The multi-institutional study offers one of the clearest pictures of what happens during the earliest stages of disease. The findings could help researchers develop new ways to detect and prevent heart disease before plaque builds up inside arteries.

“We analyzed proteins and gene activity in coronary artery tissue from young adults who died of trauma and had no known coronary artery disease, and we found that more than half already had preclinical atherosclerosis,” said study first author Sarah Parker, PhD, an associate professor of Cardiology and Biomedical Sciences and co-director of the Proteomics and Metabolomics Core at Cedars-Sinai Health Sciences University. “This suggests that changes in cellular metabolism and communication begin before the inflammation long considered a hallmark of the disease.”

Published in the European Heart Journal, the study findings point to previously unrecognized molecular pathways—and a potential “master regulator” called MLXIPL—that could become targets for therapies aimed at preventing plaque from developing.

The Cedars-Sinai Newsroom spoke with Parker about the findings and how proteomics—the study of proteins—is helping researchers rethink the earliest stages of heart disease.

Why are proteins so important in understanding heart disease?

Proteins are the molecules that make cells function. They tell us how the body’s cells are responding to risk factors like cholesterol, blood pressure or smoking. Two people can have identical cholesterol levels, yet only one develops plaque. Proteins may help explain why. They provide a much more direct picture of what's happening inside the artery wall and may reveal why some people are more vulnerable to heart disease than others.

What did this most recent study reveal about the earliest stages of atherosclerosis?

Previous studies had shown that the earliest artery lesions can appear in the first decade of life. What we haven’t understood is what causes those early changes to progress into dangerous plaques that lead to heart attacks. In studying coronary artery tissue before people ever developed symptoms, we were able to capture some of the earliest molecular changes that appear to set the disease in motion. One of the biggest surprises was that we saw changes in cellular metabolism and communication before we saw the classic inflammatory signals traditionally associated with atherosclerosis.

To be clear, inflammation remains a defining feature of advanced atherosclerosis. What our study suggests is that important molecular changes begin much earlier. If we want to prevent plaque from forming, we need to understand those earliest changes—not just what happens after inflammation has already taken hold.

Explain MLXIPL, the potential ‘master regulator’ you identified.

We performed a master regulator analysis to identify the genes that may be coordinating these early events. Some of the regulators we found were exactly what we expected. But one stood out. MLXIPL is a transcription factor gene involved in cellular metabolism. Previous genetic studies have linked it to coronary artery disease through its role in the liver. Our findings suggest it may also play an important role directly within the artery wall. When we altered MLXIPL activity in lab-grown human artery tissue, we saw the protein changes we predicted. That makes it an exciting candidate for future therapies that interrupt disease before plaque develops.

How could these findings change atherosclerosis prevention?

Today, we estimate cardiovascular risk using factors such as high cholesterol, diabetes, smoking, age and family history. By the time plaque is visible on imaging, disease often is well underway. We hope to identify protein biomarkers in the blood that reveal what’s happening inside the artery wall much earlier. One day, a simple blood test could identify people who would benefit from preventive treatment before symptoms develop.

That said, our findings do not change current prevention recommendations. Managing cholesterol, blood pressure, diabetes, smoking, exercise and diet remain essential.

This study relied on a decades-long collaboration. Why was that essential?

This is a collaboration more than 20 years in the making. The project was spearheaded by proteomics pioneer Jennifer Van Eyk. (Van Eyk, PhD, is director of the Advanced Clinical Biosystems Research Institute in the Smidt Heart Institute at Cedars-Sinai and co-director of the Proteomics and Metabolomics Core.)

Our collaborators included investigators from many other institutions across the country. What began as a small group has grown into an ecosystem of investigators, trainees and collaborators. This kind of large-scale molecular study simply isn’t possible without that level of long-term partnership and shared expertise.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The therapy, called deramiocel, is the first treatment shown to preserve heart function in Duchenne muscular dystrophy, a rare inherited disease that progressively weakens muscles throughout the body. Heart failure caused by Duchenne commonly leads to early death.

“After more than two decades of hard work, we have demonstrated that deramiocel can slow or even halt not only the loss of upper limb function, but also progression of heart failure in boys and young men with Duchenne,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and senior author of the study. Deramiocel is based on Marbán’s discoveries.

Duchenne muscular dystrophy primarily affects boys because it is caused by a mutation on the X chromosome. Children born with this mutation develop muscle weakness throughout the body, including in the heart. As they grow older, these children have difficulty running, jumping, pedaling a bicycle and doing other activities, and eventually lose the ability to walk. There is no known cure.

Positive Findings

The randomized, double-blind study, called the HOPE-3 trial, compared deramiocel to placebo in 106 participants ages 10 to 22 with advanced disease. Every three months for one year, participants received an IV drip of either deramiocel or a placebo.

Results showed that the therapy slowed weakening of skeletal muscles by 54% and slowed heart dysfunction by 91%. In patients diagnosed with a condition called cardiomyopathy, which impedes the heart’s ability to pump blood, those who received deramiocel showed full preservation or slight improvement of heart function.

“The benefits we observed could mean important improvements in quality of life in people with advanced Duchenne,” said Craig McDonald, MD, distinguished professor of Physical Medicine & Rehabilitation and Pediatrics at UC Davis Health and national principal investigator of HOPE-3. “If young people maintain their upper limb function, it will help preserve their ability to do normal activities, such as feeding themselves. The heart benefits could reduce mortality.”

Decades in the Making

The potential therapy takes a different approach from other therapies that have been studied for Duchenne. Deramiocel is made from cells taken from healthy hearts donated for transplantation but unable to be used as such and that would otherwise be discarded. The work began in 2004, when Marbán first isolated a population of heart progenitor cells called cardiosphere-derived cells. The first clinical studies of cardiosphere-derived cells were performed at Cedars-Sinai, on patients who had survived heart attacks.

Results published in 2012 showed that the cell infusions regenerated heart muscle damaged by heart attack. Ever since, Marbán’s team has been studying the broader therapeutic potential of these cells. The investigators have made several important discoveries, such as that cardiosphere-derived cells secrete packets of RNA molecules that help cells repair the body’s tissues.

In 2011, Catherine Jayasuriya, the mother of a child with Duchenne and a patient advocate, influenced Marbán to turn his focus from studying how cardiosphere-derived cells could repair the heart after a heart attack to studying their potential for Duchenne muscular dystrophy. Jayasuriya’s fundraising provided the seed funding needed for Marbán’s laboratory to launch initial investigations. The biotechnology company Capricor Therapeutics licensed Marbán’s technology and continued the work by running clinical trials studying the safety and efficacy of deramiocel.

“This is the first Phase III trial to show that a cell therapy is effective against a genetic disease, or any type of heart disease,” said Marbán, the Mark S. Siegel Family Foundation Distinguished Professor. 

Investigators plan to continue studying the therapeutic effects of deramiocel, including whether it can be used to treat other diseases with major unmet medical needs.

“These results represent an important advance for cell-based therapy, one driven by relentless scientific pursuit made by Dr. Marbán and team,” said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai.

Authors: A complete list of HOPE-3 investigators can be found in the supplementary appendix of the study.

Funding: The HOPE-3 trial was funded by Capricor Therapeutics Inc.

Disclosures: Eduardo Marbán, MD, PhD, is an inventor of patents licensed by Capricor Therapeutics Inc. and holds founder's equity in the company.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

A new study led by Karlstaedt and published in Circulation reports that a specific enzyme plays an important role in keeping the heart beating. The discovery could help scientists create drugs that mimic the enzyme’s role and help people with heart failure, a condition in which the heart becomes too weak to pump blood properly.  

Karlstaedt, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai, has spent more than a decade studying heart metabolism—the chemical process that powers the heart. She spoke with the Cedars-Sinai Newsroom about her dedication to uncovering treatments for the millions diagnosed with heart failure every year.

How is the heart’s metabolism different from the metabolism of other parts of the body?

There are thousands of tiny molecules called metabolites—including amino acids, glucose and fatty acids—that act as an energy source to help cells function properly. The heart is the only organ that can use almost any metabolite.

The heart is also unique because it never stops beating. It's not like other muscles, which can rest. Fueling heart cells requires fine-tuned, organized chemical reactions. The system functions perfectly until something disrupts it, and metabolism is at its center. 

What was one of the major discoveries that led to your current work? 

My colleagues and I published a study in 2016 in which we discovered that the heart uses unusual fuel-processing routes to adapt to metabolites released by cancer cells. It’s like in a city where you have streets and traffic moves along those streets. If a construction site suddenly blocks a street, traffic finds another way around. The heart does the same thing.

We also found that in response to cancer-related metabolic stress, the heart suddenly started using an unusual enzyme called ATP-dependent citrate lyase, or ACL. This enzyme drives the process that creates fatty acids, something we didn’t think happened in heart cells. But when we blocked ACL, the heart could not pump well. That told us this enzyme might be much more important for the heart than previously thought.

Could you describe your recent discovery?

We found that when ACL slows down, heart function drops. To make this discovery, we studied heart tissue samples from people with healthy hearts and people with failing hearts. We also observed ACL in the hearts of laboratory mice. When ACL activity decreased, meaning it no longer efficiently produced fatty acids, the heart tried to adapt by taking up more sugar and rewiring parts of its metabolism. But those changes did not fully protect the heart. Instead, the heart had less available energy and did not pump as well.

To dig deeper, we used CardioNet, our computational model of heart metabolism. The model pinpointed another enzyme, IDH1, that compensates for the loss of ACL. When we reduced IDH1 in our model, the heart could pump better. We're now studying whether future heart failure therapies could target IDH1.

What do you hope to accomplish as this work progresses?

Heart failure can look similar from one patient to another, but the underlying metabolic changes may be different. We hope to use our computational model to predict which fuel pathways are disrupted in people with heart failure and which treatments can get the heart working better. We are not there yet, but this study is an important step toward understanding heart failure as a disease of both mechanics and metabolism.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“The majority of people who have a sudden cardiac arrest outside of a hospital will die, so the best protection is being aware of risk,” said Kyndaron Reinier, PhD, MPH, associate director of Epidemiology in the Center for Cardiac Arrest Prevention in the Smidt Heart Institute at Cedars-Sinai and an author of both studies. 

Sudden cardiac arrest happens when a problem with the heart’s electrical system causes the heart to stop beating. It is different from a heart attack, which is caused by a lack of blood flow to the heart. More than 350,000 people experience sudden cardiac arrest outside of a hospital in the U.S. each year, and only about 10% survive. 

Experts know that people with low left ventricular ejection fraction, when the heart’s main pumping chamber is weak and pumps less than it should, are at higher risk for sudden cardiac arrest. But this marker has become less effective and other indicators are needed to capture more people at risk.

“More than two-thirds of people who have cardiac arrest don’t have low left ventricular ejection fraction, so using this marker alone misses too many people,” Reinier said. 

A study published in the journal Circulation: Arrhythmia and Electrophysiology reports that warning symptoms combined with clinical history could predict imminent sudden cardiac arrest. A second study, published in the Journal of the American Heart Association (JAHA), reports that having more than one cardiac event over time could signal rising risk. 

Reading Warning Symptoms

In the Circulation: Arrhythmia and Electrophysiology study, investigators used machine learning to identify combinations of symptoms and medical history that best predicted sudden cardiac arrest in the near future. 

The study included people enrolled in two separate, longstanding studies in Oregon and Ventura County, California, that were founded by Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention in the Smidt Heart Institute. The investigators compared 364 people who called 911 when experiencing symptoms such as chest pain and survived sudden cardiac arrest, with 313 people who called 911 for similar symptoms but did not experience sudden cardiac arrest. 

The analysis found that people with sudden cardiac arrest were more likely to have a combination of shortness of breath and diagnosed coronary artery disease or heart failure than people who did not experience sudden cardiac arrest. Seizure-like symptoms without chest pain or shortness of breath were also more common in people who experienced sudden cardiac arrest.

The investigators also found that chest pain combined with coronary artery disease predicted imminent arrest in women, while chest pain combined with heart failure predicted it in men. 

Warning symptoms most often occurred at least 15 minutes prior to the sudden cardiac arrest, a time frame that would make it possible to call 911. In earlier research, the investigators found that 81% of people delayed their 911 call, reducing their chances of successful revival by ambulance paramedics. 

These findings could be used to create risk-predicting algorithms for use by urgent care and emergency medicine providers, the investigators said. “While more research is needed, such risk prediction algorithms have the potential to avoid 911 call delays following warning symptoms of sudden cardiac arrest,” said Chugh, vice dean and chief AI health research officer at Cedars-Sinai.

Tracking Risk Over Time

The JAHA study was carried out in the Observational Study of Cardiac Arrest Risk (O.S.C.A.R.) cohort at Cedars-Sinai, established by Chugh, that has been tracking the health of approximately 400,000 residents of Los Angeles County from 2017 onward. Of these, the investigators followed more than 6,700 people hospitalized at Cedars-Sinai for heart failure and more than 2,900 people hospitalized in the health system for acute coronary syndrome, when an artery blockage reduces blood flow to the heart. 

Investigators found that patients in both groups who experienced a recurrent cardiovascular event faced a higher risk of sudden cardiac arrest. 

Patients who had a second coronary artery blockage were more than three times as likely to experience sudden cardiac arrest as those without a recurrence. Patients who were hospitalized a second time for heart failure were nearly twice as likely to experience sudden cardiac arrest. Risk climbed with each additional heart failure hospitalization. The investigators compared the findings to what was found in participants of the Framingham Heart Study, which enrolled participants about 50 years earlier. The results were similar, however the heart failure result in that study did not reach statistical significance.

Reinier said that physicians should consider sudden cardiac arrest as being more likely when a patient is hospitalized for a heart issue a second time.

“This may mean running additional tests,” Reinier said. “It may mean educating the patient about what cardiac arrest is and the importance of having a family member who knows to call 911 and start CPR immediately if their loved one collapses.”

Moving Beyond Dead Ends

Chugh, senior author of both studies, said the combined findings point toward a more flexible approach to prediction.

“Near-term and long-term predictions are parallel approaches that can help us move past roadblocks we face in preventing death from this lethal heart event,” Chugh said.

Additional research, including studies in different populations, are needed to confirm whether the factors the investigators studied could be used in prediction tools, study authors said. 

Cedars-Sinai investigators continue to study predictors of sudden cardiac arrest, and their work includes using AI to study patterns in heart tests called electrocardiograms and looking for genetic causes. 

Additional Cedars-Sinai authors in the Circulation: Arrhythmia and Electrophysiologystudy include Harpriya Chugh, BS; Vishnu Kadiyala, MD; Arayik Sargsyan, MPH; Audrey Uy-Evanado, MD; Kotoka Nakamura, PhD; Elizabeth Heckard, MS; Marco Mathias, BS.

Other authors include Tristan Grogan, MS; David Elashoff, PhD; Angelo Salvucci, MD; and Jonathan Jui, MD, MPH.

Funding: Dr. Chugh was funded by the National Heart Lung and Blood Institute, National Institutes of Health.

Additional Cedars-Sinai authors in the Journal of the American Heart Association study include Marita Knudsen Pope, MD, PhD; Harpriya Chugh, BS, MSHS; Thien Tan Tri Tai Truyen, MD; Marco Mathias, BS; and Audrey Uy-Evanado, MD.

Other authors include Honghuang Lin, PhD; Dan Atar, MD, Nichole Bosson, MD, MPH, and Emelia J. Benjamin, MD, ScM

Funding: The Framingham Heart Study is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Dr. Benjamin is partially funded by The National Heart, Lung, and Blood Institute, National Institutes of Health.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Smidt Heart Institute cardiologist Janet Wei, MD, is one of the authors of a maternal health report from the National Academies of Sciences, Engineering, and Medicine, a nonprofit organization that reviews published research and provides advice to the U.S. government. Wei, associate professor of Cardiology and Biomedical Sciences, sat down with the Cedars-Sinai Newsroom to explain how pregnancy affects women’s hearts.   

How does pregnancy increase cardiovascular risk?

Pregnancy acts as a stress test for the heart and can uncover, or even worsen, problems like high blood pressure and diabetes. During pregnancy, the heart must work harder to support a growing fetus, and cardiac stress often continues after delivery.

Cardiovascular disease is the leading cause of pregnancy-related death in the U.S., yet most of these deaths are preventable. The National Academies of Sciences, Engineering, and Medicine report on maternal health highlights that although 57% of cardiovascular-related deaths occur between seven days and one year postpartum, preventive care is often focused on the prenatal and immediate postpartum period.

What are two takeaways from the report?

The committee reviewed published medical research and gathered input from a wide range of stakeholders, including clinicians, professional societies, advocacy organizations and patients.

Several takeaways became clear. The report recommends, for example, that clinicians treat pregnant women with chronic hypertension so that their blood pressure is reduced to less than 140/90 millimeters of mercury.  This is because consistently elevated blood pressure during pregnancy can cause pregnancy complications and increase a woman’s risk for developing cardiovascular disease.

The new guidelines also recommended that clinicians caring for patients with postpartum hypertension or other hypertensive disorders give their patients home blood pressure monitors and use a program that allows the patients to report their readings. This way, clinicians can adjust treatment and set clear thresholds for action. 

Cedars-Sinai is already doing this through a postpartum blood pressure monitoring program that sends patients home with a blood pressure cuff and allows them to transmit readings to their care teams. (Kimberly Gregory, MD, MPH, director of the Division of Maternal-Fetal Medicine at Cedars-Sinai, served as an adviser to the National Academies committee that created the maternal health report.)

How often should women visit a doctor in the year after giving birth?

How frequently a woman should see her doctor during the postpartum period depends on her cardiovascular risk. 

Not every woman can easily see a doctor or health specialist—especially in rural areas or when cost is a concern. Therefore, the National Academies report recommends the Health Resources and Services Administration use its telehealth, rural health and maternal health programs to reduce geographic, financial and system barriers to preventive cardiovascular services.

What can pregnant women do to protect heart health?

The National Academies created a resource for women that includes the following advice:

Share your history. Tell your healthcare team your family history of heart disease, especially early heart attacks or strokes, and your pregnancy history, including any past complications.

Keep postpartum follow-up appointments on your calendar. It’s important not to miss these appointments because risk for complications continues through the first year after delivery.

Take warning signs seriously—trust your instincts. If something feels wrong during pregnancy or after birth, seek care right away and tell providers that you’re pregnant or that you gave birth recently.

Read more from Cedars-Sinai Stories and Insights: High Blood Pressure—What Women Need to Know

Younger people who experience sudden cardiac arrest are more likely to have a genetic cause than older people who experience it, according to new research from the

“If you have a family member who suffered sudden cardiac arrest, it is important to undergo genetic testing to determine if you harbor a genetic variant that increases your risk of sudden cardiac arrest or other heart conditions,” said Evan Kransdorf, MD, PhD, assistant professor of Cardiology in the Smidt Heart Institute and first author of the study. “For people who carry a variant linked to sudden cardiac arrest, a cardiologist can prescribe medications or lifestyle changes that can decrease the chances of experiencing this dangerous event.”

Sudden cardiac arrest, an electrical malfunction that causes the heart to beat very rapidly, is fatal in 90% of cases, according to the American Heart Association. The Cedars-Sinai Health Sciences University investigators found that 10% of people 29 and younger who have sudden cardiac arrest carry genetic variants linked with the condition.

The team analyzed blood samples from more than 3,000 people who experienced sudden cardiac arrest in Portland, Oregon, and Ventura County, California. The samples came from the ongoing Oregon Sudden Unexpected Death Study and the Ventura Prediction of Sudden Death in Multi-Ethnic Communities study—both created by Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention in the Smidt Heart Institute, to improve understanding of the condition.

