His labored breathing and exhaustion prompted him to see his physician, who ordered a battery of tests. Aster’s diagnosis: A rare cancer called a neuroendocrine tumor was causing a condition called carcinoid heart disease, and causing his heart to fail.

With treatment at the Cedars-Sinai Neuroendocrine Tumor Multidisciplinary Clinic, Aster is now back on the trail, his bike, his board and the court.

“I went from wondering how long I have to live to understanding that this can be managed,” Aster said. “I feel better than I have felt in years.”

Aster’s symptoms came on slowly over several months: crushing fatigue, bloating, loss of appetite and swelling in his legs and feet. Blood tests ordered by his primary doctor were normal, but a CT scan showed tumors in his liver, which were eventually diagnosed as stage 4 neuroendocrine cancer.

“We received the diagnosis the day we dropped the youngest of our four kids off at college,” Orr said. “We had other plans, so we just had to reset.”

Unable to sleep the night they got the news, Orr—who Aster said was his caregiver and support throughout this difficult time and credits with helping save his life—spent hours online. She clicked her way to the Neuroendocrine Tumor Research Foundation. The organization, a resource for research funding, patient education and support, directed the couple to  the Neuroendocrine Cancer Foundation, which referred them to Cedars-Sinai and its multidisciplinary clinic.

“We were concerned about Ken’s neuroendocrine tumors, which had spread to his liver and were making it difficult for his stomach to work normally,” said Andrew Hendifar, MD, who leads the clinic and is a professor of Medicine at Cedars-Sinai. “But we knew from experience that his heart failure would have to be treated first. We didn’t have a minute to lose.”

Neuroendocrine tumors begin in neuroendocrine cells, which connect the nervous system with the hormone-producing endocrine system. They can occur anywhere in the body.

Aster’s began in his small bowel and produced a hormone called serotonin, which thickened two of his heart valves and caused them to leak. The condition is called carcinoid heart disease.

Prashanth Venkatesh, MD, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai, is the cardiologist on the neuroendocrine team.

“The pulmonary valve, which sends blood from the heart to the lungs, is notoriously difficult to evaluate with standard imaging techniques because of its location in the chest and the relative rarity of pulmonary valve disease in adults,” Venkatesh said. “Significant pulmonary valve involvement in carcinoid heart disease is hence very easily missed.”

Venkatesh, a congenital heart specialist, often employs more extensive imaging techniques for patients born with structural heart defects. Aster’s results showed there was a leak in his pulmonary valve as well as a leak in his tricuspid valve. Both valves needed to be replaced.

“When there is a leaky valve, which we call regurgitation, some of the blood in the heart goes in the wrong direction,” said Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai and the Karsh Distinguished Chair in Interventional Cardiology in the Smidt Heart Institute. “With leaky pulmonary and tricuspid valves, the blood that is supposed to go into the lungs can leak back toward the upper chamber of the heart.”

Aster’s pulmonary valve was replaced via a minimally invasive procedure in which a catheter was threaded up through an artery in the groin to maneuver the valve into its proper place. Four weeks later, Makkar replaced Aster’s tricuspid valve using a similar procedure. 

“Patients with carcinoid heart disease are going through a lot because of the neuroendocrine tumor, and traditional valve replacement surgery puts them at higher risk for complications,” Makkar said. “We pioneered testing of transcatheter tricuspid valve replacement around five years ago, and this was the option we chose for Mr. Aster.”

To address the neuroendocrine tumors on Aster’s liver, Alexandra Gangi, MD, director of the Division of Surgical Oncology and co-director of the Neuroendocrine Tumor Multidisciplinary Clinc, chose another minimally invasive approach: tumor embolization.

“We accessed the tumors with a catheter, through the artery in the groin,” Gangi said. “This allows us to block off the blood flow to the specific arteries that feed the tumors. This starves the tumors, and results in shrinking and tumor control.”

