Cardiovascular News - Issue 71 - November 2023 (OUS)

November 2023 | Issue 71

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November 2023 | Issue 71

9 Statins after SAVR Emily Pan

14 Profile

Jolanda Kluin

19 TRISCEND II

Tricuspid replacement data

25 Renal denervation: First device approved in USA

AGENT IDE trial brings hope of first US coronary DCB approval

&E T RO CON ACTS CT UN FE 2 D-U RE 02 P E NCE 3 DIT ION

Featured in this issue:

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The first US randomised trial investigating the safety and efficacy on the use of a drugcoated balloon (DCB) for the treatment of coronary instent restenosis has shown the superiority of the Agent (Boston Scientific) DCB compared to conventional balloon angioplasty for a primary endpoint of target lesion failure at one year.

Marty Leon delivers PARTNER 3 trial results

Low-risk TAVI trials underscore optimism for transcatheter approach but surgical societies reserve caution “It has been a good day for TAVI [transcatheter aortic valve implantation],” commented Raj Makkar (Cedars-Sinai, Los Angeles, USA) at this year’s TCT meeting (23–26 October, San Francisco, USA), reflecting optimism regarding trial results presented during the congress on TAVI in the low-risk patient population. Though the latest results continue to fuel expectation over the performance of TAVI among lower risk patients, surgical societies continue to sound a note of caution before physicians opt to pursue a TAVI-first strategy in those at low surgical risk.

M

akkar was speaking on a TCT panel dissecting the five-year results from the PARTNER 3 trial, looking at outcomes among aortic stenosis patients deemed to be at low risk for surgery who received the Sapien 3 (Edwards Lifesciences) balloon-expandable transcatheter valve. During the session, speakers weighed up the PARTNER 3 data alongside four-year findings from the Evolut Low Risk trial, also investigating TAVI among low surgical risk aortic stenosis patients, albeit using CoreValve, Evolut R or Evolut PRO (Medtronic), self-expanding valves.

Both trials, which randomised patients to undergo either TAVI or surgical aortic valve replacement (SAVR), formed the centrepiece of the first late-breaking clinical trial session at the 2023 TCT meeting, and the results have stoked optimism over the longer-term performance of TAVI among low-risk patients, where transcatheter procedures continue to gain ground at the expense of more invasive, surgical procedures.

However, within the surgical community, some questions remain over the generalisability of the findings, due to what has been described as a high proportion of concomitant procedures among patients undergoing SAVR in both trials.

Five-year results from PARTNER 3, delivered by Marty Leon (Columbia Irving Medical Center/New York Presbyterian, New

York, USA) and published simultaneously in The New England Journal of Medicine (NEJM) continued to show equivalent performance between TAVI with the Sapien 3 device and surgery against a primary composite endpoint of death, stroke or rehospitalisation. However, Leon reported that there was an attenuation of the differences between the two groups in the primary endpoint out to five years, which had initially favoured TAVI at both one and two years.

We can tell our patients who have low-risk aortic stenosis that at five years more than 70% will be alive with a KCCQ score of greater than 75, which means either no or very mild symptoms.”

ROBERT W YEH (BETH ISRAEL Deaconess Medical Center, Boston, USA) reported the findings of the AGENT IDE trial, a prospective, randomised trial, during a latebreaking trial session at the 2023 TCT meeting (23–26 October, San Francisco, USA).

Though used widely in clinical practice in Europe, the use of DCBs in the USA is limited to investigational cases only, with no devices currently approved for commercial use. This could now change, with Boston Scientific indicating that the device’s “successful real-world use” outside of the USA alongside the promising data from AGENT IDE will support a submission to the US Food and Drug Administration (FDA) for approval of the therapy. The Agent DCB currently holds approvals in Japan, where it was licenced in 2023, and has held a CE mark since 2014 for the treatment of patients with in-stent restenosis and previously untreated small vessel coronary disease.

“It turns out that despite improvements in drug-eluting stent technology, in-stent restenosis is still quite common. In fact, 10% of all the PCIs [percutaneous coronary interventions] we do in the USA are for in-stent restenosis,” Yeh told Cardiovascular News. “We do not often have great treatments for those patients; some of those patients have multiple layers of previously placed stent, where you do not Continued on page 4

Continued on page 6

4

November 2023 | Issue 71

Top Stories

AGENT IDE trial brings hope of first US coronary DCB approval Continued from page 3

really want to put in an additional third, or maybe a fourth layer of metal, and so as a result of that, those patients even have high recurrent restenosis rates even if you do put in another stent, so we are really looking for new therapies to treat these patients.”

Boston Scientific is one of several companies hoping to bring a coronary DCB to the market, and Yeh commented that “extreme enthusiasm” for the use of the technology played a role in the faster than anticipated enrolment of the AGENT IDE trial. Patients were eligible for inclusion if they had in-stent restenosis in lesions up to 26mm in length in a coronary artery 2‒4mm in diameter.

Yeh showed in his TCT presentation that the paclitaxelcoated Agent device demonstrated statistical superiority to uncoated balloon angioplasty against a primary endpoint of target lesion failure (TLF) which occurred in 17.9% of patients in the DCB arm compared to 28.7% in the conventional balloon angioplasty arm. This represented a relative risk reduction of 37% and a 10% absolute risk reduction, favouring the Agent DCB, with a highly significant superiority p-value of 0.0063, Yeh reported, a finding that elicited applause from the TCT Innovation & Clinical Science Theater audience.

The endpoint differences were predominantly driven by reduced rates of myocardial infarction related to the target vessel (TV-MI) which occurred at a rate of 6.4% in the DCB arm versus 12.3% for patients randomised to balloon angioplasty, and the need for target lesion revascularisation (TLR), which occurred in 12.4% of patients in the DCB arm versus 24% of patients randomised to balloon angioplasty. No instance of stent thrombosis occurred in the patients treated with the DCB, though this outcome was found in 3.9% of patients treated with conventional balloon angioplasty.

These data include the first 480 of 600 patients enrolled across 40 US sites, 321 randomised to receive the DCB, and 159 to undergo balloon angioplasty. Within the patient population, 44% had multiple stent layers in the target lesion, and 51% were diabetic, nearly 50% had a prior myocardial infarction and more than 75% had a history of multivessel disease—with Yeh describing these patients as being “very high risk”.