Investigators performed whole genome sequencing, which maps a person’s entire genetic code. They identified 15 genes in which damaging genetic variants can occur and disrupt the gene’s function and increase risk of sudden cardiac arrest. They found the prevalence of damaging genetic variants decreased with age:

• 10% of people age 29 and younger harbored a damaging genetic variant.
• 7% of people age 30-49 harbored a damaging genetic variant.
• 4% of people age 50-69 harbored a damaging genetic variant.
• 3% of people age 70 and older harbored a damaging genetic variant.

In older people, sudden cardiac arrest is more likely to be caused by a narrowed or blocked heart blood vessel rather than a heart condition caused by a damaging genetic variant, according to the investigators.

The investigators said more research will help uncover other genes linked to sudden cardiac arrest.

“This study is more representative of the U.S. population than other studies because it includes data from two communities rather than data from people already being seen at a medical center,” said Chugh, who is also vice dean and chief artificial intelligence health research officer at Cedars-Sinai and senior author of the study.

Additional Cedars-Sinai authors include Marco Mathias, BS; Kotoka Nakamura, PhD; Harpriya Chugh, BE, MSHS; David Nguyen, BS; Paul D. Pharoah, MD, PhD; and Kyndaron Reinier, MPH, PhD.

Other authors include Jonathan Tyrer, PhD; Zeynep Akdemir, PhD; Eric Boerwinkle, PhD; and Bing Yu, PhD. 

Funding: The study was funded by The National Institute of Health, NHLBI Grants R01HL145675 and R01HL147358; NIH DHHS Contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, HHSN268201700005I.

Read more from Cedars-Sinai Stories and Insights: Heart Attack, Cardiac Arrest, Heart Failure—What’s the Difference?

The study, “Real-World Outcomes of Transcatheter Tricuspid Valve Replacement: Analysis From the STS/ACC TVT Registry,” published in the Journal of the American Medical Association.

“These findings show that transcatheter tricuspid valve replacement is translating well from the clinical trial setting into routine practice across the United States,” said Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai, the Karsh Distinguished Chair in Interventional Cardiology in the Smidt Heart Institute, and corresponding author of the study. “In a large, older and medically complex patient population, we saw very high procedural success, near-complete elimination of tricuspid regurgitation, and rapid improvement in how patients feel and function.”

Tricuspid regurgitation occurs when the tricuspid valve does not close properly, allowing blood to flow backward in the heart. The condition is common in older adults and can lead to worsening heart failure symptoms, repeated hospitalization and increased risk of death.

Historically, open-heart surgery was often the only treatment option for this condition, but many older patients were not candidates because of age or other medical problems. Today, transcatheter tricuspid valve replacement offers a less invasive alternative in which doctors replace the damaged valve using a catheter, or tube, threaded through a blood vessel.

Researchers analyzed 1,034 attempted TTVR procedures performed between February 2024 and March 2025 at 82 medical centers across the U.S. The average patient age was 77.

The analysis found that more than 98% of patients had the valves successfully implanted. At 30 days post-procedure, more than 97% of patients had their condition improve to mild or minimal tricuspid regurgitation, and patients reported substantial improvement in symptoms, physical and social function, and quality of life.

Study authors note that early real-world outcomes were consistent with results from the TRISCEND II randomized trial of TTVR. Patients in this new study, however, experienced lower incidence of bleeding and heart block requiring electronic pacemaker implantation than patients participating in TRISCEND II. The current study also found that outcomes were generally consistent in patients with and without preexisting cardiac implantable electronic devices such as pacemakers, an important finding because these devices are common in patients with severe tricuspid valve disease.

“For patients with severe tricuspid regurgitation, treatment options have historically been limited, especially when surgery carries high risk,” said Aakriti Gupta, MD, assistant professor of Cardiology and study author. “What is especially encouraging here is that in real-world care, not just in a randomized trial, patients experienced meaningful improvement in symptoms and quality of life within only 30 days.”

Investigators said the results support the growing role of TTVR as a treatment option for patients with severe tricuspid regurgitation and highlight the importance of continued follow-up to understand longer-term outcomes.

Moody Makar, MD, associate professor of Anesthesiology at Cedars-Sinai, is also an author of the study.

Additional authors include Brian P. O’Neill, MD; Christina Lalani, MD; Rahul Sharma, MBBS; Pradeep Yadev, MD; Tiberio M. Frisoli, MD; Vinod Thourani, MD; Mackram F. Eleid, MD; James Lee, MD; Vasilis C. Babaliaros, MD; Christiane Haeffele, MD, MPH; Tanvir J. Bajwa, MD; Peter Flueckiger, MD; Robert J. Cubeddu, MD; Laura J. Davidson, MD; Ratnasari Padang, MBBS, PhD; Pedro Villablanca Spinetto, MD; Suhail Allaqaband, MD; Akhil Narang, MD; Mathew Williams, MD; Patrick Gleason, MD; Gilbert H.L. Tang, MD; Sahil Khera, MD; John P. Vavalle, MD; Isida Byku, MD; Jeremiah P. Depta, MD; Santiago Garcia, MD; Samir Kapadia, MD; Alan Zajarias, MD; Jake M. Chanin, MD; Susheel K. Kodali, MD; Howard C. Herrmann, MD; M. Andrew Morse, MD; George Petrossian, MD; Joseph A. Sivak, MD; Rebecca T. Hahn, MD; Yang Song, PhD; Martin B. Leon, MD; Robert W. Yeh, MD, MSc; Charles J. Davidson, MD.

The study was funded by Edwards Lifesciences.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The findings, published in Science Translational Medicine, could one day improve management of heart failure, in which the heart fails to pump enough blood to meet the body’s need for blood and oxygen. Poor use of oxygen by the heart is an early indicator of heart failure, which affects nearly 7 million people in the U.S.

“Our study shows how MRI could be used to quickly and noninvasively determine heart oxygen use in the clinic,” said Hsin-Jung Yang, PhD, director of Cardiac Imaging Research in the Biomedical Research Imaging Institute and corresponding author of the study. “With further research and development, this advance could unlock new frontiers in early diagnosis, personalized therapy and next-generation treatments for heart failure.”

The current gold standard for measuring heart oxygen use, coronary sinus catheterization, requires threading a thin, flexible tube called a catheter from a patient’s neck or groin into the heart's main vein. The procedure, which takes 30 to 60 minutes and involves injection of a contrast dye to guide the catheter, is too invasive for routine heart oxygen monitoring.

MRI uses radio waves, a strong magnet and a computer to create detailed images of areas inside the body. Standard MRI can only produce clear images of the heart, which moves with every beat and every breath, if patients hold their breath at points during the exam. And in order to use these images to measure oxygen, doctors have to take multiple MRI scans—a process that takes several minutes—and draw blood at the same time.

“The system we designed addresses the motion of the heart,” Yang said. “Patients do not need to hold their breath, and it can give precise numbers within three minutes.”

The team proved the accuracy of its MRI method by using it to measure heart oxygen use in patients with and without heart failure, and comparing its readings to readings obtained by heart catheterization.

“Noninvasive testing that detects issues in the heart’s use of oxygen can provide an early warning that heart failure is developing,” Yang said. “Now that we have promising cardiometabolic therapies lined up, earlier detection may allow us to take steps to prevent and treat the condition.”

David Underhill, PhD, chair of the Department of Biomedical Sciences, said the study makes a major contribution toward improving healthcare for heart disease, the No. 1 cause of death.

“Along with its potential for saving lives through early intervention for heart failure, this accessible tool could offer new avenues for cardiac research,” Underhill said. “It could allow us to study patients who have risk for, but no symptoms of, heart failure without exposing them to catheterization, contrast or radiation.”

Additional Cedars-Sinai authors include Li-Ting Huang, Chia-Chi Yang, Archana Malagi, Xinqi Li, Ghazal Yoosefian, Xinheng Zhang, Ziyang Long, Xiaoming Bi, Janet Wei, Alan C. Kwan, C. Noel Bairey Merz and Debiao Li.

Other authors include Guan Wang, Henghui Zhang, Ranran Zhang, Hao Ho, Yuheng Huang, Michael D. Nelson, Anthony Christodoulou and Rohan Dharmakumar.

Funding: This work was supported by grants from National Institutes of Health (R01HL165211 to H.-J.Y. R01HL181091 to H.-J.Y., R01HL156818 to H.-J.Y., R01HL148788 to R.D., R01HL146158 to C.N.B.M., R01HL124649 to C.N.B.M., R01HL153500 to J.W., K23HL125941 to C.N.B.M., U54AG065141 to C.N.B.M., and U54AG094168-01 to C.N.B.M.), The Barbra Streisand Women’s Cardiovascular Research and Education Program to C.N.B.M., The Linda Joy Pollin Women’s Heart Health Program to C.N.B.M.,The Erika Glazer Women’s Heart Health Project to C.N.B.M., The Adelson Family Foundation to C.N.B.M., and US Department of Defense (HT94252510956 to H.-J.Y.).

Competing interests: C.N.B.M. serves as a director and holds stock in iRhythm. D. Li, A. G. Christodoulou, J. L. Shaw, Y. Xie, and C. Nguyen are inventors on US patent no. 10,436,871 (“Low-rank tensor imaging for multidimensional cardiovascular MRI”). H. J. Yang and C. C. Yang are inventors on a provisional US patent, US Prov 63/721,228 (PCT/US2025/055499, “Systems and methods for determining oxygen consumption using magnetic resonance imaging”). The other authors declare that they have no competing interests.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Throughout her career, Cheng has maintained National Institutes of Health funding for research aimed at uncovering the drivers of cardiovascular aging. She has authored more than 450 scientific studies, many appearing in high-impact journals, including JAMA, Circulation and The New England Journal of Medicine.

Cheng identified differences in how males and females develop elevated blood pressure and demonstrated how people vary in their responses to COVID-19 vaccines over time. Her research has garnered multiple awards and contributed to Cedars-Sinai’s reputation as an international leader in biomedical sciences.

“Dr. Cheng is the perfect leader to build and enrich our already flourishing Department of Cardiology,” said Shlomo Melmed, MB, ChB, dean of the Medical Faculty and executive vice president of Medicine and Health Sciences. “We welcome her to this academic leadership role and look forward to the contributions she will make in strengthening the Smidt Heart Institute.”

Cheng, who succeeds Christine M. Albert, MD, MPH, has served on the editorial boards of major professional journals and on leadership committees for the American Society for Clinical Investigation, the American Heart Association and the American College of Cardiology.

She founded the largest COVID-19 clinical research program on the West Coast at the outset of the pandemic in 2020. More recently, she has led research to investigate the public health effects of the 2025 Los Angeles wildfires.

Cheng has mentored dozens of junior faculty members in cardiology, anesthesiology, neurology, obstetrics and oncology, taking special pride in advising early-career investigators as well as high school and college students.

“I look forward to supporting the Smidt Heart Institute’s talented clinicians and researchers as they work to improve the lives of those affected by cardiovascular disease,” Cheng said.  

Cheng received her bachelor’s degree from Harvard College and her medical degree from McMaster University in Canada, as well as a master of medical science degree from the Massachusetts Institute of Technology and a master of public health degree from Harvard University. She completed her internal medicine training at Johns Hopkins University and cardiology training at Brigham and Women’s Hospital, where she served as associate director of the Cardiovascular Imaging Core Laboratory.

In her new role, Cheng will lead strategic clinical, research and educational growth for the Department of Cardiology. As the new department chair, she will hold the Stephen R. Corday, MD, Distinguished Chair in Cardiology.

“Dr. Cheng has strengthened our institution and made many meaningful contributions through her research laboratory since joining Cedars-Sinai seven years ago,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark Siegel Family Foundation Distinguished Chair. “We are excited for her to continue developing our world-class cardiology department.”

Read more from the Cedars-Sinai Newsroom: Cedars-Sinai Reports Heart Attacks, General Illness Spiked After LA Fires

The new, five-year grant to examine sex-based differences in multiple age-related diseases supports the Microvascular Aging Effects—Women’s Evaluation of Systemic Aging Tenacity in Heart, Brain and Frailty study, commonly called MAE-WEST HBF. The acronym is a nod to the late actor, who reportedly once said, “You’re never too old to become younger.”

MAE-WEST HBF is funded as a Specialized Center of Research Excellence (SCORE) on Sex Differences through the NIH Office of Research on Women’s Health. It builds on prior research from Cedars-Sinai’s Barbra Streisand Women’s Heart Center that showed small blood vessel disease, chronic inflammation and iron buildup in women are linked to impaired heart, brain and kidney function, and declining physical strength.

“Armed with this funding, we are eager to continue uncovering biological mechanisms behind sex-based differences in aging and heart health,” said C. Noel Bairey Merz, MD, the principal investigator of MAE-WEST HBF and director of the Barbra Streisand Women’s Heart Center in the Smidt Heart Institute. “A better understanding of the causes of common age-related conditions in women could lead to more effective prevention and treatment strategies.”

For more than two decades, Bairey Merz and her team have made landmark discoveries in women’s heart health, particularly in coronary microvascular disease—a condition that occurs more often in women and results from damage to the heart’s smallest blood vessels. Symptoms of the condition, which can be subtle, were previously often dismissed, misdiagnosed or undertreated. But improved diagnostic tools and treatments resulting from Bairey Merz’s discoveries have contributed to significant reductions in cardiovascular deaths among women.

The new study brings together a multidisciplinary team of experts, including Pascal Sati, PhD, director of the Neuroimaging Program in the Department of Neurology at Cedars-Sinai. Collaborators at UCLA will oversee biostatistical analysis, while those at the University of Texas at Arlington will lead frailty research.

“We now have effective treatments for small vessel dysfunction in the heart,” Bairey Merz said. “If we can better understand its effects on the brain and musculoskeletal system, we may be able to find ways to prevent or slow multiple age-related diseases—including declines in cognition and mobility—in both women and men.”

Although women generally live longer than men do, women experience higher rates of chronic conditions and so spend more years in poor health. Ultimately, investigators hope the new study will pave the way for a future in which healthy aging for women includes earlier screenings, advanced technology, and preventive care that identifies risks and stops diseases before they begin.

“After more than 25 years of progress in women’s cardiovascular research, this grant helps advance whole-person care that supports heart health, brain function and physical strength,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute. “All three are equally essential to healthy aging.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Using a powerful technology called single-cell proteomics, these detectives track molecules called proteins, cell by cell, to shed new light on how the human body works and how diseases develop. Their tenacity has helped make Cedars-Sinai one of the world’s leading institutions in this rapidly evolving frontier of medical science.

Proteomics, the study of the complete set of proteins expressed by an organism, provides a powerful window on what is happening in the human body. That’s because these hard-working molecules carry out nearly every bodily activity.

The challenge is that a typical laboratory sample of human tissue contains thousands of cells, and each cell is packed with multiple copies of thousands of different proteins.

To connect each protein to the correct cell, single-cell proteomics investigators rely on equipment called mass spectrometers. These machines, which are like highly sophisticated scales, use magnetic forces to separate proteins by their molecular weight or mass. With the proteins sorted, investigators can identify them and match them to the cells that contained them.

Using mass spectrometry, Cedars-Sinai investigators have uncovered new types of heart cells. They are unlocking secrets of how our arteries work. And they are developing proteomics technology that can analyze thousands of cells in minutes instead of hours or days.

More discoveries are on the way. At the Cedars-Sinai Board of Governors Innovation Center, mass spectrometers operate around the clock, seeking, sorting and scrutinizing proteins. The machines are part of the center’s Alfred E. Mann Single Cell Precision Medicine Center.

But it’s really the people, not the machines, who are most responsible for Cedars-Sinai’s leading role in this nascent discipline. Below are profiles of three investigators who rank among the top international experts in single-cell proteomics.

The Visionary

It is impossible to conduct a serious discussion of proteomics without mentioning Jennifer Van Eyk, PhD, who helped pioneer this discipline and recently served as president of the international Human Proteome Organization, the field’s premier scientific association. In 2024 she was listed by The Analytical Scientist as one of the world’s 20 most impactful analytical scientists in human health.

“I started working in proteomics before the word ‘proteome’ was coined in the 1990s,” Van Eyk said in a recent interview. “At that time, I was among just a few scientists around the world who were trying to accurately measure proteins on a large scale.”

Van Eyk’s passion is clinical proteomics, which applies scientific discoveries to patient care. At Cedars-Sinai, she directs the Smidt Heart Institute’s Advanced Clinical Biosystems Research Institute, which she founded in 2014 to foster collaboration among scientists, physicians and biotechnology companies.

One of Van Eyk’s most recent achievements was to co-lead a study revealing that cardiomyocytes, the muscle cells of the heart, are not all identical. Using single-cell proteomics, she and her colleagues discovered two new hybrids of cardiomyocytes that produce both heart- and neuron-related proteins. The team is now exploring whether gender differences in cardiomyocytes could affect how a person responds to medications.

Given that drugs generally target proteins, Van Eyk sees single-cell proteomics as a critical new tool for troubleshooting disease treatments and testing new ones.

“Suppose you have a drug that works 50% of the time,” she said. “Does that mean it's working 50% in every cell, or is it working 100% in 50% of the cells? The answer is important because it allows you to fix the problem. Single-cell proteomics can provide that information.”

As director of Basic Science Research in the Barbra Streisand Women’s Heart Center and the Erika J. Glazer Chair in Women’s Heart Health, Van Eyk has a special focus on cardiology. But she also collaborates on studies of conditions as diverse as pulmonary hypertension, breast cancer and amyotrophic lateral sclerosis, also known as ALS.

Van Eyk envisions a bright future for single-cell proteomics.

“We're finding such unexpected things that you couldn't even have thought about before using these methodologies,” she said. “And the discoveries will continue until we've done enough, and then we'll do the next breakthrough in the technology.”

The Racer

Before she was a scientist, Sarah Parker, PhD, was an aspiring Olympic speed skater. Having narrowly missed that goal in 2002, she now applies the Olympic motto of “Faster, Higher, Stronger – Together” to proteomics.

The together aspect is important. Parker, an associate professor of Cardiology and Biomedical Sciences, co-directs the Proteomics and Metabolomics Core at Cedars-Sinai with Van Eyk. During her decade-long career at Cedars-Sinai, she has been a versatile team player while heading her own laboratory that has produced breakthrough studies in atherosclerosis, cancer and proteomics applications.

Parker is also striving to make single-cell technology faster and stronger through higher volume. With colleagues, she is perfecting so-called “high throughput” techniques that enable a mass spectrometer to analyze proteins in tissues from multiple people. The bigger the sample, the better the chance of finding rare cells and discovering something new about the body.

“The challenge is that to perform this analysis, you need to quickly turn and burn through a lot of cells in a reasonable amount of time,” Parker said.

In 2023, she co-led an influential Cedars-Sinai study that devised a novel solution: Get rid of the dead time between loading one sample and acquiring the data from a subsequent sample by toggling back and forth between the two processes. Using this system, a mass spectrometer can identify more than 1,000 proteins in individual cells in 15 minutes, allowing nearly 100 cells to be measured each day. This rate was double the industry standard at the time.

In current research funded by the National Institutes of Health, Parker is using single-cell proteomics to investigate how hormones influence aortic aneurysms, the bulges in the wall of the main artery from the heart that can rupture, with life-threatening results. The potential clinical application is to design better drug treatments for both males and females with this serious condition.

Parker’s longtime interest in the cardiovascular system grew from courses she took as a college student and athlete preparing for a career in sports psychology.

After retiring from professional sports, Parker learned about proteomics while earning a PhD in physiology at the Medical College of Wisconsin in Milwaukee. As a postdoctoral fellow at Johns Hopkins University in Baltimore, she was mentored by Van Eyk, who later moved her laboratory to Cedars-Sinai and encouraged Parker to join her there.

“I really liked everything about Cedars-Sinai,” Parker said, including the collaborative ethos. “On the proteomics team, we’re on most of each other’s papers—not all of them, but most of them.”

The Data Scientist

To Jesse Meyer, PhD, an assistant professor in the Department of Computational Biomedicine at Cedars-Sinai, health comes down to one number: age.

