Faculty Spotlight: Claudio Bravo, MD
Discovering Secrets of Right Ventricular Function
Cardiologist Claudio Bravo, MD, MS, grew up in Valparaíso, Chile, under the Augusto Pinochet dictatorship. “It was very hard for low-income families like mine to access basic things like medical care,” he said. “We had to wake up very early, wait in line for hours, and if we were lucky, we got to see a doctor. My dream was to become a doctor and serve people like my family.”
From an early age he enjoyed reading library books about human anatomy and physiology. When he was about 10, he asked his mother for a secondhand copy of Claude A. Villee’s classic textbook, Biology, for Christmas. “Everyone would ask me, ‘Why do you think I’m having this medical problem?’” he recalled. “In my mind, I was already becoming a doctor when I was a kid.”
Although public schools were poorly funded and becoming a physician was nearly impossible for people of modest means, Dr. Bravo was accepted into Valparaíso’s best public high school, which had launched an initiative to educate the city’s top students. “My teachers were impressive – they were so inspiring and passionate, and I still think about them often,” he said. “Everyone was from low-income families, but my whole class went to college.
Dr. Bravo completed medical school at the Universidad Católica de la Santísima in Concepción, Chile. To pay for school, Dr. Bravo got a summer job at a hospital transporting medical charts from the archives to the cardiology unit. “I went to work super early, took the charts where they needed to go, then shadowed a cardiologist,” he said. “He showed me echoes, stress tests, and interesting cases like mitral stenosis and aortic dissection. The pathophysiology of the cardiovascular system made so much sense, so I decided to become a cardiologist.”
The desire to migrate to the U.S. developed after he watched an HBO movie, “Something the Lord Made,” about a form of congenital heart disease called tetralogy of Fallot, also known as “blue baby syndrome” because it results in low blood oxygenation levels. “I found it fascinating how physicians and scientists in the U.S. are willing to push the boundaries, and I wanted to be part of that,” said Dr. Bravo.
Opening the Window to Cardioprotection
After completing his medical degree, Dr. Bravo enrolled in a master’s in science program at the University of Chile in Santiago, investigating voltage-gated L-type calcium channel currents in cardiomyocytes using patch-clamp technique and site-directed mutations. “We were trying to understand how the regulation of calcium channels happens,” he said.
“I liked the idea of receiving further training where cutting-edge things were happening, so I moved to the U.S. to get advanced training,” said Dr. Bravo. He spent three years as a postdoctoral fellow in cardiac physiology in the lab of Stephen Vatner, MD, at Rutgers University in New Jersey. “He reshaped my life in a positive way,” said Dr. Bravo. “It was certainly a life-transforming experience, and I am very thankful for the opportunity Steve gave me.”
In Dr. Vatner’s lab, Dr. Bravo helped investigate potential heart failure treatments. “Heart failure patients who take beta blockers live longer and do better,” said Dr. Bravo. “But these medications have side effects like hypotension, slow heart rate, depression, and diabetes. We’re trying to find another target in the same pathway that is more cardiac-specific so it doesn’t affect other organs.”
They identified a specific protein, Type 5 adenylyl cyclase (AC5), that is common in the heart, and pursued avenues for blocking that enzyme. They also identified a U.S. Food and Drug Administration (FDA)-approved drug called vidarabine, also known as Ara-A, that helped mice with heart failure live longer by blocking AC5.
“We gave the drug at different time points – before the heart attack, right before we opened the coronary artery, and then after we opened the coronary artery,” said Dr. Bravo. “This drug decreased infarct size at all those points, but the most powerful effect occurred when it was given after we opened the coronary artery.” This has promising clinical implications, since patients who come to the emergency room with a heart attack could receive this type of therapeutic after getting a stent.
Heart attacks cause damage when the heart’s oxygen supply is compromised, but also later when a coronary artery is opened with a stent – a phenomenon called reperfusion injury. “You would think that once the blood supply is restored everything would go back to normal, but at the beginning of reperfusion a lot of toxins are released,” said Dr. Bravo. “Those toxins can cause more damage to the heart. Right now we don’t have any treatments, so it was exciting that this drug appeared to have an anti-reperfusion injury effect.” This could also have relevance for heart transplantation, since restoration of blood flow in a donor heart can damage a newly transplanted organ via reperfusion injury mechanisms.