Sub-group analyses showed that among those patients with multiple stent layers, there was a significant reduction in the primary endpoint, which occurred in 21.9% of Agent DCB met its endpoints in AGENT IDE

patients who were treated with a DCB compared to 39.3% of those undergoing conventional balloon angioplasty.

“This study is long overdue,” Roisin Colleran (Mater Private Network, Dublin, Ireland) commented in discussion that followed the presentation at TCT 2023. “You pointed out that about Robert W Yeh 10% of PCIs in the USA are done for in-stent restenosis and yet in 2023 there is still no coronary DCB approved for this indication despite a class I recommendation in European guidelines in 2014.

“The results are clear, a significant reduction in target lesion failure, driven by halving in rates of both target vessel revascularisation and target vessel myocardial infarction.”

Colleran comment further that the implications of the study are clear, “this trial should provide the basis for regulatory approval of this drug-coated balloon for in-stent restenosis in the USA and allow you to provide this as an available treatment option for such patients”.

In the pipeline: Drug-coated balloons under US investigation ●S eQuent Please Rex (B Braun Interventional Systems) Initially awarded breakthrough device designation for the treatment of coronary in-stent restenosis by the US FDA in 2019, B Braun Interventional Systems announced a collaboration with Infraredx to accelerate the investigational clinical trial of the device in early 2021. ● MagicTouch (Concept Medical)y Concept Medical’s MagicTouch sirolimus-coated balloon was awarded a third investigational device exemption (IDE) approval in May 2023. The approval will allow initiation of a pivotal clinical trial to identify the safety and efficacy of the device in small vessel coronary artery disease. MagicTouch devices already have investigational approvals for in-stent restenosis and below-theknee indications. ● Selution SLR (MedAlliance, now Cordis) MedAlliance—acquired this year by Cordis—received investigational device exemption approval from the US FDA for the Selution SLR sirolimus-eluting balloon in October 2022 for the treatment of coronary in-stent restenosis, and for use in de novo coronary artery lesions in January 2023. Enrolment has recently commenced in the de novo study of the device, which powered to demonstrate superiority over drug-eluting stents. ● Virtue (Orchestra Biomed) Investigational device exemptions with conditions were granted to commence the Virtue ISR-US pivotal study evaluating the efficacy and safety of Virtue sirolimuseluting balloon for the treatment of patients with coronary in-stent restenosis.

LATEST NEWS THE STORIES IN BRIEF FROM THE

CARDIOVASCULAR WORLD

n CORONARY SURGERY IN Women are 14%-22% WOMEN: less likely Women have than men historically been underrepresented in coronary surgery trials, a fact that may have contributed to a disparity in outcomes between men and women with coronary artery disease, attendees of the 2023 European Association of CardioThoracic Surgery (EACTS, 4–7 October, Vienna, Austria) annual meeting heard.

During the conference, experts discussed strategies to improve the outlook for women with coronary artery disease. to undergo CABG utilising guidelineconcordant revascularisation strategies

For more on this story go to page 10. n PACLITAXEL: Investigators hope that data from a patient-level metaanalysis, shared for the first time at TCT 2023 (23­–26 October, San Francisco, USA), will draw a line in the sand over the question of safety of paclitaxel-coated devices for the treatment of peripheral arterial disease (PAD). The data were among the decisive factors that swayed a change in stance by the US Food and Drug Administration (FDA), which since 2019, had cautioned that paclitaxelcoated devices may be associated with increased mortality.

For more on this story go to page 11. n INTELLISTENT: The developers of a novel multi-lumen stent system for the interventional adjustment of pulmonary blood flow in congenital heart disease, Heartpoint Global, won the TCT 2023 Shark Tank innovation prize. It is hoped that the device, which is placed in the main pulmonary artery and arterial branches, could fill an unmet need in children suffering with heart disease

For more on this story go to page 24.

Editor-in-chief: Simon Redwood | Publisher: Stephen Greenhalgh | Content Director: Urmila Kerslake | Head of Global News: Sean Langer Senior editor: Will Date will@bibamedical.com | Editorial contribution: Jamie Bell, Jocelyn Hudson, Éva Malpass and George Barker Design: Terry Hawes, Wes Mitchell and David Reekie Advertising: Melanie Stevenson melanie@bibamedical.com Subscriptions: subscriptions@bibamedical.com | News or advertising queries Tel: +44 (0)20 7736 8788 Published by: BIBA News, which is a subsidiary of BIBA Medical Ltd | BIBA Medical, Europe, 526 Fulham Road, Fulham, London, SW6 5NR, United Kingdom Tel: +44 (0) 20 7736 8788 BIBA Medical, North America, 155 North Wacker Drive, Suite 4250, Chicago, IL 60606, United States Tel: +1 708-770-7323 Printed by: Buxton Press Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the United Kingdom address. © BIBA Medical Ltd, 2023. All rights reserved.

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6

November 2023 | Issue 71

Low-Risk TAVI

COVER STORY continued

Low-risk TAVI trials underscore optimism for transcatheter approach but surgical societies reserve caution Continued from page 3

The trial enrolled 1,000 patients with severe symptomatic aortic stenosis between March 2016 and October 2017 to undergo TAVI using the Sapien 3 balloon-expandable valve (n=503) or surgery (n=497) for severe aortic stenosis. Outcomes are due to be reported out to 10 years.

At one- and two-year timepoints PARTNER 3 demonstrated superior or similar results for TAVI for its primary endpoint, Leon said in his presentation.

Presenting the primary endpoint results at five years, Leon reported a non-hierarchical composite of allcause death, all stroke, or rehospitalisation of 22.8% in the TAVI arm, versus 27.2% in the SAVR arm, a narrowing of the difference seen between the two therapies from the trial’s earlier results.

In the TAVI arm, all-cause mortality was 10%, cardiovascular mortality was 5.5% and disabling stroke was 2.9% at five years. Leon pointed out that there were similar rates of cardiovascular death in both arms but noted that there was a higher prevalence of non-cardiovascular death in the patients who received TAVI. Rehospitalisation was less than 3% per year over five years. Valve durability indicators were also stable over time with no difference in the incidence of bioprosthetic valve failure related to structural valve deterioration (1.4% vs. 2%) or reintervention rates (2.6% vs. 3%) between TAVI and SAVR. “We can tell our patients who have low risk aortic stenosis that at five years more than 70% will be alive with a KCCQ [Kansas City Cardiomyopathy Questionnaire] score of greater than 75, which means either no or very mild symptoms,” Leon said, summarising the key messages of the trial. “We can also tell them that after five years, more than 85% would be alive with a durable valve, [and] no bioprosthetic valve failure with either treatment.

