Faculty Spotlight: Carlin Long, MD

“Patients tell doctors things that they don’t tell anybody – not their priest, their minister, their wives or their kids,” said Dr. Carlin Long. “That intimacy is really why I went into medicine.”

Dr. Long, who was recently recruited to the UCSF Division of Cardiology as the director of the UCSF Center for Prevention of Heart and Vascular Disease and to help expand the Cardiology Council, brings a wealth of experiences. He spent decades caring for disadvantaged patients at a safety net hospital, built a Cardiology Division from the ground up, and made laboratory discoveries on everything from inflammation in cardiovascular disease to how nanotechnology could help repair damaged hearts. What drives all of his efforts is his passion for working in partnership with patients to improve their health and their lives.

Dr. Long grew up near Phoenix, Ariz., where his father was a cardiologist. As a high school student, he accompanied his father on hospital rounds on the weekends, where he got to witness the close relationships his father forged with patients. “We’d go into a room, and the patient would light up,” recalled Dr. Long. “They held him in tremendous esteem, and viewed him as this person who was invested in their care and their health.”

In addition to caring for patients, Dr. Long knew he wanted to conduct research to learn more about the fundamental causes of disease. One of his first research opportunities came during college, when his father – the medical director for Hughes Airwest – traveled the world as a member of the Airline Medical Directors Association. Among the physicians his father befriended internationally was a famous Dutch cardiac electrophysiologist, Dr. Hein Wellens. Through that connection, Dr. Long spent two summers working in Dr. Wellens’s lab in Maastricht, the Netherlands.

Dr. Long earned his bachelor’s degree in biology from Baylor University in Waco, Texas, then earned his medical degree from the University of Texas Southwestern Medical School in Dallas. He conducted research on fatty acids in the lab of Dr. Daniel Foster, a prominent endocrinologist. Another one of his mentors was Dr. Michael Brown – who, with his colleague, Dr. Joseph Goldstein, discovered the low density lipoprotein (LDL) receptor, which controls the cholesterol level – a finding for which they were later awarded the Nobel Prize.

His mentors thought he should go to Boston for his internal medicine residency before returning to UT Southwestern. But when Dr. Long interviewed at UCSF, he said, “It was like I found my home. I just felt so welcomed.” Dr. Long completed both his residency and chief residency at UCSF, where one of his best friends was his co-chief resident, Dr. Susan Desmond-Hellmann – who later served as chancellor of UCSF, and currently is CEO of the Bill & Melinda Gates Foundation.

“This was such a great place to train,” said Dr. Long. “The residents were unbelievably smart, and you had to be on your A-game, because people expected it. Then there were the giants within cardiology, like Mel Cheitlin and Kanu Chatterjee. They lived to be on rounds with you, teaching you and helping you be better clinicians. They always had an open door, and if I couldn’t put my finger on a patient’s condition, they would say, ‘Let’s go look at the data and listen to the patient.’”

Inflammation and Heart Disease

Dr. Long enjoyed his time at UCSF so much that he stayed for his cardiology fellowship, eventually joining the faculty at the San Francisco Veterans Affairs Medical Center (SFVAMC). He wanted to learn how to do molecular biology research – delving into how DNA, RNA and signaling proteins interact to choreograph the essential functions of the body, and learning what goes awry in disease. Dr. Long trained in the lab of molecular and developmental biologist Dr. Charles Ordahl in the UCSF Department of Anatomy, then brought his new skills back to the lab of his mentor, cardiologist Dr. Paul Simpson at the SFVAMC.

As a junior faculty member, Dr. Long investigated the role of inflammation in heart disease. “I was interested in how the cells in the heart ‘speak’ to one another in both normal and abnormal growth,” he said. He and his colleagues studied the interactions of heart muscle cells – which contract and enable the heart to beat – and non-muscle cells called fibroblasts, which produce the connective tissue in the heart. The activation of fibroblast function can happen in response to a heart attack, chronic high blood pressure or valvular diseases, and can lead to an exuberant scarring process which affects heart function.

Dr. Long’s group was among the first to discover that the heart fibroblasts can be the source of a number of inflammatory signaling proteins which play critical roles in a number of cardiovascular diseases. They focused much of their work on one of these molecules, called interleukin-1 (IL-1), and how this molecule can alter the growth and function of both cardiac muscle cells and fibroblasts in the injured heart.

This research has now come full circle. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) Trial, led by Dr. Paul Ridker at Harvard, recently demonstrated that tamping down cardiovascular inflammation in patients who have already had a heart attack can reduce the risk of another heart attack, stroke or cardiovascular death.

“We’ve never before directly addressed inflammation as a risk, the way we lower people’s cholesterol,” said Dr. Long, who was one of the study’s enrolling investigators. “Now there will potentially be a therapy that targets the inflammatory cascade in cardiovascular disease patients. I think it will be a paradigm shifter, the same way that the original beta blocker trials were in terms of how we treat people with heart failure.”

Partnering with Patients

In 1998, Dr. Long was recruited to the University of Colorado faculty, and was appointed chief of cardiology at Denver Health Medical Center, the city’s safety net hospital. “The opportunity to build a program completely and make it my own was very exciting,” said Dr. Long.

