Faculty Spotlight: Roselle Abraham, MD

Dr. Maria (“Roselle”) Abraham has a bold vision: discovering what causes hypertrophic cardiomyopathy (HCM), and finding ways to cure or even prevent it. HCM is the most common inherited form of heart disease, and occurs when the heart muscle becomes overly thickened, making it harder for the heart to pump blood. It can also create problems in the heart’s electrical system, sometimes causing life-threatening arrhythmias, or abnormal heart rhythms. Tragically, HCM can kill young athletes and others who appear completely healthy.

Rather than being one disease, Dr. Abraham and her colleagues are discovering that there are likely several varieties of HCM, with different causes and degrees of severity. “Some patients with HCM can just get medical therapy and do very well,” she said. “Others have what we call ‘malignant phenotypes,’ and might die of arrhythmias or develop heart failure requiring heart transplantation. It’s important to identify those patients who will do poorly, and figure out individualized therapies to prevent complications.”

Stress and Scarring

Dr. Abraham was born in Goa, India, and followed in her great-grandfather’s footsteps, graduating from Goa Medical College. During medical school, a friend in his 20s died unexpectedly, probably from sudden cardiac death. “I thought, ‘I want to study heart rhythm problems,’ but I didn’t realize until I came to the U.S. that there was a field called electrophysiology,” she said.

She completed her internal medicine internship at Wake Forest University in Winston-Salem, N.C., and her internal medicine residency at Parkland Hospital, the public hospital in Dallas affiliated with the University of Texas Southwestern. During her cardiology fellowship at the Mayo Clinic in Rochester, Minn., she was mentored by Dr. Andre Terzic, a stem cell and regenerative medicine pioneer. She gained her first research experience in his lab, studying something called the KATP channel, which plays an important role in linking metabolism, energetics and cell excitability – the ability for electricity to transmit electrical impulses. Among other projects, she was able to measure electrical currents and voltage in live cells.

During her clinical training at the Mayo Clinic, she cared for many patients with HCM. How exactly HCM develops is not well understood, but some studies have suggested that genetic mutations in HCM patients produce inefficient heart muscle cells, or myocytes.

“The hypothesis is that the myocyte consumes more energy to do the same amount of work, which imposes a stress that can affect the electrical properties of the heart and cause arrhythmias,” said Dr. Abraham. “If you already have an inefficient system and you stress it, it can give out.” Many HCM patients also experience buildup of scar tissue, also called fibrosis, in their hearts, which can contribute to arrhythmias. “We want to figure out what’s driving the disease so we can arrest or even prevent it,” she said.

Collaborations and Lifelong Learning

During her 15 years at Johns Hopkins University School of Medicine in Baltimore, she and her husband, Dr. Theodore (“Ted”) Abraham, founded the Johns Hopkins Hypertrophic Cardiomyopathy Center of Excellence, and built a multidisciplinary team to learn more about HCM.

Her collaborators included radiologists who conducted magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of patients’ hearts, biomedical engineers who developed computational models of myocytes to better understand the relationship between metabolism and energetics, and biophysicists who used a three-dimensional printer to produce more true-to-life tissue models. She also partnered with a computer scientist at the University of Delaware to apply machine learning approaches to their clinical database of 1,500 HCM patients, trying to suss out hidden patterns that might predict which HCM patients would develop arrhythmias.

“My mentor at Hopkins, Dr. Eduardo Marban, taught me a lot about being fearless, figuring things out, and collaborating with people to go to the next step,” said Dr. Abraham.

She also challenged herself to learn new skills, taking classes at Hopkins in everything from optical mapping to microbiology and multi-modality imaging. “The ability to learn things I didn’t know anything about, then forge collaborations with experts towards a common goal, was key,” said Dr. Abraham. “I will learn whatever technique it takes to answer a question – that’s the way I approach research.”

Dr. Abraham decided to join the UCSF faculty partly to take her collaborative approach to the next level. For example, she is working with the world-class UCSF Department of Radiology and Biomedical Imaging, using new non-invasive imaging technologies to learn more about how both normal and diseased hearts process energy. These include hyperpolarized carbon-13 MRI and combined PET/MRI scans. “These are emerging technologies which have mostly been used to study cancer, but we’d like to apply them to the heart,” she said. “UCSF is one of very few centers in the world that has these tools.”

Building on their work at Hopkins, Dr. Abraham and her husband are now establishing a Center of Excellence for HCM at UCSF. She is the center’s director, and he is the co-director. The center will perform an intense evaluation of each patient, develop a treatment plan, and partner with referring cardiologists to ensure that patients are as stable and free of symptoms as possible. They will also provide genetic counseling to help determine which other family members may be at risk for HCM.

The center will also include a robust research program. Dr. Abraham is partnering with the San Francisco Veterans Affairs Medical Center to study biomarkers; Zuckerberg San Francisco General to investigate the health of the inner lining of blood vessels, called endothelial function; Dr. Jeffrey Olgin, chief of the Division of Cardiology and Gallo-Chatterjee Distinguished Professor of Medicine, and his electrophysiology colleagues on the use of animal models; Dr. Bruce Conklin at the Gladstone Institute of Cardiovascular Disease on stem cells; and UC Davis to study cardiac metabolomics, specifically both normal and disordered ways that the heart uses energy.