“We would conclude that in low risk, severe symptomatic aortic stenosis patients treated with either Sapien 3 TAVI or surgery over five years [of] followup, both TAVI and surgery were associated with similar and low clinical event rates,” he concluded, adding that the findings reaffirm the clinical and echocardiographic benefits of TAVI with the Sapien 3 valve as a “meaningful alternative” to surgical therapy for lowrisk severe symptomatic aortic stenosis patients.

Stephan Windecker (Bern University Hospital, Bern, Switzerland), who acted as the discussant for the study during the TCT late-breaking clinical trial session, commented that the “most important observation is that the early advantage of TAVI over SAVR attenuates over time” in his appraisal of the findings.

Windecker also highlighted the proportion of patients who withdrew from the trial, which was particularly pronounced in the surgical arm, as well as the disproportionate number of non-cardiovascular deaths among TAVI patients, as points for further discussion. Furthermore, he pointed to a disparity in concomitant procedures, which saw those undergoing surgery more frequently having coronary artery bypass graft (CABG) surgery, as well as other procedures, and he questioned whether these may have had an effect on later outcomes.

Following Leon’s PARTNER 3 presentation, Michael J Reardon (Methodist DeBakey Heart & Vascular Center, Houston, USA) delivered the findings at four years from the Evolut Low Risk trial, which

were also published as a research letter in the Journal of the American College of Cardiology.

“We have all seen TAVI explode into our field of structural heart,” Reardon said in the introduction to his presentation, noting that the procedure has grown rapidly in the USA in recent years. “This has been driven largely by the randomised trials, like the one I am talking about and the one you have just heard about.”

There is little reason to believe that the growth of TAVI will stop, he commented.

“The question is, do we have data to support that?”

Thomas Reardon focused on the MacGillivray association between valve performance and clinical outcomes, commenting that reporting the results more frequently in the low-risk population “will help establish the relationship between valve performance and clinical outcomes to help inform out heart teams and our patients of the appropriate treatment options”.

STS and EACTS recommend caution prior to adopting a TAVIfirst strategy in low-risk patients, particularly those patients with characteristics not specifically studied in these low-risk trials.”

The Evolut Low Risk trial is a randomised, noninferiority trial, comparing TAVI to SAVR in patients who had severe, symptomatic aortic stenosis and were at low surgical risk. Patients enrolled in the trial at 61 sites throughout the USA and 25 in Canada, Europe, Japan, Australia, New Zealand, are due to be followed out to 10 years.

Early advantage maintained?

From May 2016 to May 2019, 1,414 patients were randomised 1:1 to undergo TAVI (n=730) or SAVR (n=684). At four years, 94.7% of TAVI and 89.2% of SAVR patients were available for evaluation. The primary endpoint of all-cause mortality or disabling stroke at four years was 10.7% for TAVI vs. 14.1% for SAVR. “We all know that TAVI has an early advantage to surgery. The question has always been: ‘will this hold up or will surgery catch up to TAVI?’,” Reardon commented on the primary endpoint trend over the four years of the study, noting that the delta between the two arms has widened from 1.8% at one year to 3.4% at four years, in favour of TAVI. “This is the first time we have seen a transcatheter valve not only maintain its early advantage, but actually widen that advantage over time,” he commented.

The results for the individual components of the primary endpoint were 9% compared to 12.1% for all-cause mortality and 2.9% vs. 3.8% for disabling stroke for TAVI versus SAVR. The composite of all-cause mortality, disabling stroke, or aortic valve rehospitalisation was 18% with TAVI and 22.4% with SAVR. In addition, TAVI had significantly better haemodynamics as well as significantly less mean

gradients greater than or equal to 20mmHg (4% vs. 8.9%,) or severe prosthesis-patient mismatch, Reardon reported.

Reaction from the wider surgical community, however, reflects a level of caution over the generalisability of the results from both trials. In a joint statement, the Society of Thoracic Surgeons (STS) and the European Association for Cardio-Thoracic Surgery (EACTS) assert that while the trial data provide interesting insights, “given the highly selected cohorts of these carefully adjudicated, industry sponsored trials, we feel that some of the statements made were appropriately weighted with equipoise, but some were not”.

“When you look at isolated surgical aortic valve replacement for aortic stenosis that is one group of patients that has an expected prognosis over time,” STS president Thomas MacGillivray (MedStar Heart and Vascular Institute, Washington DC, USA) tells Cardiovascular News commenting on the reasons for this caution. STS and EACTS contend that the number of surgical patients in the PARTNER 3 and Evolut Low Risk trials who underwent concomitant procedures, which they say stands at around 26%, may colour the outcome of the comparison between the surgical and transcatheter patients.

Surgical concerns

“If you look at patients who have aortic stenosis and coronary artery disease, that is a different disease and the treatments, survival and complication rates are different. If you group them together, that does not really speak to the prosthesis or the procedure. You have to take into consideration the underlying disease and the treatment that is done.

“If you look at both the PARTNER 3 and the Evolut Low Risk Trial, a quarter of those [SAVR] patients had other procedures, whereas most of the TAVI patients had isolated procedures. It is a different patient population. Even if you look at the surgical outcomes between PARTNER 3 and Evolut Low Risk, they are different,” says MacGillivray.

In their statement, STS and EACTS point toward a real-world analysis of patients undergoing low-risk isolated SAVR from the STS Adult Cardiac Surgery Database, authored by Vinod Thourani (Piedmont Heart Institute, Atlanta, USA) and co-authored by MacGillivray as well as others. The analysis, which was published in the Annals of Thoracic Surgery ahead of the TCT meeting found that among patients undergoing isolated SAVR, 92.9% survived after five years, while at eight years, survival was close to 90%.

“The sample size was over 42,000 patients in the total cohort, with over 19,000 patients at risk for five-year survival,” the statement notes. “These data provide the real-world benchmark from which to interpret current and future analyses in low-risk patients receiving therapy for aortic stenosis.”

The societies call for the investigators from the PARTNER 3 and Evolut Low Risk trials to publish the results for isolated SAVR and isolated TAVI subcohorts from their trial arms in order to shed more light on this question.

