Cardiovascular News - Issue 72 - February 2024 (OUS) by BIBA Publishing

February 2024 | Issue 72

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February 2024 | Issue 72

Featured in this issue:

www.cardiovascularnews.com

8 Alain Cribier obituary

Remembering the TAVI pioneer

12 Renal denervation Device approvals expand horizons

16 Profile

Ajay Kirtane

21 Cerebral protection

BHF PROTECTTAVI trial update

Trial results “change the orbit” of PCI for stable angina

Jad Malas at STS 2024, picture courtesy of: Dominic Emerson

STS 2024: Data point to shift towards TAVI in patients aged under 60 New data, shared at the annual meeting of the Society of Thoracic Surgeons (STS 2024; 27–29 January, San Antonio, USA), point towards a shift in the proportion of surgery-eligible patients with severe aortic stenosis aged under 60 years receiving a transcatheter procedure.

he data, taken from a registry of patients from the US state of California spanning 2013 to 2021, constituted one of several papers presented at the STS meeting to assess changing trends in the treatment of aortic stenosis, weighing up both transcatheter and surgical approaches. Researchers from the Department of Cardiac Surgery in the Smidt Heart Institute at Cedars-Sinai in Los Angeles and the Department of Population Health Science and Policy at Mount Sinai New York compared outcomes for patients undergoing surgery and those undergoing transcatheter aortic valve implantation (TAVI). From a pool of 37,011 patients, the study identified 2,360 patients under the age of 60 years who underwent these

procedures, with 22% receiving TAVI and 78% surgical aortic valve replacement (SAVR). By 2021 almost half of patients younger than 60 years were receiving TAVI rather than SAVR. The research team followed these patients for a median time of 2.4 years after TAVI and 4.9 years after SAVR to assess their outcomes. The primary focus was on five-year survival rates. Secondary outcomes included rates of reoperation, infective endocarditis, stroke, and hospital admissions for heart failure. Propensity score matching ensured a fair comparison of 358 pairs of patients, balancing factors such as age, major health conditions, hospital volume, and urgency. The researchers reported that the 30-day mortality rates were similar (0.2% for SAVR vs. 0.4% for TAVI), but found that the five-year survival rate was better after surgery compared to TAVI (98% vs. 86%, p<0.001). For secondary outcomes, there was no significant difference between the two groups. “While we expected that the volume of transcatheter therapy would increase over the study period in this young patient cohort, we were surprised there appears to be near equipoise in terms of procedure selection, with patients and clinicians opting for procedures against the 2020 guidelines,” said study co-author

We were surprised there appears to be near equipoise in terms of procedure selection, with patients and clinicians opting for procedures against the 2020 guidelines.”

RESULTS OF THE ORBITA-2 trial have, for the first time, provided evidence that percutaneous coronary intervention (PCI) with minimal or no use of antianginal medications reduces symptoms in patients with stable angina. The findings should prompt a change in guidelines regarding the treatment of stable angina, commentators have suggested, with an editorial in the New England Journal of Medicine (NEJM) published in light of the new evidence declaring: “The orbit around PCI for stable angina has been changed.” A predecessor trial—ORBITA— published in 2017, had shown that PCI did not improve exercise tolerance or chest pain any more than a placebo procedure, a finding that had prompted a degree of controversy among proponents of PCI. “However, it is possible that the effect of stenting in ORBITA was diminished by high levels of guideline-directed background, antianginal medication, which are difficult to achieve in clinical practice,” said Rasha AlLamee (Imperial College London and Imperial College Healthcare NHS Trust, London, UK), the chief investigator in both the ORBITA and ORBITA-2 trials. ORBITA-2 enrolled 301 patients with both single and multivessel disease who were randomised either to undergo either PCI or a placebo procedure. Unlike the prior study, patients stopped all antianginal medications and underwent a twoweek symptom assessment phase before randomisation. Throughout the trial, they then reported whether they were experiencing chest pain every day using a dedicated smartphone app. The daily symptom reports and the need for chest pain medication were used to calculate an angina symptom score, the trial’s primary endpoint. Investigators found that patients Continued on page 7

Continued on page 4

February 2024 | Issue 72

Top Stories

The impact of the trial’s results continues to be dissected more widely amongst the interventional cardiology community, and the trial was singled out as one of three to have had the most impact in 2023 at the British Cardiovascular Intervention Society Advanced Cardiovascular Intervention meeting in late January (BCIS ACI; 31 January–2 February, London, UK). “ORBITA-2 has freed me to stop offering a second and third antianginal to patients if I know that they have got a PCI-able lesion,” commented Nick Curzen (University Hospital Southampton NHS Foundation Trust, Southampton, UK), who chaired the conference session at which the trial’s findings were discussed. “For me, the guidelines should change so that we can offer them a choice; you can either try additional antianginals, when you are on otherwise optimal medical therapy, or you can have your stent.” Curzen took an informal poll among BCIS ACI audience members to assess the impact of the results, asking BCIS ACI attendees whether they “felt comfortable to ignore the guidelines and only have a beta-blocker or a single antianginal before offering a stent”. There was broad acceptance of this point from those in attendance. Later in the session, Al-Lamee was

Study shows no safety risk in allowing patients to eat prior to cardiac catherisation Allowing patients to eat before elective cardiac catheterisation posed no safety risk and benefitted patient satisfaction and overall care, research published in the American Journal of Critical Care has shown. PATIENTS UNDERGOING CORONARY artery catheterisation are typically required to take nothing by mouth after midnight prior to their procedure, but there is no evidence to support this long-standing practice. Building on evidence from several studies that

Rasha Al-Lamee

asked whether, if patients can be treated with PCI at an early enough juncture, should they require any antianginal medication at all? “That’s an important question,” she commented, before adding: “The vast majority [of patients] were on no antianginal agents because we stopped them, and some people said that was controversial. However, I responded that these are non-prognostic drugs, similar to painkillers for osteoarthritis. It is absolutely fine to decide not to give that medication, as long as the risk of the procedure does not outweigh the benefit that you might have from having it up front.” Discussing the findings of the trial in an NEJM editorial, published in December 2023, Harvey D White (Auckland City Hospital, Auckland, New Zealand), writes that there are now two evidence-based pathways for the management of stable angina— initiation of medical therapy, followed by more intensive therapy and then PCI if the medical therapy fails to relieve symptoms or if the patient has unacceptable side effects from the medication, or performance of PCI without the use of antianginal medications as the initial therapy with the addition of medical therapy if the symptoms continue. “The benefits and risks of both pathways should be discussed with the patient, including the risks of PCI, the prevalence of stent thrombosis (0.5% per year), and the need for dual antiplatelet therapy with the associated risk of bleeding,” writes White.

“Patients should express a preference, which is paramount. The selection of either pathway also depends on the angiographic findings; implanting a stent in a small branch vessel in a patient who has a high risk of stent thrombosis may be inappropriate.” The trial’s findings have been welcomed by the Society for Cardiovascular Angiography & Interventions (SCAI), which issued a statement noting that the results confirmed PCI is feasible and effective at relieving angina and increasing physical performance in appropriately selected patients. “The ORBITA-2 trial is a welldesigned and executed study despite great challenges,” said George Dangas (Icahn School of Medicine at Mount Sinai, New York, USA), SCAI president. “While study enrolment was small, the results show unequivocal anginal benefit from PCI, without the use of medication in ischaemic patients. “SCAI recommends the use of PCI for symptom relief in appropriate patients. ORBITA-2 confirms the benefit of PCI in helping stable ischaemic heart disease patients, consistent with other prior trials.” Results of ORBITA-2 were presented by Christopher Rajkumar (Imperial College London, London, UK) at the American Heart Association’s 2023 scientific sessions (11–13 November, Philadelphia, USA), and published simultaneously in NEJM.

Going forward, patients and medical teams have a choice of two pathways for chest pain relief: chest pain medication or PCI.”

found prolonged fasting may be unnecessary, a randomised, controlled trial conducted at Parkview Heart Institute (Fort Wayne, USA) compared consumption of a heart-healthy, low-acid diet with standard fasting guidelines for patients in an inpatient cardiac unit undergoing elective coronary artery catheterisation. “Requiring all patients to fast for six hours or longer has remained an anaesthesia guideline for procedures requiring conscious sedation for decades,” said co-author Carri Woods, a nursing manager at the hospital. “Our findings demonstrate that fasting isn’t necessary for every patient, and patient satisfaction and comfort can safely be put at the forefront of care.” The convenience sample included 197 adult patients scheduled for elective cardiac catheterisation with conscious sedation and analgesia. Patients were randomly assigned to one of two protocol groups, with 100 patients allowed to eat a specified diet of solid food low in fat, cholesterol, sodium and acidity until the scheduled procedure. The 97 patients in the fasting group were restricted to nothing by mouth, except for sips of water with medications, from

midnight until the procedure, which was the hospital’s standard practice. Data were collected before and after sedation and throughout postprocedural assessments. Patients also completed a satisfaction survey at discharge. In the heart-healthy diet group, satisfaction with the preprocedural diet was significantly higher while thirst and hunger were lower. No patients in either group experienced postprocedural pneumonia, aspiration, intubation or hypoglycemia. Fatigue, glucose level, gastrointestinal issues and use of loading dose of antiplatelet medication did not differ between the groups. As a result of the study, the hospital has updated its protocols for inpatient and outpatient cardiology procedures to allow patients to eat prior to sedation. The study encourages future research with larger, more diverse patient populations and with patients receiving other forms of anaesthesia, the researchers say. The growing body of evidence may also lead to professional societies, such as the American Society of Anesthesiologists, reviewing recommendations and guidelines for possible changes.

February 2024 | Issue 72

Obituary

OBITUARY

Alain Cribier: 1945–2024 Alain Cribier, the pioneering cardiologist who performed the world’s first transcatheter aortic valve implantation (TAVI) procedure in 2002, has died at the age of 79. CRIBIER, WHO HAD BEEN THE director of cardiology at Charles Nicolle Hospital, University of Rouen (Rouen, France), was recognised globally for his role in advancing the treatment of aortic disease. Figures from across the world of cardiology have paid tribute to Cribier, who has been described as “a true visionary” whose life and work “stand as a testimony to all that is good in medicine”. Born in Paris in 1945, Cribier was educated at the University of Paris where he opted to specialise in cardiology. “As far as I remember, my wish has always been to become a doctor,” Cribier told Cardiovascular News in 2003, recalling that his choice of career was influenced by “outstanding physicians who dedicated their whole life to the care of other people”, particularly the writings of AJ Cronin, Georges Duhamel and Albert Schweitzer.

Early experience with catheterisation

During his early career, Cribier had the choice to specialise in cardiology or cardiac surgery, ultimately choosing the former thanks to his first experience of cardiac catheterisation in the early 1970s at Hospital Tenon in Paris. “I felt this sub-specialty opened a dramatic and exciting new world of clinical investigation,” Cribier recounted. In 1976–1977, Cribier spent a year at Cedars Sinai Hospital, Los Angeles (USA), and in 1983, after a fellowship in Los Angeles, Cribier was promoted to the position of professor of medicine and director of the cath lab at Charles Nicolle Hospital, University of Rouen. It was in Rouen in 1986 that Cribier performed the first of several pioneering procedures, the first cases of balloon valvuloplasty for calcific aortic stenosis, which were reported in The Lancet. This brought Cribier international standing, but he claimed that the limitation of the technique—a high mid-term restenosis rate—pushed him to start a new research programme on a percutaneous heart valve in the 1990s. “I thought, ‘If there is valvular restenosis, can we do something to maintain the valve open after balloon valvuloplasty?’ Then came the idea of using a mechanical device to prevent valvular restenosis after balloon

valvuloplasty. The problem was to find the right device,” Cribier said. Working with, among others, Marty Leon in the USA, Cribier helped to establish Percutaneous Valve Technologies, a start-up dedicated to the development and commercialisation of the percutaneous aortic valve replacement technology.

2002: Performing the worldfirst TAVI procedure It was through this work Cribier cemented his enduring reputation, when, on 16 April 2002, he performed the first-in-man TAVI procedure to huge interest worldwide. The patient, a 57-year-old man, was referred to Rouen having been turned down for surgery due to developing cardiogenic shock. Cribier and his team felt that the percutaneous technique that they had helped to develop could be the only possible solution, which, with the backing of the patient, they deployed using a transseptal antegrade approach. “The feeling during the first case was great,” Cribier later recounted. “The patient resuscitated on the table. Before that, he was practically dead; he had had several episodes of cardiac arrest before entering the cath lab. Immediately after the valve was implanted, the colour came back to his

My goal was to try to bring a lifesaving solution to patients who were considered non-operable.” face, and he was speaking. We could observe a true resuscitation!” More TAVI cases followed, and thanks to Cribier’s early success, Percutaneous Valve Technologies was acquired by Edwards Lifesciences in 2003, paving the way for the exceptional growth and development of TAVI in the subsequent decades. “My goal was to try to bring a lifesaving solution to patients who were considered non-operable,” Cribier told Cardiovascular News in 2022, reflecting

upon the evolution of the technique following the 20th anniversary of the first procedure. “The story with all the scientific evidence of TAVI against surgery in non-operable patients first, high-risk patients, intermediate-risk patients, low-risk patients, and today we are in a period where [for] older patients, first of all we think about TAVI for them, and surgery in case TAVI cannot be done. It is a totally different paradigm of treatment. This was not expected when I did the first patient at all.” Among his other achievements in a storied career, Cribier had served as a president of the French Society of Interventional Cardiology and was a co-founder of the IndoFrench Foundation for Interventional Cardiology. Cribier was awarded the European Society of Cardiology (ESC) Gold Medal in 2016, as well as receiving a Presidential Citation from the American College of Cardiology (ACC) in 2022 for his contribution to the development of TAVI. He was also elected an honorary member of France’s National Academy of Medicine and a Knight of the Legion of Honor.

Legacy: “A true visionary”

“A true visionary has passed,” said ACC president B Hadley Wilson. “From the first days of balloon aortic valvuloplasty nearly 40 years ago, through the first-in-man TAVI 20 years ago, until today where TAVI is now the standard of care, Dr Cribier always remained humble and committed to his colleagues and the betterment of patient care. The field of cardiology is forever changed because of his vision, leadership and persistence.” The ESC described Cribier as a revolutionary who devoted his life to innovation in cardiology, enabling millions of patients to live longer lives. Franz Weidinger, president of the ESC, said: “The passing of Alain Cribier is very sad

news. He was a giant in his field and combined his great expertise with a touching kindness and modesty. The ESC and the global cardiology community lose a friend, scientist, clinician, mentor and above all an outstanding personality. Our thoughts and prayers are with his family and loved ones.” The University of Rouen, where Cribier made his name, has announced that it will be opening a dedicated centre for research and education of heart valve disease in his memory. “Alain Cribier's ambition for the cardiology department of Rouen University Hospital was to create an institute dedicated to care, teaching and research on heart valves. He often spoke about it. In his memory, this institute will be created and will bear his name: The Alain Cribier Heart Valve Institute,” a statement issued shortly after his death pronounced.

