Faculty Spotlight: Connor O'Brien, MD

Grace Under Pressure

Growing up, Connor O’Brien, MD, loved playing rugby and football. “That was a big part of my life until age 30,” he said. Those years of making decisions in a fast-moving, adrenaline-filled environment serve him well in his work as a cardiac intensivist.

Dr. O’Brien was recruited to the UCSF faculty in 2020 as associate director of the UCSF Cardiac Intensive Care Unit (CICU). He cares for some of the sickest patients in the hospital, working with a multidisciplinary team of experts to manage their acute illness, provide the latest innovative treatments, and return as many of them as possible to a good quality of life.

Born and raised in Menlo Park, Dr. O’Brien is a grandson of internist Henry Mayer, MD, who helped found Sequoia Hospital in Redwood City in the 1950s. As a child, Dr. O’Brien developed an interest in medicine while accompanying his grandfather on rounds. He earned a bachelor’s degree in biology from the University of Pennsylvania, spent two years as a research associate at Geron Corporation, a biopharmaceutical company in Menlo Park, then earned his medical degree at Columbia University. At Stanford Hospital and Clinics, he completed his internal medicine residency, cardiovascular medicine fellowship (he was selected to be chief fellow for his final year), postdoctoral fellowship, and critical care medicine fellowship.

Advanced Tools, Complex Care

“I really liked the ICU [Intensive Care Unit] when I was training, but the expected mortality is quite high and many of the patients have irreversible underlying conditions,” said Dr. O’Brien. “What was especially appealing about the CICU was that your patients commonly have more medical and procedural options. There’s a lot you can do for people with minimally invasive devices and temporary support, allowing many to return to their previous quality of life.”

He also enjoys the interdisciplinary nature of the CICU. “Many patients are too sick to live on their own,” said Dr. O’Brien. “We work closely with CT [cardiothoracic] surgery, the interventional group, and electrophysiologists to develop therapeutic plans that support cardiac function and allow for recovery. It’s a very team-based approach, and we have great conversations about ways to innovate, develop creative solutions, and apply technologies in real time.”

Some of the advanced devices the team can offer to patients include miniature heart pumps called ventricular assist devices (VADs), as well as percutaneous devices that support the right side of the heart, including the Protek Duo and the Impella RP. The team can also offer minimally invasive, catheter-delivered closure devices to plug leaks in the heart, as well as specialized pacemakers that can resynchronize the heart and help ensure that it squeezes in a coordinated way.

To maintain adequate blood flow to a patient’s body during these procedures, the team can utilize extracorporeal membrane oxygenation (ECMO), which is similar to a heart-lung bypass machine but is small enough to be used at the bedside and can continue to be utilized until the patient’s heart and lungs are strong enough to do their jobs.

“With these procedures, patients don’t get better right away,” said Dr. O’Brien. “It takes days for the heart to adapt. Getting patients through critical illness is a delicate balance of supporting all the organs while slowly introducing new medicines that allow the heart to heal. There are also many side effects to everything we do. Understanding how to minimize harm during critical illness is a vital part of our practice. We constantly tailor therapy to maximize benefit and minimize risk.”

Because of the intricacy of caring for these very sick patients, a few years ago UCSF created the CICU, which has a dedicated team of cardiologists like Dr. O’Brien who have advanced training in caring for ICU patients with heart disease. This reflects the increasing complexity of hospitalized patients. “It used to be that 70 to 80 percent of patients in the CICU were post-heart attack,” said Dr. O’Brien. “Now they only represent 20 to 30 percent of patients. Most of today’s CICU patients have heart failure plus other problems, such as pneumonia, kidney failure or stroke. We manage all those other problems while also taking care of the heart.”

‘Time is Brain’

Dr. O’Brien credits his training at Columbia and Stanford for teaching him the benefits of responding quickly. “As long as you stick to certain criteria, intervening early and reversing pathology quickly can save a lot of lives and get people better, with good quality of life,” he said.