So far, Aster has avoided surgery and chemotherapy because of the nature of neuroendocrine tumors and the expertise of his care team in sequencing his therapies based on his sypmtoms.

“I think the difference between metastatic neuroendocrine tumors and most other types of gastrointestinal cancers is that we’re playing the long game,” Gangi said. “We often do the least invasive thing and save more aggressive options for when we really need them. These tumors tend to recur, but prognosis is generally good and patients can live a long time with them.”

Additional treatment or surgical procedures might be on the horizon, but today, Aster is doing well.

“We feel very fortunate that we were able to identify this as early as we did and intervene in the way that we did,” Hendifar said. “A few years ago, even six months ago, Ken wouldn't have been a candidate for minimally invasive valve replacements. He would have required open-heart surgery, and I'm not sure if the outcome would have been as good.”

Aster describes his current health as “great.”

“I just started cycling again in January, 13 months after the second valve replacement,” Aster said. “Now I'm doing a 25-mile ride in the hills two or three times a week with no problem. My heart feels as normal as can be.”

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, “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.

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

People living with tricuspid valve disease are gaining more treatment options, driven by research from Cedars-Sinai investigators and collaborators at other leading medical institutions.

Traditionally, cardiothoracic surgeons have repaired or replaced the tricuspid valve during open-heart surgery and only when absolutely necessary; such surgeries are complex and risky. Now, an increasing number of studies show that cardiac interventionalists can successfully use minimally invasive catheter-based techniques. Catheter-based procedures offer an alternative for patients who are not candidates for open-heart surgery.

Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention and the inaugural director of the Karsh Division of Interventional Cardiology in the Smidt Heart Institute at Cedars-Sinai, and his team of experts treat more than 10,000 patients every year. Makkar sat down with the Cedars-Sinai Newsroom to explain advances for patients with tricuspid valve disease.

What is tricuspid regurgitation, and who does it affect?

Tricuspid regurgitation is a condition where the tricuspid valve fails to close properly, allowing blood to flow backward into the right atrium. Studies estimate that severe regurgitation occurs in up to 4% of individuals 75 and older and is often linked with conditions like heart failure, atrial fibrillation or pulmonary hypertension. Women are more frequently affected, and because the condition often develops slowly, many patients are diagnosed at advanced stages when symptoms like swelling, fatigue and breathlessness impact them.

How has treatment for tricuspid valve disease evolved?

For decades, tricuspid regurgitation was largely overlooked, often addressed only during surgeries for other heart valves. Today, advances in minimally invasive treatments like transcatheter edge-to-edge repair (TEER) and transcatheter tricuspid valve replacement (TTVR) are providing new hope. These innovative procedures offer safe and effective options for high-risk patients who previously had limited or no treatment alternatives, focusing on enhancing quality of life.

Cedars-Sinai investigators, in collaboration with colleagues from other leading institutions, recently conducted a clinical trial involving patients with severe tricuspid regurgitation. The study, published in the New England Journal of Medicine, found that patients who underwent catheter-based tricuspid valve replacement combined with medical therapy reported significantly greater improvements in symptoms and quality of life compared with those receiving medical therapy alone. These findings mark a significant step forward in the treatment of this historically neglected condition.

When might a minimally invasive procedure be the best approach?

Minimally invasive procedures for the tricuspid valve are generally the only option for older or frail patients, who are unable to withstand traditional open-heart surgery. A TEER procedure, which inserts clips in the valve to reduce leakage, works well for many, but is less effective for those with complex valve anatomy. In such cases, TTVR, which replaces the valve entirely, may be a better option.

How do you discuss options with patients?

At the Smidt Heart Institute, physicians discuss the case as a group and review imaging findings and other information to determine whether a transcatheter procedure, minimally invasive surgery, medical intervention alone or a clinical trial is best for each patient.

Selecting the right treatment involves careful evaluation of the patient’s health, anatomy and goals. We prioritize improving quality of life, particularly for patients experiencing severe fatigue and breathlessness.