CAREER MILESTONES 1985: Pioneer in the field of aortic and mitral valvuloplasty, first world case of aortic balloon valvuloplasty in calcific aortic stenosis 1995: First world case of mitral commissurotomy with the metallic valvulotome 2002: First world case of percutaneous valve replacement in aortic stenosis Charles Nicolle Hospital Catheterisation Laboratory

Issue 72 | February 2024

AF after mitral valve surgery “has a strong negative influence on survival”

Large registry study demonstrates superiority of multi-arterial grafting for multivessel revascularisation

Joseph Sabik presents at STS 2024

A study of more than one million patients undergoing isolated coronary artery bypass graft (CABG) surgery has found that multi-arterial grafting CABG is associated with superior longterm survival compared to single arterial grafting.

he research, presented at the 60th annual meeting of the Society of Thoracic Surgeons (STS 2024; 27–29 January, San Antonio, USA) and published simultaneously in The Annals of Thoracic Surgery examines the ongoing controversy surrounding the choice between multi-arterial grafting and single-arterial grafting in CABG for multivessel coronary revascularisation. “Controversy persists as to whether multi-arterial grafting improves long-term survival over CABG with single-arterial grafting with saphenous vein conduits, thus limiting wider adoption in the USA,” Joseph Sabik (Cleveland Medical Center, Cleveland, USA) and colleagues write in their Annals paper. The time and technical requirements of multi-arterial grafting, often with bilateral internal thoracic artery and/or radial artery conduits, are elevated compared to a singlearterial grafting strategy, they note, adding that though several single-centre reports have shown that patients who receive multi-arterial grafting may experience better survival, recent studies, including the randomised Arterial Revascularization Trial (ART) of single versus bilateral internal thoracic artery CABG did not detect an overall difference. However, the secondary analyses of the ART trial did indeed identify a long-term survival benefit of multiarterial grafting when stratified by as-treated groups and surgeon experience. The latest research, spanning from 2008 to 2019 and involving over one million patients undergoing isolated CABG with more than two bypass grafts, found that multiarterial grafting CABG is associated with superior long-term survival compared to single-arterial grafting, establishing it as the preferred surgical strategy for multivessel revascularisation. “Multiple small studies have demonstrated a survival benefit of multi-arterial grafting. We wanted to know if this survival benefit of multi-arterial grafting observed in singlecentre studies would translate to a large national cohort,”

said Sabik. “Using the STS Adult Cardiac Surgery Database, we were able to demonstrate that it does.” At 10 years, multi-arterial grafting demonstrated improved unadjusted (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.58‒0.61) and adjusted (HR 0.86, 95% CI 0.85‒0.88) survival rates compared to single-arterial grafting. A centre volume of 10 or more multi-arterial grafting cases per year was associated with survival benefits. Multi-arterial grafting’s survival advantage over singlearterial grafting was found in various sub-groups, including stable coronary disease, acute coronary syndrome, and acute infarction. Patient data was collected from the STS Adult Cardiac Surgery Database and linked to the National Death Index for comprehensive longitudinal survival analysis. Risk-adjustment measures, including inverse probability weighting and multivariable modelling, were implemented to ensure accurate comparisons. These findings have significant implications for clinicians when deciding on the most appropriate multivessel revascularisation approach, the researchers suggest. “The survival benefit of multi-arterial grafting was observed in nearly all patients, except in those 80 or older and in those with comorbidities graded as severe, where multi and single-arterial grafting resulted in similar survival. The only patients where single arterial grafting resulted in better survival were severely obese,” said Sabik.

The survival benefit of multi-arterial grafting was observed in nearly all patients, except in those 80 or older and in those with co-morbidities graded as severe, where multi and single-arterial grafting resulted in similar survival.”

THE OCCURRENCE OF ATRIAL fibrillation (AF) after mitral valve surgery may be more harmful than previously thought, the authors of a research paper in the Journal of Thoracic and Cardiovascular Surgery (JCTVS) have stated. Whitney Fu (University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, USA) et al studied 922 adult patients with no preoperative history of arrhythmias who had mitral valve surgery between 2011 to 2022, examining rates of postoperative AF, incidence of neurologic events, development of AF and mortality The authors of the paper found in total that 39% of patients had postoperative, and almost one-quarter of those patients developed new or recurrent AF after 30 days. Almost 5% of patients with postoperative AF experienced a neurologic event, the researchers report. “Our results suggest that postoperative atrial fibrillation is more harmful that

Our results suggest that postoperative atrial fibrillation is more harmful that people once thought.” people once thought,” said Fu. “We are seeing a strong negative influence of post-op AF on survival that is consistent with past research and suggests little improvement in addressing the issue.” AF after heart valve surgery was also an independent risk factor for worse longterm survival among patients who had mitral valve surgery. “This high rate of AF after valve surgery and its potential severe downstream outcomes should encourage more research into the cause and prevention of postoperative AF, as well as the development of guidelines to manage the condition,” said the paper’s senior author, the cardiac surgeon Steven F Bolling (University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, USA). The researchers concluded that postoperative AF is associated with an increased rate of neurologic events, portends development of permanent AF, and is associated with worse longterm survival.

STS elects its first female president Jennifer C Romano has been named president of the Society of Thoracic Surgeons (STS), the first woman to hold the office in the organisation’s 60-year history. ROMANO IS A CONGENITAL heart surgeon at Congenital Heart Center/CS Mott Children’s Hospital and the Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan Medical School (Ann Arbor, USA). She was elected during the society’s business meeting taking place at the 2024 annual meeting (27–29 January, San Antonio, USA). Romano says that she sees her new role as a catalyst for increased modernisation and diversity across the organisation and the cardiothoracic surgery field. “I’m honoured and excited to be selected by the board as the new president of the Society of Thoracic Surgeons,” said Romano. “I’m ready to lead our members into this next chapter and increase our impact on the specialty and patient care.” “STS is the voice of our profession and our patients,” added Romano. “So how can we Jennifer C Romano become better advocates for each other and the patients we serve? We must be more dynamic and flexible and find ways to improve work-life balance. Because when people are happy in all areas of life—career, family, and personal hobbies—they are better surgeons and better leaders.” After graduating from Harvard Medical School, Romano looked for residency programmes that were inclusive of women and the University of Michigan was one of them. “When I started interviewing with surgery programmes, many had never trained a woman in surgery. But Michigan had a strong tradition of female surgical trainees,” Romano said. Also elected during the annual meeting was Joseph Sabik III (University Hospitals Cleveland Medical Center, Cleveland, USA) as first vice president, and Vinay Badhwar (West Virginia University, Morgantown, USA) as second vice president.

February 2024 | Issue 72

“Inevitable” advent of AI in cardiothoracic surgery gives rise to optimism and caution

“Artificial intelligence (AI) won’t replace physicians, but physicians who use AI will replace physicians who don’t,” Tom C Nguyen (Miami Cardiac and Vascular Institute, Miami, USA) tells Cardiovascular News echoing the comments of American Medical Association (AMA) president Jesse Ehrenfeld on the future impact of AI in healthcare.

guyen believes that the introduction of AI systems that will assist the work of cardiothoracic surgeons is inevitable, so much so that he pushed for the topic to be among those to feature on the programme at the 60th annual meeting of the Society of Thoracic Surgeons (STS 2024; 27– 29 January, San Antonio, USA), in a session titled ‘Automated new world: AI changing the future of cardiothoracic surgery’. The session was standing room only, as a testament to the interest and importance of AI in cardiothoracic surgery. Nguyen set the scene for the session, offering a primer on the application of AI inside and outside of medicine, as well as the possible benefits and pitfalls of the technology, and regulatory, ethical and safety considerations. Presentations in the session drilled down into specific applications of the technology in surgery including the role of AI and chatbots in managing electronic medical records, AI as an evaluation tool for technical performance, the use of AI in the detection of lung cancer, and wearable and digital technology as a predictor of postoperative complications. “AI is going to permeate pretty much everything we do,” comments Nguyen, who notes that while there are a lot of potential positive uses, there is also a need for caution. One possible application of AI systems is in the collection of patient data, potentially freeing up the physician to have more time to spend on treatment—a concept Nguyen describes as ‘keyboard liberation’. “Imagine going into a room and being able to have a conversation, with AI listening, and when you walk out the history, the physical is already written and connected to the medical record system. That is super powerful and that technology is not far away,” he says. Machine learning also has potential in aiding physicians in procedural planning and outcome prediction, given the capability to rapidly synthesise large volumes of data and to spot patterns that may be invisible to the human eye. “We learn by pattern recognition, you see something and you learn it,” comments Nguyen. “We can only know what we know, but with machine learning you can dive deep and look at patterns that we might not even recognise.” To illustrate this point, Nguyen highlights a 2022 study from the International Journal of Academic Health and Medical Research in which it was shown that a machine

Tom C Nguyen

learning model could be trained to recognise the differences in retinas between males and females and eventually outperformed trained ophthalmologists in predicting whether it was being shown a male or female retina with a high degree of accuracy. “There is something subtle about that retina that we are not picking up, but the machine picked up whatever that might be,” he explains. “It can handle thousands of pieces of information and the machine learning takes that information and tries to pick up the pattern. We do not have time to do that thousands and thousands of times, but machines can.” On occasion, AI has been reported to be smarter than doctors, Nguyen comments. There are increasing numbers of stories of patients struggling to find the correct diagnosis for their symptoms after seeing many doctors, but after entering their symptoms into ChatGPT, the correct diagnosis is made. The influence of AI has also been felt in the scientific publishing field, with the publisher of the New England Journal of Medicine (NEJM) this year launching a dedicated journal for research related to the topic—NEJM AI—bucking the trend among many in the field in the process by allowing the submission of text produced using AI. “For the first time they are actually supporting the use of AI in manuscript writing. It is progressive, because it is inevitable,” says Nguyen, who believes that this will open out scientific publishing to researchers whose use of written English may, in the past, have prohibited them from having research published. “We have to embrace the technology, but we have to regulate it,” he caveats. Reflecting on the future of AI in cardiothoracic surgery, Nguyen comments that in the future it is likely to be seen as less of a novelty, as many technologies and processes will be supported by some element of machine learning or AI.

We have to embrace the technology, but we have to regulate it.” “It has been around for a little while, but the explosion has really only happened in the past year and a half or so,” he says. “I think everything we touch will have an AI component to it. The way we type things, enter in data, make diagnoses, go to the grocery store, will all have an imprint of AI in, either a little or a lot. AI is going to impact us universally in everything we do day to day, but in medicine there are a lot of huge opportunities for it to impact us as well, and maybe 10 years from now, we won't be so dazzled by it, because it is just AI.”

Issue 72 | February 2024

Death rates after CABG and other surgeries “similar” regardless of patient-surgeon gender concordance Death rates after major surgery are similar regardless of whether a male or female surgeon operates on a male or female patient, a large US study published in The British Medical Journal (BMJ) has found. Differences seen in the study were small and not clinically meaningful, and the researchers say their findings should help improve processes and patterns of care for all patients. “IT IS IMPORTANT FOR patients to know that the quality of surgical care provided by female surgeons in the USA is equivalent to or, in some cases, slightly better than that provided by male surgeons,” said senior author Yusuke Tsugawa (David Geffen School of Medicine at University of California Los Angeles [UCLA], Los Angeles, USA). “Given that the difference in patient mortality between female and male surgeons was small, when choosing a surgeon, patients should take into account factors beyond the gender of the surgeon.” Gender concordance between patients and physicians—when the physician and patient are of the same sex—is generally linked to higher quality care processes and improved patient outcomes, owing to more effective communication, reduced (implicit and explicit) sex and gender bias, and better rapport. However, as stated in a The BMJ press release, evidence about the effect of patient and surgeon gender concordance on outcomes in patients undergoing a surgical procedure is “limited”. To address this, a team of researchers set out to determine whether patient-surgeon gender concordance is associated with death after surgery in

the USA. Their theory was that patients treated by surgeons of the same gender would have a lower postoperative death rate than patients treated by gender-discordant surgeons. They analysed data for almost three million Medicare patients aged 65–99 years who underwent one of 14 common major urgent or elective surgeries between 2016 and 2019: abdominal aortic aneurysm repair, appendectomy, cholecystectomy, colectomy, coronary artery bypass surgery, knee replacement, hip replacement, hysterectomy, laminectomy or spinal fusion, liver resection, lung resection, prostatectomy, radical cystectomy, and thyroidectomy. In this observational study, postsurgery mortality was defined as death within 30 days of the operation. Adjustments were made for patient characteristics, such as age, race and underlying conditions; surgeon characteristics, such as age, years in practice and number of operations performed; and hospital fixed effects (effectively comparing patients within the same hospital). Of 2,902,756 patients who had surgery, 1,287,845 (44%) had operations done by surgeons of the same gender

(1,201,712 male patient/surgeon [41%] and 86,133 female patient/surgeon [3%]), and 1,614,911 (56%) were by surgeons of different gender (52,944 male patient/female surgeon [1.8%] and 1,561,967 female patient/male surgeon [54%]). For urgent and elective procedures combined, the adjusted death rate 30 days after surgery was 2% for male patients treated by male surgeons, 1.7% for male patients treated by female surgeons, 1.5% for female patients treated by male surgeons, and 1.3% for female patients treated by female surgeons. And, for elective procedures, female surgeons had slightly lower patient death rates (0.5%) than male surgeons (0.8%), whereas no difference in patient mortality was seen for urgent surgeries. Several mechanisms could explain this small effect for elective procedures, the authors state. For example, female surgeons may abide by clinical guidelines more than male surgeons,

or might have better communication and increased attention to postoperative care than male surgeons, which could affect patient death rates. Furthermore, as elective surgeries allow patients to choose their own surgeon, they are more prone to influence from other factors compared with urgent procedures where patients are assigned to on-call surgeons, they add. The authors note that this was an observational study, and therefore cannot be used to establish cause—also stressing that other, unmeasured social and cultural factors may have influenced their results. In addition, they say their findings may not apply to younger populations, patients who receive procedures that are less common, or patients in countries outside of the USA. Nevertheless, they believe that understanding the underlying mechanisms of the phenomena observed in this study “allows the opportunity to improve processes and patterns of care for all patients”.

Ongoing qualitative and quantitative research will better delineate how surgeon and patient gender, along with race and other aspects of shared identity, affect quality of care and outcomes after surgery.”