“Aging is the biggest predictor of most diseases,” he said. “If we can deeply understand aging, then we can potentially delay the onset of many diseases at once instead of spending so much energy targeting each disease separately.”

The quest for that knowledge led Meyer to proteomics and data science, an interdisciplinary field that uses statistics, computer science and mathematics to uncover meaningful patterns in large sets of data.

“What is so cool about proteomics is that proteins are tiny machines in your cells, that we have so many of them and that they are so diverse,” he said.

For data scientists like Meyer, quantifying these tiny machines is a labor of love.

Meyer first encountered protein biochemistry and mass spectrometry as an undergraduate studying plants at the University of Minnesota in Minneapolis. After completing his PhD in chemistry and biochemistry at the University of California, San Diego, he decided to use his skills to help people. That led him to take a postdoctoral research fellowship at the Buck Institute for Research on Aging in Novato, California, where he learned to apply proteomics, and the study of small molecules called metabolites in cells and tissues, to problems related to aging.

Meyer established his laboratory in 2020 and relocated to Cedars-Sinai in 2022, where his research includes developing informatics tools for proteomics, optimizing single-cell workflows, and applying these approaches to single-cell and single muscle fiber proteomics studies of muscle aging.

Based on his achievements in proteomics at such an early career stage, the US Human Proteome Organization presented Meyer with the 2025 Robert J. Cotter New Investigator Award. That year’s advances by Meyer included co-leading the creation of a user-friendly web platform for analyzing mass-spectrometry data that facilitates sharing among multiple collaborators.

In a recent publication, in the peer-reviewed journal Cell Genomics, Meyer and his colleague, project scientist Amanda Momenzadeh, PharmD, offer an overview of the current state of single-cell proteomics. Despite the field’s many challenges, they conclude that single-cell proteomics is poised to transform our understanding of biological complexity.

At this critical moment, you would need a crystal ball to foretell the future of this dynamic science. But judging from their track records, Cedars-Sinai investigators are likely to be at the forefront of the next big innovation.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“Wildfires that spread into urban areas have proven to be extremely dangerous because of how quickly they move and what they burn and release into the environment,” said Susan Cheng, MD, MPH, vice chair of Research Affairs in the Department of Cardiology in the Smidt Heart Institute and senior author of the study, published in JACC. “Our research suggests the Eaton and Pacific Palisades fires had an immediate effect on people’s health.”

The Cedars-Sinai Emergency Department is located on the academic medical center’s main campus, about 10 miles from Pacific Palisades and about 20 miles from Altadena, the locations where the largest L.A. fires ignited in January 2025. Investigators collected data on emergency department visits during the 90 days after the fires started, from Jan. 7 to April 7, 2025. They compared this data with emergency visit data collected during the same calendar period in the years 2018 through 2024. 

Although there wasn’t a significant difference in total emergency department visits during the first 90 days following the start of the wildfires in 2025 as compared with other years, there was a drastic increase in emergency department visits for certain conditions. Investigators found a 118% increase in visits for general illness, 46% increase in the number of visits for heart attack, and a 24% increase in visits for pulmonary illness when compared to the average rate of these conditions diagnosed during the same time window in the past seven years. 

“Fine particles released by wildfires can enter the body and cause injury, particularly to the heart and lungs,” said Cheng, who is also the Erika J. Glazer Chair in Cardiovascular Health and Population Science in the Smidt Heart Institute at Cedars-Sinai. “Stress related to the fires may also contribute to a broad range of health issues.” 

The investigators found that abnormal blood test results related to general illness more than doubled in the 90-day period in 2025 as compared with that period in previous years. This is a finding not previously reported after major wildfires, according to the investigators.

“Abnormal blood test results could indicate that the body is responding to an external stressor such as toxins in the air,” said Joseph Ebinger, MD, MS, associate professor in the Department of Cardiology and first author of the study. “This study is an important step toward understanding how the Eaton and Palisades fires may have affected Angelenos’ health. We need more research to determine what we can do to mitigate any remaining risks and protect people from fire harm in the future.” 

This study is part of the larger LA Fire HEALTH Study, a research collaboration that seeks to determine the health effects of the fires that ignited in January 2025 in L.A. County. Investigators with Cedars-Sinai; the Harvard T.H. Chan School of Public Health; the Keck School of Medicine of the University of Southern California (USC); Stanford University; UCLA; the University of California, Davis (UCD); the University of California, Irvine (UCI); the University of Texas at Austin; and Yale University plan to study the impacts of the fires for the next 10 years. 

Additional Cedars-Sinai authors include Tzu Yu Huang, MS; Sandy Joung, MSHS, MBA; Juliane Kwong, BS; Wasay Warsi, MS, BS; Nancy Sun, MPS; Jesse Navarrette, MPA; Patrick Botting, DHSc; Zaldy S. Tan, MD, MPH; and Alan C. Kwan, MD.

Other authors include Brian L. Claggett, PhD, of Brigham and Women’s Hospital in Boston.

Funding: This work was partially supported by the Spiegel Family Fund, the Smidt Heart Foundation, and the Erika J. Glazer Family Foundation. 

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

CIRM, a taxpayer-funded state agency, supports the development of treatments for an array of diseases and conditions.

“The people of California expect us to deliver on the promise of cell and gene therapy using taxpayer dollars, a trust we take seriously,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai. “With these grants, we will work toward bringing novel therapies to patients with heart disease.”

Hope for Heart Failure

One grant of more than $10 million will allow Cedars-Sinai investigators to spend the next five years studying a treatment for a common form of heart failure called heart failure with preserved ejection fraction.

More than 6 million adults in the U.S. experience heart failure, which occurs when the heart doesn’t pump enough blood to meet the body’s needs. In heart failure with preserved ejection fraction, the most common type of heart failure, the heart is too stiff to properly fill with blood. It leads to death in more than half of people who develop the condition; no medications exist to stop the disease or extend a patient’s life.

David Lefer, PhD, director of Translational Research in the Department of Cardiac Surgery in the Smidt Heart Institute, will lead preclinical studies to investigate a new RNA drug, TY1, combined with the weight loss drug semaglutide as a new, more effective way to treat heart failure with preserved ejection fraction. Investigators aim to launch clinical trials within a few years.

“Obesity is a major risk factor for heart failure with preserved ejection fraction,” Lefer said. “We hope that creating a treatment that couples the benefits of a GLP-1 drug, and the immunomodulatory benefits of the RNA exomer TY1, might reduce the risk of death from heart failure.”

New Research Into a Cause of Sudden Cardiac Death

A second CIRM grant will provide more than $10 million over the course of five years for Cedars-Sinai investigators to study arrhythmogenic cardiomyopathy (ACM), a rare, inherited heart disease. ACM is the leading cause of sudden cardiac death in athletes and young people, and no medications exist to halt its progression. The grant will fund preclinical and safety studies of a new drug that may stop the disease and even reverse the heart damage it causes.

“Many people have no idea they have ACM until they experience cardiac arrest or heart failure,” said Alessandra Ciullo, PhD, a project scientist in the Smidt Heart Institute. “We’d like to offer those patients a treatment to reverse the disease and prolong lives.”

CIRM grants have supported several studies in the Smidt Heart Institute, including research into a potential new treatment for ventricular tachycardia and a cell therapy for pulmonary arterial hypertension.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Cedars-Sinai scientists have developed an experimental drug that repairs DNA and serves as a prototype for a new class of medications that fix tissue damage caused by heart attack, inflammatory disease or other conditions.

Investigators describe the workings of the drug, called TY1, in a paper published in Science Translational Medicine.

“By probing the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the study’s senior author. “TY1 is the first exomer—a new class of drugs that address tissue damage in unexpected ways.”

TY1 is a laboratory-made version of an RNA molecule that naturally exists in the body. The research team was able to show that TY1 enhances the action of a gene called TREX1, which helps immune cells clear damaged DNA. In so doing, TY1 repairs damaged tissue.

The development of TY1 has been more than two decades in the making. It started when Marbán’s previous laboratory at Johns Hopkins University developed a technique to isolate progenitor cells from the human heart. Like stem cells, progenitor cells can turn into new healthy tissue, but in a more focused manner than stem cells. Heart progenitor cells promote the regeneration of the heart, for example.

Later, at Marbán’s lab at Cedars-Sinai, Ahmed Ibrahim, PhD, MPH, discovered that these heart progenitor cells send out tiny molecule-filled sacs called exosomes. These sacs are loaded with RNA molecules that help repair and regenerate injured tissue.

“Exosomes are like envelopes with important information,” said Ibrahim, who is associate professor in the Department of Cardiology in the Smidt Heart Institute and first author of the paper. “We wanted to take apart these coded messages and figure out which molecules were, themselves, therapeutic.”

Scientists genetically sequenced the RNA material inside the exosomes. They found that one RNA molecule was more abundant than the others, hinting it might be involved in tissue healing. The investigators found the natural RNA molecule to be effective in promoting healing after heart attacks in laboratory animals. TY1 is the synthetic, engineered version of that RNA molecule, designed to mimic the structure of approved RNA drugs already in the clinic. TY1 works by increasing the production of immune cells that reverse DNA damage, a process that minimizes the formation of scar tissue after a heart attack.

“By enhancing DNA repair, we can heal tissue damage that occurs during a heart attack,” Ibrahim said. “We are particularly excited because TY1 also works in other conditions, including autoimmune diseases that cause the body to mistakenly attack healthy tissue. This is an entirely new mechanism for tissue healing, opening up new options for a variety of disorders.”

The investigators next plan to study TY1 in clinical trials. 

Other Cedars-Sinai authors include Alessandra Ciullo, Hiroaki Komuro, Kazutaka Miyamoto, Xaviar M. Jones, Shukuro Yamaguchi, Kara Tsi, Jessica Anderson, Joshua Godoy Coto, Diana Kitka, Ke Liao, Chang Li, Alice Rannou, Asma Nawaz, Ashley Morris, Cristina H. Marbán, Jamie Lee, Nancy Manriquez, Yeojin Hong, Arati Naveen Kumar, James F. Dawkins, and Russell G. Rogers.

Funding: This work was supported by National Heart, Lung, and Blood Institute grants R01 HL164588 and T32 HL116273, and R01 HL142579. This work was also supported by the California Institute for Regenerative Medicine grant TRAN1-15317.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

, marks a major step toward bringing automated echocardiography reports into patient care.

An echocardiogram uses ultrasound to create images of the heart and the results are analyzed by cardiologists or sonographers trained to read the results.

“Our AI model addresses a critical need,” said David Ouyang, MD, adjunct assistant professor in the Smidt Heart Institute at Cedars-Sinai and co-corresponding author of the study. “Many hospitals and clinics, especially in rural areas, do not have cardiologists or sonographers on staff. By generating accurate automated reports for physicians, we could improve access to this important diagnostic technology.”

The AI model investigators created, called EchoPrime, is a type known as a foundation model. These models are trained on massive datasets and can perform multiple tasks, including assessing ultrasound images and evaluating clinical report text. EchoPrime was trained on greater than 10 times more data than prior AI foundation models for echocardiography, making it the largest such model to date, according to the investigators. EchoPrime analyzes ultrasound images, then produces a verbal summary of heart function and structure meant to assist clinicians in diagnosing a patient.

The team trained EchoPrime on more than 12 million videos paired with cardiologists’ written interpretations of the tests. They then tested the model on data from Kaiser Permanente Northern California, Cedars-Sinai Medical Center, Stanford Health Care, Beth Israel Deaconess Medical Center in Boston, and Chang Gung Memorial Hospital in Taiwan. The investigators found that EchoPrime outperformed other foundation models for interpreting echocardiograms and matched or exceeded the performance of AI models designed to perform a single ultrasound task. It was also able to detect rare diseases of the heart.

The investigators are now conducting randomized clinical trials that compare reports generated by EchoPrime with those produced by cardiologists and sonographers. The goal is to confirm the accuracy of the model and ensure it is useful to cardiologists.

“This remarkable study from Dr. Ouyang and colleagues builds on several years of AI-enhanced imaging science at Cedars-Sinai,” said Sumeet Chugh, MD, vice dean and chief artificial intelligence health research officer at Cedars-Sinai. “EchoPrime is a unique foundational model that could potentially democratize AI-powered echocardiography interpretation on a global scale.”

Other Cedars-Sinai authors include Milos Vukadinovic, I-Min Chiu, Debiao Li and Susan Cheng.

Other authors include Xiu Tang, Neal Yuan, Tien-Yu Chen, Paul Cheng and Bryan He.

Funding: D.O. discloses National Institutes of Health NHLBI grants R00HL157421, R01HL173526 and R01HL173487.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Raj Makkar, MD, an interventional cardiologist in the Department of Cardiology in the Smidt Heart Institute, is senior author of a study published in The New England Journal of Medicine that describes the Phase III clinical trial results.

“These results show that seven years after treatment, health outcomes for patients were similar whether they underwent a minimally invasive procedure or open-heart surgery,” said Makkar, the inaugural director of the Karsh Division of Interventional Cardiology at Cedars-Sinai.

Aortic valve disease affects about 2% of the U.S. population, and risk rises with age, so the disorder is expected to become increasingly common.

The international PARTNER 3 trial involved 1,000 patients at 71 healthcare locations. Study participants had a severe form of aortic valve stenosis, a condition in which the heart’s aortic valve becomes so narrow and stiff that it cannot open fully to allow blood to pass through. The condition can cause heart failure or stroke.

Clinical trial participants were randomly chosen to undergo either open-heart surgery or a procedure called a transcatheter aortic valve replacement, also known as TAVR. All participants received a commercially available bioprosthetic valve called the SAPIEN 3 valve.

During TAVR, an interventional cardiologist threads a catheter through an artery to reach the heart and replace the diseased valve. Previous randomized controlled trials, including an earlier version of PARTNER 3, reported similar outcomes with TAVR and surgery five years after treatment in people with low to high risk for surgical complications.

For this study, investigators limited participation to patients considered to be at low surgical risk. Seven years after treatment, composite rates of death, stroke or rehospitalization related to treatment were 34.6% for TAVR (496 people) and 37.2% for surgery (454 people), a difference that was not statistically significant. The rates of failure for the bioprosthetic valve were similar: 6.9% for TAVR and 7.3% for surgery. In addition, patients in both groups reported comparable quality of life outcomes.

“These rich data exemplify the vital information clinicians need to guide patient treatment,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark Siegel Family Foundation Distinguished Chair. “We are proud to offer leading-edge clinical care while also advancing the field of cardiology with groundbreaking research.”

The Smidt Heart Institute is a global leader in treating heart valve disease surgically and with transcatheter procedures. Makkar, vice president of Cardiovascular Innovation and Intervention, leads a team of interventional cardiologists who perform almost 800 TAVRs each year.

The investigators next plan to report patient outcomes and valve durability at 10 years posttreatment.

Other authors include Martin B. Leon, MD; Michael J. Mack, MD; Philippe Pibarot, DVM, PhD; Rebecca T. Hahn, MD; Vinod H. Thourani, MD;   S.H. Kodali, MD; Philippe Genereux, MD;  Samir R. Kapadia, MD; David J. Cohen, MD, MSc; Stuart J. Pocock, PhD; Yiran Zhang, MS; Molly Szerlip, MD; Julien Ternacle, MD, PhD; S. Chris Malaisrie, MD; Howard C. Herrmann, MD; Wilson Y. Szeto, MD; Mark J. Russo, MD; Vasilis Babaliaros, MD; Tamim Nazif, MD; John G. Webb, MD.

The study was funded by Edwards Lifesciences. Makkar receives research grants and travel support from Edwards Lifesciences.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Led by interventional cardiologist Raj Makkar, MD, the six-and-a-half-year award from the Patient-Centered Outcomes Research Institute (PCORI) will fund a multi-center clinical trial of patients 50 and older who were born with a bicuspid aortic valve, a condition in which the aortic heart valve has two flaps regulating the flow of blood rather than the normal three. People with this condition typically develop aortic stenosis, when the aortic valve becomes so narrow that it impedes blood flow out of the heart.

Bicuspid aortic valve is the most common congenital heart condition, affecting approximately 2% of people, but little data exists comparing current treatments.

Heart valve disease can cause subtle symptoms at first but progress to heart failure if not diagnosed and treated early. Both surgery and transcatheter procedures are currently used to treat aortic stenosis. Transcatheter procedures use a thin, flexible tube called a catheter to reach the damaged valve. They are considered minimally invasive and are often recommended for patients who are at high risk for complications during surgery.

“Transcatheter aortic valve replacement has changed the paradigm for nonsurgical treatment of aortic stenosis, but it needs to be studied more rigorously in patients with bicuspid aortic valves,” said Makkar, a principal investigator of the study and vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai. “We look forward to addressing this important evidence gap with this PCORI-funded randomized controlled trial in collaboration with our esteemed co-investigators.”

Patients with bicuspid aortic valve stenosis enrolled in the clinical trial will be randomly assigned to have their aortic valve replaced via open-heart surgery or by a transcatheter procedure. Investigators will review results from both groups to understand which option results in better health outcomes.  

The inaugural director of the Karsh Division of Interventional Cardiology, Makkar is an authority in minimally invasive approaches to treating heart valve disease.

“The Smidt Heart Institute at Cedars-Sinai is a leader in both heart surgery and minimally invasive heart procedures,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the Mark S. Siegel Family Foundation Distinguished Professor. “This study reflects our commitment to advancing heart research and care.”

“This research is a prime example of how Cedars-Sinai fosters innovation and brings leading-edge and clinically effective research directly to patient care,” said Shlomo Melmed, MB, ChB, Cedars-Sinai's executive vice president of Medicine and Health Sciences and dean of the Medical Faculty. “The findings from this clinical trial will help doctors globally advise their patients born with a bicuspid aortic valve on the best and safest approach for treating their cardiac condition.”

The award has been approved pending completion of a business and programmatic review by PCORI and issuance of a formal award contract. PCORI is a non-profit organization with a mission to fund research designed to provide patients, their caregivers and clinicians with the evidence-based information needed to make better-informed health care decisions.

Read more on the Cedars-Sinai Newsroom: $35M Gift Creates Karsh Division of Interventional Cardiology

Although cardiovascular disease is a leading cause of death for women, they remain underrepresented in clinical trials for common heart conditions. These findings, by investigators in the Smidt Heart Institute at Cedars-Sinai, were presented at the 2025 European Society of Cardiology Congress in Madrid.

“Numbers don’t lie,” said Martha Gulati, MD, director of Preventive Cardiology in the Smidt Heart Institute and senior author of the paper. “We hope that keeping track of male-to-female participant ratios will motivate researchers to design trials that reflect the real-world population.”

Gulati presented the findings in an oral abstract at the European Society of Cardiology Congress. The results were simultaneously published in JAMA Network Open.

Gulati and colleagues reviewed data from 1,079 cardiovascular clinical trials registered on ClinicalTrials.gov from 2017 to 2023. Women accounted for 41% of the study participants. Investigators found the proportion of women included in clinical trials for certain conditions was much lower than the proportion of women who have these conditions.

The team applied a ratio called the participation-to-prevalence ratio (PPR) to capture whether the percentage of women in a clinical trial reflected how common the condition is among women. The participation-to-prevalence ratios for women were lowest for trials of coronary heart disease, acute coronary syndrome and stroke. Research on obesity and pulmonary hypertension had much higher female participation.

Investigators also found that younger women, ages 19 to 55, were more likely to participate in clinical trials than women 61 or older, and that women tended to enroll in trials studying lifestyle interventions and not trials studying procedures.

“Some studies might stop enrolling once they reach a certain number of people,” Gulati said. “It would be more equitable to continue enrolling until the number of women in the study reflects the proportion of women with that condition.”

The authors also recommend researchers improve outreach efforts to female patients.

“Although we’ve made progress, critical gaps persist,” said study co-author Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science in the Smidt Heart Institute. “It’s important to ensure that what we learn from research can be applied to women, who represent more than half of the world’s population.”

