Exposure to Moderate Air Pollution Raises Cardiovascular Disease Risk

Research from the University of Toronto shows long-term exposure to moderate air pollution increases a person’s risk of fatty build up in the blood vessels of the heart, which can lead to serious cardiovascular events like heart attack.

As reported in the journal Radiology, the study also showed that women were particularly badly affected and had an 81% increased risk for obstructive coronary artery disease if exposed to long-term air pollution.

“Even at exposure levels below current Canadian air quality standards, long-term air pollution was independently associated with more advanced coronary artery disease—suggesting current regulations may not be fully protective and that air pollution belongs alongside blood pressure, cholesterol and smoking as a modifiable cardiovascular risk factor,” said lead author Kate Hanneman, MD, associate professor at the University of Toronto, in a press statement.

The study included 11,128 people who underwent cardiac computed tomography (CT) scans who also had available data for air pollution exposure for around 10 years. The average age was 60 years and 52% were men.

In the cohort, median 10‑year exposures were 7.5 μg/m³ for PM2.5, a common measure of particulate air pollution and 13.4 ppb for nitrogen dioxide. These levels are relatively low compared with many historical and low‑/middle‑income settings but still above the latest World Health Organization guideline of 5 μg/m³ for PM2.5 and 5.3 ppb for nitrogen dioxide.

For each addition increment of PM2.5 (1 μg/m³) people in the study had had about 11% more calcium in their coronary arteries and 13% higher odds of having more atherosclerotic plaque. For each increment of nitrogen dioxide (1 ppb) small but measurable increases in calcium (aprx 1%) and plaque (about 4%) were seen in the coronary arteries of those exposed.

After taking into account age, risk factors, medicines, and other differences, each increment higher long‑term air pollution was linked to more severe, artery‑narrowing heart disease in women, but not in men. Each increment increase in PM2.5 was associated with an 80% higher chance of women having a dangerously narrowed coronary artery and each increase in nitrogen dioxide a 6% increased chance.

There was a similar trend in men, but it was not statistically significant after correcting for possible confounding factors.

“These findings add to the growing body of evidence identifying air pollution as a modifiable risk factor for atherosclerosis,” conclude the authors.

“Considering the epidemiologic data linking air pollution to cardiovascular events, these results reinforce the urgency of global public health initiatives aimed at improving air quality to reduce cardiovascular risk.”

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First Phase III for Resected CRC ctDNA-Guided Therapy Shows Mixed Results

A highly anticipated Phase III clinical trial has delivered mixed results in testing whether a blood-based test for minimal residual disease (MRD) could guide early treatment for colorectal cancer recurrence (CRC).

Published in Nature Medicine, the randomized double-blind ALTAIR trial tested whether trifluridine/tipiracil (FTD/TPI) could improve outcomes in patients with resected stage I–IV CRC who tested positive for Natera’s Signatera circulating tumor DNA (ctDNA) test after completing standard therapy but had no radiographic evidence of disease. However, the Phase III study—a collaboration between Natera and several Japanese research institutions and hospitals—failed to meet its primary endpoint for investigator-assessed disease-free survival (DFS).

The findings represent the first completed randomized Phase III “treat-on-molecular-recurrence” (TOMR) trial in CRC and underscore both the promise and limitations of ctDNA-guided intervention strategies, highlighting both the promise and limitations of precision oncology. 

A slice of the GALAXY

In the ALTAIR trail, researchers from the National Cancer Center Hospital East in Kashiwa, Kansai Medical University in Osaka, and NHO Osaka National Hospital evaluated a small subset of patients from a larger clinical trial called the CIRCULATE-Japan GALAXY study. Between June 2020 and June 2023, the GALAXY study enrolled 5,514 patients with resectable stage 0–IV CRC across 152 centers in Japan and Taiwan. The GALAXY cohort and other datasets have consistently shown that postoperative ctDNA positivity is associated with markedly increased recurrence risk. ALTAIR addressed the next critical question: whether intervening at the point of molecular relapse alters clinical outcomes.

Among the 1,104 patients who tested positive for ctDNA following surgery in the GALAXY study, 243 were included in the ALTAIR trial, where they were randomly assigned to either six months of FTD/TPI or a placebo. With a median DFS of 9.3 months in the FTD/TPI arm compared to 5.5 months with a placebo, there was a 21% decrease in the risk of recurrence (HR 0.79; 95% CI 0.60–1.05). The difference did not, however, reach statistical significance (P=0.107).