Warfarin lowers mortality risk after SAVR PATIENTS WHO RECEIVED WARFARIN after bioprosthetic aortic valve replacement had lower incidence of mortality and a decreased risk of blood clots, according to a retrospective study published in Mayo Clinic Proceedings. Research has been conflicting on whether patients would benefit from more aggressive early postoperative anticoagulation treatment, the researchers claim. Their study compared all-cause mortality and thromboembolic events in patients undergoing surgical aortic valve replacement (SAVR) receiving anticoagulation with warfarin versus

patients with no systemic anticoagulation. The researchers analysed nationwide data on more than 10,000 patients who underwent bioprosthetic aortic valve replacement. Warfarin use was associated with a 32% reduction in mortality risk, they concluded. Patients treated with warfarin early postoperatively also had an increased risk of major bleeding events. “The findings support early warfarin use in appropriately selected patients, such as patients with low bleeding risk,” says Hartzell Schaff (Mayo Clinic, Rochester, USA), a cardiovascular surgeon who

contributed to the study. “There’s often reluctance to prescribe anticoagulant treatment early after surgery due to concerns about bleeding and uncertainty about benefits. Our research finds that the small increased hazard of bleeding (4% vs. 2.3%) may be an acceptable risk given the benefits in terms of mortality risk as well as reduced risk of thromboembolism.” The Mayo Clinic study analysed deidentified patient data from 2007 to 2019 using OptumLabs Data Warehouse, which contains claims data of commercially insured and Medicare Advantage enrollees of all ages and races throughout the USA.

February 2024 | Issue 72

12 Renal Denervation

Renal denervation finds new shores following US FDA device approvals

Global study programme, which looked at the Recor Paradise device, and the SPYRAL clinical programme, assessing Medtronic’s Symplicity Spyral system, were scrutinised in detail in August at a meeting of the FDA’s Circulatory Systems Devices Panel, which voted in favour of the data supporting the efficacy and safety of both devices, though the panel was split on whether the benefits of the treatment outweighed the risks for the Symplicity Spyral system. For some who are sceptical of the technique, however, there are still questions as to Like London buses, interventionalists have had a long wait for the whether the latest round of data US Food and Drug Administration (FDA) to approve a renal denervation is sufficient to support the device for the treatment of hypertension, only for two to come along widespread adoption of renal Symplicity within days of one another. denervation, and whether the Spyral effect and durability of the THE NEWS THAT MEDTRONIC’S commercialisation of the intervention are enough to Symplicity Spyral radiofrequency system had received therapy globally, and come justify its use. approval as an adjunctive treatment for hypertension soon after endorsement of the “In my opinion, the blood from the US Food and Drug Administration technique as a treatment option pressure lowering effect of (FDA) in late 2023, came just over a week after an in patients with uncontrolled renal denervation seems to have announcement from Recor Medical, that its own, resistant hypertension from the more to do with the population ultrasound-based denervation device—the Paradise European Society of Cardiology being studied than the catheter system—had also been granted approval. (ESC) Council on Hypertension and being used,” cardiologist Andrew Foy That two devices would gain FDA approval at all the European Association of Percutaneous (Pennsylvania State University, Hershey, would have been virtually unthinkable almost a decade Cardiovascular Interventions (EAPCI), as well USA) tells Cardiovascular News, outlining his ago, when the release of results of the SYMPLICITY as the release of guidelines from the European Society concerns. “Patient populations with non-resistant HTN-3 trial dented initial optimism in renal of Hypertension (ESH) stating that renal denervation hypertension do best and seem to derive a modest denervation as a treatment for hypertension, only for a may be proposed as an adjunctive therapy in select blood pressure lowering benefit on the order of new generation of sham-controlled trials to prompt a patients with resistant hypertension. Both of these 4–5mmHg reduction in systolic blood pressure, which resurgence in interest for the therapy. developments are expected to broaden the adoption can be achieved by addition of a drug and rather easily Proponents of renal denervation—an interventional of renal denervation in Europe. in most patients.” procedure in which energy is targeted through “FDA approval certainly provides reassurance Foy has been a co-author on several meta-analyses a catheter to the renal nerves to modulate the for physicians in Europe that renal denervation looking at the technique, which have included data sympathetic signalling between the kidneys and brain indeed represents a safe and effective alternative to from both the RADIANCE and SPYRAL studies, and to reduce blood pressure—see the availability of pharmacotherapy in uncontrolled hypertension,” he says that these have pointed to a potential waning the treatment as being a potential paradigm Felix Mahfoud (Saarland University Hospital, of the effect of the therapy over time, as well as shift for the treatment of many thousands Homburg, Germany), who has played a highlighting what he sees as a questionable benefit of of patients with hypertension, key role in the research of the offering a third way for those therapy, tells Cardiovascular who cannot tolerate or adhere to News. “Although not required antihypertensive medication, or for commercial use, I’m sure for whom lifestyle modifications that FDA approval will further have had no effect. facilitate adoption of the “The approval of the renal technologies in geographies denervation systems by the outside the USA.” FDA is a game-changer for both Paradise According to Mahfoud, though interventional cardiology and there is growing consensus the treatment of hypertension,” on the use of the therapy, its George Dangas (Icahn School adoption will be shaped by the David Kandzari performs the first US procedure of Medicine at Mount Sinai, New willingness of healthcare systems to pay York, USA), president of the Society for for the treatment. the treatment in patients with resistant hypertension. Cardiovascular Angiography & Interventions “Societal consensus documents and hypertension “There seems to be a clear interaction between (SCAI), said in the aftermath of the announcement guidelines now unanimously recommend renal the efficacy of renal denervation and whether the of the Recor and Medtronic device approvals. “This denervation in certain patients with resistant or difficult patient population being studied had resistant versus innovative technology has the potential to revolutionise to control hypertension,” he comments. “Despite non-resistant hypertension,” Foy adds. “That’s a very how we approach the management of high blood these national and international recommendations, important issue when we’re talking about the clinical pressure which has grown tremendously globally, cost coverage remains challenging in some healthcare application of renal denervation in practice since, offering patients a safe and effective treatment option.” systems and countries. Overall, I think, we need to basically, its intent is to treat patients with resistant Since the FDA approvals, many centres throughout intensify our efforts to integrate patient preference hypertension and not non-resistant hypertension. the USA have begun offering the therapy to their into decision-making, not limited to hypertension I think there are good reasons why we see this hypertensive patients. Barry Bertolet (Cardiology management.” interaction and it is very likely to be valid.” Associates of North Mississippi, Tupelo, USA) Much of the impetus for the FDA’s decision comes Renal denervation advocates, though, acknowledge performed the first commercial case using from the generation of new evidence of the efficacy that careful patient selection is important, and the Medtronic system in the southern US in and safety of both devices. Data from the RADIANCE stress that the therapy is not an alternative to the late November. current standards of care, medication and lifestyle “Performing the first commercial case in our region modification, but should be offered when these have was important for two main reasons,” Bertolet tells been found to be unsuccessful or are not possible. Cardiovascular News, reflecting on the significance “We will first educate the area primary care of the milestone. “Number one, it represented the providers on initial guideline directed medical start of a new era in the treatment of hypertension— therapy,” says Bertolet of the decision-making meaning that an option beyond lifestyle modification process in his practice. “If a patient fails or and medications was available—and, number two, is intolerant to an honest attempt to blood it represented the culmination of years of research pressure control, then they should be referred and product development, which my team and I were to our clinic for evaluation of secondary dedicated to.” causes of hypertension. If no secondary causes Though both the Recor and Medtronic systems of hypertension are noted, we will discuss the have been CE marked for some time, the FDA option of additional medications versus Felix Mahfoud approvals potentially open the door to wider renal denervation.”

I’m sure that FDA approval will further facilitate adoption of the technologies in geographies outside the USA.”

CMY

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CMY

February 2024 | Issue 72

14 Coronary Interventions

Settling the paclitaxel versus sirolimus DCB debate

Bernardo Cortese Point of View Bernardo Cortese (Fondazione Ricerca e Innovazione Cardiovascolare, Lodi, Italy and DCB Academy) has been among the leaders in research on the use of drug-coated balloons (DCBs) in percutaneous coronary intervention (PCI) across Europe. As the approach continues to gain ground among physicians, new devices using novel coatings such as sirolimus as an alternative to the current standard of care, paclitaxel, have begun to enter the market. Here, Cortese considers the important issues to consider when evaluating these two drugs.

aclitaxel-coated balloons have been available in Europe since 2007 when the PACCOCATH study came out and since then many technologies with good outcomes have emerged. Sirolimus has taken quite a bit longer, with the first device marketed in 2016— Magic Touch (Concept Medical). From one point of view, sirolimus is more appealing to physicians as limus has won the war against paclitaxel in stents, and those who have come to DCBs relatively recently may hold this view. And, while sirolimus is bringing an important novelty to the field, we have seen a lot of data that paclitaxel works very well. The drugs are truly different. As paclitaxel stays in the vessel wall for weeks and in some cases months, it can exert some cyotoxic effects in the case of over-dosage. At TCT 2023 (23–26 October, San Francisco, USA) Aloke Finn (University of Maryland School of Medicine, Baltimore, USA) presented data from a study comparing paclitaxel and sirolimus DCBs, showing that the

latter was very keen to the vessel wall without any sign of toxicity, whereas the former was associated with some sort of toxicity. We do not understand if this is good or not, but we do know that in 60–70% of cases paclitaxel exerts late lumen enlargement. When we started to test sirolimus with the Magic Touch DCB in Europe we decided to follow two different strands. One is to compare sirolimus to paclitaxel in a mechanistic study—TRANSFORM I—as well as in clinical studies in a broad population in comparison to stents (TRANSFORM II trial, ongoing). TRANSFORM I compared Magic Touch to Sequent Please (B Braun), which is a well-studied, well-performing paclitaxel-coated balloon. Magic Touch was just outside of the margin for noninferiority as regards to the angiographic performance of the two devices, and we have speculated a lot about why this may be, with some important items to underline. As a co-chairman of the study,

MASTER DAPT analysis shows benefit among highrisk female patients for short DAPT

Female patients at high risk of bleeding experience no higher rate of bleeding and ischaemic events than their male counterparts when receiving a onemonth dual antiplatelet therapy (DAPT) regimen after percutaneous coronary intervention (PCI).

I admit there are some drawbacks, including that we observed a consistent difference among the centres in terms of angiographic outcomes. We had some difficulty in enrolling patients, in part because of COVID-19, and so we had to lower the threshold of the quality of the centres in terms of their experience with DCB angioplasty. In one centre where paclitaxel worked much better, we observed that the lesion complexity was much higher. In another centre where Magic Touch performed better the lesions were much simpler. TRANSFORM I has provided important data to the field, and I believe it shows that in terms of angiographic performance, paclitaxel will always win over sirolimus. One hypothesis that I would like to investigate, and is now being examined in PICCOLETO VI, is whether paclitaxel is better in penetrating into the vessel wall even if you have not achieved perfect lesion preparation. My hypothesis is that in complex lesions, sirolimus is not able to enter the vessel wall if you have not prepared the lesion perfectly. PICCOLETO VI is collecting data from the Sequent Please, Sequent Sirolimus (B Braun), Elutax (AR Baltic Medical), Selution (MedAlliance), Magic Touch, Prevail (Medtronic) and Pantera Lux (Biotronik) devices. We are studying not only angiographic performance at six months, but also physiology, and we have some interim analysis showing very interesting information from this study. The study has been sent for consideration as a presentation at EuroPCR 2024 (14–17 May, Paris, France) as a late-breaking clinical trial.

I think that the future is bright for DCBs, at least in terms of preparing and creating a good programme of clinical trials.”

This is the finding of a secondary analysis of the MASTER DAPT trial, published in JAMA Cardiology, evaluating the association of sex with the comparative effectiveness of abbreviated and standard DAPT. Twelve-month results of the multicentre, randomised, MASTER DAPT clinical trial, presented at the European Society of Cardiology’s 2021 congress (ESC 2021, 27–30 August, virtual) and published in the New England Journal of Medicine, demonstrated that one month of DAPT following stent implantation in high bleeding risk patients preserves ischaemic benefits and reduces bleeding risk. For the latest analysis, investigators compared the effect of the two DAPT regimens among the 1,408 female patients, representing 30.7% of the overall trial population, against the trial’s 3,171 male participants. Their analysis found that abbreviated DAPT was associated with comparable net adverse clinical event

The second line of investigation, starting back in 2018, was EASTBOURNE, an investigator-driven prospective study with more than 2,100 patients. The 12-month follow-up, published in JACC: Cardiovascular Interventions in 2023, shows the safety and efficacy of the Magic Touch device in a broad population of coronary artery disease patients including small vessel disease and in-stent restenosis. We presented the two-year follow-up at EuroPCR 2023 (16–19 May, Paris France) and it is currently under review for publication, and we hope to have the three-year follow-up available this year. Interestingly we are doing a lot of sub-analyses, and have just published the Bifurcation and acute/stable coronary syndromes sub-analysis. The study of single antiplatelet therapy (SAPT) with DCB, as well as the performance in diabetic patients have been submitted. We are gaining a good amount of angiographic data comparing sirolimus and paclitaxel DCBs, and I think that now we should compare the devices with good clinical backgrounds to drug-eluting stents. Physicians are using too many stents, so it is important that the comparator arm should be a stent, and this is one of the purposes of TRANSFORM II, another investigatordriven study. In this trial, we are randomising patients to Magic Touch versus any everolimus-eluting stent in de novo lesions. Now, we want to see with a clinical endpoint, if there is non-inferiority in the primary endpoint of target lesion failure (TLF), and also subsequent superiority in terms of net adverse clinical events (NACE), because we are reducing the duration of dual antiplatelet therapy (DAPT) with the sirolimus-coated balloon. So far we have enrolled over 660 patients and we are aiming for 1,825, and we hope to finish enrolment within one year. I think that the future is bright for DCBs, at least in terms of preparing and creating a good programme of clinical trials. The outcomes we do not know, but we need to run these studies before we know the answer. So far, some well-studied paclitaxel DCBs should be used in the majority of patients, with sirolimus DCBs increasing their role in the arena.

(NACE) rates in men and women, but they report that there was evidence of heterogeneity of treatment effect by sex for major adverse cardiac or cerebral events (MACCEs), with a trend toward benefit in women but not in men. There was no significant interaction for non-major bleeding (MCB) across sex, although the benefit with abbreviated DAPT was relatively greater in men than in women, they add. The results remained consistent in patients with acute coronary syndrome and/or complex PCI, the study team reports. “Our findings suggest for the first time that abbreviated DAPT should be considered for women with high bleeding risk in particular because they derive not only bleeding benefit, similarly to men, but also no discernible incremental ischaemic risk compared with standard DAPT,” study author Antonio Landi (Cardiocentro Ticino Institute, Lugano, Switzerland) et al write.