Although he is a cardiologist, Dr. O’Brien often focuses on preserving brain function. “We think very much like stroke doctors,” he said. “Time is brain. Whenever you’re in a cardiac arrest situation or you’re trying to figure out how to support our sickest patients, you’re hoping that the brain is not injured. Other organs can be supported, replaced, or have high regenerative potential. You can cut out part of an intestine. Livers usually recover. You can do dialysis. We can implant a heart pump. But whatever you lose of the brain, there’s no going back. If you’re going to save the brain, you have to move really fast.”

Part of what makes that possible is having a highly trained team onsite at all times. “The biggest part of mobilizing everything is identifying the problem early,” said Dr. O’Brien. For example, he has expertise in echocardiography and critical care ultrasound. “When people are really sick, a lot of times they can’t go get scans,” he said. “One of the new fundamentals of critical care training is bedside ultrasound, so you can figure out what’s going wrong. With full body ultrasound, we can do clot surveillance throughout the body, as well as ultrasound of the abdomen, lung and kidneys. Often you can insert a needle to find infections and drain fluids that are causing problems. By being onsite, we can look at the heart and lungs right away, and diagnose the problem quickly.”

That timely diagnosis of new problems allows cardiac intensivists like Dr. O’Brien to mobilize the cardiac surgery or interventional cardiology teams early, when aggressive interventions have the best chance of success.

Balance and Communication

Dr. O’Brien points to several key ingredients to success in the CICU. “Running an ICU requires a lot of checklists and things to be done quickly within very narrow ranges in order to deliver good patient care, but you also need people who are very flexible,” he said. “It’s challenging, because often there isn't a lot of data that drives care. Unlike caring for outpatients in the cardiology clinic, where huge clinical trials offer high-quality guidance, we have limited data to guide decision making. Most clinical trials exclude critically ill patients.”

Navigating the gray zone of medicine requires strong teamwork and communication. “The intensivist functions like the quarterback,” said Dr. O’Brien “We need an intimate understanding of the patient’s condition, treatment options, and risks of treatment. For example, when a critically ill patient requires cardiac surgery, timing is everything. We also need to know when procedures offer more harm than benefit. Making the decision to not intervene is often harder than deciding to operate.”

Secondly, Dr. O’Brien balances rapid initial intervention with knowing when to slow down and stay ahead of complications. “A big part of the intensivist role is harm reduction,” he said. “We move quickly upfront to fix the most pressing problem, and then navigate a host of other issues while the heart recovers. For example, we have to maintain patient nutritional status, prevent blood clots, and minimize lung injury from a ventilator. We spend a lot of time keeping the body at homeostasis.”

Third, communicating effectively with patients and their families is vital. “If a patient is critically ill, how you deliver that information and set expectations is nuanced and must be tailored to the patient and family,” said Dr. O’Brien. “Because ICU care commonly involves invasive procedures, we have to understand our patients’ goals. Meeting our patients where they are in life is central to developing a tailored treatment plan. Staying in close contact is important, since prognosis can change quickly. Helping patients and families understand their options and feel supported is a big part of our job.”

Investigating New Measures of Heart Disease

In addition to his work in the CICU, Dr. O’Brien has an active research portfolio. At Stanford, he helped lead several clinical trials of stem cell transplants to treat heart failure. “Patients who are treated with stem cells often feel better after treatment and have improvements in exercise and physiology,” he said. However, transplanted cardiac stem cells do not engraft, produce new heart muscle, or reduce scar. The cells all die shortly after transplant.

Dr. O’Brien and his colleagues hypothesize that the transplanted stem cells may actually deposit beneficial factors that mitigate cell injury, even if the stem cells themselves do not survive. One of those factors may be mitochondria, which are the energy-producing parts of a cell. Recent research has suggested that cells can actually donate mitochondria to other cells, and that this mitochondrial transfer may help an injured cell repair itself.

He recently received grant funding to investigate whether markers of mitochondrial damage and circulating mitochondria might be useful predictors of disease severity and clinical outcomes for patients with heart disease. For example, clinicians could take a “liquid biopsy” by obtaining a blood sample. When damaged mitochondria die, a cell releases fragments of mitochondrial DNA into the bloodstream, which can be measured through DNA analysis of the liquid biopsy. The same approach could be used to quantify the level of intact mitochondria circulating in the bloodstream, as well as inflammatory markers that could shed additional light on a patient’s health.