Arriving at Denver Health was like parachuting into a startup. When he arrived, Dr. Long became the third cardiologist in Denver Health Medical Center’s bare bones Cardiology Division. Many of their patients were the working poor, and about half were Hispanic. By the time Dr. Long was recruited back to UCSF nearly two decades later, his division had grown to 11 cardiologists and expanded to include programs in interventional cardiology and electrophysiology. His division was also one of the most productive academic groups at the hospital, encompassing outcomes research, epidemiology, and basic research.

One of his first priorities was partnering with patients to improve their health. “The average educational level of our patients was third grade, and our population had zero health literacy,” said Dr. Long. “We really needed to develop an educational program that met patients at their level, and helped them understand why many of them now needed to take five medications for life after a heart attack. It’s not like pneumonia, where we give you an antibiotic and two weeks later, you’re cured.”

To help accomplish this, his division developed a robust cardiac rehabilitation program called Healthy Hearts, which sought to improve the heart health of patients who have had a heart attack or other form of heart disease, through a combination of exercise, nutritional counseling and other lifestyle modifications.

They also partnered closely with the hospital to provide intensive case management to “frequent flyer” patients, who were the most likely to end up in the emergency room or hospital due to complications of heart failure. “Many of those patients had mental health and substance abuse issues that required social work, substance counseling and other services,” said Dr. Long. “Our program became a successful model for case managing these notoriously difficult patients.”

The average 30-day readmission rate for heart failure patients is between 25 and 30 percent at safety net hospitals, but Denver Health was able to bring that down to about 18 percent – even lower than the national average of about 21 percent, which is remarkable given that Denver Health serves vulnerable populations facing complex economic and health challenges.

Dr. Long’s team also led the Latinos Using Cardio Health Action to Reduce Risk (LUCHAR) study, a clinical trial sponsored by the National Institutes of Health which examined disparities in cardiovascular risk among Hispanic patients, and piloted computer-based interventions to help participants increase exercise, improve nutrition and quit smoking.

Tiny Scale, Big Potential

While building his group’s clinical and research capabilities, Dr. Long also continued some of his own investigations. During a 2006 sabbatical at the University of Trieste in Italy, he began collaborating with engineers, developmental biologists and others on various projects, including an effort to use nanotechnology to assist in cardiac repair.

He and his colleagues took immature heart muscle cells from baby rats, and tried to improve their ability to grow these cells so they developed the electrical conductivity of mature adult heart muscle. Rather than growing them on the usual glass slides, they found they got better results when they cultured them on carbon nanotubes – extremely small, carbon-based scaffolds. They got even better outcomes when the carbon nanotubes were combined with a special gel – creating an “ecosystem” that more closely approximates the heart’s own environment, rather than the artificial, rigid conditions of a glass slide.

One hope is that learning more about how to grow heart muscle cells with mature electrical conductivity will help scientists engineer a cardiac tissue patch for heart attack survivors that would seamlessly integrate into the electrical system of his or her heart, beating in sync with the rest of the heart. “Integration is everything in the tissue regeneration field,” said Dr. Long.

He and his colleagues are also investigating how a mutation in a structural protein gene, lamin A, is associated with a type of inherited heart disease linked to premature heart failure. Drawing on Dr. Long’s expertise in molecular biology and cell culture, they found that expression of these mutant proteins is associated with an increase in cell stiffness – which could explain the abnormalities in heart function in these patients – and that increasing production of the normal protein can allow it to compete with the abnormal lamin A protein and rescue an abnormal cell.

In addition, they are investigating small molecule chemical inhibitors used in cancer treatments that may also help reduce abnormal cell stiffness. “That would be the first step in the proof of principle to see whether we could do a clinical trial in lamin A patients to see whether their cardiomyopathy gets better,” said Dr. Long.

Prevention 2020

While Dr. Long relished his time in Denver, he and his wife always hoped to return to the Bay Area, partly to be closer to family. The opportunity to help bring the UCSF Center for Prevention of Heart and Vascular Disease to the next level was too good to turn down.

“At Denver Health, our efforts were focused on secondary prevention – trying to prevent subsequent events in patients with known cardiovascular disease – but we never had the resources to develop a primary prevention program, which focuses on people who have never had a cardiovascular event but are at risk of one,” said Dr. Long. “I’ve got all kinds of ideas about what a comprehensive prevention center at UCSF might look like.”

He calls this vision “Prevention 2020,” and a key component is behavioral medicine, which addresses the lifestyle habits which play such a large role in cardiovascular health and disease. “When we tell somebody, ‘You need to stop smoking, cut down on alcohol and exercise more,’ most people leave the appointment having been chastised, but we haven’t actuated change for them,” said Dr. Long.