February 2024 | Issue 72

16 Interview

PROFILE

view social media as ‘social’ at all, I view it as paradoxically antisocial (except for the funny memes and jokes). I’m fairly certain that many agree with this sentiment, but for many there is too much fear of missing out to let it go, which of course is exactly the way it’s designed.

AJAY KIRTANE

How do you see interventional cardiology evolving over the next decade?

For Ajay Kirtane (Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, USA), success in medicine involves marrying a humanistic approach to care with a thorough understanding of clinical data. An accomplished trialist, physician and educator, he tells Cardiovascular News about his career and expectations for the future of interventional cardiology.

Why did you choose to become an interventional cardiologist?

Don’t all Indian-Americans aspire to become interventional cardiologists?! To be honest, I was actually somewhat anti-medicine growing up because, as an Indian-American, it is quite common to follow your parents into medicine or engineering. I am really thankful that my parents did not push me overtly in that direction. I was interested in the biological sciences and was on the path to doing a PhD, but ultimately I missed the absence of human interaction in the lab. I’ve always thought that the biggest draw of medicine is that it is scientific and analytic but has human interaction at its core. Looking back over the years, one of the things I am most proud of is winning an award for humanism in medicine when I was in medical school. I didn’t realise the significance of it at the time, but looking back on my career I hope that the traits that likely led to that recognition are what I am ultimately known for. Interventional cardiology came later. I really liked the evidence-based medicine approach in cardiovascular disease combined with the fact that we could diagnose conditions and treat them therapeutically, but also with longitudinal care over time. Interventional cardiology isn’t just doing a procedure and never seeing the patient again—we manage patients both in and out of the hospital and even for years after their procedure. It’s the therapeutic aspects of the field—when someone has a problem that we can address with technical skill and also by using our brain—those are the parts of the field that most appeal to me.

Who have been the biggest influences on your early career?

My parents are both physicians and their kindness to others was a big influence on me. My mother taught me that in the long run it is best to be honest and fair, even if that leads to others hearing things they might not want to hear in the moment. She is under 5ft tall but never intimidated by anyone. My father is really cerebral but has always been the person that our relatives or friends call, no matter what medical condition they have. He always takes the call and provides whatever support they need. They are both athletes in their 80s. Starting out in cardiovascular disease, Mike Gibson was my mentor. I met him in California and then subsequently we worked together for four years in Boston along with David Cohen and others. I have had the fortune to train and work in numerous places and I really appreciate the fact that I could learn from different people along the way. When I came to Columbia, Marty Leon, Jeff Moses, Roxana Mehran and Gregg Stone

were all huge influences on me, along with so many others in our group. With anyone who is an influence the most important thing is to recognise that they are human beings. I’ve always looked to individual mentors for their specific strengths and tried to emulate and combine these with my own experiences and upbringing. We end up being the strongest we can possibly be because we are an amalgamation of the different attributes of all of the people, including our parents, that we have interacted with over time. But, it is also important to be unique. Trainees too often think they should emulate a specific mentor in every way and that can be too hard or disappointing. I try to take the good things that each has to offer and incorporate or emulate these in the best way that I can manage.

What has been the biggest technological advance during your career? In my opinion it is the structural heart revolution. When I was a trainee, structural heart disease was basically just balloon mitral valvuloplasty for rheumatic mitral stenosis and the occasional aortic valvuloplasty. When I came to Columbia, transcatheter aortic valve implantation (TAVI) was in its infancy. Now we can treat all sorts of conditions that were either off limits to patients because they were too high risk for surgery or even offer a less invasive approach to those who previously only had surgery as an option. It is super impressive to see the results of the clinical studies as well as the techniques and the impact that they have had on our patients.

What has been the biggest disappointment?

I am an optimistic person by nature, so it is hard to get overly disappointed. Even a trial or a technology that has a negative result is a learning experience. One area where I have been dilillusioned more recently has been with the promise of social media to democratise medical education. While social media allows for rapid dissemination of information, so many of the negatives (for example, the loudest voices get the most play irrespective of merit) limit its ability to be a good educational tool. But, I would also bet that of the people one might describe as being loudmouths or even trolls on social media, if you sat down and talked to many of them in real life, you might find them to be engaging and thoughtful people with valuable insights. In my estimation, the “social media world” is a very distorted version of the actual world, and that is why I’ve lost interest. I still hold out hope that there could be ways to use some version of it productively, but right now I don’t

FACT FILE CURRENT APPOINTMENTS Director, Columbia Interventional Cardiovascular Care program Professor of Medicine, Columbia University Irving Medical Center Chief Academic Officer, Division of Cardiology, Columbia Interventional Cardiovascular Care Program Director, Cardiovascular Research Foundation (CRF) Transcatheter Cardiovascular Therapeutics (TCT) conference

EDUCATION AND TRAINING AB in Molecular Biology, Princeton University MD, Columbia University College of Physicians and Surgeons SM in Clinical Epidemiology, Harvard School of Public Heath Internship, Residency and Chief Residency, University of CaliforniaSan Francisco Medical Center Cardiology and Interventional Cardiology Fellowship, Beth Israel Deaconess Medical Center/ Harvard Medical School

I think some of the work that is being done in data science will spill over to the world of clinical trials. It could be argued that the randomised controlled trial was what really brought evidence-based medicine to the forefront of medicine. But one of the challenges that we have now is that even in a large randomised trial we get an average treatment effect across a large population of patients, but we know that in real life each of those patients are very different. The next leap forward would be some application of personalisation within the context of a randomised trial, so that we don’t have to spend many millions of dollars for the ISCHEMIA trial, for example, to come out with an average treatment effect that we know a priori is nuanced when we try to apply it to our individual patients. I think it would be much better if we could really start to hone in on the patients that may or may not benefit from therapies in a much more intelligent way through the integration of personalised medicine with evidence-based medicine.

As an investigator of renal denervation for hypertension treatment, what impact do you see the recent US approval of two devices for this condition having?

I am excited by it. It has been a long road, and along that road I discovered how poorly treated hypertension is worldwide. To have a therapy that is independent of adherence and synergistic with medication and lifestyle modification is really important, especially for the highest risk patients. I am an optimistic person, but also realistic, and I think what remains to be determined is how durable is the effect over the long-term. Is the responder rate what we think it is? If a third of patients are not going to get a response then that is going to be disappointing for them. But I do think that this is a new paradigm in that it allows us to take care of patients in ways other than medication, and as physicians, too often in the office we prescribe medicine and assume patients are going to take it, but in real life patients don’t necessarily want to do that. So I am excited by it and I am certainly thankful to everyone who collaborated to bring this therapy forward.

What are your other current research interests?

Beyond getting renal denervation approved and furthering the study of its use, we just presented data that will hopefully lead to the first drug-coated balloon approval for use in the coronaries in the USA. On another front, we have completed the largest trial of adjunctive plaque modification for severe calcium—the ECLIPSE trial of orbital atherectomy—which we plan on presenting later this year. I am very excited about the ALL-RISE trial that has just started, studying how angiography-based physiology with the CathWorks system compares to just wirebased physiology. I think everybody would

Issue 72 | February 2024

alisonlang.com

Interview 17

agree that it is good to do physiology but it is often a pain to do and that is one of the reasons why it is underutilised. The idea of being able to get physiologic measurements using the coronary angiogram alone is appealing intuitively and we hope to show that the clinical outcomes will be similar or better compared to wire-based physiology, which I think could really change the way we look at diagnostic catheterisation going forward. I feel that while a lot of our field’s attention has shifted to structural heart, the coronary space is still alive and well, and there is a lot we can still do to improve the care of patients with coronary artery disease.

Which recent studies have been particularly influential on your practice?

Sticking with the coronary theme, I would say the combination of the ISCHEMIA trial results and then the definitive sequel to the ORBITA trial, ORBITA-2, were pretty influential. Both tell stories that fit a picture, and that is that if you have either severe symptoms or severe disease, those are the types of patients that can

benefit the most from what we would have to offer in the cath lab. We certainly have a lot to offer outside the cath lab with respect to medical therapy and prevention, but in the cath lab, the patients that benefit are those that are going to have the most severe symptoms or the most severe disease. Contrary to the popular (oversimplified) take on ISCHEMIA, there actually is a prognostic benefit to diagnosis and revascularisation of the most severe forms of coronary artery disease.

What is the most rewarding part of your job?

Every physician develops their own individual style—some would even call it a “brand”—and for me it is thoughtful clinical medicine. Medicine is at its heart based upon common sense, guided by knowledge and understanding. That means taking the data, understanding it well, understanding the nuances, trying your best to apply them to individual patients and their families within the context of their preferences and their upbringing, and having the technical ability

“While a lot of our field's attention has shifted to structural heart, the coronary space is still alive and well.”

and judgement to safely get them through a procedure if they need it. To me there is nothing better than that.

What keeps you occupied outside of medicine?

I have an amazing family. My wife has been a bedrock for me since we started dating at the age of 18. We have two grown-up kids and a dog and we love spending time together—I am really fortunate in that way. I am so thankful that while my kids are different from one another, both are truly wonderful—probably mostly due to the influences of my wife and extended family who have always surrounded us all with love. The four of us play music together, and that is a lot of fun. Now that the kids are out of the house, I find myself playing the guitar much more than I used to. Sports and exercise are always things that I have been interested in, and I love skiing in particular. I also have more time to read now too, especially given that I am off social media, and that is something I enjoy and have started to do more often.

February 2024 | Issue 72

18 Advertorial THIS ADVERTORIAL IS SPONSORED BY JENAVALVE

TAVI offers promise in the “underdiagnosed and undertreated” aortic regurgitation population

Transcatheter aortic valve implantation (TAVI) has transformed the treatment of aortic stenosis, with hundreds of thousands of patients worldwide receiving the minimally invasive therapy since it entered practice nearly two decades ago. However, for patients with aortic regurgitation, treatment options remain more limited. UNTREATED, SEVERE, symptomatic aortic regurgitation is associated with high mortality, and surgery is recommended for patients with native severe aortic regurgitation. However, there are a number of patients who are high-risk for surgery and are not offered the treatment. “The most recent data from prevalence studies, largely related to patient populations over the age of 65, indicate about a 2–4% prevalence of significant aortic regurgitation,” Martin Leon (Columbia University, New York, USA) tells Cardiovascular News, relating to patients with moderate-tosevere, or severe, often symptomatic, aortic regurgitation. “That is larger than people would predict, and in some studies it exceeds the prevalence of symptomatic, significant aortic stenosis.” Leon describes the criteria for making an accurate diagnosis of aortic regurgitation severity as “frustratingly burdensome”, contributing to what he sees as a large number of eligible patients not receiving treatment. “There are estimates that in a population of significant aortic regurgitation patients, who by most guideline criteria would be operable candidates, only as many as 25% actually get treated within the first few years of diagnosis,” he explains. “So, aortic regurgitation is underdiagnosed, it is undertreated, it is more prevalent, and guidelines have been very static over a period of two decades in terms of suggesting which patients should be treated.” Anatomical features make currentgeneration TAVI devices, which have been engineered for use in the treatment of aortic stenosis, largely inappropriate in the setting of aortic regurgitation. “The predicate understanding of using a transcatheter valve in the aortic position is that you have a platform, which is a high friction, calcified aortic valve complex, that will allow the metallic frame to adhere to it so that it is stable,” explains Leon. “All of those predicate anatomic assumptions are invalid if you are dealing with aortic regurgitation. You have a compliant, almost elastic, annulus. You have very little in the way of calcification. The valves are somewhat larger, and none of the presently approved transcatheter valves take that into consideration.”

The availability of a dedicated transcatheter device for the treatment of aortic regurgitation with proven performance is likely to change the outlook, and results from the ALIGNAR pivotal trial, presented at the 2023 TCT meeting (23–26 October, San Francisco, USA), have raised hope that this is a realistic prospect. ALIGNAR studied the use of the Trilogy (JenaValve) transcatheter system in high-risk patients with symptomatic, severe aortic regurgitation. The device currently has a CE mark, but is yet to be approved for use outside of clinical trials in the USA. The Trilogy valve features locators that clip onto native leaflets and enable secure anchoring in the absence of calcium, as well as large-open cells that are designed to facilitate future coronary access. “The fixation of the valve is both at the annular zone, with a self-expanding frame, but also it clips onto the three leaflets so that that creates stability and fixation in a noncalcified structure,” Leon says of the device. “That is why it is so ideally suited for the aortic regurgitation patients.” The landmark, prospective, singlearm investigation device exemption (IDE) ALIGN AR study enrolled a total of 180 patients at 20 US sites, assessing the safety and efficacy of the Trilogy system within high-risk patients with symptomatic aortic regurgitation. The

measured favourably on the efficacy of the device, determined by the rate of all-cause mortality at one year, with a rate of 7.8% reported by investigators compared against a 25% prespecified historical control. “That is dramatically lower than what you would expect to see in an untreated aortic regurgitation patient Martin Leon population,” comments Leon. Trilogy was also shown to perform favourably in terms of safety, which was assessed against a composite of 30-day all-cause mortality, stroke, lifethreatening or major bleeding, major vascular complications, acute kidney injury (AKI), valve intervention, new permanent pacemaker or moderate or greater paravalvular regurgitation (PVR), with the device meeting the non-inferiority criteria needed to achieve its primary endpoint, with a rate of 26.7% recorded against a prespecified non-inferiority margin of 40.5%. Leon also notes that patients saw an improvement in symptoms as a result of the therapy, demonstrated by increased Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, as well as a low rate of PVR and improvement in left ventricular (LV) remodelling. “From all parameters from ALIGN-AR we should be enthusiastic that this is an effective therapy for managing patients with aortic regurgitation,” he comments. Plans for a randomised study assessing the therapy in patients eligible for surgery are “progressing rapidly”, according to Leon, who explains that this will be the next stage for research in this arena. “When we first started TAVI we were doing only what we called inoperable, not just high-risk, but extreme- or prohibitive-risk patients.” he

“We have been static with this disease for decades and now we have an opportunity to make some very significant impacts on patient care.” study is intended to support a premarket approval submission to the US Food and Drug Administration (FDA), with clinical evaluation, echocardiography, functional and quality of life assessments scheduled at 30 days, six months, one year and annually up to five years. The results reported at TCT 2023

The Trilogy TAVI valve

comments. “Everybody said that this was a small population. The reality is that it was not a small population, especially in a globally ageing population, there are more and more of these patients. So, certainly I think we have underestimated the clinical significance of this group of patients for aortic regurgitation as well.” Leon describes himself as “bullish” for the prospects of advancing TAVI among patients with aortic regurgitation, telling Cardiovascular News that he believes this to be a “seminal turning point” in the management of the disease. “We have been static with this disease for decades and now we have an opportunity to make some very significant impacts on patient care both with managing the patients by guideline-appropriate candidates that are not being treated, and also to look at earlier stage treatment, which we call pre-emptive treatment in severe aortic regurgitation, thinking that we can alter the natural history effectively, now that we have what we believe is a safe and effective device,” he says. Though TAVI in the aortic stenosis population has taken years to reach maturity, Leon believes that experience from this process could speed up the advance of TAVI for those with aortic regurgitation. “It took us 15 years to go through all of the different patient population scenarios in aortic stenosis, now that we have a better understanding of what to expect, the operators are much more mature, well trained, [and] have great experience,” he proffers. “I think we can extrapolate those positive experiences from the aortic stenosis side and we can accelerate the development of the aortic regurgitation platform.”