Although the primary endpoint was formally negative, several exploratory analyses suggested biologic activity. Six-month DFS was 70.5% with FTD/TPI versus 45.5% with placebo, indicating an early separation of the survival curves. The benefit, however, decreased over time, with recurrence curves converging by around 24 months—a trend that aligns more with delayed recurrence than with the lasting elimination of residual disease.

The strongest signal emerged in patients with resected oligometastatic stage IV disease. In this subgroup, FTD/TPI reduced the risk of recurrence or death by 47% (HR 0.53; P=0.012). Investigators noted that stage IV patients also had the highest baseline ctDNA burden, suggesting that molecular tumor load may influence responsiveness to MRD-directed therapy.

A post hoc blinded central radiology review also shifted the primary analysis into nominal statistical significance. After adjudication of discordant imaging events, median DFS was 9.2 months with FTD/TPI versus 5.5 months with placebo (HR 0.75; P=0.0406). However, because the analysis was exploratory and non-prespecified, investigators emphasized that it does not alter the trial’s formally negative outcome.

The ctDNA dynamics themselves proved highly prognostic. Patients achieving sustained ctDNA clearance had dramatically superior outcomes compared with those with transient or persistent positivity. In patients with sustained clearance, median DFS was not reached, while it was 11.8 months for those with transient clearance and only 4.4 months for patients with persistently detectable ctDNA.

Notably, spontaneous or transient ctDNA clearance occurred in a subset of placebo-treated patients, highlighting an emerging challenge in MRD-directed oncology: distinguishing biologically meaningful ctDNA positivity from low-level fluctuation or transient shedding.

Tomorrow’s TOMR

The study also raises important questions regarding treatment intensity in asymptomatic patients with molecular relapse alone. Toxicity with FTD/TPI was substantial. Grade ≥3 adverse events occurred in 73% of treated patients versus 3.3% with placebo, driven primarily by hematologic toxicity. Severe neutropenia occurred in 56.6% of patients receiving FTD/TPI, and more than one-third required dose reductions. Despite these toxicities, no treatment-related deaths or new safety signals were observed.

The ALTAIR data arrive amid broader uncertainty regarding ctDNA-guided treatment escalation in CRC. The recent DYNAMIC-III trial similarly failed to demonstrate improved recurrence-free survival with ctDNA-guided intensification in stage III disease. Together, the studies suggest that while ctDNA robustly identifies high-risk patients, translating that prognostic information into effective therapeutic intervention remains challenging.

Still, the investigators argue that ALTAIR establishes the feasibility of large-scale MRD-directed trials and provides a framework for future studies using more active regimens, including immunotherapy combinations or anti-angiogenic strategies.

For now, the trial reinforces a central emerging reality in precision oncology: detecting molecular recurrence is increasingly possible. Preventing clinical relapse after detection remains the more difficult task.

 

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Digital Pathology and the NHS: Overcoming Barriers to a More Connected Future

As demand on National Health Service (NHS) U.K. pathology services continues to rise, the shift toward digital pathology has never been more critical. While the NHS 10 Year Plan identifies it as one of the system’s most transformative enablers, digital pathology adoption remains uneven. Damian Doherty, Editor in Chief of Inside Precision Medicine, sat down with Olga Colgan, PhD, strategic marketing director at Leica Biosystems, and Darren Treanor, MB BCh, PhD, consultant histopathologist at Leeds Teaching Hospitals NHS Trust, to explore the pressures facing today’s pathology departments, the transformative potential of digital workflows, and how collaborative partnerships are helping accelerate progress and unlock the full value of digital diagnostics.

 

Q: The NHS 10 Year Health Plan identifies digital pathology as one of three fundamental shifts, yet adoption remains limited. What are the key barriers?

Olga Colgan
Olga Colgan, PhD

Olga Colgan: Many pathology departments today are already stretched thin by managing growing workloads, which can make it difficult to pause and do a thorough workflow examination and consider process improvements. Transitioning to digital pathology requires an investment and openness to change. For decades, pathology has been optimized for glass slide review under a microscope, so moving to digital is not just a technology upgrade, but a cultural shift for laboratory staff and clinicians who value the familiarity and comfort of traditional methods.