Dr. Long and his Center for Prevention colleagues will take advantage of the latest apps and wearable technology. They will partner with experts such as Dr. Kirstin Aschbacher, a clinical psychologist and data scientist who was also recently recruited to the Division of Cardiology, in their efforts to better help patients in areas such as:

• Exercise: An exercise physiologist will develop a customized “exercise prescription” in a monitored setting, to ensure that the routine is safe and within a specific patient’s capabilities. Dr. Long also hopes to make the exercise physiologist available to answer questions and help patients develop their own exercise habit, either at a UCSF facility or their local gym. Wearables such as a Fitbit or Apple Watch can also provide information about a patient’s ongoing activity level, helping the team strategize together about creating a realistic and effective routine.

• Substance use: “Two glasses of wine a day can easily become – ‘I’m just going to have a cocktail before I leave downtown, and when I get home, I need a cocktail to calm down, and then I’ll have my wine with dinner, and then I’m going to have an after-dinner drink,” said Dr. Long. People may not think they have a drinking problem, but it may creep up on them. He also asks patients about any illicit drug use. “We want to meet people in a sensitive way,” he said. “If this is something that patients need to address, we will have behavioral psychologists involved to provide a safe environment for them to do that.”

• Stress: A new Center for Prevention patient might wear a 24-hour blood pressure monitor for a week after the initial visit to help with assessment. “We want to find out what’s happening to them after they leave our clinic and are out in the real world,” said Dr. Long. “When they go to their office in the morning, does their blood pressure go from being controlled to very clearly not controlled for eight hours? If that’s the case, we need to know about it so we can treat it. It sounds a little woo-woo, but their stress may physiologically really affect them. I ask patients, ‘Do you want your job controlling you, or do you want to take back control of your job and your body?’”

Dr. Long hopes to partner with a behavioral psychologist to develop tailored mini-interventions, such as an app that delivers mindfulness meditations that the patient can listen to during a work break. “We’re not telling people they have to leave their job or go to some ashram – we just need them to spend 10 or 15 minutes during the work day bringing themselves back to center,” he said.

• Sleep: There is a growing body of evidence that good sleep is critical to cardiovascular health. “There is a whole range of reasons for poor sleep, from people being tied to their electronic devices all the way to sleep apnea,” said Dr. Long. The Center for Prevention will assess sleep quality through questionnaires, measuring oxygen saturation levels through the night, and using wearable technology to monitor whether a patient is tossing and turning.

Behavioral psychologists can work with patients to improve sleep hygiene. For example, they can help patients develop good sleep habits, such as going to bed at the same time each night, refraining from excessive drinking or eating before bedtime, having a calming routine such as reading before turning out the light, and not watching television or using digital devices before bed. “Most people say that having a routine helps them fall asleep and have a better quality of sleep at night,” said Dr. Long.

Also, the Center for Prevention can help identify and treat patients with sleep apnea, which can increase the risk of hypertension, premature coronary disease, and rhythm disturbances like atrial fibrillation if left untreated.

• Lipid evaluation: Center for Prevention cardiologist Dr. Eveline Oestreicher Stock is a lipid expert who will assess each patient’s comprehensive lipid profile and make customized recommendations.

• Precision medicine: While some diseases are caused by a single genetic abnormality, such as cystic fibrosis, there are many different clusters of genes that contribute to cardiovascular disease. By applying cutting-edge DNA sequencing technology, Dr. Long hopes to determine whether a specific patient has genetic mutations associated with specific types of heart disease, and to tailor interventions accordingly. DNA analysis may also help predict which patients are most likely to respond favorably to a particular drug. This approach could also provide valuable information about how a person’s genome affects lipid levels and inflammatory response.

“My vision for the UCSF Center for Prevention of Heart and Vascular Disease is a comprehensive program that looks at all facets of cardiovascular health,” said Dr. Long. “The challenge with primary prevention is that you have to treat a lot of people to move the needle towards preventing deaths. But some of the ‘softer’ outcomes are just as important to patients and the health system, such as quality of life and people’s sense of their own health. At the end of the day, people want to feel better.”

“Dr. Long is a perfect choice as the new leader for our Prevention Center, and as my partner in leading the Cardiology Council,” said Dr. William Grossman, the Charles and Helen Schwab Endowed Chair in Preventive Cardiology and founder and co-director of the Center for Prevention of Heart and Vascular Disease. “He is a true physician-scientist, and it is that blend of expertise in both science and the practice of medicine that marks our enterprise as unique. I am truly thrilled that we have been able to recruit Dr. Long to this key leadership position at UCSF.”

Dr. Long takes his own prevention message to heart, biking to and from his Mill Valley home to the ferry terminal each work day, and hiking on the weekends. He enjoys fine wine and is an avid Giants fan. He and his wife, Dr. Elizabeth O’Donnell, have a teenaged son, Evan.

“I’m really excited to be here at UCSF,” said Dr. Long. “This is going to be the culmination of who I am and my career. I’ve always viewed myself as a physician-scientist, but I’ve been really invested in patient care for the last 20 years, helping people understand their illness and being partners in their path to health. I love seeing patients – it harkens back to seeing the intimacy of the relationship my dad had with his patients. I think we’ve lost that sense of relationship medicine in this country in the last decade or two, and I’d love to be part of bringing that back again.”

 

– Elizabeth Chur