Issue 72 | February 2024

Structural Heart Interventions Clinical outcomes similar at one-year for leading TAVI platforms in real-world registry, but stroke rates differ A comparison of two latestgeneration self-expanding and balloon-expandable transcatheter aortic valve implantation (TAVI) systems has found comparable rates of all-cause mortality and heart failure hospitalisation between the two devices, but a higher rate of disabling stroke with the selfexpanding device.

Didier Tchétché presents at PCR London Valves

Projected rise in aortic valve-invalve procedures prompts interest in leaflet splitting device Details of the first pivotal trial assessing the use of a dedicated leaflet splitting device to facilitate future coronary access in patients undergoing transcatheter aortic valve implantation (TAVI) who may be at risk of valve-in-valve induced coronary obstruction were shared at PCR London Valves (19–21 November, London, UK).

hortCut (Pi-Cardia) is designed to split the leaflets of pre-existing valves to enable coronary access and prevent obstruction during TAVI procedures in failed bioprosthetic surgical (valve-in-valve) or TAVI valves (TAV-in-TAV). The device is delivered transfemorally over a routine left ventricular wire and once it reaches the target area at the base of the leaflet, a small blade is advanced which, once manually pulled through, creates a split in the leaflet. “There are a growing number of patients available for TAVI due to the expansion of indications and the eligibility of younger patients,” said Didier Tchétché (Clinique Pasteur, Toulouse, France) of the current outlook for the technology in a presentation that detailed the latest status of the ShortCut pivotal trial during a late-breaking trials session at PCR London Valves. “These patients will require redo interventions in the future, and we know from US market forecasts that TAVin-TAV is going to be more frequent than valve-in-valve in the future. In 2035 see that there is going to be a six-fold increase in the number of valve-in-valve procedures, [so] there will be need for leaflet modification techniques.” The pivotal study of the device which is the first to be designed specifically to address the need for leaflet splitting, has enrolled 60 patients at sites in the USA, Europe and Israel. The trial was designed to test safety, including the occurrence of mortality and stroke up to 30 days, and efficacy of the procedure assessed intraprocedurally by transoesophageal echocardiography as well as freedom from coronary obstruction or reintervention out to 30 days. Patients have been included in the study if they were undergoing a valve-in-valve procedure at deemed to be

at risk of coronary obstruction based upon a heart team decision. Tchétché described the trial population as being at “high-risk”, with a mean age of 77 and an average Society of Thoracic Surgeons (STS) risk score of 4, with a high number of comorbidities. There was a large variety of different devices that were seen during the trial, Tchétché detailed. “I would say that you could split any kind of failed bioprosthesis, whether it be stented, non-stented, externally mounted leaflets, or even TAVI devices,” he commented. The majority of cases involved failed surgical bioprosthesis, but some TAV-inTAV procedures were also included. Risk of coronary obstruction was determined by virtual valve-to-coronary (VTC) and valve to sinotubular junction (VTS) distances, which stood at an average of 3.3mm and 2.2mm respectively. Dual leaflet splitting was required in 37% of cases. “We are going to see more and more in the future effective controlled splitting of single or double leaflets,” Tchétché commented, adding that the procedural times seen in the trial were on average 30–47 minutes. Results of the trial are expected upon completion of follow-up, which is likely to be in 2024, Tchétché noted.

Evolut Pro and Sapien Ultra devices showed similar clinical efficacy in real-world TAVI practice including challenging anatomical subsets.”

ONE-YEAR FINDINGS FROM THE OPERA-TAVI registry, an investigatorinitiated, multicentre registry looking at the latest iteration Evolut (Medtronic) selfexpanding platform alongside the Sapien 3 (Edwards Lifesciences) balloon-expandable TAVI platform, were presented at PCR London Valves (19–21 November, London, UK) by Giuliano Costa (AOU Policlinico “G Rodolico– San Marco”, Catania, Italy). The findings were published simultaneously in EuroIntervention. The OPERA-TAVI registry reflects realworld usage of the two platforms, and includes newer iterations of the two devices—Evolut PRO and Evolut PRO+ as well as Sapien 3 Ultra. A total of 1,897 consecutive patients were enrolled in the study at 15 centres in Europe and North America, treated between September 2017 and January 2022. Patients who received either of the devices were propensity matched into 587 pairs based upon clinical and anatomical characteristics, Costa explained, and detailed that the make-up of the two groups was well balanced, with a median age of 82 years in both groups. Primary endpoints were one-year all-cause death, disabling stroke and heart failure hospitalisation, with secondary endpoints including the single components of the primary endpoint. Investigators also sought to probe the difference between the two devices in five pre-specified subgroups of patients, including leaflet or left ventricular outflow tract (LVOT) calcification, annulus dimensions, aortic angulation or leaflet morphology. The primary endpoint occurred in 14% of patients who received the self-expanding device, Costa reported, compared to 11.9% of patients implanted with the balloon-expandable platform, with analysis of the single endpoint components showing the biggest disparity being in the rate of disabling stroke, which stood at 2.6% in the self-expanding TAVI group and 0.4% amongst patients receiving the balloon-expandable TAVI device. “Of note, these results were consistent across all the five prespecified subgroups of patients,” Costa said. “Similar results were recorded in patients with moderate-to-severe leaflet or left ventricular outflow tract calcification, patients with bicuspid native valves, patients with horizontal aorta, and patients with annulus diameter below 23mm.”

20 Structural Heart Interventions

February 2024 | Issue 72

AI-derived risk score may improve planning of TEER for secondary mitral regurgitation A novel risk score derived from artificial intelligence (AI) may be more effective than current models at predicting one-year survival prognosis and identifying individuals at extreme risk of mortality or lack of clinical improvement among patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER). LUKAS STOLZ (KLINIKUM der Universität München, Munich, Germany) detailed the design and validation of the EuroSMR score during a late-breaking trial session at PCR London Valves (19–21 November, London, UK). “We have learned from the COAPT and MITRA-FR trials that patient selection and risk stratification prior to mitral TEER is key in order to optimise outcomes after the procedure,” Stolz commented. Existing scores have been validated against patients undergoing surgery, he explained, and have other limitations including having been derived from relatively small datasets or lacking independent validation. Stolz and colleagues used data from 4,600 patients from the European registry of transcatheter repair for secondary mitral regurgitation— EuroSMR—to develop their risk score, seeking to predict a patient’s mortality

and freedom from New York Heart Association (NYHA) heart failure class III or IV at one year. The researchers fed an AI model with 28 relevant clinical, echocardiographic, laboratory and medication parameters, and the algorithm identified the 18 parameters which had the strongest contribution to an optimised risk prediction of one-year mortality. “We can find some typical predictors in the field of valvular heart disease, for example symptomatic status of our patients, right ventricular dysfunction, left ventricular dysfunction, renal dysfunction, we have comorbidities like diabetes, but also guideline-directed medical therapy (GDMT) plays an important role,” said Stolz of the parameters that were found to make the greatest contribution to risk prediction. Detailing the validation of the risk prediction model, Stolz commented that the score “differentiates well”

French registry study finds fewer cardiovascular deaths among mitral regurgitation patients receiving TEER The results of a propensity-matched analysis of all patients undergoing mitral valve surgery or transcatheter edge-to-edge repair (TEER) for severe mitral regurgitation, taken from France’s national administrative hospital discharge database, suggest that TEER was associated with lower cardiovascular mortality than mitral surgery at mid to longterm follow-up. PIERRE DEHARO (CHU TIMONE, MARSEILLE, France) and colleagues from centres across France detailed their findings in a paper published in the European Heart Journal, having collected information for all consecutive patients treated for mitral regurgitation in France with isolated TEER or isolated mitral valve surgery between 2012 and 2022. The study period postdates the introduction of the transcatheter MitraClip (Abbott) system in the country, which arrived in early 2011, and reflects a “consistent” increase in indications for TEER and the number of patients treated using the therapy, the authors note.

Lukas Stolz presents at PCR London Valves

between surviving and dying patients. “What we can also see is that the surviving Kaplan-Meier charts of the derivation of the validation cohorts were more or less superimposed, which means the score does not only work in the derivation cohort but also in the validation cohort,” he said. The model outperformed existing risk scores such as Euroscore II, the MITRA Score and the COAPT Score, Stolz added, achieving an area under the curve (AUC) of 0.789. “The AI derived EuroSMR risk score is a novel and improved risk calculator, not only for prediction of one-year mortality, but also one-year mortality free from heart failure symptoms,” Stolz said in the conclusion to his presentation. “The EuroSMR score might not only facilitate talking to your patient and finding the right therapy, but it could possibly be an important aid for the heart team to take a decision.

During the 10-year duration of the study, Deharo et al report that a total of 598,036 adults were hospitalised and had a principal, related, or significantly associated diagnosis of mitral regurgitation. Patients were followed until 30 June 2022 for the occurrence of outcomes, with the study team aiming to evaluate the incidence of all-cause death, cardiovascular death, ischaemic stroke, rehospitalisation for pulmonary oedema, myocardial infarction, major or life-threatening bleeding, new onset of atrial fibrillation, endocarditis, cardiac arrest and pacemaker implantation. The researchers identified that, over the course of their analysis, 57,030 patients underwent either isolated mitral valve surgery or isolated mitral TEER. In the unmatched patient population, those treated with TEER were typically older, with higher rates of cardiovascular risk factors, vascular disease, chronic kidney disease and percutaneous coronary intervention (PCI) history. Patients undergoing each procedure were propensity-score matched based upon baseline characteristics, with the resulting groups for each treatment comprising 2,160 patients. It is interesting to note that surgery followed a steady number during those 10 year while TEER mean year of inclusion was late 2019 showing the exponential curve of adoption of this technology in France At three-year follow-up, the study team reports that TEER was associated with a significantly lower incidence of cardiovascular death, pacemaker implantation and stroke, though the incidence of noncardiovascular death, recurrent pulmonary oedema and cardiac arrest were more frequent after TEER. There were no significant differences observed between the

We have learned from the COAPT and MITRA-FR trials that patient selection and risk stratification prior to mitral TEER is key in order to optimise outcomes after the procedure.” Lukas Stolz

two groups regarding all-cause death, endocarditis, major bleeding, atrial fibrillation and myocardial infarction. Discussing their findings, Deharo and colleagues write that as in previous reports, the population in their study shows a marked difference in risk factors among those undergoing TEER versus those undergoing surgery. “Patients undergoing TEER remained typically a sicker population at baseline, and may, therefore, be at increased risk for adverse events,” they write. “In our cohort including all TEER and isolated mitral surgery in France, non-cardiovascular death was significantly more frequent in the TEER group to surgery. This may be related to the more fragile and comorbid patients undergoing TEER and potentially to factors not taken into account in the matching process.” However, they note, over time the potential improvement in TEER device implantation and physicians’ expertise may have led to a shift in patient characteristics for eligibility, procedural success and ultimately, clinical outcomes. “Overall, the lower incidence for cardiovascular death following TEER is in favour of the benefit of this treatment in current indications and practices at a nationwide level.” Significant interaction was observed with increased benefit of TEER in patients older than 75 and with a EuroSCORE II score of >4%. Therefore, those patients may particularly benefit from TEER, Deharo and colleagues suggest. The authors acknowledge several limitations to their work, notably the retrospective, observational nature of the study, and its potential residual confounding factors and biases. The findings should be confirmed in ongoing dedicated randomised trials, the authors stress in their concluding remarks.

Issue 72 | February 2024

Structural Heart Interventions 21

BHF PROTECT-TAVI trial poised to answer key questions about use of cerebral embolic protection during TAVI