Disclosures: Dr. Makkar reports research grants from Edwards Lifesciences, Abbott Vascular, Boston Scientific, JenaValve and Medtronic; he has received travel support from Edwards Lifesciences, JenaValve, Abbott Vascular and Boston Scientific.

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

The Karsh family’s contribution will advance care and research across the field of interventional cardiology at the medical center. Interventional cardiology is a branch of medicine focusing specifically on minimally invasive, catheter-based procedures to correct structural heart problems such as leaking valves. The gift is in honor of Martha’s mother, Sybil Lubin, a now-healthy and active 94-year-old who experienced a catastrophic mitral valve rupture two years ago. She credits Raj Makkar, MD, and the interventional cardiology team at Cedars-Sinai with saving her life.

Makkar is the inaugural director of the Karsh Division of Interventional Cardiology and will also serve as the Karsh Distinguished Chair in Interventional Cardiology. An authority in advanced catheter-based therapies, Makkar’s team of experts treat more than 10,000 patients annually. Makkar says his mission is to perform and teach other physicians how to perform these advanced therapies so that many more patients can and will benefit.

“Our interventional cardiology programs are available around the clock to provide urgent care to those who need it most,” said Makkar. “Thanks to the incredible generosity of the Karsh family, we not only are able to sustain this critical service but also enhance and grow it. Their gift makes them true partners in our mission, helping us continue to provide the highest level of care, and we are deeply grateful for their support.”

Cardiovascular disease remains the leading cause of death globally, as cited by the World Health Organization. Cedars-Sinai ranked #1 in California and #6 nationally for Cardiology, Heart & Vascular Surgery in U.S. News & World Report’s "Best Hospitals 2024-25" listings. The newly established interventional cardiology division will treat conditions including valvular defects, electrical rhythm disorders, heart muscle dysfunctions and congenital heart disease.

The Karsh family says mindful merging of a common mission is the basis for their partnership with Cedars-Sinai. “’Education, Community, Democracy’ is a motto of our foundation,” the family said. “With this gift, we aim to amplify our commitment to both our community and medical education. Ultimately, what we hope to contribute to the world of medicine on a global scale with Cedars-Sinai is a powerful testament to what results from intention put into action.”

Peter L. Slavin, MD, president and CEO of Cedars-Sinai, expressed his gratitude for the Karsh family’s generosity and commitment to the highest quality care.

“The Karsh family has an enduring commitment to transformative medicine, and they’re building an even more profound legacy of philanthropy with the Karsh Division of Interventional Cardiology,” said Slavin. This new gift adds to their past visionary contribution that birthed the nationally ranked Karsh Division of Gastroenterology and Hepatology. Both enterprises address vital areas primed for innovative, groundbreaking advancements with the resources required for our patients.”

Read more on the Cedars-Sinai Newsroom: Smidt Heart Institute Advances Valve Replacement

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

The first 100 minimally invasive tricuspid procedures were done as part of the TRISCEND II clinical trial. The trial studied replacing a malfunctioning tricuspid valve with a bioprosthetic valve to treat patients with tricuspid regurgitation, a condition in which the heart’s tricuspid valve does not close tightly, causing blood to leak backward from the heart into the veins of the body.

The tricuspid valve has historically been the most challenging of the heart’s four valves to treat because of its location in the back of the heart.

“The Smidt Heart Institute is the only institution to have completed this many minimally invasive tricuspid valve replacement procedures, bringing extensive expertise and new options to patients impacted by tricuspid valve disease,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark S. Siegel Family Foundation Distinguished Professor. “This impressive feat is a testament to our team’s skill in difficult-to-treat valvular conditions.”

Raj Makkar, MD, associate director of the Smidt Heart Institute and vice president of Cardiovascular Innovation and Intervention for Cedars-Sinai, was the principal investigator for the TRISCEND II trial at Cedars-Sinai.