Frederick Berro Rivera, MD, is first author of the study. Other authors include John Vincent Magalong, MD; Nathan Ross B. Bantayan, BSc; Nicole Tesoro, MD; Mark Jason Milan, MD; Vikramjit Purewal, DO; Polyn Luz S. Pine, MD, MBA; Chieh-Mei Tsai, MD; Ann Marie Navar, MD, PhD; Sharon L. Mulvagh, MD; James Januzzi, MD; C. Michael Gibson, MD; Anuradha Lala-Trindade, MD; Kyla Lara-Breitinger, MD; and Mayra Guerrero, MD.

Funding: This work was supported by contracts from the National Heart, Lung, and Blood Institutes, General Clinical Research Center, National Center for Advancing Translational Sciences, Department of Defense, Gustavus and Louis Pfeiffer Research Foundation, Women’s Guild of Cedars-Sinai Medical Center, Ladies Hospital Aid Society of Western Pennsylvania, QMED, Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships (Cedars-Sinai Medical Center), Barbra Streisand Women’s Cardiovascular Research and Education Program (Cedars-Sinai Medical Center), Society for Women’s Health Research, Linda Joy Pollin Women’s Heart Health Program, Erika Glazer Women’s Heart Health Project, Adelson Family Foundation (Cedars-Sinai Medical Center), Robert A. Winn Diversity in Clinical Trials Career Development Award, and the Anita Dann Friedman Endowment in Women’s Cardiovascular Medicine & Research.

Read more on the Cedars-Sinai Blog: Why Diversity Matters in Clinical Trials

Coronary artery disease occurs when cholesterol deposits build up in the walls of the heart’s arteries, leading to formation of plaques that begin as areas of inflammation. When inflamed plaques grow large, they become prone to rupture, which can cause heart attack. Evolocumab is in a class of drugs called PCSK9 inhibitors that can dramatically reduce cholesterol.

“This discovery has important implications for understanding how evolocumab improves cardiovascular outcomes,” said Daniel S. Berman, MD, director of Cardiac Imaging in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and principal investigator of the study published in JACC: Cardiovascular Imaging.

Investigators administered evolocumab to 47 patients, all of whom had substantial buildup of noncalcified plaque in their coronary arteries. This type of plaque is regarded as higher risk than calcified plaque because it is softer and more likely to rupture and cause harm.

Before and 18 months after treatment with evolocumab, investigators studied inflammation in the coronary arteries using radioactive sodium fluoride and imaging with positron emission tomography (PET). They also used coronary computed tomography angiography (CCTA) coupled with a novel artificial intelligence quantitative method developed at Cedars-Sinai to measure changes in inflammation and plaque volumes in the coronary arteries.

The scans showed that, on average, plaque inflammation decreased and noncalcified plaque became smaller with evolocumab.

“Most attention has been placed on the cholesterol-lowering effects of PCSK9 inhibitors,” said Donghee Han, MD, a Cedars-Sinai internal medicine resident who is also a researcher in Berman’s laboratory and joint first author of the study. “Our findings demonstrate that reducing inflammation may be an important mechanism for reducing the risk of heart attack with these powerful drugs.”

Other Cedars-Sinai authors include Rebekah Park, Heidi Gransar, Mark Hyun, John D. Friedman, Sean W. Hayes, Louise E. J. Thomson, Alan C. Kwan, Prediman K. Shah, Sarah Wetzel, Chloe Findling, Piotr J. Slomka and Damini Dey. Other authors include joint first author Evangelos Tzolos, Matthew Budoff, Jacek Kwiecinski and co-senior author Balaji K. Tamarappoo.

This study was supported in part by NIH grants 1R01HL148787-01A1 and R35HL161195, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and Amgen Inc.  

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Michelle Kittleson, MD, PhD, director of Post Graduate Medical Education in Heart Failure and Transplantation, received the American College of Cardiology 2025 Distinguished Teacher Award. Richard Wright, MD, an advanced heart failure and transplant cardiologist and board chair of Pacific Heart Institute, an affiliate of Cedars-Sinai, received the Master of the ACC Award. And postdoctoral researcher Andrew Lin, MBBS, PhD, under the mentorship of Damini Dey, PhD, professor of Biomedical Sciences at Cedars-Sinai, is the co-recipient of the Jagat Narula Award for Outstanding Scholarship from JACC: Cardiovascular Imaging.

“Congratulations to Dr. Kittleson, Dr. Wright and Dr. Lin on this notable recognition from the ACC and JACC,” said Christine Albert, MD, MPH, chair of the Department of Cardiology and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. “We are proud of their substantial contributions to all aspects of cardiovascular medicine that encompass education, research and clinical care. It’s gratifying to see them receive recognition from their peers for their pioneering leadership in the field.”

The Distinguished Teacher Award recognizes a fellow of the ACC who has demonstrated innovative, outstanding teaching characteristics and compassionate qualities and has made major contributions to the field of cardiovascular medicine.

Kittleson, a professor of Cardiology, also is associate editor of the JACC. She is widely known as a participant in national educational efforts, including helping develop evidence-based cardiomyopathy and heart failure guidelines. She also is known for fostering an active and engaged social media community, sharing cardiology-related discussion points, questions and pearls of wisdom with followers.

“I’m humbled and grateful to be among the cardiovascular physicians and researchers nominated for and receiving this recognition from the American College of Cardiology,” Kittleson said. “Teaching is of great interest to me, and I consider it a privilege to teach new physicians as well as the public. As an academic medical center, we want our teaching to go far beyond the walls of Cedars-Sinai.”

The Master of the ACC Award honors fellows of the ACC who are consistent contributors to the goals and programs of the college and who have provided leadership in important college activities, serving with distinction for at least 15 years and providing leadership on various programs and committees.

Wright has served as president of the California Chapter of the ACC. He is a highly regarded lecturer and was co-author of the U.S. guidelines on management of patients with heart failure. He also is a previous recipient of the Specialist of the Year Award from the California Chapter of the ACC.

“The ACC is known for its pronounced focus on setting new standards in cardiovascular medicine,” Wright said. “I’ve enjoyed and learned much from my peers as part of the ACC over many years.”

Lin’s research focuses on coronary plaque phenotyping using coronary computed tomography and artificial intelligence techniques.

The Jagat Narula Award for Outstanding Scholarship was awarded to Lin and Márton Kolossváry, MD, PhD, based on their manuscript, “Coronary Plaque Radiomic Phenotypes Predict Fatal or Nonfatal Myocardial Infarction: Analysis of the SCOT-HEART Trial,” published in 2024 in JACC: Cardiovascular Imaging.

“I pursued cardiovascular research to be at the forefront of innovation and help advance evidence that improves care for patients with coronary heart disease,” Lin said. “I’m especially grateful to JACC for recognizing our research into ways to better predict heart attack risk.”

As the mentor for Lin and Kolossváry, Dey also expressed gratitude to JACC for recognition of their research and added, “We are committed to continuing important investigations into new ways of predicting and preventing heart attacks.”

ACC President Cathleen Biga, MSN, extended congratulations, saying, “These heart experts have each demonstrated exceptional work that will further the ACC’s mission to transform cardiovascular care and improve heart health for all.”

In addition to the awards presented at the ACC’s Annual Scientific Session, the California Chapter of the ACC named C. Noel Bairey Merz, MD, director of the Barbra Streisand Women's Heart Center, the 2024 Elliot Rapaport Cardiologist of the Year. Bairey Merz received the award at a Chapter meeting in January.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The investigators’ findings were published in the peer-reviewed Journal of Clinical Investigation.

Heart attacks occur when the heart muscle is damaged by reduced blood flow from one or more arteries. They strike more than 800,000 people in the U.S. each year and are a leading cause of death. The new technique, as described in the study, addresses a major challenge to treating this disorder: uncontrolled inflammation.

“Thanks largely to medical advances, more than 90% of people in the U.S. survive their heart attacks,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the study’s senior author. “But a significant percentage of these patients suffer tissue damage when their immune systems overreact. This can trigger inflammation, which weakens the heart and raises the risk of heart failure.”

To solve this problem, the study’s investigators focused on increasing the body’s supply of regulatory T-cells (Tregs), which modulate the immune system and help keep it from overreacting to injuries. A number of clinical trials involving various diseases have sought to accomplish this goal through a weekslong process of extracting these rare cells from a patient, expanding them in the laboratory and infusing them back into the patient. But this method is too slow to help in an acute crisis like a heart attack.

Cedars-Sinai investigators wondered: What if we could stimulate the body to boost its own production of Tregs? The new method that they developed achieves this goal in mice through infusions of extracellular vesicles that overexpress an RNA molecule called BCYRN1. Extracellular vesicles are small fluid-filled sacs containing bioactive substances that are secreted by cells and circulate in the bloodstream.

By performing laboratory experiments on human tissue samples, the investigators first discovered how BCYRN1 works to increase the number and activity of Treg cells. Acting on these findings, they infused extracellular vesicles containing overexpressed BCYRN1 into mice 15 minutes after the mice had heart attacks.

The data showed that mice that received the infusions had more Tregs in their hearts and sustained less cardiac tissue damage and inflammation from the heart attacks than did mice that did not receive such infusions. Their hearts also retained more of their pumping power.

“These results reveal the important role of BCYRN1 in reducing inflammation and damage from heart attacks,” said Ke Liao, PhD, a project scientist in the Smidt Heart Institute at Cedars-Sinai and first author of the study. “They also validate the effectiveness of using extracellular vesicles to deliver these benefits in mice.”

The extracellular vesicles used in the study were produced by cardiosphere-derived cells, or CDCs, which naturally contain high levels of BCYRN1. These progenitor cells, derived from human heart tissue, were developed by Marbán over many years of work.

“Although this Smidt Heart Institute study was performed on animals, its findings have the potential to generate new and exciting immunotherapies,” said Jeffrey A. Golden, MD, director of the Burns and Allen Research Institute and executive vice dean for Research and Education at Cedars-Sinai. “These therapies could have applications not only for heart attacks but for lupus, organ transplant rejection and other human disorders.”

Other Cedars-Sinai authors include: Jiayi Yu, Akbarshakh Akhmerov, Zahra Mohammadi Goldar, Liang Li, Weixin Liu, Natasha Anders and Ahmed G.E. Ibrahim.

Funding: KL was supported by a training grant from the National Heart, Lung, and Blood Institute (T32 HL116273). This work was funded by NIH (R01HL168296 to E.M.) and the California Institute for Regenerative Medicine (CIRM DISC2-14899 to K.L.). E.M. holds the Mark S. Siegel Family Foundation Distinguished Chair of the Cedars-Sinai Medical Center. JY was supported by Tsinghua University. We thank all other members of the Marbán Laboratory for their support, and the Cedars-Sinai Medical Center Flow Cytometry Core. We acknowledge the use of BioRender for the preparation of figures in this manuscript.

Conflict of interest: E. Marbán owns founder’s equity in Capricor Therapeutics.

Follow Cedars-Sinai Academic Medicine on LinkedIn for more on the latest basic science and clinical research from Cedars-Sinai.

An artificial intelligence (AI) program can identify chronic liver disease from videos taken during a common heart test known as an echocardiogram, Cedars-Sinai investigators report.  

“Incorporating AI into echocardiograms, which capture images of the heart and the liver, can lead to a diagnosis of liver disease without additional costs,” said Alan Kwan, MD, assistant professor in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, and senior and corresponding author of the study, published in NEJM AI.

Echocardiography is the use of ultrasound to visual the heart and its associated structures. The imaging test is a common early screening test doctors prescribe if they suspect a patient has cardiovascular disease. A standard echocardiogram study often contains more than 50 videos, of which a few typically include images of the liver.  

“People with heart disease often develop chronic liver disease, distinguishing between primary liver disease and liver injury secondary to heart disease can be challenging,” said David Ouyang, MD, a cardiologist in the Department of Cardiology in the Smidt Heart Institute, an investigator in the Division of Artificial Intelligence in Medicine, and a senior author of the study. “Our deep-learning model can help doctors spot liver disease that might have gone unnoticed and thus direct appropriate follow-up testing.”

An estimated 4.5 million people have been diagnosed with liver disease, according to the U.S. Centers for Disease Control and Prevention. But experts with the American Liver Foundation say many more people likely have undiagnosed steatotic liver disease, the condition formerly called fatty liver disease.  

“These novel findings exemplify how AI models are helping us to augment clinical diagnostics at a body-systems level instead of just individual organs,” said Sumeet Chugh, MD, director of the Division of Artificial Intelligence in Medicine at Cedars-Sinai.

Investigators trained an AI program to study patterns in more than 1.5 million echocardiogram videos. The program, EchoNet-Liver, was able to detect cirrhosis (scarring of the liver) or steatotic liver disease by studying images of the liver picked up during the echocardiograms. The technology builds upon EchoNet, technology developed by Ouyang and colleagues that can identify and analyze patterns in echocardiograms.

The investigators compared the deep-learning model’s predictions with diagnoses made using patients’ abdominal ultrasounds or MRI images. The AI program proved similar to detecting liver disease by these traditional imaging studies read by radiologists.

The study authors said their next step is to test EchoNet-Liver in studies that track patients’ health over time.

Other Cedars-Sinai authors include Yuki Sahashi, MD, MSc; Milos Vukadinovic, BS; Hirsh Trivedi, MD^; Susan Cheng MD, MMSc, MPH. Other authors include Fatemeh Amrollahi PhD; Justin Rhee, BS; and Jonathan Chen, MD, PhD.

Disclosure of interest: YS reports support from the KAKENHI (Japan Society for the Promotion of Science: 24K10526), oversea research grant from SUNRISElab, Japan Heart Foundation and Ogawa Foundation and honoraria for lectures from m3.com inc. DO reports support from the National Institutes of Health (NIH; NHLBI R00HL157421 and R01HL173526) and Alexion, and consulting or honoraria for lectures from EchoIQ, Ultromics, Pfizer, InVision, the Korean Society of Echocardiography, and the Japanese Society of Echocardiography. ACK reports consulting fees from InVision and support from the American Heart Association (AHA; 23CDA1053659) and National Institutes of Health (NIH; UL1TR001881).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Senior authors of the study were Jennifer Van Eyk, PhD, director of Basic Science Research in the Barbra Streisand Women’s Heart Center; Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute; and Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute. The work was spearheaded by postdoctoral scientists Lizhuo Ai and Vladimir Zhemkov.

Investigators tracked protein changes in individual cells as they developed from stem cells into heart cells, and revealed important differences in the structure and metabolism of these cells as compared with naturally occurring heart cells. While single-cell RNA methods are widely available now and allow thousands of genes to be assessed simultaneously, there is very little data looking at the inventory of proteins within single cells simultaneously. Cedars-Sinai is pioneering new single-cell technologies at its Innovation Center and using the most advanced protein analysis equipment to get more resolution of proteins within single cells for the first time. 

“We looked at cardiomyocytes, which are heart muscle cells,” said Aleksandra Binek, PhD, project scientist and co-first author of the study. “We discovered two distinct types of cardiomyocytes and found rare hybrid cells expressing both heart- and neuron-related proteins, suggesting that heart cells may have more protein flexibility than previously thought. These discoveries will help us create more detailed, realistic models of human heart cells.”

Additional authors: Jae Hyung Cho, Ali Haghani, Simion Kreimer, Edo Israely, Madelyn Arzt, Blandine Chazarin, Niveda Sundararaman, Arun Sharma

Funding: This work was supported by NIH R01 HL144509-01 (JVE) and R01 HL155346-01 (JVE/EM). Lizhuo Ai and Vladimir Zhemkov were supported by the California Institute for Regenerative Medicine (CIRM) Scholar Training Program (CIRM EDUC4-12751). Arun Sharma and Madelyn Arzt were supported by American Heart Association Career Development Award (AHA 856987). Clive Svendsen and Arun Sharma were supported by NASA In Space Production Award (NASA NNJ13ZBG001N).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The study is funded by an $8 million grant from the highly respected Leducq Foundation and is one of only four awarded this year as part of the foundation’s 2024 International Networks of Excellence Program, which promotes collaborative global research in cardiovascular and neurovascular diseases.

Karumanchi—an expert on hypertension, or high blood pressure, during pregnancy—is the first Leducq Foundation grant recipient at Cedars-Sinai. He will work with an international network of investigators to identify how problems with the placenta—the organ in the uterus that connects mother and baby during pregnancy—can cause heart defects in newborns and lead to heart and blood vessel issues in the mother. The research team also aims to discover new treatments for these conditions.

“Heart disease is typically studied by looking at the heart, blood vessels, cholesterol and blood pressure,” said Karumanchi, the study’s principal investigator. “Thanks to the generous support of the Leducq Foundation, we can explore the origins of heart disease from a different perspective. Previous studies have linked placenta problems with cardiovascular diseases, including congenital heart disease, but scientists haven’t fully understood why. This new funding will help close that research gap.”

Didier Stainier, PhD, from the Max Planck Institute for Heart and Lung Research in Germany, will co-lead the team of placental and developmental biologists, physician-scientists, cardiovascular biologists and epidemiologists from the University of Pennsylvania, the University of Calgary in Canada, Centro Nacional de Investigaciones Cardiovasculares in Spain and the University of Bristol in England.

“Dr. Karumanchi has assembled an exceptional global investigative team of experts from various fields to tackle this important research and ultimately find new ways to understand and treat placenta-related heart diseases,” said Jeffrey A. Golden, MD, executive vice dean of Research and Education and director of the Burns and Allen Research Institute. “Having Cedars-Sinai at the helm of this collaboration speaks to our leadership in this pioneering field of placenta-related cardiovascular disease.”

Recently, Karumanchi identified a biomarker to help diagnose and predict preeclampsia, a hypertension-related disorder and one of the most common pregnancy complications, which also is thought to occur because of problems with the placenta.

Now, new genetic and molecular research tools are allowing Karumanchi and the international team to study the placenta in far greater detail. Growing collections of human tissue and blood samples from mothers and babies with heart problems will enable scientists to make progress in understanding the role of the placenta in maternal and fetal cardiovascular health and disease.

“What an incredible honor to receive this award from the Leducq Foundation,” Karumanchi said. “It’s recognition that our research team has a promising idea with exciting potential implications. We look forward to uncovering new ways to better understand, prevent and treat certain heart diseases.” 

Read more on the Cedars-Sinai Blog: Five Things We Know About the Placenta—and a Few We Wish We Did

The study, published in Circulation: Cardiovascular Imaging, details how investigators trained a deep learning program to look for patterns in a commonly used heart test called computed tomography angiography. The results showed that plaque volumes increased with age and were higher in male patients. Women presented with lower plaque volumes compared to men of the same age. Patients in higher percentiles for plaque volume (which takes into account these differences in age and gender) were more likely to experience a heart attack.

Patients typically have a computed tomography angiography for chest pain. The AI software can measure plaque in the coronary arteries and also provide a percentile score for a patient’s age and gender.

When plaque builds up in the arteries, it can lead to a condition called atherosclerosis, in which arteries harden and narrow. If blood supply to the heart is reduced, a heart attack may result. The condition also can lead to heart failure, stroke and loss of limbs.

“The use of AI to measure coronary plaques will significantly influence clinical practice,” said Damini Dey, PhD, professor of Biomedical Sciences at Cedars-Sinai and corresponding author of the study. “In addition to telling a patient their total plaque volume, it may be easier to understand their heart attack risk from plaque volumes relative to other patients of similar age and sex.”

Other Cedars-Sinai authors involved in the study include Robert J.H. Miller, MD; Nipun Manral, MSc; Andrew Lin, MBBS, PhD; Aakash Shanbhag, MSc; Caroline Park, BSc; Aditya Killekar, MSc; Priscilla McElhinney, BSc; Aryabod Razipour, MD; Kajetan Grodecki, MD, PhD; Alan C. Kwan, MD; Donghee Han, MD; Keiichiro Kuronuma, MD; Guadalupe Flores Tomasino, MD; Jolien Geers, MD; Heidi Gransar, MSc; Sebastien Cadet, MSc; Daniel S. Berman, MD; and Piotr J. Slomka, PhD.