arguing that this underscores the merit of its use during TAVI. “Whilst PROTECTED TAVR showed a significant reduction in the incidence of disabling stroke, it wasn't powered for this secondary endpoint. In contrast, BHF PROTECT-TAVI will have adequate power to confirm this effect,” said Ali. At the time of the presentation, 32 out of the UK’s 33 TAVI centres have been recruited in the study, with enrolment standing around six months ahead of schedule, making a completion date of early 2025 possible if this is maintained. “The trial is recruiting well,” BHF PROTECT-TAVI lead researcher Rajesh Kharbanda (John Radcliffe Hospital, Oxford, UK) commented following Ali’s presentation. “I get a text every time a patient is recruited, so I know that we are at 5,814 this morning. Investigators behind the largest randomised trial to date to assess the use of cerebral We are 75% through the recruitment.” embolic protection to guard against stroke during transcatheter aortic valve implantation Furthermore, Kharbanda revealed that the (TAVI)—BHF PROTECT-TAVI—have reported that the trial is enrolling ahead of schedule investigators are planning to aggregate the findings and is expected to settle unresolved questions about stroke prevention in TAVI. of both trials in the form of a meta-analysis with the PROTECTED TAVR study team, adding up to a he trial is enrolling 7,730 patients undergoing and left common carotid arteries by filtering debris sample size of more than 10,000 patients. “You need TAVI at centres throughout the UK, randomising embolised during the TAVI procedure. During the those sorts of numbers to show efficacy in these low 1:1 to TAVI with or without the use of the Sentinel SENTINEL investigational device exemption (IDE) frequency but serious events,” Kharbanda said. (Boston Scientific) cerebral embolic protection device. trial, debris was captured in 99% of cases, Ali noted, The Sentinel device is currently the furthest Sentinel is designed to be used during TAVI to reduce but the question remains whether this advanced cerebral embolic protection system the risk of stroke by capturing and removing debris translates into a meaningful reduction in the market, though others are under dislodged during the procedure before it reaches in the incidence of stroke. investigation. In the second half of the brain. In his presentation, Ali 2023, EnCompass Technologies A prior trial, PROTECTED TAVR, which involved addressed whether BHF granted conditional IDE around 3,000 patients from centres in North America, PROTECTapproval by the US Food Europe and Australia, had shown that the use of TAVI and Drug Administration the device did not have a significant effect on the remains (FDA) for its F2 incidence of periprocedural stroke, though a difference relevant cerebral embolic Sentinel in rates of disabling stroke, a secondary endpoint in given the findings protection system, the trial, was believed to confer some benefit to the of PROTECTED whilst the Emboliner use of the technology—at least among advocates of TAVR, noting (Emboline) system the technology. BHF PROTECT-TAVI investigators that there are key is also being hope that their trial—which is taking in solely patients differences between investigated in the treated in the UK—will provide definitive evidence as the two trials that USA in a head-to-head to whether embolic protection should be considered as render this question trial with Sentinel, an important adjunct to TAVI. still an important one enrolling its first patient Speaking at the recent British Cardiovascular to be answered. “Firstly, in May of the same Intervention Society (BCIS) Advanced Cardiovascular BHF PROTECT-TAVI year. Filterlex Medical Intervention meeting (BCIS ACI; 31 January–2 is substantially larger, has also conducted a February, London, UK) Noman Ali (Leeds Teaching aiming to recruit almost 8,000 first-in-human (FIH) study Hospitals NHS Trust, Leeds, UK) offered an update on patients, compared to the 3,000 demonstrating the safety, the status of the trial, as well as setting out the rationale in PROTECTED TAVR,” said Ali. feasibility, and performance of its Captis for another large-scale randomised study to look at “It is also powered to detect a more realistic full-body embolic protection device in TAVI. this issue. treatment effect, aiming for a relative risk reduction in During the BCIS ACI session, Kharbanda was asked “Despite significant advances in TAVI over the the incidence of stroke of 33% compared to the 50% of whether BHF PROTECT-TAVI would reflect cerebral last 15 years or so, periprocedural stroke remains an PROTECTED TAVR.” embolic protection as a strategic approach, or if important issue in contemporary practice, with an Furthermore, unlike the prior study, BHF the results would suggest a device-specific outcome incidence of between 2 and 4% across the spectrum PROTECT-TAVI is “truly an all-comers trial” Ali with Sentinel. patient risk,” Ali explained. noted, enrolling around 40% of all UK TAVI patients, “The trial has been designed as a test of strategy,” The Sentinel device is the most widely used cerebral compared to a figure closer to 10% of eligible he said. “Other devices are making their way through embolic protection device, Ali commented, comprising TAVI patients in PROTECTED TAVR. Another key the regulatory process, but I think given the power two baskets which protect the right brachiocephalic difference is that there will be no routine assessment and magnitude of this trial, this will tell us whether by a stroke physician, meaning that, though some embolic protection has any chance of being successful minor strokes may be missed, the trial will place more or not.” emphasis on clinically relevant strokes, and may “tease out the benefits of cerebral embolic protection devices more effectively”, said Ali. BHF PROTECT-TAVI will also provide more data to shed light on one of the important findings of PROTECTED TAVR—the difference in rates of disabling stroke. In PROTECTED TAVR, the incidence of stroke within 72 hours after TAVI or before discharge—the trial’s primary endpoint—did not differ significantly between the cerebral embolic protection group and the control group (2.3% vs. 2.9%), whereas disabling stroke—a secondary endpoint—occurred in 0.5% of the patients in the cerebral embolic protection group and in 1.3% of those in the control group, a significant difference. This finding has coloured much of the debate over the merits of cerebral embolic protection since the release of the data in 2022, with proponents of the technology Noman Ali at BCIS ACI 2024

Despite significant advances in TAVI over the last 15 years or so, periprocedural stroke remains an important issue in contemporary practice, with an incidence of between 2 and 4% across the spectrum patient risk.”

February 2024 | Issue 72

22 Coronary Interventions

BIOPATTERN trial seeks precision approach to coronary artery disease treatment PlaqueTec has received approval from UK’s Medicines and Healthcare products Regulatory Agency (MHRA) to continue its BIOPATTERN trial following recruitment of the first 10 patients with coronary artery disease.

he trial has been designed to improve understanding of the pathobiology of atherosclerotic cardiovascular diseases (ACVD) and how it varies between individuals, to aid the development of novel treatment approaches. The BIOPATTERN trial will use PlaqueTec’s proprietary blood sampling device, the Liquid Biopsy System (LBS), to collect samples at multiple sites along a patient’s diseased coronary artery. Thousands of proteins and other blood molecules will be measured in each sample, enabling the assessment of transplaque gradients between samples. These data will be analysed and used to generate a more detailed picture of the disease and enhance clinicians’ understanding of which proteins and biomolecules play key roles in coronary artery disease progression towards heart attack.

The trial aims to recruit 300 patients with established coronary artery disease who have been scheduled for a coronary angiogram. Patients will be recruited across eight UK National Health Service (NHS) specialist cardiac centres, with four sites now open, including lead site Royal Papworth Hospital in Cambridge, UK, where chief investigator Stephen Hoole is an interventional cardiologist, and Norfolk and Norwich University Hospital, Royal Bournemouth Hospital, and the Bristol Heart Institute. The trial is managed by Papworth Trials Unit Collaboration in collaboration with PlaqueTec and is overseen by a trial steering committee chaired by Peter Libby (Harvard Medical School, Boston, USA), president of the International Atherosclerosis Society (IAS). Cardiovascular disease is the leading cause of death worldwide, with coronary artery disease being the most common type, accounting for 49% of the 18.6 million cardiovascular disease-related deaths in 2019. The BIOPATTERN trial will establish the safety and functionality of the LBS device and confirm transplaque protein signals seen in earlier pilot studies. PlaqueTec then aims to use the data collected to generate a new data platform based on novel site-ofdisease insights to enable the stratification of patients with distinct disease endotypes and the development of precision medicine approaches to improve treatment outcomes for patients with coronary artery disease. “A population approach to managing cardiovascular risk is generally used at present to treat coronary artery disease patients and prevent progression to heart attack, whereas a more tailored, precision medicine approach that accounts for each patient’s individual disease profile and health needs has exciting potential

Profiling plaque to guide treatment of coronary artery disease

Stephen Hoole Point of View Chief investigator in the BIOPATTERN trial, Stephen Hoole, a consultant cardiologist at Royal Papworth Hospital (Cambridge, UK), offers an insight into the project.

Broadly define the concept of “precision medicine”— how does this differ from current models of care?

Precision medicine targets treatments to specific patients with defined disease traits to improve the therapeutic effect; the better you understand what is driving the disease in an individual, the better you can target current therapy or develop new therapies to improve their health. At present, medication to control cardiovascular disease focuses on targeting standard risk factors prevalent within a population—namely high blood pressure, high cholesterol, diabetes and smoking. Yet the natural history and

presentation of cardiovascular disease can vary greatly, and in many patients it will still progress despite efforts to control these standard risk factors. Given the prevalence of coronary disease, advances in precision medicine could really have an impact. Precision medicine is mainstay in other areas like oncology—just less so in cardiovascular disease and we hope new innovations such as this may close the interdisciplinary knowledge gap.

How does the Liquid Biopsy System (LBS, PlaqueTec) work?

The LBS system is a single use coronary catheter. The catheter is designed

benefits. By better targeting of new therapies to those patients at highest risk and who most need them, we hope to efficiently stabilise their disease and improve outcomes,” said Hoole. “The BIOPATTERN trial provides a novel opportunity to use the LBS device to help us better understand and characterise coronary artery disease on an individual patient level and potentially enable better patient care by identifying novel precision medicine targeted treatments to improve the outcome of patients with coronary artery disease in the future.” Simon Williams, general manager, PlaqueTec, said: “Reaching the 10-patient landmark and securing MHRA approval to continue to recruit to the BIOPATTERN trial is a huge success and enables us to pursue our ambition of opening a new frontier of precision medicine for patients with coronary artery disease. We are very grateful to all the patients and NHS site staff who have made this landmark possible and now look forward to progressing towards the 300-patient target.”

The BIOPATTERN team at Royal Papworth Hospital

to be positioned under fluoroscopy across an identified coronary lesion, then once in place the sampling ports and baffle clusters can be unsheathed to create local mixing to gather biomolecules in the outer edges of flow or on the endothelial wall, in the so-called boundary layer. Vacuum pressure is then applied at the handle which simultaneously draws four blood samples from the sampling ports at different points in the coronary artery—upstream and downstream of the stenosis. The samples are collected and sent for analysis. By comparing the concentration of numerous biomolecules in downstream versus upstream samples we can build a plaque-specific biochemical profile for that patient’s disease. We can enrich the profile with optical coherence tomography (OCT) imaging, genetic and clinical data to build up a detailed understanding to help stratify patients into sub-groups with certain disease profiles. We hope these site-of-disease insights will help inform and/or justify particular therapy for certain patients and identify new targets for novel or re-purposed medicine for some patients. In terms of intervention, in time there is potential to develop an on-table point-of-care test for samples obtained using the LBS that may guide decisions such as whether to stent or even which type of stent to use.

How straightforward is the sample collection process?

If you select the right vessel of the right size and anatomy, avoiding tortuosity, it is pretty straightforward to position the device and collect the samples. The device is delivered over a standard

0.014” guide wire and is 6Fr guide catheter compatible, so there is certainly potential for wider use once the clinical utility is established. The sample collection takes about five minutes, then the analysis depends on what you are analysing. As mentioned, a fast point-of-care test could be really useful in future, but in the BIOPATTERN trial the samples are undergoing an extensive battery of tests including high-throughput proteomics which will measure thousands of proteins in each sample and this takes a couple of weeks to process.

What are the aims of the BIOPATTERN trial?

The core aims of the trial are to confirm the device is safe and works as intended and also to confirm some of the transplaque gradients of certain proteins that were seen in an earlier pilot study. In addition, as discussed above, a big aspect of the trial is exploratory, looking at thousands of different proteins in each sample to better understand the local plaque expression of biomarkers that we hope will better inform us about the biological nature of plaques, what governs their progression towards rupture, how these aspects vary between patients and to identify new candidate treatment targets. There are also specific sub-studies, including pressure-wire derived coronary physiology data, to also understand how plaque biomarkers might influence microvascular dysfunction in trial participants. We have four sites open and recruiting and will open more sites next year with a view to completing recruitment of the full 300-participant cohort in early 2025.

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February 2024 | Issue 72

Analyses provide “hard evidence” of benefit of intravascular imaging-guided PCI

Two meta-analyses comparing the use of intravascular imaging to angiography for the guidance of percutaneous coronary intervention (PCI) provide “hard evidence” that the use of the imaging technology has an impact on patient survival and outcomes, researchers have claimed. BOTH ANALYSES, ONE FROM RESEARCHERS in Europe and another from a team in the USA, include data from more than 20 randomised trials comparing the outcomes of PCI guided by coronary angiography or intravascular imaging in the form of intravascular ultrasound (IVUS) or optical coherence tomography (OCT). The first, published online ahead of print in Circulation and authored by Daniele Giacoppo and Claudio Laudani (both University of Catania, Catania, Italy) and colleagues, includes data from more than 15,000 patients, using studies to have compared at least two PCI guidance strategies. “The analysis of available evidence from randomised trials indicates that IVUS-guided PCI was associated with reduced any-type and ischaemia-driven target lesion revascularisation compared with invasive coronary angiography-guided PCI, whereas no significant differences were observed between OCTguided and invasive coronary angiography-guided PCIs for the same outcomes,” the study’s authors observe. However, they add, “neither IVUS- nor OCTguided PCI was associated with reduced myocardial infarction (MI) and target vessel myocardial infarction compared with invasive coronary angiographyguided PCI”. Previous meta-analyses predating numerous largescale trials, have focused upon a single intravascular imaging modality, have pooled observational studies and trials using outdated devices, and used simpler meta-analytic methodology, relying generally on frequentist statistics, pairwise comparisons, and a very limited number of sensitivity analyses, Giacoppo and Laudani write. Their analysis incorporates some of the latest randomised trial data to have emerged, as well as employing frequentist random-effects network meta-analyses and Bayesian random-effects models to compare the imaging modalities. Among the recent trials to have been included in the analysis are the RENOVATE-COMPLEX-PCI trial, a 1,639-patient randomised trial in which it was shown that the use of intravascular imaging guidance for PCI in patients with complex coronary artery lesions led to a lower risk of a composite of death from cardiac causes, target vessel-related MI or clinically driven target revascularisation than procedures using only angiography. Giacoppo and Laudani describe this as a “prelude” to the results of both the ILUMIEN IV trial, looking

at OCT-guided PCI in high-risk patients, and the OCTOBER trial, which assessed OCT-guidance in bifurcation lesions; both of which were presented at the European Society of Cardiology (ESC) 2023 congress (25–28 August, Amsterdam, The Netherlands). “The ILUMIEN IV trial, including a total of 2,487 patients with clinical and angiographic high risk criteria randomly assigned to OCT- or invasive coronary angiography-guided PCI, showed no significant difference in two-year target lesion failure between guidance strategies. In contrast, the OCTOBER trial including 1,201 patients with bifurcation disease randomly assigned to OCT- versus invasive coronary angiography-guided PCI showed a significant reduction in major adverse cardiac events at two years associated with OCT guidance,” the researchers write.

With these results, we now need to shift from performing more studies to determine whether intravascular imaging is beneficial, to increasing efforts to overcome the remaining impediments to the routine use of OCT and IVUS, including better training of physicians and staff and increasing reimbursement.” These recent data have added growing weight to the calls from proponents of intravascular imaging technology who say that its use optimises outcomes for PCI. A state-of-theart review paper published in

the Journal of the American College of Cardiology (JACC) in April last year recommended that all cardiac cath labs should have the capability for intravascular imaging to augment conventional angiography. Research presented at the American College of Cardiology (ACC) 2023 Scientific Sessions (4–6 March, New Orleans, USA) has pointed to a growing use of intravascular imaging in the USA, albeit only rising to as many as 15.4% of cases by 2019, and some commentators have described uptake of the technology as having been slow. These latest trials are included in the second of the two new analyses, authored by Gregg Stone (Icahn School of Medicine at Mount Sinai, New York, USA) and colleagues, published in The Lancet. Stone et al’s study examined 22 trials in total, including data from close to 16,000 patients, dating up to September 2023. The primary endpoint of the analysis was target lesion failure, defined as the composite of cardiac death, target vessel-MI, or target lesion revascularisation, assessed in patients randomly assigned to intravascular imaging guidance versus angiography guidance. “Our study, representing a synthesis of all early and recent clinical studies, has shown for the first time that the routine use of intravascular imaging guidance improves survival and enhances all aspects of the safety and effectiveness of coronary stenting, even with excellent contemporary drug-eluting stents,” said Stone. “Prior studies had shown benefits of intravascular imaging, but never to this extent. The addition of four recent trials in which 7,224 patients were enrolled now shows that intravascular imaging reduces all-cause death and all heart attacks across the wide range of patients who undergo stent treatment. As such, the routine use of intravascular imaging to guide stent implantation is one of the most effective therapies we have to improve the prognosis of patients with coronary artery disease.” During follow-up ranging from six to 60 months with a mean of two years, patients who received intravascular imaging guidance experienced a 25% reduction in all-cause death, 45% reduction in cardiac death, 17% in all MIs, and 48% reduction in stent thrombosis compared with angiography guidance, Stone et al report. The study also found that intravascular imaging reduced target vessel-MI by 18% and target lesion revascularisation by 28%. The outcomes were similar for OCT-guided and IVUSguided PCI, the researchers report. “With these results, we now need to shift from performing more studies to determine whether intravascular imaging is beneficial, to increasing efforts to overcome the remaining impediments to the routine use of OCT and IVUS, including better training of physicians and staff and increasing reimbursement,” Stone said. “In this regard, we now have better “hard evidence” that intravascular imaging guidance of PCI procedures makes a greater impact to improving our patients’ lives than other routine therapies which are more widely used and reimbursed.”