During a minimally invasive tricuspid valve replacement procedure, an interventionalist threads a thin, flexible tube called a catheter through a vein to reach the tricuspid valve. Early results of the trial led to the FDA approving the Edwards EVOQUE Tricuspid Valve Replacement System to treat eligible patients with tricuspid regurgitation.

Makkar led the Smidt Heart Institute team that performed the first EVOQUE implantation following FDA approval and has the most extensive experience globally in this groundbreaking procedure.

“We are proud and humbled to be the first in the U.S. to have implanted the world’s first commercially available transcatheter tricuspid valve,” said Makkar, the Stephen R. Corday, MD, Chair in Interventional Cardiology. “It is moments like this that further our dedication, commitment and passion to the field of interventional cardiology.”

The heart has four valves (aortic, mitral, pulmonic, and tricuspid) that open and close to move blood through the heart and to the rest of the body. If a valve cannot open or close fully it can interfere with blood flow and cause a host of health issues, including heart attack and stroke.

Moderate and severe tricuspid disease is common in the U.S. and affects an estimated 1.6 million people. Some people can manage their valvular heart disease with medications, but others need to have the damaged valve repaired or replaced.

The tricuspid valve is typically replaced during open-heart surgery. In contrast, the catheter-based approach used at Cedars-Sinai involves a tiny incision and patients typically go home the same day.

"The transcatheter tricuspid valve replacement system is a game-changer for patients with tricuspid regurgitation, a condition that has traditionally been overlooked," said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai. “We are proud to be the center with the most experience in transcatheter tricuspid valve replacement, demonstrating our commitment to pioneering new treatments and expanding options for those impacted by tricuspid valve disease.”

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

The novel findings, published today in the peer-reviewed journal The Lancet, are significant because recent randomized clinical trials have shown that TAVR is a meaningful treatment option for both younger and lower-risk surgical patients.

“We now know that redo TAVR with balloon-expandable valves may be a reasonable treatment for failed TAVR procedures in select patients,” said Raj Makkar, MD, Cedars-Sinai’s vice president of Cardiovascular Innovation and Intervention and the study’s senior author. “This is increasingly important, as the patients treated with TAVR are younger than they were a decade ago, meaning they will likely need a repeat procedure at some point in their lifetime.”

At both the 30-day post-procedure mark and at one year, Makkar’s team found no difference between redo TAVR or first-time TAVR in terms of death or stroke rates.  

“Our findings also suggest that redo TAVR was associated with a significant improvement in quality of life,” said Makkar, who is also the associate director of the Smidt Heart Institute at Cedars-Sinai, director of the Interventional Cardiology Division in the Department of Cardiology, and the Stephen R. Corday, MD, Chair in Interventional Cardiology.

Transcatheter aortic valve replacement is a procedure that replaces a diseased aortic valve with a man-made valve. The procedure is now the standard treatment for patients with symptomatic severe aortic valve stenosis—a narrowing of the opening of the aortic valve that can cause a heart attack, heart failure, or stroke.

To generate their findings, Makkar and team utilized the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry—a national database of all consecutive patients undergoing commercial TAVR in the United States.

Among the 350,591 patients who underwent TAVR between November 2011 and December 2022, 1,320 individuals required redo procedures. The patients who underwent a repeat procedure had a mean age of 78 years old. About 58% were male and 42% female. 

“Fixing damaged valves is something in which we excel at the Smidt Heart Institute,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark Siegel Family Foundation Distinguished Professor. “Our finding that TAVR can be redone safely is yet another step in establishing this as the default technology for aortic valve disease.”

Interventionalists in the Smidt Heart Institute at Cedars-Sinai have successfully completed more than 6,000 minimally invasive transcatheter aortic valve replacements to date, with more than 650 performed in fiscal year 2022.

DOI: https://doi.org/10.1016/S0140-6736(23)01636-7

Funding: This research was supported by Edwards LifeSciences.

Read more from the Cedars-Sinai Blog: Pioneering Heart Valve Care Expands and Improves Lives