In a related investigation, Dr. Bravo investigated ischemic preconditioning, a well-described mechanism in which briefly blocking and then restoring blood flow through a coronary artery can have a protective effect if there is a major blockage soon after. “That first short blockage of the coronary artery prepares the heart for the longer event,” said Dr. Bravo. “There are two ischemic preconditioning windows: one that occurs after the brief blockage of the coronary artery, and a second window several hours later.”
Dr. Bravo and his colleagues described a third window, created when they partially decreased coronary artery blood flow for 30 minutes twice a day for several days, similar to what occurs in patients with chronic stable angina. “We found that this type of cardioprotection lingered,” he said. Dr. Bravo measured the metabolites associated with the first, second, and third windows. He hoped to identify a pathway in the third window that could be activated or blocked by a novel therapeutic to induce longer-lasting cardioprotection.
The Transformative Power of Heart Transplantation
After his postdoctoral fellowship, Dr. Bravo completed his internal medicine residency at Bridgeport Hospital, part of the Yale New Haven Health System, and his cardiology fellowship at Montefiore Medical Center in New York, affiliated with Albert Einstein School of Medicine.
“Montefiore was a very hands-on program, and I had the opportunity to do a lot,” said Dr. Bravo. “Their emergency room is one of the busiest in the country. I learned about cardiology, but also how to handle stress. It was common to have multiple emergencies happening at the same time – one patient might be crashing in the ICU, while another one was having a STEMI in the ER.” That intense experience taught him invaluable skills. “When experiencing difficult situations, I always advise fellows to pause, step back, look at the problem from different perspectives, and avoid getting stuck in one point of view,” he said.
He also confronted the challenging aspects of his clinical work. “Especially in cases where I’m emotionally involved, it’s been difficult to accept that we can’t help everyone, and that some of our patients will face death,” said Dr. Bravo. “I’ve come to accept that medicine, science, and we as health care providers aren’t able to help everyone. I try to stay emotionally healthy by spending time with my wife and kids, exercising, and staying in touch with my family back in Chile. The uncertainties of how to solve some problems in the daily care of patients raise questions that I try to answer through my research.”
During the early months of the COVID pandemic, Dr. Bravo completed his fellowship in advanced heart failure and transplantation at New York Presbyterian Hospital and Columbia University. He was attracted to this subspecialty because of his research, the opportunity to manage complex cases, and the privilege of establishing long-term relationships with patients.
“When I see a patient in the heart failure clinic, if medications don’t help them, sometimes I follow them through the difficult process of getting a transplant or LVAD,” said Dr. Bravo. “One of my patients had hypertrophic cardiomyopathy, and had experienced chest pain and shortness of breath her entire life. When she got a transplant, she told me, ‘I don’t have any more chest pain. I can go with my husband and walk my dog!’ It wasn’t until her 60s that she was able to live her full life.”
He is excited about the future directions of this subspecialty. “We have great therapies that have prolonged patient survival,” said Dr. Bravo. “We have emerging drug therapies, xenotransplantation (transplantation of tissues or organs from other species into human patients), new strategies to expand the donor pool, and new devices. It’s a great field to be in.”
Translating the Languages of Science
After completing his clinical training, Dr. Bravo joined the faculty at the University of Washington, Seattle, where he also completed a master’s degree in epidemiology. “I learned biostatistics and epidemiology, and spent a significant amount of time coding,” he said. “It was a good complement to my basic science and translational research training. I’ve gone through the whole spectrum of research from basic science to outcome research. My long-term plan is to become a translational researcher who can channel basic science findings into medicine, and bring clinical findings back to basic science. I’m trying to be a ‘translator’ of science’s many languages.”
Dr. Bravo spent a year in private practice as transplant medical director for Medical City Healthcare in Dallas, but missed academic medicine. “When I saw this job opening at UCSF, it was a great opportunity,” he said. “During the interview process, I learned that [Chief of the UCSF Division of Cardiology] Jeff Olgin and [Director of the Advanced Heart Failure Comprehensive Care Center] Liviu Klein are very supportive and lead a growing team. UCSF has a very strong pulmonary hypertension group, which is linked to my research interests in right ventricular failure. The volume of [heart] transplant and LVAD (left ventricular assist device) is one of the highest in the country. This was the perfect place for me.”