“Until we have these data, any statements or conclusions from these trials are interesting but still hypothesis generating and speculative,” the societies state. “STS and EACTS therefore recommend caution prior to adopting a TAVI-first strategy in low-risk patients, particularly those patients with characteristics not specifically studied in these low-risk trials.”

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9

Issue 71 | November 2023

On-X aortic valve “remains safe and effective with low dose warfarin

EACTS 20 2 3

Statin treatment may benefit SAVR patients

Emily Pan at EACTS 2023

Ongoing statin treatment may be beneficial for patients after isolated surgical aortic valve replacement (SAVR), research presented at the 2023 European Association of Cardio-Thoracic Surgery (EACTS) annual meeting (4–7 October, Vienna, Austria) has shown.

T

he paper, presented by Emily Pan (University of Turku, Turku, Finland), was one of a handful of studies selected for presentation during a “President’s Choice” session, which spotlighted important studies across a number of surgical domains.

“Statins are known to have lipid lowering effects but also many pleiotropic effects, which include anti-inflammatory, antithrombotic and antiproliferation properties, and they are also known to stabilise the atherosclerotic plaques and to improve the endothelial functions,” Pan said in her presentation. “These properties of statins could potentially benefit patients after valve replacement.”

Though previous reports have shown that statin use is associated with better survival after transcatheter aortic valve implantation (TAVI), little is known about statin use after SAVR, the presenter stated, meaning that there are no specific recommendations within guidelines, either in the USA or Europe, regarding medication after SAVR, apart from treating other comorbidities.

Pan presented the findings from multiple populationbased registries, with data from close to 12,000 patients investigating the associations between time-updated statin use and major cardiovascular events (MACE) including myocardial infarction (MI), stroke and all-cause mortality, as well as secondary endpoints which included each component of MACE, cardiovascular mortality, peripheral arterial disease (PAD), heart failure and new aortic valve intervention.

Potential associations between statin use and MACE in predefined subgroups based on age, sex, type of prosthesis and comorbidities were also categorised, as well as the potential associations between statin treatment intensity and MACE. Of the 11,893 patients included in the study, all of whom were treated between 2006–2020, 50.5% were dispensed with statins at baseline, 26.6% with high intensity, 68.4% with intermediate intensity, and 3.5% low intensity. The median follow-up time was 5.4 years, Pan reported, as well as noting that patients with statins at baseline were significantly older, more often male, had higher body mass index and more comorbidities than those not receiving statin treatment.

The results presented by Pan indicate that ongoing statin

use in patients with aortic stenosis after SAVR is associated with significantly lower risk for MACE, all-cause mortality and cardiovascular mortality in both adjusted Cox regression model and after propensity score matching, while ongoing statin therapy was also associated with significantly lower risk for MACE in all predefined subgroups.Both intermediate- and high-intensity statins were associated with a reduced risk for MACE and all-cause mortality, she noted.

“All in all we conclude that ongoing statin treatment appears to be beneficial for patients after isolated surgical aortic valve replacement, and should be considered in the future for updated guidelines,” Pan said.

Detailing the strengths of the analysis, Pan commented that the study was carried out using a large pool of population based data that has been updated recently and represents a real-world setting in homogenous healthcare system, employing different analytical methods that arrived at complementary findings.

However, she also acknowledged a number of limitations, including the retrospective nature of the study, which she said may still have residual confounding and selection bias. Furthermore, she said, the researchers did not have information on blood cholesterol levels nor the causes of interruptions to medication among some patients, and the study did not take account of other potential lipid lowering medications.

All in all we conclude that ongoing statin treatment appears to be beneficial for patients after isolated surgical aortic valve replacement, and should be considered in the future for updated guidelines.”

DATA FROM THE ON-X AORTIC heart valve low international normalised ratio (INR) post-market study, presented during a late-breaking science session at the 2023 EACTS annual meeting, confirm that the device remains safe and effective with low-dose warfarin.

The On-X aortic low INR postmarket study is a prospective, international, multicentre, observational study to assess the occurrence of bleeding, valve-related thromboembolism and valve thrombosis with the On-X Aortic (Artivion) prosthetic valve when targeted at an INR level of 1.8 (1.5‒2 range) during a five-year follow-up period.

The trial is designed to compare adverse event rates for patients with target INR range of 1.5 to 2 per On-X instructions for use, to rates from the previous investigational device exemption (IDE) trial. The trial consisted of 510 participants who have only an On-X aortic prosthetic heart valve implant. The combined primary efficacy and safety endpoints determine the impact of the On-X Aortic prosthetic valve on reducing thrombotic events, major bleeding events, and mortality.

Aung Oo, clinical lead for Aortovascular Surgery at Barts Heart Centre (London, UK) presented realworld experience of 510 On-X aortic valve replacement patients treated with low dose warfarin. This included at least one-year and up to five years of clinical data on study participants, with median follow-up time of 3.4 years.

The results show a significantly lower composite primary endpoint of thromboembolism, valve thrombosis, and major bleeding (linearised occurrence rate (LOR) of 2.31% compared to the pre-defined historic control rate of 5.39%, p<0.0001), driven by an 85% reduction in major bleeding and a 73% reduction in all bleeding. Notably, the data reflected an improvement in outcomes compared to the On-X aortic low INR IDE study data first published in 2014.

Oo said: “Heart valve replacement therapy presents several postoperative challenges for patients, especially the need for blood thinners and the related risk of bleeding and thrombotic events.

These long-term data demonstrate the clinical benefits of a lower-dose postoperative warfarin regimen, further validating the use-case for On-X valves with low-dose warfarin.”

10

November 2023 | Issue 71

EACTS panel sounds call to action over sex disparities in coronary surgery A historic underrepresentation of women in clinical trials for coronary artery bypass graft (CABG) surgery has contributed to a disparity in outcomes between men and women, delegates at the 2023 European Association of Cardio-Thoracic Surgery (EACTS) annual meeting (4–7 October, Vienna, Austria) heard.