Proper capital allocation and investment are critical to unlock the benefits of digital pathology. For example, information technology (IT) infrastructure must be capable of supporting high-resolution imaging, secure storage, and rapid sharing of thousands of slides. Regulatory needs must also be considered, as each lab must validate digital workflows to ensure appropriate compliance.

While these upfront hurdles can seem daunting, they lead to significant long-term gains. Digital workflows enable faster slide sharing, improve access to subspecialists, and ultimately improve turnaround times—delivering real benefits for both laboratory teams and patients eagerly waiting for critical results.

 

Q: What are the key benefits of digital pathology that make it such a crucial step for modernizing NHS pathology services—particularly in terms of workflow efficiency, diagnostic accuracy, and collaborative decision-making?

Colgan: Digital pathology is the quintessential modernization of a pathology laboratory, driving efficiencies in workflows, accuracy, and collaboration. Centralized digital storage provides instant access to prior cases and supports predictive analytics. Eliminating physical slides from the workflow after scanning reduces breakage risks and concerns, misidentification risks, along with space and storage needs.

Beyond efficiency gains, digital pathology unleashes the power of remote collaboration. The ability to share whole-slide images instantly means pathologists can quickly leverage remote expertise within their network, or obtain second opinions in minutes rather than days, accelerating diagnostic confidence and treatment decisions. It also extends expertise beyond geographic boundaries, removing the “postcode-lottery” and providing a basis for equity in pathology diagnostics. This enables rural or underserved regions to access pathologists without the delays, costs, and concerns of physical slide transport. This connectivity transforms pathology into a truly networked resource, ensuring that expertise is available whenever and wherever it’s needed, even after hours.

Further, although in the early stages of routine usage, artificial intelligence (AI) models can add another layer of support by bringing greater quantification and reproducibility to slide analysis, highlighting subtle patterns or abnormalities that may be difficult to identify by eye. Effectively, AI can act as a second set of eyes to further build diagnostic confidence and augment—rather than replace—pathologist review.

 

Q: How are companies like Leica Biosystems supporting NHS trusts in overcoming digital pathology adoption challenges?

Colgan: It starts with listening. We understand that every laboratory and every pathology department has unique workflows, bottlenecks, and priorities, so our first step is a conversation and analysis to identify those needs and design a tailored roadmap for transformation. This isn’t just about technology; it’s about creating solutions that make the pathology workloads more sustainable, especially at a time when the profession faces significant workforce shortages.

Leica Biosystems partners with labs to deliver systems that meet their demands today, while anticipating future growth and scalability. A great example is Leeds Teaching Hospital and the National Pathology Imaging Co-operative. Combined, they make up the largest national integrated digital pathology network in Europe for routine diagnostics—a milestone that demonstrates what’s possible when technology and collaboration come together. The Leeds Guide to Digital Pathology, volume one and volume two, is packed with practical tips and pragmatic approaches to support successful digital pathology adoption.

 

Q: What influenced Leeds Teaching Hospital to adopt digital pathology, and what transformation have you experienced?

Darren Treanor
Darren Treanor, MB BCh, PhD

Darren Treanor: We’ve been involved with digital pathology since the very early days of the technology, and it has become the essential foundation of our teaching and research work at the University of Leeds. We had taken a cautious approach to clinical adoption until we were convinced that the technology was ready—both in terms of clinical safety and technical readiness—and we could ensure that it worked and was safe.

We decided that the threshold for adoption for clinical use was reached in 2015, when we established that the clinical safety was acceptable and that the scanners and viewing software were fit for purpose and would not slow us down. Working in partnership with Leica Biosystems, we adopted a phased approach to 100% digital scanning, starting with a “meaningful pilot” with our four breast pathology colleagues. This group was the most pro-digital in the department and, being located in a separate building, had experienced frustrating delays in the delivery of glass slides between the main lab and their offices. They actively pursued us to “go digital.” The pilot with them was critical for us in planning the laboratory and clinical workflow reconfigurations needed to go digital and, importantly, developing a verification and validation process that allowed us to transition from glass to digital slides while maintaining safety. This process became the foundation of the U.K. Royal College of Pathologists guidelines for digital pathology, which have been adopted in many other countries as well.