One of Dr. Bravo’s main areas of research is right ventricular heart failure. “Heart failure research has been mostly focused on the left ventricle, and the right ventricle has been understudied,” he said. “The drugs we use for left ventricular failure don’t work for the right ventricle because the mechanisms and molecular pathways associated with right ventricular failure seem different.”
Although the left and right ventricles are both lower chambers of the heart, separated by the interventricular septum, they have very different anatomies and physiologies. “The left ventricle is oval and works in a high-pressure system to push blood into the aorta and throughout the entire body,” said Dr. Bravo. “By contrast, the right ventricle is a crescent-shaped chamber with much thinner walls. It works in a lower-pressure system, pushing blood into the lungs where it is oxygenated – so the resistance in the pulmonary system is much lower.” The right ventricular outer or “free” wall, the septum, contraction of the left ventricle, and the pericardium – the thin sac surrounding the heart – all play a role in right ventricular function.
Understanding Right Ventricular Failure
One of his key interests is right ventricular failure that develops after LVAD implantation, which affects about one in four LVAD recipients and lacks any good treatments. “Right ventricular failure is a big Achilles heel in the LVAD population, and we haven’t made any progress,” said Dr. Bravo.
Although LVADs can greatly improve the function of the left ventricle, they can paradoxically cause the right ventricle to fail, for reasons that remain unclear. One theory is that as the LVAD suctions blood from the left ventricle, it pulls the septum away from the right ventricle and reduces its contribution to right ventricular pumping function. Another is that pulling on the septum opens the tricuspid valve, which can worsen tricuspid valve regurgitation and cause right ventricular volume overload and failure.
Another hypothesis is that the increased blood flow powered by the LVAD creates volume overload to the right ventricle. Yet another theory is that cutting the pericardium to implant the LVAD compromises the integrity of that enveloping sac, distorting the normal right ventricular 3D structure and function. “There are many hypotheses, but none have actually been proven yet,” said Dr. Bravo, who detailed these in a recent review article.
Dr. Bravo suspects that the right ventricle itself might be the culprit. “Something else might contribute, but I think the walls of the right ventricle are the problem,” he said. To investigate this further, he and his collaborators are collecting heart tissue from patients with LVAD who receive a heart transplant. They are measuring RNA expression, protein concentrations, and metabolites from each heart, and comparing the results between LVAD recipients with and without right ventricular failure. “Our goal is to understand which pathways are altered in the setting of right ventricular failure, and to understand the molecular mechanisms,” he said. If they identify relevant pathways, he hopes to unearth clues that might lead to novel therapeutics.
He is also using a multiomics approach to look for biomarkers that could identify patients who have developed LVAD-associated right ventricular failure, or are at risk. “We’re looking at the level of proteins, mRNAs, and metabolites, but the challenge is how to integrate all this data,” said Dr. Bravo.
He wants to use LVAD-associated right ventricular heart failure as a model. However, many other conditions also affect the right ventricle; Dr. Bravo’s research could shed light on heart failure with preserved ejection fraction (HFpEF), pulmonary hypertension, severe tricuspid regurgitation, and some forms of adult congenital heart disease (ACHD), among other conditions. “We might be able to extrapolate findings in LVAD-associated right ventricular heart failure to these other forms of right ventricular failure, but the mechanisms for how the right ventricle fails might be different,” he said. “Multiomics can help us form hypotheses that we can further explore using basic science approaches.”
There is a crying need to improve treatment for all forms of right ventricular failure, since there are currently very limited treatment options. Patients sometimes can receive a right ventricular assist device (RVAD) or a repurposed LVAD to support the right ventricle. Another approach is a total artificial heart, in which most of the heart except for the right and left atria is removed and replaced with a pump. However, all these measures are temporary solutions, serving as a bridge to transplant, unlike LVADs, which patients can potentially live with for several years.
Dr. Bravo has also conducted research about ways to expand the donor pool for transplanted hearts. Until recently, only brain-dead patients were eligible to become organ donors. These “donor after brain death” (DBD) organs are recovered after a patient has passed away, but while the heart continues to beat. However, a few years ago the eligibility guidelines were expanded to allow for “donor after circulatory death” (DCD) organs. These donors cannot survive without a ventilator and are comatose with no possibility of recovery. If the family decides to withdraw life support, they can donate their loved one’s organs after the patient’s heart has stopped. The post-transplant outcomes with either method are similar in patients not supported by LVADs.