Other authors include Jacek Kwiecinski, MD, PhD; Aditya Killekar, MSc; Hidenari Matsumoto, MD, PhD; Aryabod Razipour, MD; Markus Goeller, MD; Mohamed Marwan, MD; MSc; Balaji K. Tamarappoo, MD, PhD; Victor Y. Cheng, MD; Stephan Achenbach, MD; Stephen J. Nicholls, MBBS, PhD; Dennis T. Wong, MD, PhD; Lu Chen, MD; J. Jane Cao, MD; Marc R. Dweck, MBChB, PhD; David E. Newby, MD, PhD; Michelle C. Williams, MBChB, PhD.

Dr. Miller has received consulting fees and research support from Pfizer. S. Cadet, Dr. Slomka, Dr. Dey, and Dr. Berman received software royalties from Cedars-Sinai Medical Center and report equity in APQ Health Inc. outside of the current work. Dr. Berman, Dr. Slomka, and Dr. Dey hold a patent (US8885905B2/WO2011069120A1, Method and System for Plaque Characterization). Dr. Grodecki reports grants or contracts from the Foundation for Polish Science and Polish Society of Cardiology. Dr. Kwan reports partial effort support from the Doris Duke Charitable Foundation Grant. Dr. Kuronuma is supported by grants from The Society of Nuclear Medicine and Molecular Imaging Wagner-Torizuka Fellowship and Nihon University School of Medicine Alumni Association .S. Cadet reports financial support from the Miriam and Sheldon G Adelson Medical Research Foundation Grant. Dr. Nicholls reports grants or contracts from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and consulting fees from AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr Dweck reports consulting fees from Novartis, Jupiter Bioventures, and Silence Therapeutics; and payment or honoraria from Pfizer and Novartis. Dr. Newby reports a grant from the British Heart Foundation (RE/24/130012, CH/09/002, and RG/F/22/110093) and Wellcome Trust. Dr. Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. The other authors report no conflicts.

The study was supported by grants from the National Heart, Lung, and Blood Institute, USA (1R01HL148787–01A1 and R01HL151266), the Miriam & Sheldon G Adelson Medical Research Foundation, and a grant from the Winnick Family Foundation.

Follow Cedars-Sinai Academic Medicine on LinkedIn for more on the latest basic science and clinical research from Cedars-Sinai.

, suggest doctors could use a tool called the Geriatric Nutritional Risk Index to identify patients who would benefit from changes to their diet.

“This study adds to a growing body of research showing good nutrition is associated with better outcomes after surgery,” said Abirami Kumaresan, MD, assistant professor of Anesthesiology and Cardiac Surgery at Cedars-Sinai and first author of the study. “Doctors and clinical care teams have an opportunity to help patients modify their risk with conversations centered on improvements in diet.”

Investigators reviewed data from patients 65 and older who underwent nonurgent coronary artery bypass grafting or a valve repair or replacement procedure in a single center between July 2011 and March 2022. After adjusting for several factors, the investigators found that low scores on the Geriatric Nutritional Risk Index were associated with 4.8-fold greater odds of in-hospital mortality, 8.7-fold greater odds of 30-day mortality, and 3.7-fold greater odds of needing extended hospital care.

For all patients, the postoperative in-hospital mortality rate was 1.4% and 30-day mortality rate was 5.5%.

Other Cedars-Sinai authors involved in the study include George Gill, MD; Tao Shen, MBBS; Michael Bowdish, MD; Joseph E. Ebinger, MD, MS; and Susan Cheng, MD, MPH.

No conflicts of interest to disclose.

Follow Cedars-Sinai Academic Medicine on LinkedIn for more on the latest basic science and clinical research from Cedars-Sinai.

The U.S. Food and Drug Administration recently approved the new stent, a metal mesh tube that keeps blood vessels open, for use in newborns, infants and children who have narrowing in the aorta or pulmonary artery. Because the stent expands, it is meant to save these children from additional surgeries as they age and need a larger stent for their growing bodies.  

“This approval represents a monumental shift in the way we care for babies with congenital heart disease,” said Evan Zahn, MD, who helped develop the new stent and is director of the Pediatric Congenital Heart Program at Guerin Children’s and in the Department of Cardiology in the Smidt Heart Institute. “It is a joy to know how many patients and families will be positively impacted now that the stent is more widely available.”

Cedars-Sinai is one of the few hospitals in the U.S. where interventional cardiologists are trained in deploying the stent and where children who need it can get that specialized care.

About 40,000 babies are born with a heart defect every year in the United States, according to the U.S. Centers for Disease Control and Prevention. Many of these children have narrowing in the aorta, the artery that carries blood from the heart to the rest of the body, or in the pulmonary artery, which carries blood from the heart to the lungs.

The FDA approved the first-ever stent in 1994, but for adults. Since then, the only option for babies with narrowing has been to resize an adult stent to fit their tiny vessels and replace the stent multiple times as their bodies grow.

“The stents we have had up to this point have had a fixed maximum diameter, meaning that baby is going to need to get it replaced, typically through open-heart surgery,” Zahn said.

To place the stent, an interventional cardiologist makes a tiny hole in the child’s leg and feeds a long, thin tube called a catheter through the groin and into the narrowed blood vessel. A balloon at the end of the catheter expands the vessel and allows the cardiologist to place the stent.  

Over the past five years, Zahn collaborated with engineers at a company called Renata Medical to develop and study the new stent, known as the Minima Stent System. It is made with a unique cell design that allows it to expand to fit a child’s growing body. The expansion is done during a two-hour catheterization procedure rather than through open-heart surgery. Children are expected to be well enough to go home the day after the procedure.

Cedars-Sinai was one of four medical centers involved in an early feasibility study that contributed to the approval of the new stent. The results of that study, published in May, report that the stent was safely implanted and opened narrowed blood vessels.  

“This is the start of a game changer for scores of children all around the world,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark S. Siegel Family Foundation Distinguished Chair. “It’s a privilege knowing Cedars-Sinai has been intimately involved in the creation of this device.”

Disclosure: Evan Zahn, MD, is chief medical officer of Renata Medical, the company that makes the Minima Stent.

Read more on the Cedars-Sinai Newsroom: Making Strides in Treating the Smallest Heart Patients

The program’s findings, published in Circulation, may help clinicians identify patients whose mitral valve regurgitation is manageable with medication as well as patients with more severe cases who would benefit from a minimally invasive valve repair procedure or surgery.

“Mitral regurgitation is a common but often missed valvular heart disease. It can be challenging to precisely assess the disease severity, which is critical to know which patients can take a watch-and-wait approach and which should proceed to an intervention,” said David Ouyang, MD, a cardiologist in the Department of Cardiology in the Smidt Heart Institute, an investigator in the Division of Artificial Intelligence in Medicine, and corresponding author of the study. “The program we developed may one day be used by doctors when considering the best treatment approach for individual patients.”

The AI program further cements the Smidt Heart Institute’s longstanding leadership in heart valve care. Interventionalists with the Smidt Heart Institute are believed to have performed more mitral valve repairs than any other center in the U.S., with outcomes that place Cedars-Sinai among the top-performing programs nationally. The Smidt Heart Institute team has also completed more than 1,500 robotic mitral valve repairs with a near 100% success rates.

“This could improve how we identify patients with mitral regurgitation, which is becoming more prevalent in our aging population, and to personalize treatment even more so than we already do,” said Raj Makkar, MD, associate director of the Smidt Heart Institute, vice president of Cardiovascular Innovation and Intervention for Cedars-Sinai and a leader in treating mitral valve disease.

The heart has four valves that open and close to move blood throughout the body. In some people the mitral valve, located on the left side of the heart, does not close properly, which allows blood to flow backwards, a condition called mitral valve regurgitation. The condition prevents enough blood from circulating throughout the body and, over time, can lead to shortness of breath, arrhythmia and heart failure.

“At Cedars-Sinai we are pursuing the use of AI as a complementary tool in diagnosing and treating conditions such as mitral valve regurgitation,” said Sumeet Chugh, MD, director of the Division of Artificial Intelligence in Medicine and the Pauline and Harold Price Chair in Cardiac Electrophysiology Research.

In developing the new program, investigators used more than 58,000 transthoracic echocardiograms from Cedars-Sinai. Echocardiograms are video images of patients’ hearts taken by ultrasound and is the most common way to assess mitral regurgitation. The investigators tested the program on echocardiograms from 1,800 patients at Cedars-Sinai as well on echocardiograms from 915 patients from Stanford Healthcare in Northern California.

The model was able to automatically identify moderate and severe mitral valve regurgitation with high precision.

“Our deep learning model analyzed videos from more than 50,000 echocardiogram studies and can pinpoint the most relevant and important videos to assess mitral regurgitation severity,” said first author Amey Vrudhula, a fellow at Cedars-Sinai.

To treat severe mitral valve regurgitation, experts at the Smidt Heart Institute at Cedars-Sinai rely on either the minimally invasive TEER procedure or minimally invasive surgery. All patients meet with an interventional cardiologist as well as a cardiac surgeon before making their treatment decision.

Other Cedars-Sinai authors involved in the study include Grant Duffy B.S., Milos Vukadinovic B.S^., Susan Cheng, M.D., M.M.Sc., M.P.H.

This work was supported in part by the Sarnoff Cardiovascular Research Award, research grants NIH R01-HL131532, NIH R01-HL142983, R00 HL157421, and R01HL173526.

Read more from the Cedars-Sinai Blog: Treatment Options for Heart Valve Disease

Atrial fibrillation is an irregular heart rhythm that can cause heart palpitations, shortness of breath, lightheadedness and other symptoms in some patients.

“Atrial fibrillation is a really common disease,” said Jessica Mao, MD, a cardiology fellow at the Smidt Heart Institute and first author of the study. “Our study aimed to understand why some patients have symptoms and others do not.”

Investigators specifically sought to better understand paroxysmal atrial fibrillation, a type of atrial fibrillation that lasts only a few hours or days. They aimed to correlate the magnitudes of skin sympathetic nerve activity with symptoms in patients with this type of arrhythmia.

Cedars-Sinai investigators followed symptoms in 35 patients with paroxysmal atrial fibrillation over seven days. The patients were fitted with a skin patch electrode on the chest that monitored skin sympathetic nerve activity. They were told to press a button on the device when they experienced symptoms that they usually would have during an atrial fibrillation episode. The most reported symptoms were palpitations, dizziness, shortness of breath and chest pain.

Among the enrolled patients, 16 had at least one episode of atrial fibrillation, and 24 had symptoms. The investigators noted that sympathetic nerve activity was elevated when people reported symptoms. They also noted that the symptoms may occur during normal rhythm or atrial fibrillation.

Studies show patients have fewer symptoms after they undergo catheter ablation, a procedure that destroys small areas of heart tissue and blocks abnormal electrical impulses. 

“The fact that many patients have fewer symptoms after this procedure while still having documented atrial fibrillation could indicate that the procedure modulates the nervous system,” Mao said.

Investigators plan additional studies with a larger patient population to strengthen their findings.

Other Cedars-Sinai investigators who worked on the study include Xiao Liu, MD, PhD; Anxhela Kote, BS; Taiga Andersson, MSHS; Xiaochun Li, PhD; Christine M. Albert, MD, MPH, FHRS; and Peng-Sheng Chen, MD, FHRS.

Funding: The study was partially funded by National Institutes of Health grants R01HL116690, R01HL139829, 1OT2OD028190, and T32HL116273, an American Heart Association grant 23IPA1052289, and the Burns & Allen Chair in Cardiology Research, Cedars-Sinai Medical Center.

Conflicts of Interest: Dr. Peng-Sheng Chen is a co-inventor of U.S. patent No: 10,448,852 awarded to Indiana University.

Visit Research News and follow Cedars-Sinai Academic Medicine on LinkedIn for more on the latest basic science and clinical research from Cedars-Sinai. 

Acute coronary syndrome refers to any condition that involves the blockage of blood flow to the heart, such as a heart attack.

The investigators previously reported the immune system of patients with acute coronary syndrome seems to be reactive to LL-37. Other studies have reported that LL-37 triggers an immune response that plays a role in autoimmune diseases such as psoriasis and systemic lupus. This led the investigators to hypothesize that LL-37 might contribute to an immune response that increases inflammation and leads to a tightening of blood vessels.

In this new study, published in JACC: Basic to Translational Science, the research team reports that LL-37 binds to antibodies, forming complexes that then bind to and activate platelets. These activated platelets form clots and can restrict blood flow.

“Platelets that normally should be quiescent become active in acute coronary syndrome, and they stay active even after a heart attack,” said Paul Dimayuga, PhD, research associate professor in the Department of Cardiology in the Smidt Heart Institute and first and corresponding author of the study. “Our data suggest the immune complex formed by antibodies against LL-37 adds to the platelet activation.”

To conduct the study, the investigators collaborated with the laboratory of Daniel Berman, MD, in the Smidt Heart Institute and the Department of Imaging. The laboratory is collecting blood plasma from study participants who undergo coronary artery CT imaging to evaluate their risk for a heart attack. They are following the patients over time to learn how the composition of their plasma changes.

The investigators studied the composition of the blood plasma of patients who went on to have a heart attack, as well as the blood plasma of patients who did not. Patients who suffered a heart attack had significantly higher levels of LL-37 antibodies before the heart attack than people who did not experience a heart attack. The investigators also found that people with acute coronary syndrome had increased levels of immune complexes that formed between these antibodies and LL-37.

Experiments demonstrated these complexes have the propensity to activate platelets, suggesting a novel immune-mediated pathway of platelet activation during a heart attack and potentially a target for therapy.

With additional research, the investigators hope to understand why some people have higher levels of LL-37 antibodies than others.

“The question is: Is there a biological process that drives certain people to have an immune response to LL-37, but not others?” Dimayuga said. “We would like to study the immune cells of these individuals to see if there is something peculiar about these cells.”

Other Cedars-Sinai investigators who worked on the study include Kuang-Yuh Chyu, MD, PhD; Xiaoning Zhao, PhD; Jianchang Zhou, PhD; Nicole Wai Man Lio, BS; Fernando Chernomordik, MD; Daniel Berman, MD; Prediman K. Shah, MD; and Bojan Cercek, MD, PhD.

Funding: The Heart Foundation, Eisner Foundation, Peterson Foundation, Corday Foundation, Spielberg Fund (Los Angeles, CA [PS]); The Eleanor and Harold Foonberg Endowed Chair in Cardiac Intensive Care Fund (Los Angeles, CA [BC]); Academic Affairs Department, Cedars-Sinai Medical Center (Los Angeles, CA), The Lydia Kitner Scholarship for Advanced Cardiovascular Training, the Milovicz grant for the Development of the Future Generation of Leaders in Medicine, and the Prof. Arieh Roth Scholarship from the Working Group in Acute Cardiac Care of the Israel Heart Society (Israel [FC]).

Read more in Cedars-Sinai Discoveries Magazine: A Better Model of Heart Disease Prediction

), effective July 1.

Gupta, an interventional and structural cardiologist, is one of the journal’s new executive associate editors. Kittleson, director of Heart Failure Research and director of Post Graduate Medical Education in Heart Failure and Transplantation, is an associate editor specializing in heart failure.

“It’s an honor to join the editorial team of JACC during this exciting time in medical publishing,” said Gupta, an assistant professor of Cardiology. “The field is at an inflection point with the maturation of artificial intelligence—an area of special interest to me—and I’m thrilled to be a part of that transformation. I’m also excited to work closely with my peers on the JACC editorial team as we help shape contemporary research priorities, and as such, propel improvements in clinical care to ultimately improve patient outcomes.”

As a JACC executive associate editor, Gupta will lead the publication’s strategic relationships with health policy and research organizations, such as the Heart Valve Collaboratory and Duke-Margolis Institute for Health Policy, in areas pertaining to structural interventional cardiology. She also will lead and assess content initiatives, manuscript assignment and peer-review processes.

Gupta is an expert in performing transcatheter valvular interventions and complex coronary interventions. She has authored more than 100 scientific publications in leading medical journals, including Nature Medicine, Lancet, JAMA, Circulation and JACC. She has been a section editor for Circulation: Cardiovascular Outcomes and Research, authored book chapters, and in 2022 was a finalist for the Samuel A. Levine Early Career Clinical Investigator Award from the American Heart Association.

As a JACC associate editor, Kittleson will review manuscripts in the fields of heart failure, transplant and cardiac amyloidosis to assess suitability for publication, as well as contribute to strategic journal initiatives. 

Previously, Kittleson was interim editor-in-chief of the Journal of Heart and Lung Transplantation and helped develop evidence-based cardiomyopathy and heart failure guidelines. She also has served on the board of directors of the Heart Failure Society of America. Kittleson’s essays have been published in The New England Journal of Medicine, Annals of Internal Medicine and JAMA Cardiology, and she is author of the book Mastering the Art of Patient Care.

“Serving on the JACC editorial team is an exciting opportunity,” Kittleson said. “I'm looking forward to contributing to this role under the new leadership of JACC—a journal I have long studied and admired—as we look to build on its successes and make it better than ever before.”

Christine Albert, MD, MPH, chair of the Department of Cardiology and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, said, “Congratulations to Drs. Gupta and Kittleson on their well-deserved appointments to the JACC editorial team. With their expert guidance, JACC will be poised to lead the field in advancing the most promising cardiovascular science.”

Read more from Cedars-Sinai Discoveries Magazine: New Insights May Yield Improvements in Heart and Brain Health

Cingolani, director of Cardiogenetics and Preclinical Research in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, is exploring new ways to help patients with ventricular tachycardia (VT), a recurring, abnormally fast and irregular heartbeat that starts in the lower chambers, or ventricles, of the heart. If VT lasts for more than a few seconds at a time, it can be life-threatening.

Current therapies for recurrent VT are not very effective and have unpleasant side effects. Cingolani is studying the effectiveness of a novel, noninvasive cell-based therapy to treat VT. His approach uses stem cell-derived exosomes—tiny fluid-filled sacs found in cells—to help regrow healthy heart muscle and prevent disruptive electrical signals. His next step is to move his promising research into a first-in-human clinical trial.

Thanks to a $6 million grant from the California Institute for Regenerative Medicine (CIRM), the state’s taxpayer-funded stem cell research initiative, Cingolani is closer to that goal.

Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark S. Siegel Family Foundation Distinguished Professor, said the funding is the first-ever CIRM grant focused on VT as well as the first to receive clinical research funding from CIRM for the use of exosomes as a therapy.

“This grant is the most advanced offered by the California Institute for Regenerative Medicine to fund the laborious studies required to procure regulatory approval for first-in-human trials,” Marbán said. “The new approach to treating VT is based 100% on Cedars-Sinai discoveries.”

The Cedars-Sinai Newsroom recently talked with Cingolani, an associate professor of Cardiology, to learn more about his quest to find an effective new treatment for VT.

Tell us about VT and why it can be such a serious heart condition.

VT is caused by faulty electrical signaling in the heart and sometimes develops after a heart attack. Patients experience a very fast heart rate—often 150 times a minute or more. A normal resting heart rate for adults is between 60 and 100 beats a minute. The rapid heartbeat may only last for a few seconds, but during that time, the heart is beating so fast that it can’t get enough blood to the rest of the body. Patients may feel a fluttering in the chest, chest pain, shortness of breath and dizziness or lightheadedness as a result. If VT is not treated, it can lead to cardiac arrest, which is when the heart stops beating. In fact, VT is the most common cause of sudden cardiac arrest.

How is VT typically treated?

Right now, there are several treatment options, but none of them are optimal. They include medications that are not very effective and cause unpleasant side effects, an implantable cardioverter-defibrillator (or ICD) that provides an internal shock to correct the heartbeat, and a procedure called catheter ablation. This is a complex procedure that destroys the abnormal heart tissue that’s causing the rapid heartbeat. Unfortunately, ablation also destroys healthy heart tissue in the process. Another drawback is that ablation is often limited to patients who can access specialized centers that perform the procedure.