We then looked toward the further summit of “100% digital” and took a phased approach, starting with immunohistochemistry (IHC). As a separate part of the lab, this activity could be separately digitized. With digital review of IHC being a lower-risk activity clinically, it allowed us to introduce the rest of our over 40 pathology consultants to the idea of diagnosis on a digital image. Once that was completed, we moved in one final big step to 100% digital scanning, reaching that milestone on a summer’s day in 2018.

 

Q: What lessons can other NHS trusts learn from your digital transformation journey, and what should be considered as they examine their current workflows?

Treanor: Because of our academic background and partnership with Leica Biosystems, we were very keen to share our experiences of going digital and how to do it. Too many deployments would talk of the great success in using whole-slide imaging, but gloss over the challenges and effort involved in getting there.

We wrote the Leeds guides to provide really simple general-purpose assistance to other labs that are new to digital pathology and didn’t have the benefit of in-house expertise yet.

Looking back, being early adopters, we had the unique challenge of being one of the first centers to go fully digital and pave the way at a time when scanners, displays, and software were just good enough, and the combined global experience of digital pathology was low. We have run many workshops to share our experiences, and it has been interesting to see how the field has evolved in recent times and how much easier it is now to go digital. There are far fewer “unknowns” when going digital now, and modern scanners and workflows are significantly better. For example, our current setup has a very smooth transition from H&E [hematoxylin and eosin] stainer to scanner, which saves a lot of time in the lab and removes a major obstacle to lab operation that we had to work around in the early years. In our early workshops, a deployment was often a multi-year project with a lot of uncertainty and need for a lot of preparatory work; nowadays, labs are much more digital-ready, the timelines are much shorter, and success rates are much higher!

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Diabetes Drug Linked to Reduced Heart Failure in High-Risk Gene Carriers

A medication already used to treat type 2 diabetes may substantially reduce the risk of heart failure hospitalization among people who carry inherited genetic variants associated with cardiomyopathy, according to researchers from the Mass General Brigham Heart and Vascular Institute and the Broad Institute of MIT and Harvard. The study, published in Nature Medicine, found that dapagliflozin reduced the risk of heart failure hospitalization by about 80% in patients carrying cardiomyopathy-associated genetic variants, compared with placebo, indicating that genetic testing could help identify people who could benefit from preventive treatments.

“Historically, identifying a genetic variant for cardiomyopathy mostly meant telling a patient they were at high risk and not having a specific preventative therapy to offer. These data show we do have tools to lower risk in these individuals,” said co-lead author Shinwan Kany, MD, a visiting scientist at the Cardiovascular Research Center with Mass General Brigham Heart and Vascular Institute and the Broad Institute.

Previous studies have already shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin can reduce hospitalizations for heart failure in patients with diabetes and cardiovascular risk factors. The current study sought to find out if patients carrying rare pathogenic variants linked to cardiomyopathy might experience even more benefit from the drug.

The research was driven by an increasing body of evidence that inherited cardiomyopathies contribute to heart failure risk and that pathogenic or likely pathogenic variants are present not only in patients with diagnosed disease but also in asymptomatic individuals. The researchers noted that genetic testing is increasingly used in cardiomyopathy care and family screening, but clinician often don’t know how to proceed when identifying a relevant genetic variant in otherwise healthy carriers.

For this study, the team analyzed whole-exome sequencing data from the DECLARE-TIMI 58 trial, a randomized Phase III trial of dapagliflozin in adults with type 2 diabetes and elevated cardiovascular risk. Of the 12,685 participants with genetic sequencing data, the team identified 121 carriers of pathogenic or likely pathogenic variants in high-confidence cardiomyopathy genes.

Analysis of the data showed that the cardiomyopathy variant carriers faced substantially higher risk of heart failure hospitalization when treated with placebo and experienced an eightfold increased risk of heart failure hospitalization.

Over a median follow-up of 4.2 years, 16% of variant carriers receiving placebo were hospitalized for heart failure. Among carriers treated with dapagliflozin, that figure fell to 3%, representing an 82% relative reduction in risk. By comparison, noncarriers experienced a smaller reduction in heart failure hospitalization risk.