Gregg Stone

Pitchy/stock.adobe.com

24 Intravascular Imaging

February 2024 | Issue 72

26 CX 2024 Preview

The BASIL-2 trial was a highlight at CX 2023 C

First-to-podium presentations spotlight aortic and peripheral controversies at CX 2024 The full line-up of Podium First and late-breaking trials to be presented at the 2024 Charing Cross (CX) International Symposium (23–25 April, London, UK) has been released, with highlights including first-in-the-world insights on lower limb revascularisation and acute aortic dissection.

he three-day CX Symposium comes from a new location, the ExCeL convention and exhibition centre in London’s Docklands, with attendees also tuning in virtually from across the globe. It is anticipated that the event will welcome more than 3,000 in-person attendees, with over 1,000 remote participants. CX continues its three-year cycle of raising vascular and endovascular controversies to challenge the available evidence to be able to reach a consensus after discussion with an expert audience. Sessions across the three days will explore controversies in all vascular domains, spanning aortic, peripheral, venous, acute stroke and vascular access, punctuated by CX debates, live and edited cases and workshop demonstrations. The presentation of the long-awaited BASIL-2 (Bypass versus angioplasty for severe ischaemia of the leg) trial results was the undoubted talking point at CX 2023. The trial found that 63% of patients randomised to a vein bypass-first strategy of treatment underwent a major amputation or died during follow-up, compared to just 53% of those allotted to a best endovascularfirst approach. BASIL-2 chief investigator Andrew Bradbury (University of Birmingham, Birmingham, UK) returns to the CX podium in 2024 to outline the next phase of the programme—BASIL-3—a multicentre randomised controlled trial of the clinical- and cost-effectiveness

of drug-coated balloons (DCBs), drug-eluting stents, and plain balloon angioplasty with bail-out bare metal stent revascularisation strategies for severe limb ischaemia secondary to femoropopliteal disease. Bradbury will also feature alongside Matthew Menard (Brigham and Women’s Hospital, Boston, USA), an investigator in the BEST-CLI randomised controlled trial, as part of a late-breaking comparison of the two trials, subtitled “outcomes when comparing apples with apples”. In BEST-CLI it was shown that surgical bypass with adequate single-segment great saphenous vein (GSV) was a more effective revascularisation strategy for patients with chronic limb-threatening ischaemia (CLTI) who are deemed to be suitable for either an open or endovascular approach. The session will seek to reconcile important differences between the BASIL-2 and BEST-CLI trials and put the results into context. Elsewhere, the CX 2024 peripheral programme features Podium First presentations from CX cochair and executive board member Andrew Holden (Auckland University School of Medicine, Auckland, New Zealand), offering a first look at the PREVISION first-in-human trial evaluating a novel sirolimus DCB, the first results of the SAMBA trial comparing a paclitaxel DCB to plain balloon angioplasty in the below-the-knee arteries, presented by CX executive board member Gunnar Tepe (Klinikum Rosenheim, Rosenheim, Germany), and final results of the

DEEPER LIMUS trial, presented by Leyla Schweiger (Medical University Graz, Graz, Austria). The aortic programme at CX 2024 will bring forward new data to fuel the debate over controversies in the aortic space. Highlights from this section of the programme include a Podium First presentation from Arun Pherwani (University Hospitals of North Midlands, Stoke-on-Trent, UK), in which he will detail outcomes of aortic dissection in the UK. Other Podium First highlights include real-world registry findings of low-profile thoracic endovascular aortic repair (TEVAR), delivered by Vincent Riambau (Hospital Clínic de Barcelona, Barcelona, Spain), and details of a phantom study examining whether operator position influences radiation dose from Fiona Rohlffs (University of Hamburg, Hamburg, Germany).

CMY

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Peripheral Podium First Presentations: ● Podium First: BASIL-3 podium first presentation Andrew Bradbury (Birmingham, United Kingdom), Tuesday, 23 April ● Late Breaker: BEST-CLI vs BASIL-2 - outcomes when comparing apples with apples - Matthew Menard (Boston, United States) & Andrew Bradbury (Birmingham, United Kingdom), Thursday, 25 April ● Podium First: First look at the PREVISION FIH trial evaluating the novel sirolimus DCB catheter - Andrew Holden (Auckland, New Zealand) Wednesday, 24 April ● Podium First: First results of the SAMBA trial: A randomised trial comparing a paclitaxel DCB to POBA in BTK arteries - Gunnar Tepe (Rosenheim, Germany), Wednesday, 24 April ● Podium First: Final results of the DEEPER LIMUS trial Leyla Schweiger (Graz, Austria), Wednesday, 24 April

Aortic Podium First Presentations: ● Podium First: Outcomes of acute aortic dissection in the UK - Arun Pherwani (Stoke-on-Trent, United Kingdom), Wednesday, 24 April ● Podium First: Low profile TEVAR durability in a realworld registry - Vincent Riambau (Barcelona, Spain), Wednesday, 24 April ● Podium First: Operator position influences radiation dose: A phantom study - Fiona Rohlffs (Hamburg, Germany), Thursday, 25 April

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CX2024 Inhouse Programme Highlights - CVN - Vascular and Endovascular Highlights - Feb 2024-v3.pdf

CONTROVERSIES

15/02/2024

09:49

CHALLENGES

CONSENSUS

Vascular & Endovascular

Controversies Update Aortic Controversies

Peripheral Arterial Controversies

Venous & Lymphatic Controversies

Carotid & Acute Stroke Controversies

Vascular Access Controversies

The Hurting Leg Controversies

Vascular Trauma Controversies

23–25 APRIL 2024 TUESDAY-THURSDAY NEW VENUE, ExCeL LONDON, UNITED KINGDOM

CMY

Programme Highlights

Vascular and Endovascular CONTROVERSIES

CX CO-CHAIRS:

• BASIL-3 Podium First Presentation: Including clinical and health economic results Tuesday, 23 April • Late Breaker: BEST-CLI vs BASIL 2 - outcomes when comparing apples with apples Thursday, 25 April

• Great Debate: Best medical treatment remains the standard for uncomplicated type B aortic dissection Wednesday, 24 April

ANDREW HOLDEN

DITTMAR BÖCKLER

ERIN MURPHY

45 YEAR LEGACY OF VASCULAR EDUCATION CONTINUES EDUCATION

INNOVATION

EVIDENCE

February 2024 | Issue 72

28 Market Watch

Product News

Evoque

Evoque becomes first transcatheter tricuspid system to gain US FDA approval

Edwards Lifesciences has announced that its Evoque tricuspid valve replacement system is the first transcatheter therapy to receive US Food and Drug Administration (FDA) approval for the treatment of tricuspid regurgitation (TR). The Evoque system is indicated for the improvement of health status in patients with symptomatic severe TR despite optimal medical therapy, for whom tricuspid valve replacement is deemed appropriate by a heart team. The Evoque system is comprised of a nitinol self-expanding frame, intraannular sealing skirt and tissue leaflets made from bovine pericardial tissue. The Evoque valve will be available in three sizes, delivered through the same low-profile transfemoral 28Fr system. “Patients suffering with tricuspid regurgitation endure life-impairing symptoms and, until today, had no approved transcatheter treatment options,” said Susheel Kodali (Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, USA). “The Evoque system is able to replace the native tricuspid valve, virtually eliminating TR in a wide range of patients. We see significant improvements in patients’ symptoms and quality of life, including not feeling short of breath and being able to care for themselves, which ranked highest on a patient preference survey conducted at baseline with TRISCEND II pivotal trial patients.” The Evoque system received CE mark approval in October 2023, making it the world’s first transcatheter valve replacement therapy to receive regulatory approval to treat TR.

TriClip gets positive vote from US FDA advisory panel

The Circulatory System Devices Panel of the Medical Devices Advisory Committee for the US Food and Drug Administration (FDA) confirmed 13 to 1, with 0 abstentions, that the benefits of Abbott’s TriClip transcatheter edge-to-edge repair (TEER) system outweighed the risks for the treatment of people with tricuspid regurgitation (TR). The panel’s decision was based on clinical data from the TRILUMINATE pivotal trial, as well as expert testimony. The panel’s vote will be considered by the FDA when making a decision regarding the approval of TriClip, a transcatheter device

specifically designed to treat the tricuspid valve. “Tricuspid regurgitation can put added strain on the heart and lead to other cardiovascular issues, which can significantly worsen a person’s quality of life, but historically there have been few treatment options,” said Lars Søndergaard, chief medical officer and divisional vice president of medical affairs of Abbott’s structural heart business. “Abbott recognised the unmet need for people with this condition and explored the use of our proven clipbased technology to find a truly lifechanging intervention. TriClip offers an urgently needed alternative that is safe and effective for people who require tricuspid valve repair but are not able to withstand surgery.” Delivered through a vein in the leg, TriClip’s TEER technology works by clipping together a portion of the leaflets to repair the tricuspid valve and help blood flow in the right direction without the need for open surgery. TriClip is approved for use in more than 50 countries, including in Europe and Canada, and has been used to treat more than 10,000 people with TR. It is an investigational device in the USA.

navigate tortuous coronary anatomy while maintaining sustained mechanical aspiration with the Penumbra Engine. As shown in the CHEETAH study, CAT RX demonstrated high rates of blood clot removal, blood flow restoration and myocardial perfusion in conjunction with percutaneous coronary intervention (PCI) in patients with high thrombus burden.

Flower embolic protection device gains CE mark

AorticLab has announced CE mark certification for the Flower transcatether embolic protection device (EPD) indicated for the cerebral and systemic protection of patients undergoing transcatheter aortic valve implantation (TAVI) procedures. The CE certification of Flower, a class III medical device obtained in full compliance with the Medical Device Regulation (MDR), will allow for the production and commercialisation of the device throughout Europe, the company said in a press release. Flower is equipped with Catch&Flow technology and captures emboli up to 60μm in size, protecting the brain and peripheral organs from ischaemic events during TAVI. Filippo Scalise (Policlinico di Monza, Monza, Italy), principal

Biotronik’s Freesolve resorbable magnesium scaffold gains CE mark

Biotronik has announced the CE approval and launch of the Freesolve resorbable magnesium scaffold (RMS). This third generation RMS has been engineered to provide optimised vessel support, yet achieves magnesium resorption within 12 months, the company says in a press release. “Having closely observed the evolution of resorbable magnesium scaffolds, the Freesolve RMS achieves a 99.3% resorption rate at 12 months and provides better scaffolding than its predecessors,” said Michael Haude (Rheinland Klinikum, Neuss, Germany). “The enhanced properties of the Freesolve RMS can establish a true alternative to DES, benefitting from the advantages of a resorbable device while maintaining a reliable and predictable outcome with the longterm safety profile that has already been shown in many RMS trials with previous versions.”

Penumbra launches Indigo system CAT RX catheter in Europe to treat acute coronary syndrome Penumbra has secured CE mark for its Indigo system CAT RX designed to address the limitations of traditional management strategies in acute coronary syndrome (ACS), the company has announced. Traditional modalities utilising syringe aspiration suffer from diminished vacuum once fluid enters the system, the company says in a press release. Now commercially available in Europe, CAT RX is designed to

management of aortic stenosis calls for leaflet modification solutions like ShortCut to ensure that we are carefully addressing the risk of coronary obstruction before implanting a valve. From what we have seen regarding the ability to easily teach and perform the procedure, ShortCut could be easily adopted by every TAVI centre as a critical step pre-implantation, so that patients at risk of coronary obstruction will be safely treated, without disruption of TAVI workflow.”

Endotronix submits premarket approval application to US FDA for Cordella pulmonary artery sensor

Endotronix has submitted a premarket approval (PMA) application for its Cordella pulmonary artery (PA) sensor system to the US Food and Drug Administration (FDA). Cordella is a heart failure patient management platform that delivers proactive PA pressure data and non-invasive vital health data for comprehensive heart failure management at home. Its devices securely transmit daily health information to the managing clinician, supporting optimal dosing of guidelinedirected medical therapy to reduce congestion and engaging patients with trended health data to enable healthy lifestyle choices.

Medtronic launches Penditure LAA exclusion system in the USA

Flower

investigator of the Nautilus clinical study, comments: “Flower will be part of the new frontier of cardiovascular medical devices; EPDs can make a difference for our patients, providing a higher and more comprehensive level of protection against embolic events during TAVI procedures. The Flower medical device offers an intuitive user interface that allows for rapid device positioning and stable anchoring in the aortic arch during the procedure.”

US FDA grants breakthrough designation for Pi-Cardia’s ShortCut leaflet splitting device

Pi-Cardia has received breakthrough device designation from the US Food and Drug Administration (FDA) for the ShortCut leaflet modification device facilitating valve-in-valve transcatheter aortic valve implantation (TAVI) procedures in patients at risk of coronary obstruction. The announcement comes after completion of enrolment in the ShortCut Pivotal study in the USA and Europe in September 2023. “Having been part of Pi-Cardia’s rigorous clinical programme, I am thrilled to see the recognition in the importance of ShortCut,” said Philippe Genereux (Morristown Medical Center, Morristown, USA). “Lifetime

Medtronic has announced the launch of its Penditure left atrial appendage (LAA) exclusion system in the USA. The Penditure LAA exclusion system is an implantable clip that comes pre-loaded on a single-use delivery system for use in left atrial appendage management during concomitant cardiac surgery procedures. Medtronic completed the acquisition of the Penditure device technology from Syntheon in August 2023. The acquisition expands the company’s cardiac surgery product portfolio to include left atrial appendage management. The first cases using the device were performed by Gorav Ailawadi and Basel Ramlawi at the University of Michigan Frankel Cardiovascular Center (Ann Arbor, USA) and Lankenau Heart Institute (Wynnewood, USA), part of Main Line Health, respectively. Medtronic will begin enrolment in the exClusion of the left atrial appendage with PendITure (CLIP-IT) post-market study, early this year. The study will aim to further evaluate the performance and clinical outcomes of the Penditure LAA exclusion system in subjects undergoing concomitant cardiac surgery. CLIP-IT will be a multicentre, single-arm, nonrandomised, interventional, post-market study enrolling approximately 150 patients at 25 US sites. The Penditure LAA Exclusion System received a 510k clearance in August 2023 and is commercially available in the USA on a limited basis.