T

his was among the messages from a session titled ‘Improving CABG outcomes in women: A call to action’, during which speakers tackled the imbalance of available data concerning CABG outcomes in women, the need for dedicated coronary surgery trials for women, and future strategies to improve outcomes “When we talk about disparities in outcomes of CABG between women and men, what we need to recognise is that in the treatment of coronary disease in women there is a disparity along every step of the way—from preoperative to postoperative—that contributes to these differences in outcomes that we are seeing,” Sigrid Sandner (Medical University of Vienna, Vienna, Austria) said in her opening presentation.

Sandner’s presentation set the tone for the session and highlighted some of the existing data to detail disparities in care among patients receiving coronary bypass surgery. She pointed to analysis from the Society of Thoracic Surgeons (STS) database, showing that women less frequently receive a left internal mammary artery (LIMA) graft to the left anterior descending artery, less frequently receive multiple arterial grafting, and were also less likely to undergo complete anatomic revascularisation than men.

Operative outcomes

Sandner also drew on the findings of a retrospective cohort study of over one million US patients, published earlier this year in JAMA Surgery, in which women were found to have a significantly higher risk of operative mortality and postoperative complications after isolated CABG when compared with men.

Importantly, said Sandner, who was a co-author on the paper alongside another of the session’s speakers, Mario Gaudino (Weill Medical College, New York, USA), the research also showed that there had been no change in excess operative risk for women between 2011 and 2020, the entire period of the study.

“Women had increased operative mortality and morbidity compared with men in every single year across the entire study period,” she said. “There was also an attributable risk for female sex. It is a very elaborate statistical analysis, but what it basically gives you is the added risk of female sex on top of baseline risk. This was present for mortality and morbidity, across the study period, and it has remained largely unchanged over the past decade.”

Following Sandner, Jennifer Lawton (Johns Hopkins Medicine, Baltimore, USA) addressed evidence and surgical challenges for multiple arterial CABG in women.

“Women have a higher risk of mortality with coronary bypass grafting compared to men,” Lawton commented, adding that this has been shown “time and again” in retrospective and propensity matched studies. “It is multifactorial, as Dr Sandner mentioned, probably related to knowledge of clinicians, also patient factors, and the fact that women tend to present

for surgery about ten years older and with multiple comorbidities.”

Turning to the question of how to improve mortality in women undergoing coronary surgery, Lawton pointed to a study led by Stephen Fremes (Sunnybrook Health Sciences Centre, Toronto, Canada), published in Heart in 2020, in which it was shown that women who received multiple arterial grafts had improved long-term survival over a ten-year period and a higher rate of freedom from major adverse cardiovascular events. A further propensity matched meta-analysis, conducted by Gaudino and colleagues, also found a higher survival probability in women that received multiple arterial grafts.

“This is something that we as surgeons can do,” Lawton said, in reference to the adoption of multiple arterial grafting among female patients, something that appears to be currently underutilised.

Lawton also highlighted the findings from the analysis of the Society of Thoracic Surgeons (STS) database, first shared in 2021, containing procedural data from more than 1.2 million patients, showing that women were 14–22%

What we need to recognise is that in the treatment of coronary disease in women, there is a disparity along every step of the way.” less likely to undergo revascularisation strategies including grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, complete revascularisation, or multiarterial grafting.

Lawton suggested a number of potential strategies to encourage adoption of multiarterial grafting, including better training in these techniques or embedding the use of a second arterial graft within quality metrics.

She ended with a quote from Maya Angelou, summing up the need for more evidence in this arena.

“Do the best you can until you know better, then when you know better, do better.”

If studies focusing on CABG outcomes in women have been lacking to date, one trial is looking to begin the process of bridging this gap. ROMA Women—a spin-off of the ROMA (Randomization of single vs multiple arterial grafts) study—is a global trial that will seek to randomise over 2,100 female patients undergoing primary isolated non-emergent CABG to either single or multiple arterial grafts.

Gaudino followed Lawton’s presentation by offering an update on the trial’s progress to date.

“Even though the evidence is limited, there is reason to believe that multiple arterial grafting may be beneficial in the general CABG population, but even more so in women undergoing bypass surgery,” Gaudino commented.

“This is exactly the reason why I believe a randomised trial of multiple arterial grafting in women is necessary. Contrary to what we have traditionally believed, we have no evidence that multiple arterial grafting is better—we will find out in a couple of years—but one reasonable option is that the treatment effect is different by sex.”

The ROMA trial, which had a majority male population, completed enrolment with over 4,000 patients and is expected to report its first outcomes in 2026. Enrolment has remained open solely for female patients, with a further 1,310 expected to be included alongside the 690 recruited in the main ROMA trial. At the time of his presentation, Gaudino noted that a total of 273 female patients had been enrolled in ROMA Women, with a “better than expected” rate of recruitment in its first few months.

“If we can keep this pace we can make this impossible trial to undergo CABG possible even faster utilising guidelinethan we thought,” concordant he said. revascularisation strategies The final speaker in the session, Rashmi Yadav (Royal Brompton & Harefield Hospitals, London, UK), reminded attendees that the “data gap” between women and men extends far beyond coronary surgery. “Although cardiovascular disease causes one third of deaths in all women, it is understudied, underrecognised, undertreated and women are underrepresented in clinical trials,” she said.

Yadav highlighted that there are some technical, anatomical differences between men and women that can pose challenges for surgeons, as well as what she described as “non-technical, unquantifiable” challenges.

“There is evidence that women are more perceptive of a non-empathetic physician. Compared to a male patient, a women is more likely to be affected by the manner of her surgeon,” Yadav commented. “That brings me to the thorny question of whether it matters that there is sex concordance between the surgeon and the patient and does it matter for postoperative outcomes?”

In answer to this question, Yadav commented that in her view, it did not matter for the vast majority of patients, “but every once in a while you will come across a patient where it matters to them whether their surgeon is a woman or not”.

Women are 14–22% less likely than men

Issue 71 | November 2023

TCT 20 2 3

Paclitaxel Update 11

First presentation of complete patientlevel dataset on paclitaxel and death that helped sway the US FDA

(l-r) William Gray, Sahil Parikh and Peter Schneider

Data from a patient-level meta-analysis—a factor in the US Food and Drug Administration’s (FDA) recent change of position on the use of paclitaxel-coated devices to treat peripheral arterial disease (PAD)—were made public for the first time at TCT 2023 (23–26 October, San Francisco, USA).

THE ANALYSIS LED investigators to conclude that there is no association between mortality risk and paclitaxel-coated device exposure or dose, and should provide reassurance to patients, physicians and regulators on the safety of paclitaxel-coated devices, they say.