How do exosomes work to treat VT?

Exosomes are tiny vesicles, secreted by cells, that naturally heal heart scars. The idea is to infuse the exosomes into diseased heart muscle that is predisposed to VT with the goal of decreasing scar tissue and preventing VT. Current ablation procedures destroy heart tissue and tend to worsen heart function. Even when they work, VT often recurs over time. Our therapy might prevent VT without those limitations.

How does CIRM grant funding help future patients?

The grant is significant because it allows us to complete the necessary preclinical research as well as the safety and efficacy studies that are needed before the therapy moves into a clinical trial for patients. It represents a unique opportunity to advance our therapy to the next level and potentially be able to treat patients with ventricular arrhythmias in a better way, without destroying healthy heart tissue. I’m grateful to the California Institute for Regenerative Medicine for helping us advance this science.

How quickly might we see a clinical trial for patients?

We are aiming to obtain permission from the FDA [Food and Drug Administration] to perform a first-in-human study within the next two years. This would be an exciting development for research and for patients.

Read more on the Cedars-Sinai Blog: Cardiac Rhythm Disorders & Advanced Therapeutic Program for Ventricular Tachycardia

and their Cedars-Sinai colleagues can detect a type of abnormal heart rhythm that can go unnoticed during medical appointments, according to a new study.

The study’s findings, published in npj Digital Medicine, suggest AI could one day be employed to analyze images from a common imaging test called an echocardiogram, which uses sound waves to capture pictures of the heart.

Abnormal heart rhythms are often caused by—and also lead to—heart structure abnormalities. Researchers hypothesized that an AI program trained to analyze echocardiograms might help clinicians detect early, subtle changes in the hearts of patients with undiagnosed arrhythmias.

“We were able to show that a deep learning algorithm we developed could be applied to echocardiograms to identify patients with a hidden abnormal heart rhythm disorder called atrial fibrillation,” said Neal Yuan, MD, a staff scientist with the Smidt Heart Institute and first and corresponding author of the study. “Atrial fibrillation can come and go, so it might not be present at a doctor’s appointment. This AI algorithm identifies patients who might have atrial fibrillation even when it is not present during their echocardiogram study.”

During atrial fibrillation, the heart's upper chambers sometimes beat in sync with the lower chamber and sometimes they do not, making the arrhythmia often difficult for clinicians to detect. In some people, atrial fibrillation causes no symptoms. In others, it can cause heart palpitations, fatigue, shortness of breath, dizziness, and other symptoms that interfere with daily life. Left untreated, atrial fibrillation can cause stroke and heart failure.

An estimated 12.1 million people in the United States will have atrial fibrillation in 2030, according to the Centers for Disease Control and Prevention (CDC). Deaths related to atrial fibrillation have been increasing for more than two decades, according to CDC data.

“We’re encouraged that this technology might pick up a dangerous condition that the human eye would not while looking at echocardiograms,” said David Ouyang, MD, a cardiologist in the Department of Cardiology in the Smidt Heart Institute and a researcher in the Division of Artificial Intelligence in Medicine, and a senior author of the study. “It might be used for patients at risk for atrial fibrillation or who are experiencing symptoms associated with the condition.”

The team trained a program to study more than 100,000 echocardiogram videos from patients with atrial fibrillation. The program distinguished between echocardiograms showing a heart in sinus rhythm (a period of normal heart beating) and echocardiograms showing a heart in an irregular heart rhythm. The program predicted which patients in sinus rhythm had experienced or would develop atrial fibrillation within 90 days.

The model evaluating the images performed better than estimating risk based on known risk factors.

“The fact that this program predicted which patients had active or hidden atrial fibrillation could have immense clinical applications,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and a study author. Being able to identify patients with hidden atrial fibrillation could allow us to treat them before they experience a serious cardiovascular event.”

Other Cedars-Sinai investigators who worked on the study include Nathan R. Stein, MD; Grant Duffy; Roopinder K. Sandhu, MD; Sumeet S. Chugh, MD; Peng-Sheng Chen, MD; Carine Rosenberg,^, Susan Cheng, MD, and Robert J. Siegel, MD.

This work was funded in part by the National Institutes of Health (K99 HL157421, R01HL139829), grants OT2OD028190, AHA 23IPA1052289, the Burns & Allen Chair in Cardiology Research, and Cedars-Sinai.

Read more from the Cedars-Sinai Blog: Atrial Fibrillation—Know the Warning Signs

at Cedars-Sinai and colleagues report that women with Type 2 diabetes diagnosed with hypertension before age 50 may benefit from intensive blood pressure treatment.

The findings, published in Diabetes Care, show the risk of developing cardiovascular disease is reduced in women with Type 2 diabetes diagnosed with hypertension in middle age who underwent intensive blood pressure treatment. This risk was not reduced in women diagnosed with hypertension at age 50 or older, or in men.  

“We have known for some time that women with Type 2 diabetes have greater cardiovascular disease risks than men with Type 2 diabetes,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science in the Department of Cardiology in the Smidt Heart Institute, and co-corresponding author of the study.

“We also know blood pressure in women rises faster than in men. Given these two findings, we wanted to find out whether certain women might benefit from more intensive treatments,” added Cheng, who is also director of the Institute for Research on Healthy Aging in the Smidt Heart Institute.

Blood pressure readings measure the force of blood pushing against the walls of the arteries. The readings measure two numbers: The larger number (systolic) is the pressure when your heart beats, and the smaller number (diastolic) represents the pressure between beats.

Experts define intensive blood pressure treatment as aiming to achieve and maintain a blood pressure below 120 mmHg systolic. Standard blood pressure treatment aims to achieve and maintain a reading less than 140 mmHg systolic. Uncontrolled blood pressure can damage the arteries and cause heart attack, stroke and other cardiovascular issues.

Intensive blood pressure treatment typically involves higher doses of antihypertensive drugs but can also involve increasing the number of antihypertensive drugs a patient is taking to achieve the blood pressure target.

The investigators analyzed data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which randomized 4,733 people with Type 2 diabetes to intensive or standard antihypertensive treatment targets. A total of 3,792 participants provided their age at hypertension diagnosis.

Women with Type 2 diabetes and early-onset hypertension who received intensive compared to standard antihypertensive treatment had significantly fewer strokes, heart attacks, and other cardiovascular events over the course of 4 ½ years than women with Type 2 diabetes and hypertension diagnosed at a later age.  

“This study could help clinicians consider situations where more intensive lowering of blood pressure may be beneficial,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. “Research findings such as these remind us that we have to consider individual differences, including differences between women and men and between people who developed their conditions earlier or later in life.”

Prospective studies are needed to validate these findings, according to the authors.

“This may be the first study to suggest intensive antihypertensive treatment is a preferred approach for women with Type 2 diabetes and early-onset hypertension,” said Joseph Ebinger, MD, associate professor of Cardiology in the Department of Cardiology in the Smidt Heart Institute and one of the study’s authors. “Our results are in line with the well-known adage that treating hypertension soon after diagnosis prevents many health issues later in life.”

Alan Kwan, MD, assistant professor in the Department of Cardiology at Cedars-Sinai, also worked on the study. Other authors include Hongwei Ji, MD; Karen Reue, PhD; Jennifer C. Sullivan, PhD; and John Shyy, PhD.

This work was funded in part by part by the National Natural Science Foundation of China (82103908), the Natural Science Foundation of Shandong Province (ZR2021QH014), Shuimu Scholar Program of Tsinghua University, National Postdoctoral Innovative Talent Support Program (BX20230189), and National Institutes of Health (grants U54-AG065141, U54-HL170326, and U54-HL169191).

Read more from the Cedars-Sinai Blog: Cedars-Sinai Investigators Exploring the Connection Between the Microbiome and Diabetes

The findings were published in the peer-reviewed journal Nature Communications.

“These results are likely practice-changing for many patients because this technology can accurately identify cardiovascular risk without the use of invasive tests or contrast dye that some patients cannot receive,” said Piotr J. Slomka, PhD, director of Innovation in Imaging at Cedars-Sinai, professor of Medicine in the Division of Artificial Intelligence in Medicine and senior author of the study.  

Slomka, a professor of Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, said that more than 15 million CT scans are performed in the U.S. each year— and many of these are underutilized or understudied. Clinicians currently can evaluate cardiovascular risk using a CT scan, but usually with contrast.

“This novel AI algorithm makes it possible to get crucial heart health insights from cheaper scans that use less radiation, potentially making detailed heart evaluations part of regular diagnostic procedures,” Slomka said.

Investigators incorporated two artificial intelligence models to evaluate data on coronary calcium and heart muscle chamber sizes from nearly 30,000 patient imaging records. They were able to determine that those measures are a better indicator of cardiac risk than a radiologist’s identification of abnormalities.

Sumeet Chugh, MD, director of the Division of Artificial Intelligence in Medicine, who was not involved in the study, says this technology allows for large-scale use of existing CT data to spot individuals at risk sooner.

“Coronary artery disease is the leading cause of disability and death at a global level,” said Chugh, associate director of the Smidt Heart Institute. “These findings highlight how AI tools could leverage existing CT images performed for lung disease investigation, to make a cost-effective, public health impact on heart disease.”

The collective group of Cedars-Sinai investigators that developed these findings also included teams from the Smidt Heart Institute, the Biomedical Imaging Research Institute and the Department of Biomedical Sciences.

Other Cedars-Sinai authors include Robert J. H. Miller, Aditya Killekar, Aakash Shanbhag, Bryan Bednarski, Anna M. Michalowska, Mark Lemley, Konrad Pieszko, Serge D. Van Kriekinge, Paul B. Kavanagh, Joanna X. Liang, Cathleen Huang, Damini Dey and Daniel S. Berman. Other investigators include Terrence D. Ruddy, Andrew J. Einstein and David E. Newby.

This research was supported in part by grant R35HL161195 from the National Heart, Lung, and Blood Institute/National Institutes of Health (NHLBI/NIH) (PI: PS) as well as R01EB034586 from the National Institute of Biomedical Imaging and Bioengineering (PI: PS). The authors thank the National Cancer Institute for access to NCI’s data collected by the National Lung Screening Trial (NLST) accessed under project number NLST-981. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Read more from the Cedars-Sinai Blog: An AI Ally for Mental Health

This study, led by investigators in the Smidt Heart Institute at Cedars-Sinai, applies novel artificial intelligence (AI) methods to measure heart function. Investigators have designed a program that can be applied to standard heart ultrasounds to measure global, longitudinal myocardial strain, which is a marker of muscle function.

The project addresses current problems in measuring myocardial strain, such as large variations in standard measurements and proprietary software, which may require specialized pictures and processing. The program created by Smidt Heart Institute investigators is openly available and can be applied to standard images, making it well suited for large datasets of heart ultrasounds.

EXPERT COMMENTARY

“We are developing deep-learning approaches to extract information from medical images that may not be readily visible to the human eye,” said Alan Kwan, MD, an assistant professor in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and first author of the study. “We want to ensure we are using safe, rigorous, and understandable methods, in order to fully leverage the information from medical imaging and improve clinical care and research.”

BACKGROUND

The function of the heart is frequently measured by ejection fraction, but many physicians say a more precise measurement is cardiac strain—where the actual shortening of the heart muscle is detected to identify subtle findings of cardiac dysfunction. In echocardiography, “speckle tracking” is used to calculate longitudinal strain; however, the application of this method can vary significantly between both machine vendors and sonographers. This variation can impact the reproducibility of strain measurements across multiple studies. 

In this study, Smidt Heart Institute investigators built upon prior research where they developed deep-learning algorithms to identify the contour of the left ventricle for measurement of ejection fraction—a calculation of the heart’s ability to pump oxygen-rich blood out to the rest of the body. The investigators then repurposed the tool to measure strain.

The result is an automated, open-source, vendor-agnostic method to retrospectively measure global longitudinal strain to improve research applications and streamline patient analysis. 

IMPACT

This deep learning-based strain program is open source and freely available, which makes it broadly applicable to already existing datasets. By providing access to anyone who wishes to use it, Cedars-Sinai researchers aim to address current barriers to access and difficulties with comparison between different brands of strain.

Additionally, because the algorithm is applicable to standard clinical images and does not require specific image acquisition, it is ideal for research application to large clinical databases and can be easily run on existing data.

This study advances the application of deep learning in echocardiography, along with other projects by the investigators that are aimed at improving cardiac patient care, by more accurately identifying hidden signs of cardiovascular disease.

JOURNAL

The research was published in the peer-reviewed journal JACC: Cardiovascular Imaging.

AUTHORS

Cedars-Sinai authors involved in the study are Alan C. Kwan, MD; Ishan Jain; John Theurer, BS; Robert Siegel, MD; Susan Cheng, MD, MMSc, MPH; and David Ouyang, MD. Additional authors are Ernest Chang, MD, PhD; Xiu Tang; Nadia Francisco, MSc; Francois Haddad, MD; David Liang, MD, PhD; Alexandra Fábián, MD, PhD; Andrea Ferencz; Neal Yuan, MD; Béla Merkely, MD, PhD, DSc; Attila Kovács, MD, PhD; and Márton Tokodi, MD, PhD.

FUNDING

Alan C. Kwan reports funding support from the Doris Duke Charitable Foundation Grant 2020059, American Heart Association Career Development Award 23CDA1053659 and NIH R01HL131532-06. Ernest Chang reports funding from National Institutes of Health T32HL097129-13. This study was partially supported by the National Research, Development, and Innovation Fund of Hungary within the framework of the Artificial Intelligence National Laboratory Program and by the Thematic Excellence Program (2020-4.1.1. – TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging thematic program of the Semmelweis University. This work was supported in part by the National Institutes of Health NIH K99 HL157421-01.

Follow Cedars-Sinai Academic Medicine on X, formerly Twitter, for more on the latest basic science and clinical research from Cedars-Sinai. 

The findings, published in Arteriosclerosis, Thrombosis, and Vascular Biology, suggest that a treatment therapy that inhibits interleukin-1-beta might help patients, including the approximately 20% of children who don’t respond to current therapies.

Kawasaki disease was first described by Japanese pediatrician Tomisaku Kawasaki in 1967, but its cause remains unknown. The condition typically affects children under the age of 5, and patients with the disease usually present with a sudden, high fever; rash; redness of eyes, lips and tongue; and swelling of hands and feet that last for 10 days or longer.

In Japan, Kawasaki disease cases are on the rise after a significant decrease in 2020.

“The disease is treatable in most children if caught early, but some children continue to have fever and become at risk of developing cardiovascular complications, such as coronary artery aneurysms or arrhythmias,” said Moshe Arditi, MD, executive vice chair of the Department of Pediatrics for Research at Cedars-Sinai Guerin Children’s, the GUESS?/Fashion Industries Guild Chair in Community Child Health, and a co-senior author of the study.

The standard of care for children with Kawasaki disease is to administer intravenous immunoglobulin and aspirin to reduce inflammation and fever. But recent clinical trials have found that blocking proteins called inflammatory cytokines, such as tumor necrosis factor alpha or interleukin-1-beta, improves symptoms in children.

Drugs that block tumor necrosis factor alpha are already being used in patients. A potential new therapy currently being investigated, anakinra, suppresses and blocks the function of the interleukin-1 receptor, which binds the inflammatory interleukin-1 cytokines.

This study sought to identify which cytokines might be involved in the biologic processes that cause cardiovascular complications in children with Kawasaki disease.

Arditi, who is also director of the Infectious and Immunological Diseases Research Center in the Department of Biomedical Sciences and a professor of Pediatrics, and Eugenio Cingolani, MD, who is director of Cardiogenetics and Preclinical Research at the Smidt Heart Institute at Cedars-Sinai and an associate professor of Cardiology, brought their labs together to work on the study.

Together, the investigators studied publicly available datasets showing gene expressions in children with Kawasaki disease. They found elevated expression of the genes of cytokines interleukin-1-beta and tumor necrosis factor alpha in patients with the disease.

“We sought to identify whether one protein caused more cardiac dysfunction and arrhythmias in this mouse model of Kawasaki disease,” Cingolani said.

The team performed several experiments in laboratory mice with a disease model resembling Kawasaki disease in humans. The investigators injected mice with drugs that block the expression of interleukin-1-beta or tumor necrosis factor alpha. They found that drugs that blocked interleukin-1-beta signaling but not tumor necrosis factor alpha signaling prevented abnormal changes in how the heart pumps blood and the heart’s rhythm. 

“We need to test whether these observations in an animal disease model remain true in children with Kawasaki disease,” said Thassio Ricard Ribeiro Mesquita, PhD, a research scientist with the Smidt Heart Institute, an assistant professor of Cardiology at Cedars-Sinai and first author of the study. “If so, they would further support the use of therapies that block interleukin-1-beta in patients with Kawasaki disease.”

Based on the experimental studies from the Arditi Laboratory on the role of interleukin-1-beta in Kawasaki disease, anakinra—the drug that blocks the interleukin-1 receptor—is now in Phase III clinical trials in children.

Other Cedars-Sinai investigators who worked on the study include Shuang Chen, Youngho Lee, Rodrigo Miguel-dos-Santos, Asli Atici, Magali Noval Rivas and Yen-Nien Lin.

The study was funded by the National Institutes of Health, the American Heart Association, the California Institute for Regenerative Medicine and the Cedars-Sinai Board of Governors.

Follow Cedars-Sinai Academic Medicine on X for more on the latest basic science and clinical research from Cedars-Sinai.

“Sudden cardiac arrest is a mostly lethal condition, and prevention will make the biggest impact, but we need to find novel clinical tools to make that possible,” said Sumeet Chugh, MD, director of the Division of Artificial Intelligence in Medicine at Cedars-Sinai and senior author of both studies. “Using AI algorithms to improve prediction of sudden cardiac arrest could help doctors identify which patients might be at higher risk of experiencing this devastating condition.”

More than 350,000 people have an out-of-hospital sudden cardiac arrest in the United States every year, according to the Centers for Disease Control and Prevention.

During sudden cardiac arrest, a change in the heart’s electrical activity causes it to suddenly stop beating. Having a heart condition can make a person more likely to experience sudden cardiac arrest, but it also can occur in people with no known heart condition.  

In a study published in Communications Medicine, David Ouyang, MD, assistant professor of Cardiology and Medicine at Cedars-Sinai, along with Chugh and fellow investigators trained a deep learning algorithm to study patterns in electrocardiograms, also known as ECGs, which are recordings of the heart’s electrical activity.

The model studied electrocardiograms from people who experienced sudden cardiac arrest and people who did not. The study included 1,827 pre-cardiac arrest electrocardiograms from 1,796 people who later experienced sudden cardiac arrest. It also included 1,342 electrocardiograms taken from 1,325 people who did not experience sudden cardiac arrest. 

The investigators found the Cedars-Sinai-developed AI model more accurately predicted who would experience out-of-hospital sudden cardiac arrest than did the more conventional method, called the ECG risk score. This is a way for doctors to calculate a person’s risk for sudden cardiac arrest that incorporates information from electrocardiogram readings.

“The entire digital electrocardiogram signal performed significantly better than a few of its components,” said Chugh, who is also the Pauline and Harold Price Chair in Cardiac Electrophysiology Research and associate director in the Smidt Heart Institute. “We plan to continue to study this AI method to learn how it could be used in a clinical setting.”

In another study, published in Circulation: Arrhythmia and Electrophysiology, Chugh along with fellow investigator Piotr Slomka, PhD, director of Innovation in Imaging at Cedars-Sinai and a research scientist in the Division of Artificial Intelligence in Medicine and the Smidt Heart Institute; and other colleagues trained an AI model to differentiate between two underlying causes of sudden cardiac arrest: pulseless electrical activity and ventricular fibrillation.