Issue 72 | February 2024

Market Watch 29

Clinical News Three valve-in-valve procedures completed using DurAVR transcatheter valve Anteris Technologies has announced the successful completion of three new valve-in-valve (ViV) cases using DurAVR, a biomimetic transcatheter heart valve. These are the fourth, fifth and sixth patients treated with DurAVR under Health Canada’s special access programme (SAP), which allows healthcare professionals to access unlicensed medical devices for emergency use when conventional therapies have failed, are unavailable, or are unsuitable to treat a patient. The approval is based on past patient outcomes, safety data and physician support. Transcatheter ViV replacement is performed by implanting a transcatheter heart valve within a

Institut de Cardiologie de Montreal cardiologists mark the ViV cases

failing bioprosthetic aortic valve. The transcatheter ViV operation is a less invasive procedure compared with reoperative surgical aortic valve replacement (SAVR). Anita Asgar (Institut de Cardiologie de Montreal, Montreal, Canada) commented: ‘‘The challenge we face as clinicians is the need to preserve coronary access, but these are patients who are also reasonably active, and we need to give them a good haemodynamic result, we need to really improve their symptoms so they can have a good quality of life.” Asgar stated: “As a clinician, it’s a great opportunity to have access to a technology that may help us with what is probably going to be a tsunami of valve-in-valve procedures that we are going to have to do.”

Early feasibility study of TAVI platform for treatment of aortic regurgitation completes enrolment

Genesis MedTech has announced the completion of enrolment in its US early feasibility study (EFS) using its dedicated transcatheter aortic valve implantation (TAVI) platform, the J-Valve transfemoral system. The US Food and Drug Administration (FDA)-approved EFS trial involved patient enrolment at five centres across the USA. The trial focused on evaluating symptomatic individuals with severe aortic regurgitation (AR). The last patient was successfully

enrolled by Ron Waksman and Lowell Satler (MedStar Washington Hospital Center, Washington, DC, USA). The EFS co-principal investigators were Dean Kereiakes (Christ Hospital Heart and Vascular Institute, Cincinnati, USA) and Michael Reardon (Houston Methodist Hospital, Houston, USA). Patients meeting the inclusion criteria received treatment using the J-Valve transfemoral system. The outcomes of this clinical experience will be presented later this year. “TAVI has proven results for patients with aortic stenosis. An unmet need remains for patients with AR,” Reardon said. “The J-Valve being a dedicated TAVI design has shown promise in treating patients with AR. We are pleased with our findings to date and look forward to the successful initiation of the pivotal trial.” Developed by JC Medical, the J-Valve TF system has been granted breakthrough designation for the indication of treating severe native AR and AR-dominant mixed aortic valve disease. Patients are assessed by a heart team to be eligible for the device and at high risk for surgical aortic valve replacement. The J-Valve transfemoral system is an investigational device in the USA and Canada.

ANGIODAPT trial launches with first patient enrolment

iVascular has announced the initiation of its first randomised trial of an abbreviated dual antiplatelet therapy (DAPT) regimen after implantation of the angiolite drug-eluting stent (DES). The first patient was enrolled by the team of the principal investigator of the trial, Manel Sabaté (Hospital Clinic Barcelona, Barcelona, Spain), launching the ANGIODAPT global investigation. The trial is iVascular’s 2×2 factorial, all-comer, multicentre, randomised controlled trial set up to evaluate the ischaemic and bleeding outcomes after iVascular Angiolite stent implantation and an abbreviated DAPT regimen of one month. A total of 2,312 patients with coronary artery disease, who require percutaneous coronary intervention (PCI) and DAPT, will be included across 40 sites located in Spain, Belgium and France. Patients will be randomised firstly to one two stents types (Angiolite versus Xience [Abbott]) and secondly assigned to one of the treatment options (abbreviated DAPT vs. standard-of-care DAPT) and will be followed up one, six and 12 months after the intervention and annually for five years. The trial’s two co-primary endpoints are to determine the rate of target lesion failure (TLF) at one year between the angiolite and Xience stent family (tested for non-inferiority) in both the ‘abbreviated DAPT’ and the ‘standardof-care DAPT’ regimen groups. The co-primary endpoint is to determine

the rate of clinically relevant bleeding events at one year between ‘abbreviated DAPT’ and the ‘standard-of-care DAPT’ (tested for superiority of the ‘abbreviated-DAPT arm’). The main secondary endpoint is to determine the rate of ischaemic events between both therapies (tested for non-inferiority). Moreover, other exploratory outcomes such as the rate of patient-oriented composite endpoint, myocardial infarction (MI), target lesion and vessel revascularisation, stent thrombosis, clinical device and procedural success, bleeding events, net adverse clinical endpoints, the major adverse cardiac and cerebral events and transfusion rates will be assessed. Sabaté stated: “The enrolment of the first patient in the ANGIODAPT trial is an important milestone to get robust evidence on DAPT regimen in coronary artery disease patients who have receivedan Angiolite stent. I am sure that the 2,300 patients will be enrolled on time thanks to the cooperation of the participant sites and their teams.”

First patient randomised in BACKBEAT study of AVIM therapy for uncontrolled hypertension Orchestra BioMed has announced the first patient was randomised in the BACKBEAT pivotal study in late December 2023. The BACKBEAT pivotal study will evaluate the efficacy and safety of atrioventricular interval modulation (AVIM) therapy (also known as BackBeat CNT), for the treatment of pacemaker-indicated patients with uncontrolled hypertension despite the use of antihypertensive medications. AVIM therapy is an investigational patented therapy, administered using a standard dual-chamber pacemaker, designed to immediately, substantially

J-Valve

and persistently reduce blood pressure. Orchestra BioMed and Medtronic formed a strategic collaboration for the development and commercialisation of AVIM therapy for hypertensive pacemaker patients in July 2022. If approved, Medtronic will have exclusive rights to commercialise AVIM-enabled pacing systems for this target population, and Orchestra BioMed will share in the revenues generated from Medtronic sales of the AVIM-enabled pacing systems.

US FDA approves ENGULF US pivotal trial of Hēlo thrombectomy system

Endovascular Engineering (E2) has announced US Food and Drug Administration (FDA) investigational

device exemption (IDE) approval for its ENGULF US pivotal trial. The study will evaluate the safety and effectiveness of the Hēlo thrombectomy system in treating pulmonary embolism (PE). The approval of the IDE follows the successful completion of the company’s 25-patient feasibility study. “We are excited to be at the forefront of this innovative procedure with the completion of the ENGULF feasibility study. This significant achievement sets the stage for definitive results in the ENGULF pivotal trial. The Hēlo thrombectomy system represents a significant leap forward in pulmonary embolism treatment, and I am enthusiastic about investigating its full potential in the upcoming phase of the study,” said Jay Giri (University of Pennsylvania, Philadelphia, USA) the national principal investigator (PI) for the ENGULF feasibility study.

Topaz tricuspid valve replacement system used for the first time in a patient with a pacemaker TRiCares SAS has announced the successful implantation of its Topaz transfemoral tricuspid heart valve replacement system in a patient with a pacemaker at the University Medical Center of Mainz (Mainz, Germany). Topaz is a minimally invasive device designed specifically to help patients suffering from severe tricuspid regurgitation (TR), without the need for open heart surgery. The Topaz device was implanted in a 74-year-old female patient with a pacemaker lead passing through the tricuspid annulus, classed as having New York Heart Association (NYHA) class III heart failure and presenting with torrential TR. The procedure took less than 30 minutes, and the valve was implanted at the precise location required, with regurgitation reduced to trace with no transvalvular leakage, the company reports in a press release. Importantly, it says, the performance of the pacemaker was not affected by the valve. Two months later the patient came back for a follow-up visit which confirmed the excellent results of the Topaz implantation. This took place at the University Medical Center of Mainz in Germany, led by Ralph Stephan von Bardeleben and Hendrik Treede. Tobias Ruf was responsible for echo guidance, supported by Pascal Lim. The procedure was recorded as a live case for European Association for CardioThoracic Surgery (EACTS) and presented at the organisation’s 2023 congress (4–7 October, Vienna, Austria). Von Bardeleben commented: “I am proud to have been involved in another successful patient implant of the Topaz tricuspid valve replacement system, particularly given the severity of the patient’s disease and presence of a pacemaker. This innovative solution has the potential to provide a muchneeded solution to this patient group which lacks effective long-term treatment options.”

February 2024 | Issue 72

30 Market Watch

Industry News Investors offer backing for developer of transcatheter mitral chord repair technology

CardioMech AS, a medical device company developing a transfemoral, transseptally delivered mitral valve chordal repair technology in Fridley, USA, has announced that it has closed on US$13 million in fresh capital. CardioMech received financial support from existing and new investors, including a non-disclosed strategic investor. The oversubscribed round further demonstrates investors’ expectations that chordal repair may be a firstline therapy for degenerative mitral regurgitation patients, the company said in a press release. The CardioMech device is an artificial chord that is designed to reduce or eliminate regurgitation and to restore the native anatomy. The catheter-based therapy is intended to be a simple and straightforward procedure and an alternative therapy option for both patients eligible for open-heart surgery and those considered surgically ineligible.

Haemonetics completes acquisition of OpSens

Haemonetics Corporation has completed its acquisition of OpSens, the company announced in a press release in December 2023. Haemonetics acquired all outstanding shares of OpSens for CAD$2.90 per share in the all-cash transaction, representing a fully diluted equity value of approximately US$255 million at the current exchange rate. “Expanding our hospital portfolio with OpSens’ products creates exciting growth and diversification opportunities, while providing immediately accretive financial benefits,” said Chris Simon, Haemonetics’ president and chief executive officer. “We are pleased to officially welcome OpSens to Haemonetics and look forward to driving greater access to OpSens’ essential solutions and benefits for

physicians and patients throughout the world.” OpSens offers commercially and clinically validated optical technology for use primarily in interventional cardiology. Core products include SavvyWire, a sensor-guided threein-one guidewire for transcatheter aortic valve implantation (TAVI) procedures, that acts as a pacing and pressure monitoring wire, as well as OptoWire, a pressure guidewire that aims to improve clinical outcomes by measuring fractional flow reserve (FFR) and diastolic pressure ratio (dPR) to aid clinicians in the diagnosis and treatment of patients with coronary artery disease.

“Structural heart leader” joins Cardiac Dimensions as chief medical officer

Cardiac Dimensions, a developer of invasive treatment modalities to address patients suffering from heart failure with functional mitral regurgitation (FMR), has announced that interventional cardiologist Satya Shreenivas has joined the company as chief medical officer. Shreenivas has led the structural heart programme and cardiac cath lab at the University of Cincinnati and spent several years with The Christ Hospital in Ohio. There, he served as an investigator in many high-profile clinical trials, including several significant structural heart studies. His industry roles have included serving as chief medical officer for HLT Medical, a transcatheter heart

Satya Shreenivas

valve company, as chief of cardiology with Optum/United Health subsidiary SCA Health, and as medical director for clinical research organisation Medpace. Shreenivas has been instrumental in advising Cardiac Dimensions on its EMPOWER trial of the Carillon mitral contour system. “I’ve seen the compelling clinical evidence on Carillon therapy from Europe and look forward to helping the team expand the supportive body of evidence for this intriguing technology with the US pivotal EMPOWER Trial,” said Shreenivas. “I have always been energised by my work with emerging technologies that fill an unmet clinical need and am excited by the opportunity this therapy presents to enhance the lives of heart failure patients in a way that isn’t possible today.”

facilitate AI-based segmentation and contouring as well as dosimetry analysis for patients across their treatment journeys and in the growing fields of radiology, molecular imaging, and radiation oncology.

Simona Zannetti returns to Medtronic to lead aortic business

Medtronic recently announced that Simona Zannetti has been appointed as the general manager of its aortic business. Zannetti previously spent 21 years at Medtronic. She returns after serving as senior vice president of clinical research at Penumbra, where she helped drive the strategic and commercial business goals of the company as a member of the senior leadership team. During Zannetti’s time at GE HealthCare to acquire Medtronic, she played a AI-imaging specialist pivotal role in establishing GE HealthCare has endovascular treatment entered into an options as a standard of agreement to acquire care for abdominal and MIM Software, a thoracic disease. She provider of artificial most recently served as intelligence (AI)-enabled vice president of clinical image analysis and research and medical science workflow tools across multiple for the Peripheral Vascular Simona Health Operating Unit. care areas, including oncology, Zannetti urology, neurology, According to Medtronic, and cardiology Zannetti earned her Doctor of GE HealthCare expects to leverage Medicine, residency in general surgery, MIM Software’s imaging analytics and fellowship in vascular surgery and digital workflow capabilities at the University of Perugia Medical across various care areas to accelerate School in Perugia, Italy. She completed innovation and differentiate its a two-year research fellowship in solutions for the benefit of patients and vascular surgery at the Massachusetts healthcare systems around the world, General Hospital, Harvard Medical the company says in a press release. School in Boston, USA. The company MIM Software’s portfolio of imaging notes that Zannetti’s extensive clinical solutions provides a variety of features, experience will contribute significantly including: the integration of diagnostic to Medtronic and Medtronic Aortic’s images from multiple modalities into work to drive commercial excellence treatment plans; automation to help and develop life-saving treatments. reduce repetitive tasks and manual “After a great sixteen months at interventions; quantitation and Penumbra where I worked alongside advanced processing in diagnostic a fantastic team, I am excited to share imaging and nuclear medicine to help that I am returning to Medtronic determine therapy response; and a as general manager for the aortic platform to assist with theranostics business,” Zannetti shared on LinkedIn. imaging and dosimetry. “I look forward to going back to my GE HealthCare expects to integrate roots where my career began 23 years MIM Software solutions into its ago and to work with my friends advanced visualisation offerings to at Medtronic.”

Conference calendar 9–12 March Cardiovascular Research Technologies (CRT) 2024 Washington, DC, USA crtmeeting.org

14 March Global Cardiovascular Awards London, UK globalcardiovascularawards.com

21–23 March JIM GISE Congress Rome, Italy jimgise2024.it

21–23 March The Houston Aortic Symposium Houston, USA

houstonaorticsymposium.com

6–8 April American College of Cardiology (ACC) scientific session Atlanta, USA expo.acc.org

23–25 April Charing Cross (CX) Symposium London, UK cxsymposium.com

2–4 May Society for Cardiovascular Angiography & Interventions (SCAI) scientific session Long Beach, USA scai.org/scai-2024-scientificsessions

14–17 May EuroPCR 2024 Paris, France

pcronline.com/Courses/EuroPCR

5–7 June New York Valves: The Structural Heart Summit New York, USA

nyvalves2024.crfconferences.com

30 August–2 September European Society of Cardiology (ESC) Congress London, UK

escardio.org/Congresses-Events/ ESC-Congress

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