The release of the data, which was also published in The Lancet, draws a line in the sand over the question of the safety of paclitaxel, which is used in peripheral interventions to prevent restenosis, after data from a summarylevel meta-analysis put forward in 2018 pointed to an increased risk of death at two and five years following the use of paclitaxel-coated devices in the femoropopliteal artery.

William A Gray (Lankenau Heart Institute, Wynnewood, USA) told TCT attendees that the analysis provides the most complete and current follow-up data of pivotal studies associated with FDA-approved paclitaxel-coated devices and represents the most complete patient-level analysis to date, or likely to be available in the future.

Gray presented the findings on behalf of an independent physician steering committee, comprising Sahil Parikh (Columbia University Irving Medical Center, New York, USA), Peter Schneider (University of California San Francisco, San Francisco, USA), Christopher Mullin and Tyson Rogers (both North American Science Associates [NAMSA], Minneapolis, USA), who were enlisted by the regulator and industry to dig into the final and updated patient-level datasets and address limitations of prior paclitaxel meta-analyses. Funding for the study came from BD, Boston Scientific, Cook, Medtronic, Philips, Surmodics and TriReme Medical, though the funders of the study had no role in its design, data analysis, data

interpretation, or writing of the report, but did provide patient-level data for the analysis, which was independently conducted.

The use of paclitaxel-coated devices for the treatment of PAD dropped by as much as 50% due to changes in practice patterns worldwide, Gray said, which was in response to the FDA’s 2019 statement that use of paclitaxelcoated balloons and paclitaxel-eluting stents was “potentially associated with increased mortality”. This change in position came after a meta-analysis from Konstantinos Katsanos (University of Patras, Patras, Greece) et al had first raised the spectre of a mortality risk.

FDA removed the red flag in July this year, stating that “additional data from the pivotal randomised controlled trials (RCTs) ha[ve] become available” in a letter to healthcare providers in which it set out the decision.

To inform this decision, Gray and his co-investigators analysed randomised trials that evaluated FDA-approved paclitaxel-coated devices versus uncoated devices for the treatment of femoropopliteal artery disease, looking primarily at the mortality risk on an intention-to-treat basis, with key secondary analyses including dose/ mortality and covariate interactions.

Data from 10 trials were included, encompassing 2,666 participants over a median follow-up of 4.9 years. Oneyear follow-up was available in 98.7% of evaluable participants and five-year follow-up in 95%, which Gray noted represents an additional 3,355.5 patient years since a 2020 analysis by VIVA Physicians, in which investigators identified an absolute 4.6% increased mortality risk associated with paclitaxelcoated devices, albeit demonstrating a weaker mortality signal than was initially reported in December 2018 by Katsanos et al.

Results of the latest analysis presented

by Gray and published in The Lancet demonstrated an overall hazard ratio (HR) for the intention-to-treat population of 1.14 (95% confidence interval [CI] 0.93–1.40). In post-hoc analyses assessing the proportional hazards assumption, there was no evidence the assumption was violated.

HRs for individual studies ranged from 0.32 to 1.52, and there were no studies in which the CI did not include the null value of 1. The HR for the astreated analysis was 1.13 (0.92–1.39).

Furthermore, the as-treated crossover analyses also did not show a significant difference in deaths between the paclitaxel-coated and control groups, with an HR of 1.07 (0.87–1.31) when late crossovers were censored, and 1.04 (0.84–1.28) in the time-varying analysis of late crossovers. Examination of late crossover using iterative parameter estimations also failed to detect a significant effect on deaths.

Speaking to Cardiovascular News following the presentation of the updated dataset at TCT 2023, Gray said that the new data “almost certainly” resolves the safety question over the use of paclitaxel-coated devices for the treatment of peripheral arterial disease.

“There will be very few, if any, paclitaxel versus non-paclitaxel femeropopliteal trials, so the data are what we have today, and they are not likely to be enhanced any further,” he said. “The data that we have are the most complete data that we are going to get. The follow-up is 95%, a lot of credit [goes] to industry for going out and getting those data, it is really important as part of the larger effort.

industry and with regulatory bodies all over the geography, but especially with FDA, [which] has been extremely collaborative and has been all about problem solving since the beginning of this issue.”

“Here we have probably the most complete dataset that will be feasible from the randomised controlled trials,” comments Parikh. “We looked at the overall percentage of patients identified with vital status at five years, and it was 95% of the total cohort of almost 2,700 patients. I think it will be hard to find a more complete dataset at this level of detail.”

More importantly, adds Parikh, was the opportunity to conduct crossovers analyses.

“We are identifying exposure to paclitaxel in any way, to the maximum extent possible, and, with each subsequent iteration of the analysis, our findings showed a closer and closer point estimate to no hazard at all, to unity,” he says. “That really emphasises that going the extra mile to identify every exposure to paclitaxel, in this case most often with a contralateral limb intervention or reintervention, was the appropriate approach to adjudicate paclitaxel exposure and its risk.”

Lessons to be learned

Asked for his reflection on the lessons learned from the controversy, Gray summarised comments by Michael Conte (University of California, San Francisco, San Francisco, USA) and Eleni Whatley of the US FDA, who spoke during the same TCT session at which he delivered the updated meta-analysis.

There will be very few, if any, paclitaxel versus non-paclitaxel femeropopliteal trials, so the data are what we have today, and they are not likely to be enhanced any further.”

“What I would say is, that this is a three year effort, it involved the FDA, industry, NAMSA, physician scientists and so on, and it would be very difficult to imagine recapitulating that effort and getting a different answer, or even having any reason to do that, given that the dataset that I just described is unlikely to change.”

“The most important takeaways are that: Number one, we [have] learned a tremendous amount about how future studies should be planned, so that we do not go down a blind alley again to be fooled by a summary level meta-analysis,” Schneider told Cardiovascular News, reflecting on the takeaways from the research.

“The second thing is that this was a tremendous effort to resolve this problem, and that included collaboration like we have never had before between physicians of different specialties in different parts of the world, with

“Basically, we have to do better follow-up and to do better trial design in order to understand what medical therapy is being given to the patient because that has an impact on mortality,” he said. “We have to understand better what the crossover rates are in any therapeutic [strategy]. If someone is getting a therapeutic and we are not counting the crossovers, we are missing lots of the effect potentially.