Pulseless electrical activity means that the heart’s electrical signals are too weak to produce a heartbeat. It cannot be treated with a defibrillator and often leads to death. Ventricular fibrillation is a type of irregular heartbeat that can cause the heart to stop beating, but an electric shock from a defibrillator can trigger the beating again. 

After the AI model reviewed patterns in electrocardiogram readings as well as patient characteristics, investigators were able to determine risk factors for both types of sudden cardiac arrest.

People who had pulseless electrical activity sudden cardiac arrest, for example, were more likely to have been older, been overweight, have had anemia, or experienced shortness of breath as a warning symptom. Those who had ventricular fibrillation were more likely to be younger, have had coronary artery disease or experienced chest pain as a warning symptom.

“We have ways of preventing sudden cardiac arrest through technologies like a defibrillator, but the challenge is knowing who is most likely to benefit from this intervention,” said Lauri Holmstrom, MD, PhD, a visiting postdoctoral scientist at Cedars-Sinai and first author of both studies. “These findings could help cardiologists identify which patients are likely to have a pulseless electrical activity sudden cardiac arrest or ventricular fibrillation sudden cardiac arrest, and help them prevent these events from occurring.”

The AI models used in both studies were trained, tested, and validated using data from two ongoing studies of sudden cardiac arrest founded and led by Chugh: the Oregon Sudden Unexpected Death Study and the Ventura Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) study.

“These studies exemplify the potential for AI to detect patterns in the body that the human eye and standard medical tests cannot,” said Paul Noble, MD, the Vera and Paul Guerin Family Distinguished Chair in Pulmonary Medicine and chair of the Department of Medicine at Cedars-Sinai, who was not involved in the studies. “We are getting closer to being able to use AI to prevent dangerous events such as sudden cardiac arrest.”

Other Cedars-Sinai investigators who worked on the Communications Medicine study include Harpriya Chugh; Kotoka Nakamura, PhD; Ziana Bhanji; Madison Seifer; Audrey Uy-Evanado, MD; and Kyndaron Reinier, PhD.

Other Cedars-Sinai investigators who worked on the Circulation: Arrhythmia and Electrophysiology study include Bryan Bednarski; Harpriya Chugh; Habiba Aziz; Hoang Nhat Pham, MD; Arayik Sargsyan, MD; Audrey Uy-Evanado, MD; Damini Dey, PhD; and Kyndaron Reinier, PhD.

Funding: Both studies were funded, in part, by the National Heart, Lung, and Blood Institute.

Read more on the Cedars-Sinai Blog: Heart Attack, Cardiac Arrest, Heart Failure—What's the Difference?

Atrial fibrillation is an irregular heart rhythm that begins in the upper part of the heart. It is the most common type of arrhythmia.

“Once somebody has persistent AFib, our ability to put them back into a normal rhythm with ablation and medications is lower,” said Christine Albert, MD, MPH, chair of the Department of Cardiology, the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, and senior and corresponding author of the study. “In addition, several studies suggest that once you have persistent AFib, you may actually have a greater risk for stroke, heart failure and dying from cardiovascular disease.” 

This more recent study found that risk factors for new-onset, persistent AFib include being older, male, overweight, having a higher BMI (≥30 kg/m2) and, interestingly, having post-college education.

Investigators theorized that the association between higher levels of education and persistent AFib may be related to people with greater health literacy being able to more easily access healthcare services. This correlation is presumed to make those with a higher education more likely than people with less education to receive an ECG, which can detect asymptomatic, persistent episodes of AFib.

The findings were released as part of a sub-analysis of the VITamin D and OmegA-3 TriaL (VITAL), an ongoing study investigating whether daily dietary supplements of vitamin D3 or omega-3 fatty acids reduce risk for developing cancer, heart disease or stroke.

For this sub-analysis, investigators examined associations in lifestyle, clinical and socioeconomic risk factors among more than 25,000 people without a history of cardiovascular disease, AFib or cancer.

Over the course of 5.3 years, 900 participants developed AFib and 346 (38.4%) had persistent AFib at the time of diagnosis.

“As cardiologists, we tend to think that we have some time, that we can intervene and prevent this particular type of atrial fibrillation,” Albert said. “This data suggests a substantial percentage of patients present this way, so it’s important to think about risk factor modification in the population that does not yet have known AFib, but who are at risk for developing AFib in the future.”

Albert said more trials are needed to learn how weight loss interventions might prevent people from developing persistent AFib.

“This research shows which groups of people might be most at risk for developing persistent AFib,” Albert said. “You could design a screening study targeted toward those populations to see if you could pick up atrial fibrillation sooner, so that it can be treated.”

Other Cedars-Sinai investigators who worked on the study include Melissa Middeldorp, PhD, MPH; Roopinder Sandhu, MD, MPH; and Jessica Mao, MD.

Funding: The VITAL Rhythm Trial was supported by R01HL116690, and the VITAL Trial was supported by grants U01 CA138962 and R01 CA138962, which included support from the National Cancer Institute, National Heart, Lung and Blood Institute, Office of Dietary Supplements, National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health of the National Institutes of Health.

Follow Cedars-Sinai Academic Medicine on Twitter for more on the latest basic science and clinical research from Cedars-Sinai.

The findings, published in the Journal of the American College of Cardiology (JACC), show that women can exercise less often than men, yet receive greater cardiovascular gains.   

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” said Martha Gulati, MD, director of Preventive Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, the Anita Dann Friedman Chair in Women's Cardiovascular Medicine and Research and co-lead author of the study. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

Investigators analyzed data from 412,413 U.S. adults utilizing the National Health Interview Survey database. Participants between the time frame of 1997 to 2019—55% of whom were female—provided survey data on leisure-time physical activity. Investigators examined gender-specific outcomes in relation to frequency, duration, intensity and type of physical activity.

“For all adults engaging in any regular physical activity, compared to being inactive, mortality risk was expectedly lower,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study. “Intriguingly, though, mortality risk was reduced by 24% in women and 15% in men.”

The research team then studied moderate to vigorous aerobic physical activity, such as brisk walking or cycling, and found that men reached their maximal survival benefit from doing this level of exercise for about five hours per week, whereas women achieved the same degree of survival benefit from exercising just under about 2 1/2 hours per week.

Similarly, when it came to muscle-strengthening activity, such as weightlifting or core body exercises, men reached their peak benefit from doing three sessions per week and women gained the same amount of benefit from about one session per week.

Cheng said that women had even greater gains if they engaged in more than 2 1/2 hours per week of moderate to vigorous aerobic activity, or in two or more sessions per week of muscle-strengthening activities. The investigators note their findings help to translate a longstanding recognition of sex-specific physiology seen in the exercise lab to a now-expanded view of sex differences in exercise-related clinical outcomes.

With all types of exercise and variables accounted for, Gulati says there’s power in recommendations based on the study’s findings. 

“Men get a maximal survival benefit when performing 300 minutes of moderate to vigorous activity per week, whereas women get the same benefit from 140 minutes per week,” Gulati said. “Nonetheless, women continue to get further benefit for up to 300 minutes a week.”

Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, says concrete, novel studies like this don’t happen often.

“I am hopeful that this pioneering research will motivate women who are not currently engaged in regular physical activity to understand that they are in a position to gain tremendous benefit for each increment of regular exercise they are able to invest in their longer-term health,” said Albert, professor of Cardiology.

Other Cedars-Sinai authors include Tzu Yu Huang, MSc; Alan Kwan, MD; David Ouyang, MD; and Joseph Ebinger, MD. Other authors include Hongwei Ji, MD; Kaitlin Casaletto, PhD; Kerrie L. Moreau, PhD; and Hicham Skali, MD, MSc.

Funding: This work was supported in part by NIH grants K23HL153888, K23AG058752, R21HL156132, R01HL142983, R01HL151828, R01HL131532, R01HL143227, R01AG072475, U54AG062319, and U54AG065141, and the Erika J Glazer Family Foundation, National Key R&D Program of China (2022YFC2502800), National Natural Science Foundation of China (82103908), Shandong Provincial Natural Science Foundation (ZR2021QH014), Shuimu Scholar Program of Tsinghua University, and National Postdoctoral Innovative Talent Support Program (BX20230189).

Read more from the Cedars-Sinai Blog: High Blood Pressure: How to Recognize and Treat It

But there is hope, according to Natalie Bello, MD, MPH, director of Hypertension Research in the Department of Cardiology, and colleague Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, who recently authored a perspective article in the journal Circulation Research.  

The paper reflects on women’s cardiovascular health during the past century and looks ahead to the many advances happening in the field. Bello spoke with the Cedars-Sinai Newsroom to share more.

What do women need to know about their cardiovascular health?

Heart disease is the No. 1 cause of death in women, but surveys show women tend to think they are more likely to die of cancer, particularly breast cancer. The most important thing to remember is that heart disease kills more women than all types of cancer combined.

Are some women at greater risk than others?

Almost 20% of women who get pregnant experience complications, such as high blood pressure, preeclampsia or gestational diabetes, that have important implications for their future heart health. These conditions are associated with a higher incidence of heart disease that often happens early in the lifespan.

What progress has been made?

Thanks to pioneers like C. Noel Bairey Merz, MD, director of the Barbra Streisand Women's Heart Center in the Smidt Heart Institute, the medical community is now actively involved in the advancement of women’s heart disease research and care. Her leadership in this area has broadened visibility to gender differences in things like heart attack symptoms and the diagnosis of small vessel heart disease.

Could you give an example of how increased research into women's cardiovascular health has led to better treatment for women?

There is a now a blood test approved by the U.S. Food and Drug Administration, developed by Cedars-Sinai investigators, that we can use to understand a woman's risk for preeclampsia. It helps tell us when a pregnant woman is safe to go home, or if she needs to stay in the hospital for closer monitoring, treatment or early delivery. We use it very frequently.

This is just one of many examples of how Cedars-Sinai has led in women’s heart health.

When should women think about their cardiovascular health?

At age 20, women should establish care with a primary care physician and have their cardiovascular risk assessed. At minimum, all women should visit a primary care provider annually for a blood pressure check.

What are the best ways to prevent cardiovascular disease?

Learn about your personal risk and ways you can modify the disease. That advice is based on the knowledge that 80% of cardiovascular disease is preventable. By doing things like stopping smoking, eating healthy, maintaining a healthy body weight, exercising and sleeping well, we can prevent or delay the progression of heart disease.

Why is it that women's cardiovascular health has been ignored?

In a paper published in 1912, a researcher named Dr. James Herrick and colleagues described heart disease as something that occurred in men. But they published another paper in 1928 showing that the same thing was happening in women. For whatever reason, the follow-up work never gained traction, and that set the stage for heart disease being seen as a man’s issue.

Early epidemiologic research also demonstrated a delay in the onset of heart disease in women compared with men. Noting that women’s risk seemed to increase after menopause, estrogen was believed to be protective and premenopausal women’s risk for heart disease was thought to be low. We now realize that societal issues and habits at the time also influenced risk: Men were more likely to smoke, and women didn’t start smoking socially until later in the last century. Unfortunately, when smoking became socially acceptable for women, there was an uptick in women's heart disease as a result.

I think one of the main reasons women’s cardiovascular health wasn't really investigated is that there was not as much diversity in science and medicine at the time. If you don't experience things, you don't know what questions to ask. I'm not saying it's impossible, but a bunch of men sitting around a table aren't necessarily going to ask each other, “I wonder how excessive menstrual bleeding impacts heart disease risk?” and decide to examine that in a research study.

What can women who aren’t scientists do to ensure the medical system addresses their needs?

It often takes people outside of the scientific community to remind us that we need to be examining certain issues in women’s health. A lot of times it comes from patients who experienced something in their own pregnancy or in their own heart health journey and either started a foundation or lobbied elected officials to increase funding for research related to women. It’s also important for women to feel empowered to discuss their concerns with their clinicians, and if they feel they aren’t being listened to, they should find another person to listen to their symptoms and work them up appropriately.

Read more from the Cedars-Sinai Blog: High Blood Pressure: How to Recognize and Treat It

The investigators, whose results are published in the peer-reviewed journal npj Digital Medicine, say their AI measurement tool offers new help in predicting heart attacks and cardiovascular disease.

“Our research shows that people with a larger volume of heart fat—a key indicator of metabolic health—and those with more dense heart fat—a marker of inflammation—are at higher risk for cardiovascular disease,” said Piotr J. Slomka, PhD, director of Innovation in Imaging at Cedars-Sinai and a professor of Medicine in the Division of Artificial Intelligence in Medicine. “This novel technology uses AI to more quickly and accurately assess the volume and density of heart fat, offering valuable insight beyond traditional methods.”

Slomka and colleagues hope to translate these findings into clinical use more broadly, offering doctors and clinicians this specialized software.

“These results underscore the efficiency and clinical importance of AI in heart disease risk assessment, offering a fast and reliable tool for predicting cardiovascular risk,” said Slomka, also a professor of Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai.

Investigators included 8,781 patients from four clinical sites in their study. None of the patients had known coronary artery disease—a type of heart disease—at the time of the study, and all underwent heart imaging.

Key results include:

• AI measurements of heart fat were performed in under two seconds, compared with 15 minutes typically required for manual measurement.
• During the follow-up period, which was 2.7 years, individuals with larger volumes of heart fat and higher densities of heart fat experienced greater incidence of heart-related issues or death.
• The risk of cardiovascular-related death, and heart attacks, was almost three times higher in patients with both elevated heart fat volumes and density.
• The association with cardiovascular risk persisted, even after taking into account other risk factors like age, medical history, past heart imaging results and coronary artery calcium scores.

Study results align with previous research but offer new insight through the use of AI.

“These findings validate the use of AI for quick and accurate heart fat measurement, highlighting a potential shift toward more AI-assisted diagnostic methods in cardiology,” said Sumeet Chugh, MD, Cedars-Sinai’s director of the Division of Artificial Intelligence in Medicine and associate director of the Smidt Heart Institute.

Chugh, who was not involved in the study, said that by establishing a clear link between heart fat and cardiovascular risk, the study encourages further research into heart fat as a key factor in heart disease.

“This approach serves as a practical, real-world test of the application's effectiveness when implemented in clinical settings,” Chugh said.

As a next step, investigators plan to further test their algorithm in a more diverse patient population to ensure accuracy and generalizability of the findings.

Other authors involved in the study include Robert J. H. Miller, Aakash Shanbhag, Aditya Killekar, Mark Lemley, Bryan Bednarski, Serge D. Van Kriekinge, Paul B. Kavanagh, Joanna X. Liang, Valerie Builoff, Attila Feher, Edward J. Miller, Andrew J. Einstein, Terrence D. Ruddy, Daniel S. Berman, and Damini Dey.

This research was supported in part by grants R01HL089765 and R35HL161195 from the National Heart, Lung, and Blood Institute at the National Institutes of Health (PI: Piotr Slomka).

Read more on the Cedars-Sinai Blog: Graduate Students Are Using AI in Medical Imaging

The findings, published in the peer-reviewed Journal of Hepatology, highlight the need for women who are at risk of developing liver disease to avoid excess alcohol consumption.  

Formerly known as fatty liver disease, steatotic liver disease occurs when too much fat accumulates in the liver. In some people, it can lead to long-term liver damage. Steatotic liver disease is also linked with heart disease.

Experts are unsure what exactly causes steatotic liver disease, but associated factors include obesity, diabetes, high blood pressure and high cholesterol.

“Steatotic liver disease is a major and increasingly prevalent condition that is likely an underlying precursor to many conditions, including those involving the heart,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute and lead author of the study. “We are paying even more attention to steatotic liver disease because we are seeing how it tracks closely with established cardiovascular risk factors such as hypertension, high cholesterol and diabetes.”

Medical experts recently created new terms to classify the different types of steatotic liver disease:

• metabolic dysfunction-associated steatotic liver disease (MASLD)
• alcohol-related liver disease (ALD)
• metabolic dysfunction-associated and alcohol-related liver disease (MetALD)

Cedars-Sinai investigators sought to learn how these types of steatotic liver disease may affect men and women differently.

The investigators analyzed data from 1988 to 1994 collected through the National Health and Nutrition Examination Survey III. Study participants completed questionnaires and underwent medical exams and laboratory tests, which included providing information on alcohol use, cardiometabolic risk factors, and undergoing imaging scans of the liver.

The investigators identified more than 10,000 people age 21 and older living in the U.S. who had data available from the liver scans and other medical exams.

Nearly one-fifth of the whole cohort, totaling 1,971 people, had steatotic liver disease, and more than 75% of these adults had MetALD. Although all forms of steatotic liver disease were about twice as common in men than women, the data showed that risk of death was significantly higher in women over a median period of 26.7 years. For example, having MetALD increased risk of dying 83% more in women than in men, when compared with people who did not have liver disease. Even further, women with ALD had a 160% greater mortality risk than men with ALD.

“These findings are especially concerning in the context of the COVID-19 pandemic, during which alcohol use and related death, particularly in women, has increased,” said Alan Kwan, MD, a research instructor in the Department of Cardiology at Cedars-Sinai who also worked on the study.

Being overweight or obese, having prediabetes or diabetes, high blood pressure, or abnormal cholesterol levels in the blood could be signs of underlying metabolic liver disease. Women with these risk factors should be especially cautious about excess alcohol intake, according to the investigators.

The Centers for Disease Control and Prevention defines moderate drinking for women as one drink or less a day.

The investigators plan to continue to study why the female liver is more affected by alcohol than the male liver and what lifestyle changes, in addition to reducing alcohol intake, might reduce a woman’s risk for steatotic liver disease.

They also point out that because the study analyzed data collected between 1988 and 1994, more studies are needed to learn how the prevalence of liver disease and alcohol use may have changed over time.

Cedars-Sinai investigators Yee Hui Yeo, MD, and Hirsh Trivedi, MD, also worked on the study.

Funding: The study was funded by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, and the National Institutes of Health. 

Read more about Cedars-Sinai research: Study: Long-Term Alcohol Consumption Plays Role in Pancreatitis Progression

Follow Cedars-Sinai Academic Medicine on Twitter for more on the latest basic science and clinical research from Cedars-Sinai.

at Cedars-Sinai aimed to understand the possible connection between COVID-19 vaccination and a difficult-to-diagnose heart condition called postural orthostatic tachycardia syndrome, or POTS. The study validated that patients who were immunized with a COVID-19 mRNA vaccination and then went on to have new or exacerbated POTS all had preexisting conditions that can lead to a POTS diagnosis.

POTS is associated with nervous system dysfunction and causes an abnormal increase in heart rate after standing or sitting up. It used to affect primarily women of childbearing age. However, for POTS cases that developed during the COVID-19 pandemic, men were equally affected.

“We were surprised when all the patients in our small cohort already had conditions that could make them more likely to develop POTS even without vaccination, such as palpitations, fast heart rates, orthostatic intolerance, hypermobile joints, asthma, systemic lupus, fainting and chronic abdominal pain,” said Peng-Sheng Chen, MD, the corresponding author of the study and an international expert on the condition who leads one of only a few specialty clinics on the syndrome in the nation.

“These findings suggest it may be helpful to keep an eye on patients with underlying health issues after COVID-19 vaccination to monitor for post-vaccine POTS,” said Chen, who also holds the Burns and Allen Chair in Cardiology Research at Cedars-Sinai.

The observational study, recently published in the peer-reviewed journal Heart Rhythm and presented during the American Heart Association Scientific Sessions, analyzed data from 10 patients treated at the Cedars-Sinai multidisciplinary POTS clinic between July 2021 and June 2022. When provided guideline-directed care, all study participants reported an improvement in their POTS condition.

Although there is an association between POTS and COVID-19 vaccination, a previous study of patient data across the Cedars-Sinai Health System found that patients diagnosed with COVID-19 were five times more likely to develop the cardiac condition after infection than after vaccination.

