history includes some of the world’s greatest advances in transplants and artificial hearts, as well as the now widely accepted chest-compression-only CPR Ewy is known for, Gregorio and Sweitzer envision a future in which problems can be caught and treated long before cardiac arrest occurs.

How does genetic mutation cause a disease?
“We’re going from the whole organ to the molecular level, going back to say what caused cardiac arrest? Can we screen for it?” Gregorio said. “We study heart development. It’s very important when you think about congenital disease or when things go wrong during early human development. How do genetic mutations cause a disease?”

The vast amounts of data required to perform scientific research at the genetic level requires a greater collaboration with bioinformatics and biostatistics – evolving fields that are finding themselves aligned more with translational research than their theoretical pasts.

“Historically, university departments of biostatistics are filled with biostatisticians who are doing math discovery,” Sweitzer said. “They’re coming up with new ways to analyze things and that’s how they built their careers. It doesn’t help them in their career development to help the scientists with discovery – and that’s a problem. Finding a biostatistician who will dedicate time and thought and effort to (our research) has been difficult historically – but in the last 10 years, biostatisticians have figured out there’s a great deal to be discovered in these collaborations.”

Sweitzer is seeking faculty members in medical departments who have backgrounds in bioinformatics as well as crucial skill sets that combine big-data management and medical understanding.

“You’ll see faculty moving here who bridge those skill sets as well as bioinformatics faculty who have medical backgrounds and become integral team members in patient-oriented research,” Sweitzer said.

Opportunity for “big leap” in clinical trials
The Sarver Heart Center is committed to UA President Ann Weaver Hart’s goal of doubling university research activity by 2020, and Sweitzer is looking to clinical trials as one area that has an opportunity to make a big leap.

“The doubling of the research enterprise at the Sarver Heart Center, in the beginning, is going to be in the clinical and translational areas – where we take things the scientists are discovering and put them into patients,” she said.

“Dr. Sweitzer is nationally recognized for her strong leadership and experience in clinical research,” said Dr. Joe G.N. “Skip” Garcia, senior VP for health sciences and professor of medicine at the UA. “These unique talents will help her build impactful bridges between the clinical and basic science enterprises, and increase discovery in the areas of translational and personalized
cardiovascular medicine.”

Sweitzer is a board-certified advanced heart failure and transplant cardiologist with her Ph.D in physiology. She said her focus has always been on providing the best care to the sickest patients with heart disease.

“From my perspective, what I need here are patients. We need patients so we can have opportunities to try new therapies on people with the diseases,” Sweitzer said. “What I see myself inheriting is a really strong scientific enterprise here – but one that is very basic and not very patient-oriented on a day-to-day basis.”

Despite the size of Tucson and the size of the UA, the clinical enterprise at the Sarver Heart Center – with doctors actively seeing patients – is relatively small.

“My first priority is to expand the clinical operation to see more patients, to bring more people in and deliver excellent care to those people,” Sweitzer said.

“Simultaneous to that is building a clinical research infrastructure and operation so every patient who comes in who is eligible gets offered the opportunity to participate in a trial of a new therapy or a change in the way we diagnose or treat heart disease.”

The infrastructure historically for clinical trials at the Sarver Heart Center has been a bit rudimentary, Sweitzer said. Some investigators have been very successful, but everybody built what they needed individually to be effective. To boost clinical trials, Sweitzer will build a clinical infrastructure available for all faculty to use, with experienced clinical trial nurses and staff to draw on.

Looking for genetic markers
“It will give the patients at the University of Arizona and the Sarver Heart Center access to more cutting-edge therapies in heart disease,” she said. “I’m hoping we can get a group of patients who are getting terrific, state-of-the-art cardiovascular care but the opportunity also to see what’s coming and participate in that.”

For an example of the opportunity in larger clinical trials, Sweitzer pointed to one national project in which she participated – a longitudinal study of more than 4,000 heart failure patients that looks for genetic markers that can predict the course of the disease.

“There’s tremendous potential. As we’ve gotten into the molecular intricacies of the disease, we’re getting smarter. It’s not just the gene – but it’s what happens to that protein when it’s made and how it’s modified afterward,” she said.

“I’m really excited and I’m hoping to build, along with Dr. Garcia, scientific strengths in this area so that we can start drilling down at the individual level to what are the molecular abnormalities in a patient’s heart disease and how we can address those so your heart works best.”

Though the terms elsewhere might be individualized or personalized medicine, the preferred name at the UA is precision medicine – which better connotes the alignment between diagnostics and treatment.

“The therapy right now is if you have clinical heart failure and you meet two or three features, you get the same five drugs as everyone else. They work in most people – but not everyone,” Sweitzer said. “It’s very imprecise now.”

Next generation of scientists
Another priority for the Sarver Center is improving the competitive rankings of the graduate programs and attracting students who will boost the reputation of the Sarver Heart Center and the University of Arizona as they begin their own research careers.

“We’re really focused on the next generation of scientists, the students we teach. One initiative is to bring in stronger graduate students and build the program. They’re the ones that leave and build their own labs for cardiovascular research,” Gregorio said. “When a donor asks me how to make a big impact, I suggest giving money for cutting-edge research and for training the next generation of scientists.”

Sweitzer also has a leadership development agenda that spreads across the Sarver Heart Center. Those goals include teaching doctors to communicate better – and to approach research, patient care and education in a more scholarly way, learning and improving every day.

“The one word that guides whatever I do is excellence. My philosophy is no matter how good you are, you can always be better,” Sweitzer said. “I’m going to strive for excellence in all phases of our operation – from delivery of care to the research enterprise to the philanthropic enterprise to our educational enterprise. We’re going to examine everything we do and work to do it better.”