Dr. O’Brien hopes to establish a biobank to study potential markers of disease severity in the CICU. He is also collaborating with UCSF cardiologist Maria (“Roselle”) Abraham, MD, who has expertise in studying cardiac mitochondria.

“If mitochondrial DNA or damage provided a way to quantify a patient’s disease progression, we could get a sense of a patient’s trajectory,” said Dr. O’Brien. “This information could provide feedback about whether a patient is getting better, worse, or staying the same in response to interventions. Without objective markers of disease severity, knowing when to change care or move forward with invasive procedures is challenging.”

Among his other research projects, Dr. O’Brien co-founded CARDIO-COVID, a multi-site national registry that quantifies COVID-19-related heart injury among ICU patients. So far there are 16 participating sites around the country. “It’s a rich database, and provides a very deep dive in this specific patient population,” he said.

A Team Effort

Dr. O’Brien chose to join the UCSF faculty for the chance to help lead the recently created CICU. “It was an opportunity to grow a service,” he said. So far, the average census of the CICU has grown from two patients in 2018 to about eight patients now. He is also excited to be part of other new initiatives that leverage his expertise, including rapid response teams for pulmonary embolism and cardiogenic shock.

“The acuity of cardiac critical care has grown tremendously with the widespread adoption of temporary and durable mechanical circulatory support, as well as ECMO,” said Richard Cheng, MD, who leads the cardiogenic shock program. “With that comes the need for a new kind of specialist who understands cardiac pathophysiology, anticipates clinical deterioration, and rapidly delivers the necessary care for patients with cardiogenic shock. Dr. O'Brien is dually trained in cardiology and critical care, a rare combination that makes him uniquely suited to be a leader in the field, and to help patients take their first steps away from critical illness and towards returning to their loved ones at home.”

As the cardiology liaison for the UCSF Adult Integrated Transfer Center, Dr. O’Brien fields calls from referring physicians with acutely ill cardiology patients. “If someone calls, we will pick up the phone almost immediately and try to get patients over as fast as possible,” he said. “For the CICU, we take all referrals, including Medi-Cal patients, which a lot of hospitals won’t take. We’ll bring patients in, perform complete diagnostics, and get them through their acute issues. If we determine they could benefit from a procedure, we try to stabilize them to the point where they would be a candidate for that procedure or surgery. Because we’re there at the bedside, we do all that really fast.”

Dr. O’Brien appreciates UCSF’s highly collaborative environment, from his fellow cardiologists to his cardiac surgery colleagues, including Tom Nguyen, MD, who was recruited to UCSF at the beginning of 2021 as the new chief of the Division of Adult Cardiothoracic Surgery. “Tom is a fantastic colleague and leader,” said Dr. O’Brien. “When I’m on service, I call him frequently. He always picks up the phone, and we are able to coordinate complex care in short order. Dr. Nguyen is building innovative treatment services within cardiothoracic surgery. We are working together to develop collaborative, multidisciplinary teams. We’ve had patients who were really sick who did very well, because of excellent teamwork.”

In addition to taking care of patients and conducting research, Dr. O’Brien enjoys teaching. “Working with trainees is a very rewarding part of the job,” he said. “Our challenging cases offer excellent opportunities for residents and fellows to learn complex physiology as well as how multidisciplinary teams work. We try to get them as involved as possible, while ensuring they are set up to succeed. Developing a supportive environment is essential when trainees are taking care of critically ill patients.”

Dr. O’Brien also serves as faculty for two ultrasound teaching groups, including an international critical care ultrasound course run by the Society of Critical Care Medicine. During medical school and residency, he also volunteered in Guatemala, Brazil and Zimbabwe, including teaching colleagues in low-resource settings how to use ultrasound to effectively care for cardiac intensive care patients. “These physicians work in a very different clinical environment, treating many conditions we don’t commonly see in the US,” he said. “I learned a great deal from these experiences, and developed many clinical skills that I incorporate regularly in the CICU.”

Dr. O’Brien is married to Shannon O’Brien, DPT, a pediatric physical therapist and New Yorker. They met at Columbia during graduate school and share a love for New York City. Outside of the hospital, he enjoys rugby, scuba diving, and spending time outdoors with his wife and their two daughters, Ava and Maddie.

-Elizabeth Chur