“COVID-19 infection itself seems to be either causing or unmasking a startling amount of POTS or POTS-like conditions globally,” said Debbie L. Teodorescu, MD, a cardiology fellow at the Smidt Heart Institute and first author of the study. “In our cohort, most patients responded well to treatment, but a subsequent COVID-19 infection tended to bring significant setbacks in recovery. That is why we urge all patients to be meticulous about avoiding COVID-19.”

Read more from the Cedars-Sinai Blog: Long COVID: What to Know

at Cedars-Sinai found that women who developed signs of elevated blood pressure during pregnancy were more likely to have residual evidence of abnormal heart structure and function up to a decade after the pregnancy.

“This study helps to clarify that, for some women, pregnancy is not just a ‘stress test’ that unmasks underlying cardiovascular risks,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study. “This risk may also affect the heart years after pregnancy.”

The study, recently published in the peer-reviewed journal Hypertension, looked at more than 5,000 Hispanic/Latina women with at least one prior pregnancy and identified those who had hypertensive disorders of pregnancy, such as gestational hypertension, preeclampsia or eclampsia.

“This study confirms the results of others and demonstrates that women who experience a hypertensive disorder during their pregnancy are more likely to have lasting changes in the structure and function of their hearts than women who have normal blood pressure during their pregnancy,” said Natalie Bello, MD, MPH, director of Hypertension Research in the Smidt Heart Institute and co-author of the study. “Further, this work shows that only a portion of the abnormalities in the heart are explained by the woman’s current blood pressure.”

After accounting for other cardiovascular risk factors that might otherwise lead to early signs of heart disease, researchers found that the approximately 14% of study participants who had developed hypertensive disorders during pregnancy had several persistent heart-related issues found on cardiac imaging. These included greater heart-wall thickness, more frequent abnormal left-ventricle geometry and lower ejection fraction when compared to women who also had a prior pregnancy but without any related hypertensive disorder.

Although they make up a large and growing population of the United States, historically, Hispanic/Latina women have been underrepresented in medical studies. Using data from the Hispanic Community Health Study/Study of Latinos—a multicenter community-based study—investigators were able to engage this diverse population in their research. However, study authors say that given the underlying diversity of Hispanic/Latinx people, the findings of this study are not likely to be specific to any particular ethnicity, race or national origin.

“Cedars-Sinai has long invested in women’s heart health research, and this newest, critical study deepens our understanding of who is most at risk for hypertensive disorders in pregnancy,” said Christine M. Albert, MD, MPH, who is chair of the Department of Cardiology in the Smidt Heart Institute and holds the Lee and Harold Kapelovitz Distinguished Chair in Cardiology and was not involved in this study.

Read more from Cedars-Sinai Discoveries Magazine: Bridging the Data Gap on Hypertension During Pregnancy 

The clinic is the newest offering from the heart institute’s dedicated Aortic Program, an interdisciplinary team of highly specialized cardiologists, cardiac and vascular surgeons, radiologists, genetic counselors, and nurses treating the full spectrum of aortic disorders.

“When patients hear that they have an aortic aneurysm, they often think they are ticking time bombs, but that is not always the case,” said Robbin Cohen, MD, professor of Cardiac Surgery and director of the Cardiac Surgery Program at Huntington Health, a Cedars-Sinai affiliate. “Most of the patients that we see—many with genetic conditions affecting the heart—have aortas that are not large enough or serious enough to need surgery, but they do require ongoing monitoring.

“Through the Aortic Surveillance Clinic, we offer reassurance that they are being carefully and closely monitored and that proper therapy, including surgery, will be offered if needed.”

Smidt Heart Institute patients benefit from access to a multidisciplinary team including cardiac and vascular surgeons skilled in treating a range of aortic conditions.

“We take pride in our collaborative approach, which benefits patients with various complex aortic diseases,” said vascular surgeon Ali Azizzadeh, MD, professor and director of Vascular Surgery, associate director of the Smidt Heart Institute at Cedars-Sinai and an aortic aneurysm expert. “Our team is versed in innovative, minimally invasive procedures, in which cardiac surgeons and vascular surgeons are thorough and thoughtful in how best to manage each individual patient’s needs.”

Cohen has more than 25 years of experience monitoring and treating patients with aortic aneurysm.

“Aortic surgeons know that over time, they will accumulate hundreds of patients with aneurysms that they are following and not operating on,” Cohen said. “This requires expertise in aortic imaging, the natural history of aortic disease, and the guidelines and criteria for surgery—areas in which the Smidt Heart Institute team is highly skilled.”

The aorta is the largest and most important artery. It carries blood away from the heart into the rest of the body. Careful monitoring of a significantly enlarged aorta, or aortic aneurysm, can help prevent the possibility of a life-threatening condition, such as aortic dissection—a tear that develops along the inner layer of the aorta.

The Aortic Surveillance Clinic also provides expert care for patients with certain genetic syndromes, such as connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome, as well as other genetic disorders affecting the aorta and aortic valve, such as Turner syndrome. These patients are at high risk of developing an enlarged aorta and subsequently, a tear or dissection in the aorta due to abnormalities in the heart and blood vessels. Because these disorders also can affect other areas of the body, the Aortic Surveillance Clinic goes a step further and addresses these issues by connecting patients with genetic counselors, ophthalmologists, orthopedists, psychologists, reproductive endocrinologists and other specialists, as needed.

“We are pleased to have the ability to focus on a subset of patients when they don’t need surgery—and educate them on how to prevent acute aortic events, which can be fatal,” said Joanna Chikwe, MD, chair of the Department of Cardiac Surgery and the Irina and George Schaeffer Distinguished Chair in Cardiac Surgery in the Smidt Heart Institute at Cedars-Sinai. “And if these patients do need surgery—which can be complex and challenging—the Smidt Heart Institute has the expertise of a comprehensive, multidisciplinary team to take care of them, with superb results.”

The Aortic Surveillance Clinic is located at 127 San Vicente Blvd., in Los Angeles and is open for patient evaluation the second Friday of each month. Patients can call 310-423-3851 for more information.

Cedars-Sinai once again has been recognized by U.S. News & World Report, this year as the #2 program in the nation for Cardiology, Heart & Vascular Surgery. The Smidt Heart Institute is also #1 for Cardiology, Heart & Vascular Surgery in California and Los Angeles (highest U.S. News ranking in the region).

Read more on the Cedars-Sinai Blog: The Cedars-Sinai Specialist Aortic Service and Acute Aortic Dissection

The results, published in The Lancet Digital Health, include data from patients from three healthcare systems: Cedars-Sinai, Stanford University and Columbia University. All patients in the study underwent a surgical procedure, including open heart surgery, other major surgeries, and minimally invasive procedures involving a catheter or endoscope.

Investigators trained an AI model on pre-operative electrocardiograms, discovering a new use for the 130-year-old test. Invented in the late-1800s, an electrocardiogram is a commonly deployed test that involves placing electrodes on the skin to measure the heart’s electrical activity and assess how well the heart is functioning.  

“This is the first electrocardiogram-based AI algorithm that predicts post-operative mortality,” said David Ouyang, MD, a cardiologist in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, and a corresponding author of the study. “Previously, algorithms have been used to assess long-term mortality as well as individual disease states, but determining post-surgical outcomes helps inform the actual decision to do surgery.”

Investigators paired patients’ electrocardiograms from before the surgery or procedure, with their outcomes after the surgery or procedure, and asked the algorithm to find associations or patterns in the electrocardiogram waveforms.

While classifying most patients as low risk, those individuals the algorithm identified as high risk had nearly a 9-fold increased probability of post-operative mortality.

“As it now stands, clinicians only have a modest ability to predict how a patient is going to do after surgery,” said Ouyang, also a faculty member in the Division of Artificial Intelligence in Medicine at Cedars-Sinai. “Current clinical risk prediction tools are insufficient. This AI model could potentially be used to determine exactly which patients should undergo an intervention and which patients might be too sick.”

Every medical intervention comes with risk, and doctors currently rely on guidelines from medical societies to determine a patient’s individual risk.

“In cardiology, we're fortunate to have many life-saving procedures, everything from catheter-based procedures to open-heart surgery, so we're often trying to think about who are the right patients for the right procedure,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the other corresponding author of the study. “A better understanding of risk, particularly by using a commonly obtained diagnostic test, can inform important medical decisions.”

Investigators are currently studying how the algorithm could be translated into a web application that would be widely available for physicians and patients.

Other Cedars-Sinai investigators who worked on the study include John Theurer; Nathan R. Stein, MD; Neal Yuan MD; Grant Duffy; Roopinder K. Sandhu, MD; Joseph Ebinger MD; Patrick Botting; Melvin Jujjavarapu; Michael Nurok, MD; Sumeet S. Chugh, MD; and Susan Cheng, MD.

The study was funded by the National Heart, Lung, and Blood Institute.

 Read more in Discoveries: A New Partner In Heart Disease Prediction—AI

The Phase I clinical trial results are published in the peer-reviewed journal eBioMedicine, a Lancet journal.

“Although several drugs are approved for pulmonary arterial hypertension, mortality remains high,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai, the Mark S. Siegel Family Foundation Distinguished Professor and senior author of the study. “We tried a fundamentally different approach—cell therapy delivered into the pulmonary artery—and found encouraging results, in patients already on combination conventional therapy." 

Pulmonary arterial hypertension is a rare disease, affecting fewer than 100 people per million. There currently is no cure and the average median life expectancy on treatment for most patients is roughly 6.2 years after diagnosis.

Currently approved medications for the condition aim to open up blood vessels in the lungs, allowing for better blood flow; however, studies on lungs in patients on treatment still show severe occlusive vessel changes. Further, these medications don’t address many of the complex underlying mechanisms that cause the high pulmonary pressures. Even on medication, people with pulmonary arterial hypertension can develop severe dysfunction in the right ventricle of the heart, the part that pumps blood to the lungs and whose function correlates best with survival.

Cedars-Sinai investigators are experimenting with using cardiosphere-derived cells (CDCs) to address some of the biological processes involved in pulmonary arterial hypertension. CDCs were first developed and characterized by Marbán. They have been used in multiple clinical trials for a variety of diseases, most recently, Duchenne muscular dystrophy. These are cells derived from human heart tissue that Marbán and colleagues have discovered reduce inflammation in the body and exert beneficial effects on the immune system.

Called the ALPHA study, this clinical trial was conducted in two phases. In the first, six people with pulmonary arterial hypertension received an infusion of CDCs into their lungs. Three patients received an infusion of 50 million CDCs and the other three received an infusion of 100 million CDCs.

In the second phase, 10 people with pulmonary arterial hypertension were randomized to receive an infusion of 100 million CDCs and 10 people were randomized to receive infusions containing a placebo. Investigators performed right heart catheterization and cardiac MR imaging on each study participant before the infusions and four months after the infusions.

All the participants were on combination pulmonary arterial hypertension-specific medications throughout the course of the study.

The investigators tracked the health of participants for 12 months after the infusions. No adverse effects related to the infusions occurred during this time. Although this study was only designed to assess the safety of the CDC infusions, the investigators observed encouraging changes that might indicate the 16 people who had received the CDC infusions had improved cardiopulmonary health. People who received the infusions, for example, showed improved functioning in the heart’s right ventricle and, at two months post-infusion, were able to walk a greater distance during a six-minute test than people who received placebo.

“The most important takeaway is that this approach is safe and feasible to do in people with pulmonary arterial hypertension,” said Michael I. Lewis, MD, director of Respiratory Care Services at Cedars-Sinai, and first and corresponding author of the study. “These are encouraging exploratory findings that motivate moving on to more advanced studies.”

The investigators plan additional trials to study the effects of repeated infusions of CDCs given to people with pulmonary arterial hypertension.

Cedars-Sinai investigators Mamoo Nakamura, MD; Dael Geft, MD; Yuri Matusov, MD; James Mirocha; Antoine Hage, MD; Victor Tapson, MD; Oleg A. Karpov, PhD; and Jennifer Van Eyk, PhD, also worked on the study.

Funding: The study was funded by the California Institute for Regenerative Medicine (CIRM), one of the world’s largest institutions dedicated to three key areas of regenerative medicine—research, education and patient access.

Read more on the Cedars-Sinai Blog: Pulmonary Hypertension: A Patient’s Advice

Follow Cedars-Sinai Academic Medicine for more on the latest basic science and clinical research from Cedars-Sinai. 

The retrospective study was part of the Women’s Ischemia Syndrome Evaluation (WISE), a multiyear, multicenter research project sponsored by the National Heart, Lung, and Blood Institute to study detection and assessment of heart artery disorders in women.

The study’s senior and corresponding author Janet Wei, MD, assistant professor of Cardiology in the Smidt Heart Institute, said that a possible explanation for the findings is that evidence-based, guideline-directed cardiovascular care provided at academic medical centers can help ensure equal health opportunities for Black women, who are at an increased risk of dying from cardiovascular disease compared to non-Black women.

“Our findings suggest that when women with coronary artery disease are treated in an academic setting—as were the women involved in the WISE study—they may experience less racial and ethnic discrimination and receive appropriate guideline-directed therapy,” said Wei, who also is associate medical director of the Biomedical Imaging Research Institute and co-director of the Stress Echocardiography Lab in the Smidt Heart Institute.

While heart disease is the leading cause of death for women in most racial and ethnic groups in the U.S., previous studies have shown striking disparities in heart disease outcomes in Black versus non-Black women, including earlier development of cardiovascular disease and a nearly 20% higher rate of cardiovascular-related death.

But the reasons for these disparities have been unclear, leading Wei and other investigators to explore the factors associated with long-term adverse outcomes in Black women with obstructive coronary artery disease.

Using data from the WISE original cohort of 944 women, investigators studied middle-aged women who had coronary angiograms revealing obstructive coronary artery disease (one-third of the cohort). The women were followed for more than a decade to monitor for heart attack, stroke, hospitalization due to chest pain or heart failure, or any cause of death.

Compared with non-Black women in the group, Black women had higher rates of cardiovascular risk factors, such as obesity (average body mass index was 31 in Black women vs. 28 in non-Black women) and hypertension (90% vs. 64%); lower levels of education (50% vs. 19%) and income (62% of Black women earned less than $20,000 per year vs. 32% of non-Black women); and a higher proportion of public health insurance (51% vs. 39% were on Medicare and 21% vs. 6% were on other public insurance, while 23% vs. 49% had private insurance).

However, Black women had a similar or higher use of guideline-directed treatment, including cholesterol- and blood pressure-lowering medications, for coronary artery disease compared to non-Black women. And their long-term cardiovascular outcomes—including cardiovascular mortality—were similar to that of non-Black women with obstructive coronary artery disease (28% of Black women died vs. 20% in non-Black women).

“Recent studies have attributed social determinants of health and structural racism to disparities in cardiovascular health,” Wei said. “But if racial disparities in cardiovascular treatment are reduced, racial disparities in cardiovascular outcomes may be lessened or even eliminated.”

In a separate, recent study, Cedars-Sinai investigators found that Black women with signs and symptoms of ischemia with no obstructive coronary artery disease (INOCA) have increased long-term risk of heart attack, stroke or death.

In addition, they reported that women with INOCA are less likely to be prescribed cardiac medications compared to women with obstructive coronary artery disease, in part because traditional cardiology training advises physicians to look for blockages in coronary arteries when diagnosing coronary artery disease, making INOCA a commonly overlooked cardiac condition.

“Increasing understanding and awareness of how cardiac conditions affect women is so important,” said C. Noel Bairey Merz, MD, principal investigator of the WISE clinical trial, director of the Barbra Streisand Women’s Heart Center, director of the Linda Joy Pollin Women’s Heart Health Program, and the Irwin and Sheila Allen Chair in Women’s Heart Research at the Smidt Heart Institute. “Also critical is the need for appropriate guideline-directed care for all women, regardless of where they go for treatment.”

Bairey Merz, Wei and other investigators in the WISE study into more equitable outcomes for Black women recommended that physician and community education campaigns aimed at evidence-based and guideline-directed care be used in community healthcare settings to help mitigate structural racism.

Other Cedars-Sinai investigators involved in the study include Galen Cook-Wiens, MS, biostatistician.

Read more on the Cedars-Sinai Blog: Women’s Health and Sex Differences: Research Update

“This is proof of a novel concept that while our current prediction methods measure a snapshot in time, increased risk of sudden cardiac arrest can have a measurable, dynamic component,” said Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and senior author of the study.

The study published today in the European Heart Journal and was presented simultaneously during the American Heart Association Scientific Sessions 2023.

Sudden cardiac arrest occurs when an electrical circuit in the heart malfunctions and abruptly causes the heart to stop beating. The condition is lethal in 90% of cases. Patients found to be at high risk for sudden cardiac arrest can be preemptively treated with medications or have a defibrillator implanted surgically that can shock a stopped heart into beating.

Medical knowledge is a moving target, however, and over the last two decades it has become more challenging to pinpoint the best candidates for the surgically implanted defibrillator.

“Based on these findings, we now know that electrocardiogram abnormalities are escalated over time in people who have sudden cardiac arrest compared to people who are not destined to experience the condition,” said Chugh, who is also medical director of the Heart Rhythm Center. “We can potentially leverage this dynamic change to improve how we identify candidates who will benefit the most from an implantable defibrillator.”

Investigators looked at the trajectory of electrocardiogram changes in patients who ended up having a cardiac arrest compared to patients who never did.

The team pulled the study population from two ongoing, community-based studies led by Chugh: the Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) Study in Ventura County, California, and the Oregon Sudden Unexpected Death Study (SUDS), based in Portland, Oregon. This study marks the 100^th publication from the Oregon Sudden Unexpected Death Study, which was founded on Feb. 1, 2002.

The investigators analyzed data in people who had at least two electrocardiograms. They defined variability based on six previously validated markers of electrical risk, which were initially published in the European Heart Journal in 2017.

These markers include the patient's heart rate, left ventricular hypertrophy (thickening of the walls of the heart) and four measures of how the heart muscle undergoes electrical stimulation and relaxation.

In their latest research, investigators carried out this work in two stages.

In the first, investigators compared electrocardiograms from people in the Oregon study who had sudden cardiac arrest with electrocardiograms from people in Oregon who did not. In the second study, they attempted to test these findings in corresponding groups of people in California. In both regions, people who suffered from sudden cardiac arrest had a substantial increase in their electrical risk measured by the electrocardiogram, but this was not observed in the comparison groups.

Evaluating further, the investigators found that the increased electrical risk was observed uniformly in the five years leading up to the sudden cardiac arrest. Participants who had sudden cardiac arrest and those who did not were matched by sex, age and duration between their two electrocardiograms. When all clinical conditions, the static electrocardiogram, and the dynamic change in electrical risk were analyzed together, the dynamic change further improved prediction of risk.

“This highly novel study demonstrates that combining dynamic risk with static risk will enable better identification of individuals at high risk for sudden cardiac death,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute, who was not involved in this study. “Our nationally recognized Center for Cardiac Arrest Prevention has studied sudden cardiac arrest for over two decades. This important research brings us closer to being able to predict the event.”

This concept will need to be tested further before taking it to the clinic. The investigators are currently designing a study that will track how well these dynamic changes predict sudden cardiac arrest in patients who are followed over time. 

Other Cedars-Sinai investigators who worked on the study include Hoang Nhat Pham, MD; Lauri Holmstrom, MD, PhD; Harpriya Chugh; Audrey Uy-Evanado, MD; Kotoka Nakamura, PhD; Zijun Frank Zhang, PhD; Angelo Salvucci, MD; Jonathan Jui, MD; and Kyndaron Reinier, PhD.

Funding: The study was funded by National Heart, Lung, and Blood Institute grants R01HL145675 and R01HL147358 to Dr. Chugh.

DOI: 10.1093/eurheartj/ehad770

Read more on the Cedars-Sinai Blog: New Research on Sudden Cardiac Arrest Shows Racial Gap

Follow Cedars-Sinai Academic Medicine  for more on the latest basic science and clinical research from Cedars-Sinai.