The findings were particularly notable among patients who had not yet developed heart failure. About 82% of the variant carriers in the study had no prior history of heart failure at enrollment. Among that group, dapagliflozin reduced the absolute risk of heart failure hospitalization by 12.8%, compared with a reduction of 0.6% among noncarriers.

“Cardiomyopathy variants represent an actionable genotype which can be used to identify patients who derive a larger benefit from dapagliflozin,” said co-lead author Nicholas A. Marston, PhD, a cardiologist at the Brigham and Women’s Hospital. “This is especially relevant for patients without established heart failure, where such treatment may not be otherwise initiated.”

The researchers noted that the findings should be interpreted within the context of a post-hoc analysis and that the number of variant carriers was relatively small. Because all participants had type 2 diabetes and elevated cardiovascular risk, it remains uncertain whether the same degree of benefit would occur in people without diabetes.

Future research will focus on confirming the findings in prospective clinical trials specifically designed to evaluate preventive heart failure therapies in carriers of cardiomyopathy-associated genetic variants.

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David Sinclair plans to test whole-body rejuvenation drugs in the XPrize competition

The outspoken longevity scientist David Sinclair has been predicting that one day, you’ll go to the doctor and get a prescription that will make you 10 years younger.

Now MIT Technology Review has learned that he has plans to launch human tests of an oral “reprogramming” drug as part of a $101 million competition organized by the XPrize Foundation. 

The foundation is offering cash awards to teams able to “restore” a person to an earlier apparent age, as measured by improvements in immune, cognitive, and muscle function. 

The grand prize goes to any team able to show a 10-year (or greater) relative improvement after one year of treatment. 

Reached by phone, Sinclair, a biologist at Harvard Medical School, confirmed that he plans to give an oral drug mixture to volunteers in a bid to seek “evidence for age restoration in humans.”

The trial, if it goes forward, will be a significant new development in the race to harness so-called epigenetic reprogramming. That technology is based on the discovery, 20 years ago, of powerful genes able to turn an adult cell into a stem cell similar to those found in embryos.

The age-reversal effect is believed to occur via a resetting of molecular controls on DNA known as epigenetic marks, which help determine a cell’s overall metabolism and identity.

Companies are now racing to use that phenomenon for a new form of rejuvenation medicine. Only this January, one of Sinclair’s companies, Life Biosciences, made news by winning approval to launch an initial human trial using a set of powerful reprogramming genes. The company announced today it had treated its first patient. 

But that test involves a complex gene therapy and is limited to patients’ eyes, where it could treat conditions like glaucoma. 

Sinclair’s new plan is bolder: a reprogramming drug you’d swallow in order to promote such effects across the body. 

“What we’re aiming to do is to epigenetically restore the animal and eventually the person,” he says. “It is true that we’ve been doing extensive animal studies with the oral agent and are looking to compete in the XPrize.”

This alternative method, chemical reprogramming, uses drugs to mimic the effects of the embryonic genes. That is significant because drug compounds can travel through the bloodstream, reaching most or all cells in a person’s body. 

Some experts expressed caution, saying the chemical process, at least as used in labs, is extremely harsh and not even particularly effective. “Who doesn’t dream of whole-body rejuvenation? I think it’s a great goal,” says Sergiy Velychko, founder of Soxogen, a stealth reprogramming company in Boston. “But these chemicals are used in very, very high concentrations for cell reprogramming.”

Sinclair declined to describe the exact makeup of the drug candidate, code-named SL-100, calling its contents “highly, highly confidential.”

However, he has previously published lab studies of what he called “epigenetic age-reversal cocktails,” which mixed powerful chemicals with known supplements and commercially available medicines. 

It’s those latter components that would be easiest to test on people, since doctors are free to prescribe them, even for unusual objectives like age reversal. James Clement, head of Betterhumans, an organization that specializes in life-extension studies using existing drugs, said in a message that he is “running clinical trials” of an oral reprogramming cocktail for Sinclair’s XPrize team.

Sinclair’s team is competing in the XPrize Healthspan Competition, launched in 2023. It follows several previous competitions that focused on commercial spaceflight, lunar landings, and other goals. The XPrize Foundation is led by executive chairman Peter Diamandis, also an active promoter of longevity research.

“If two teams are equivalent, they would split the award,” says Jamie Justice, a doctor and executive director for the contest, which was bankrolled by Saudi Arabia’s Hevolution Foundation, “But it will be incredibly hard to even get to one winner.”