“Dr Conte made the point which is that the follow-up time periods for the pivotal trials were probably too short, and if they are not going to be lengthened—and I understand why we do not necessarily want to do that, to speed the devices to the market—then we have to have more robust postmarket surveillance. So, there are lots of things that we have learned, I think all of them are very much positive, and I know they will be incorporated in trials going forward.”

November 2023 | Issue 71

12 CX 2024 Aortic Preview

CX 2024 PREVIEW

Data and debate to bring new light to aortic controversies at CX 2024

Discussion and debate at CX 2023

The aortic programme at the 2024 Charing Cross (CX) Symposium (23–25 April, London, UK) promises to be “packed with new data” to fuel the debate over controversies in the aortic space. This is according to CX Executive Board member Tilo Kölbel (University Heart Center Hamburg, Germany), who spoke alongside the recently appointed CX co-chairs Dittmar Böckler (University Hospital Heidelberg, Heidelberg, Germany) and Andrew Holden (Auckland City Hospital, Auckland, New Zealand) in a CX Vascular Live broadcast that previewed the upcoming edition of the event.

T

he trio spoke upon the release of the CX 2024 preliminary programme, which offers a glimpse of what to expect from the three days of education, evidence and innovation in the treatment of aortic disease. The aortic segment of the CX Symposium—which Kölbel describes as one of the strongest he has seen in the symposium’s history— begins on Tuesday 23 April with a deep dive into aortic techniques and technologies, followed by a full day of presentations, debate and discussion of controversies in juxtarenal and aortic pathologies on Wednesday 24 April, and then by aortic arch and dissection controversies on Thursday 25 April. Alongside these main sessions, Alexander Zimmermann (University Hospital Zürich, Zürich, Switzerland) will be reprising the hands-on aortic workshop that aims to promote learning in an interactive setting.

“On the one hand we are going to have a very similar setup of sessions divided into techniques and technologies on [the] Tuesday,” Kölbel said of the opening day highlights. The focus will be on new devices and techniques, he explains, with an emphasis on edited cases. The focus on Wednesday and Thursday will switch to more “evidence-based” discussion.

“The most important thing is that this is a controversies year, so the focus will be on the debates,” explains Kölbel. “We have picked a number of very important discussions at the moment and very good discussants to help us answer important questions like what to do with juxtarenal aneurysms and how to treat them, the right minimal volume for aortic practices, balloon-expandable versus self-expanding stents, polymer-based filling technologies, and spinal cord drainage in thoracoabdominal repair.”

The abdominal aortic aneurysm (AAA) segment of the programme, which takes place on Wednesday

very early data were presented last year for the first time. At Charing Cross, a symposium was run on small aneurysm treatment globally and this year we plan to carry on that with an updated result on technologies which have shown some great promise.”

Turning to the thoracoabdominal portion of the programme, Böckler highlights that the unanswered question of how to treat patients with uncomplicated 24 April, features two Great Debates, with type B dissections will be addressed. Furthermore, a speakers debating the best treatment for juxtarenal great debate will seek to establish whether best medical AAAs, including motions in favour of fenestrated treatment remains the standard for uncomplicated endovascular aortic repair (FEVAR) or endovascular acute type B aortic dissection. suture aneurysm repair (ESAR), as well as the “It is still a burning question, [that is] not answered volume-outcome relationship of AAA repair calls for a yet. We have had two randomised trials, and Charing combined recommendation of endovascular aneurysm Cross has always been the symposium to get the repair (EVAR) and open aneurysm repair (OAR) newest evidence and we are going to see and listen to hospital volumes. new trials coming up,” says Böckler.

Alongside controversiess, innovation will be a key Crucially, explains Böckler, the programme focus in 2024, Holden says. “To touch on a few things, features 90 presentations, eight great debates and we are getting some new data on the branched graft 15 first-to-podium presentations which continue the technologies that we are seeing. Not only in the arch, legacy of innovation, education and evidence that which we are seeing an explosion the Symposium has embodied in technologies, including off-thethroughout its 45-year history. shelf options for treating complex Outside of the aortic arch disease, but also some programme, a full schedule of alternative technologies to manage sessions will dig into the current that juxtarenal segment as well,” controversies in all vascular For the he explains. domains, spanning peripheral, first time in 2024, the CX Imaging technologies, including venous, acute stroke and vascular Symposium 3D imaging software and access, punctuated by CX will be intravascular ultrasound (IVUS), debates, live and edited cases housed at a are also likely to be an important and workshop demonstrations. new venue, feature, Holden adds, as well In 2024, CX comes from a the ExCeL London exhibition and conference as technologies geared towards brand-new location, the ExCeL centre in London's Docklands. As the prevention of aortic disease exhibition and conference centre well as offering easy access to progression. in London's Docklands.

Central London and airports via “We have been really interested the newly-opened Elizabeth Line, in some technologies that are the venue also offers expanded To view the exhibition and conference space, treating aneurysms that are entire CX allowing a return to the open sub-threshold, to prevent them 2024 preview, workshop experience and the scan this QR ever getting to the threshold to introduction of an expanded code or visit need treatment,” Holden details. workshop hub in the centre of the cxvascular.

“Multiple centres around the world exhibition hall. com/cxvascular-live/ have been involved, and some

CX 2024: A new home for a new era

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45 YEAR LEGACY OF VASCULAR EDUCATION CONTINUES CX CO-CHAIRS

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November 2023 | Issue 71

14 Interview

PROFILE

JOLANDA KLUIN

Inspired by a passion for nature, Jolanda Kluin began her career in medicine in Africa, before returning to her home country, The Netherlands, to specialise in cardiac surgery. Today she is the head of the department of cardiothoracic surgery at Erasmus Medical Centre in Rotterdam and chairs the European Association of Cardio-Thoracic Surgery (EACTS) Women in Cardiothoracic Surgery Committee. She tells Cardiovascular News of her work and life outside of medicine.

Why did you initially choose to become a doctor, and what was it that made you decide to specialise in cardiothoracic surgery?

As far back as I can remember I wanted to be a doctor, though I do not come from a family of doctors. When I was beginning my career, I had a particular interest in working in Africa, which was also something that nobody in my family had ever done. Originally, I wanted to specialise in tropical medicine, which led me to Ivory Coast, where I stayed for seven months. After spending some time with other specialists in tropical medicine, I realised that if you choose that specialism you are away from home for the rest of your life, unless you want to undertake a teaching role.