HCM and Atrial Fibrillation

One of the major focuses of Dr. Abraham’s work is the connection between HCM and atrial fibrillation – an abnormal heart rhythm in the upper chambers of the heart which causes the heart to quiver instead of pumping efficiently. Atrial fibrillation is different from ventricular arrhythmias, which can cause sudden death but can be prevented by implanting a cardiac defibrillator to shock the heart back into a normal rhythm. “Atrial fibrillation doesn’t kill you, but it can be very difficult to prevent atrial fibrillation or its complications,” she said.

Atrial fibrillation contributes to heart failure, a condition in which the heart is not able to pump enough blood to the rest of the body. This can cause patients to be fatigued, dizzy and short of breath. Atrial fibrillation is also associated with a higher risk of stroke, because sluggish blood may pool in the heart and form clots, which can travel to the brain.

A high proportion of HCM patients will develop atrial fibrillation – about 20 to 25 percent – and their risk of stroke is higher than garden-variety atrial fibrillation patients. “HCM and atrial fibrillation is very different from regular atrial fibrillation,” said Dr. Abraham. “Yet there’s been very little research about how atrial fibrillation develops in HCM patients, how we could identify which patients are at high risk of stroke, and what we could do to prevent complications.”

With her imaging colleagues, Dr. Abraham conducted MRI and echocardiography studies of HCM patients. They found a substantial amount of fibrosis in these patients’ atria, even if they had not yet developed atrial fibrillation. Although there was a correlation between the amount of fibrosis in the atria and ventricles, there was significantly more scarring in the upper chambers than the lower chambers.

Also, while HCM patients with atrial fibrillation might have normal functioning of their ventricles, it was lower than that of patients without atrial fibrillation. In addition, the heart muscle’s “strain,” or its ability to stretch, was lower in HCM patients with atrial fibrillation. Dr. Abraham and her team also used machine learning approaches to identify clinical features that might predict HCM patients who would develop atrial fibrillation. Their findings suggest that the presence of atrial fibrillation in HCM likely reflects a more severe type of HCM.

“Our goal is to figure out who could develop atrial fibrillation, identify when fibrosis develops and what we could do to prevent it, then treat those people aggressively so they never develop complications and have good quality of life and normal longevity,” said Dr. Abraham. “We want to address problems right from the beginning, so there isn’t any thickening or scarring of the heart. Can we prevent the transition from normal to abnormal hearts, or boost patients’ compensatory mechanisms so they never manifest the disease?”

Working with Talented People

In order to answer these questions, Dr. Abraham wants to do in-depth imaging and metabolic studies of large numbers of patients over time – both those with and without HCM. She also wants to use stem cell techniques – reprogramming patients’ own skin cells to turn them into heart muscle cells – to illuminate the various causes of HCM, and to develop targeted therapies. “I’m very fortunate to work with some very talented people,” said Dr. Abraham. “That’s the exciting part of academic medicine – having all these very smart people to partner with to answer questions and help patients.”

Her colleagues appreciate her contributions as well. “Roselle Abraham has proved to be a great asset since she recently arrived from Hopkins,” said Dr. Edward P. Gerstenfeld, chief of the Cardiac Electrophysiology and Arrhythmia Service at UCSF Medical Center and Melvin M. Scheinman Endowed Chair in Cardiology. “Not only is she an experienced cardiologist with expertise in caring for patients with hypertrophic cardiomyopathy, but her scientific expertise has added to our research capabilities and her presence has greatly strengthened our competitiveness in applying for scientific grants.”

She is very pleased to have joined the UCSF faculty. “There is such a supportive environment for women physician-scientists here, and UCSF has very open-minded, strong leaders,” said Dr. Abraham. “It’s a winning combination.” She also enjoys cultivating the next generation of researchers and clinicians. “I like giving residents a broad exposure to different aspects of cardiology, and making them focus on pathophysiology – what’s the mechanism?” said Dr. Abraham. “One you understand the pathophysiology, you can figure out what’s going on with a patient and how to treat them.

“I also believe in giving research opportunities to anybody who wants them, because somebody once gave me an opportunity,” said Dr. Abraham. “I write papers with students from all over the world – China, Taiwan, Peru, Turkey, Germany and the United Kingdom. These are all motivated people who came to my lab as visiting students, worked intensely, and are now writing first-author papers.”

In addition to research and education, she loves clinical care. “You get instant gratification,” said Dr. Abraham. “Often it takes a while to get an experiment to work, but I can see some patients, figure things out for them, and they’re really happy. Making a difference in patients’ lives is a privilege.”

Dr. Abraham and her husband have a young daughter, Anya. When she’s not in the lab or clinic, Dr. Abraham enjoys playing the piano and taking her daughter to parks and museums.

– Elizabeth Chur