Justice says a judging panel is now in the process of picking 10 finalists from 65 teams that have been exploring health foods, lifestyle interventions, digital trackers, and drug compounds. 

Sinclair’s team, Justice says, was a late entrant to the contest, but like all teams, it would be required to move into wider human tests starting this year. “You have to be ready and in trials,” she says.

The race to harness the reprogramming phenomenon and apply it to living people is heating up, even outside the XPrize competition. On June 2, a startup called NewLimit, founded by the crypto billionaire Brian Armstrong, said it had raised a further $435 million, from investors including Peter Thiel’s Founders Fund, to support what it calls “age reprogramming.” 

The company says it is working toward delivering genetic reprogramming instructions to the liver, to treat diseases of that organ.

But Sinclair has been saying that whole-body rejuvenation is a possibility too. And for that, chemicals, rather than gene therapy, could be the most practical strategy. 

Sinclair says his lab has been searching for such compounds and is starting to use AI “to improve the oral agents that we’re testing.”

Chemical reprogramming cocktails, as used in labs, typically involve a mix of vitamins, approved drugs, and experimental molecules. For instance, one recipe Sinclair filed a patent on includes the supplement forskolin,  the antidepressant tranylcypromine, and an experimental chemical, laduviglusib, which has been tested against Alzheimer’s, among other ingredients.

“In those days it was a six-factor cocktail,” Sinclair says of his earlier research. “But we’ve come a long way. I can’t disclose what’s in it, but it’s an improvement and an advance on that, and we’ve done a number of animal studies. They are not published, but we’ve been doing them for a long time, and we want to make sure that we’ve done a full investigation of safety and efficacy before we release any of the data.”

While Sinclair’s results aren’t published, other teams say attempts to reverse the age of entire animals using chemical drugs haven’t worked yet. Last year, the lab of Vadim Gladyshev, another Harvard biologist and a member of a different XPrize team, reported on its attempt to rejuvenate mice by installing pumps in their bodies that released controlled doses of seven compounds.

Gladyshev says the procedure proved to be toxic. “The idea was to see if we could rejuvenate whole animals. Unfortunately, we have not found [the right] conditions,” he says. “At low concentrations there was no effect, and high concentrations were toxic.”

Gladyshev says he doesn’t know what is in Sinclair’s cocktail, but says that “trying to improve the combinations makes sense.”

Sinclair, who is the author of several books on aging and has a large social media following, has frequently been criticized by other scientists for making unproven rejuvenation claims. 

In 2024, he resigned as president of the Academy for Health and Lifespan Research after claiming that a supplement developed by a company his brother runs had “reversed” the age of dogs, a claim for which there was so little evidence that one scientist called it a “lie.”

Part of the problem is that scientists still disagree on how to measure aging. And they don’t have a reliable way to measure age reversal, either, should it ever be achieved.

Justice, the XPRIZE director, says a primary purpose of the competition is to solve that problem by encouraging the development of standardized measures of aging. That is so that anti-aging drugs can be assessed reliably, and, one-day, approved by regulators if they work.

 “We as a scientific field have been forced to ask, ‘If a medicine improves how we age, how would we know?” Justice said during a public meeting with FDA officials in May. “If something worked, what would convince us as scientists, what’s meaningful to the general public?”

Finalists in the Healthspan competition will be announced in August.

Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants

Nature Medicine, Published online: 08 June 2026; doi:10.1038/s41591-026-04439-x

In a whole-exome sequencing analysis, the beneficial effects of the SGLT2 inhibitor dapagliflozin in reducing the risk of future heart failure hospitalization in individuals with type 2 diabetes were markedly greater in individuals who carried a cardiomyopathy-associated genetic variant compared with noncarriers, suggesting a personalized preventative therapy based on genetic information.

Edwards Lifesciences makes a simple change for a first-of-its-kind tricuspid valve

The first-of-its-kind Edwards Lifesciences Triformis Resilia doesn’t look all that different from the structural heart device developer’s other prosthetic valves, but a simple yet critical design change allows it to address an unmet patient need. Edwards earned FDA approval for Triformis Resilia in May 2026. It’s the first surgical valve designed for the tricuspid position.…

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