“Similarly, we found that LVAD patients can safely get a transplant from a DBD or DCD donor,” said Dr. Bravo. “The only difference was that rejection rates were higher with DCD donor hearts.”
Grateful Member of the Team
In addition to research, Dr. Bravo has a busy clinical schedule. He cares for patients with HFpEF and heart failure with reduced ejection fraction (HFrEF), LVAD recipients, and those who have undergone heart transplantation. His main focus is patients with transplant, LVAD, or other types of long-term mechanical support. He also conducts procedures, biopsies, right heart catheterization exercise tests, and invasive hemodynamic studies.
He enjoys teaching and mentoring, one of the reasons he decided to return to academic medicine. “I enjoy working with fellows,” said Dr. Bravo. “Most of my mentees are in the early stages of their careers, and I’m proud of their progress.”
He finds deep joy in witnessing his patients’ lives improve. “Seeing someone who came to the hospital who was dying and was able to receive a transplant or LVAD, and then seeing them in clinic living a normal life, makes me really happy,” said Dr. Bravo. “They get to see their loved ones again. It’s also amazing to see patients who do very well on medications. When they go from a very symptomatic disease to being able to work and enjoy life again, it’s very satisfying.”
He has had the opportunity to care for underserved patients. “At the University of Washington, I took care of patients from different native tribes, some of them from remote villages in Alaska,” said Dr. Bravo. “I learned a lot about their traditions and cultures. During selection committee meetings, we had to consider how they would access care, including during the harsh winters. Sometimes the local hospitals could help with blood draws, and we were able to follow up with them by video. Here at UCSF, I’ve been involved in caring for patients from remote islands in Hawaii and other underserved areas, including here in California. It makes me happy to care for patients who wouldn’t have received medical care otherwise because of their socioeconomic background or geographic location.”
He appreciates providing care to Spanish-speaking patients without needing a translator. “It’s not just about the language, but also about our unique culture,” said Dr. Bravo. “For example, it’s not rare in the Hispanic culture to have the entire family involved in a medical decision. Having these kinds of complicated conversations in a patient’s native language, with an understanding of their culture, makes it much easier for patients and their families.”
Dr. Bravo appreciates being part of the UCSF Division of Cardiology. “Everyone I’ve met is impressive and extremely committed to patient care,” he said. “You can find experts in any area, either here or somewhere within the UC system. Most colleagues at UCSF think both about how to give the best care to our patients and how to advance science. The advanced heart failure and transplant team is amazing. We have a great team of coordinators, social workers, pharmacists, nurses, advanced practice providers, surgeons, and physicians. Everyone is rowing in the same direction, and I’m proud to be part of the team.”
“Dr. Bravo brings deep expertise in mechanical circulatory support and LVAD therapies, with a rigorous research focus on improving these therapies, including optimizing underlying right ventricular function,” said Jacqueline DesJardin, MD. “He pairs his research interests with excellent clinical judgment and a strong commitment to teaching, making him a fantastic addition to the UCSF Advanced Heart Failure team.”
“Dr. Bravo is deeply committed to advancing our understanding of right ventricular failure following LVAD implantation and is passionate about improving access to advanced heart failure therapies,” said Pooja Prasad, MD. “I greatly admire his clinical acumen and dedication to patient care, and I am grateful to have him on our team.”
“Dr. Bravo is an exceptional cardiologist whose clinical judgment, technical skill, and deep commitment to patients elevate every aspect of our program,” said Dr. Klein. “He is a trusted colleague and a generous team player who consistently goes above and beyond for patients, trainees, and advanced practice providers. As a physician-scientist, his work in right ventricular function, LVAD physiology, and translational research reflects genuine curiosity and purpose, helping bridge fundamental discovery with meaningful improvements in patient care at UCSF.”
Aside from medicine and research, Dr. Bravo is a lifelong swimmer and has recently become an amateur triathlete. He and his wife, Cecilia Vasquez, an elementary Spanish schoolteacher in Marin County, enjoy family time, ice cream outings, and spending time in nature with their two daughters, Sophia and Emilia. “I have been lucky to receive unconditional support from my mom, dad, wife, and kids, as well as to meet and learn from many great people along my journey,” said Dr. Bravo.
- Elizabeth Chur