I then considered paediatric medicine, and upon gaining some experience in surgery, I knew immediately that this was something I wanted to do. I did my PhD in general surgery, but by that time there was already something appealing about cardiac surgery.

That is when I began my training as a resident in the cardiac surgery department in Rotterdam.

Who were the biggest influences on your early career and what did you learn from them?

The entire group who trained me in The Netherlands, especially the head of the department Ad Bogers, a fantastic paediatric surgeon, and also A Pieter Kappetein, who worked as a cardiac surgeon in Rotterdam and is now at Medtronic.

From a technical point of view, Bogers was a fantastic surgeon, who I learned a lot from. Kappetein taught me a lot about the specialty, including the importance of taking other people with you, building a real team, and also making the young ones enthusiastic for the specialty. It can be difficult as a young surgeon to get involved in societies like EACTS without having someone to introduce you. That I learned from him, the importance of having a mentor.

You are known for your part in the development of the soft robotic heart, HybridHeart, for the treatment of patients with end-stage heart failure. How did this idea come about, and what is the latest status of the project?

Around seven years ago, I was reading the weekend science section in the newspaper, where there was an interview with a Dutch researcher who had just returned to The Netherlands from Boston, USA, where he

had developed a soft robotic octopus. I was struck by the picture, and I thought that if a soft robot could move like an octopus, it could also move like a heart.

We began working together and wrote a proposal for European Union (EU) funding, from which we got a little over €3 million to start the research five years ago. We recently got €11 million from the Dutch government to proceed with the project.

We are currently writing what we have learned and hoped to have this published in Nature, but this is a once in a lifetime chance for me. We just did an animal experiment in which the heart was implanted. We were able to completely wean the animal from cardiopulmonary bypass, and it lived with this heart for one hour.

There are more and more people living with heart failure now, and the therapies we have— left ventricular assist devices (LVADs)—are life-saving but result in a rather low quality of life. Heart transplant is the gold standard, but there are not enough donors. For some specific diseases, such as pulmonary hypertension patients or congenital heart disease patients in which there are no options, hopefully this heart can be an option.

What are your other current research priorities?

I have worked for a long time on tissue engineered heart valves, or synthetic, pliable heart valve development. I am also interested in using large databases to improve results, in areas such as aortic valve repair surgery, mitral valve repair surgery and aortic surgery.

Collaborating with other institutes is the way to go. Single-centre retrospective studies do not add much to our knowledge, you really have to have a combined effort.

What are the key unanswered questions in cardiac surgery that you would like to see prioritised in future research projects?

To me it is fascinating that we can put a man on the moon, but we do not have a valve that lasts forever without any anticoagulation, for example, or that we are not able to make a total artificial heart with little complication. If you look back over our specialty, though, it is only 50 years old, and you see what we have achieved since the start, it is incredible.

What has been the technological advance that has had the biggest impact during your career?

Although it is not really cardiac surgery, I

FACT FILE CURRENT APPOINTMENTS Head of Department of Cardiothoracic Surgery, Erasmus Medical Centre (Rotterdam, The Netherlands) Chair, Women in Cardio-Thoracic Surgery Committee, European Association of Cardio-Thoracic Surgery (EACTS) Associate editor, Cardiac and Vascular Surgery Team, European Heart Journal Coordinator, HybridHeart project

PREVIOUS APPOINTMENTS (SELECTED) Staff cardiothoracic surgeon, University of Utrecht (Utrecht, The Netherlands) Congenital cardiac surgeon, Academic Medical Center (Amsterdam, The Netherlands) Professor in translational cardiothoracic surgery, Academic Medical Center (Amsterdam, The Netherlands)

MEMBERSHIPS EACTS European Society of Cardiology (ESC) Nederlandse Vereniging voor Thoraxchirurgie (NVT) Heart Valve Society (HVS) International Society for Heart and Lung Transplantation (ISHLT)

think the answer is transcatheter aortic valve implantation (TAVI). There are surgeons that are feeling bad about TAVI, but I would have loved to have invented it! It is really important, we can help a lot of people that were not healthy enough for surgery, so that is a fantastic invention and it shows we should really collaborate with our cardiology colleagues. However, I also feel that this is very industry driven, and that is difficult.

In cardiac surgery, it is the arrival of minimally-invasive procedures. Doing mitral valve repair without sternotomy, roboticassisted coronary artery bypass grafting (CABG) and those kinds of things. Though the incision is small for mitral valve repair, you still have to put the patient on bypass and arrest the heart. That is the big difference between TAVI and cardiac surgery. On the other hand, also with sternotomy, I think most people can cope with that very easily.

In the end, if you get a perfect repair with a sternotomy, it is not a big deal.

What does the heart team look like in your practice?

Interestingly, in The Netherlands we have always had a heart team. When it became a big topic, I thought it looked very familiar!

Then, I realised that in other countries it was not like that at all, patients were referred to the surgeon, others were referred to a cardiologist.

In the Netherlands we discuss every patient together with cardiologists.

To have a successful team, you should not be afraid to lose out on patients. That is not what our job is as physicians. You should aim for the best solution for your patient, and not the best solution for your practice. Never look at it from that point of view. For me it would be interesting to see more patient involvement in the heart team. A lot of patients want to have a conversation with you, a lot of them want you to make the decision, but I can imagine that younger people are keen to be a part of the discussion.

Has there been any recent research that has had a major impact on your practice?

Research that shows that building a team where you have a sense of belonging is connected to the quality of your work has been important. It is not only about new technical issues or learning that one technique is better than another, but when you have a really good team where everyone feels that sense of belonging, then you have higher efficiency, but more importantly higher quality.

Issue 71 | November 2023

alisonlang.com

Interview 15

I put a lot of effort into team building and people management, so that everyone goes to the hospital with a smile and delivers the best that he or she can.

How did the EACTS Women in CardioThoracic Surgery Committee come about, and what are the committee’s key aims?

It is around three years since EACTS first installed this committee, of which I became chair. I think it was really time, as there were already similar committees in the USA. We are 50% of the population, but not 50% of cardiac surgeons, so there is some work to do.

I would prefer to focus on diversity, not just for women, but it is a good way to start.

In the past three years we have focused on awareness. Awareness of unconscious bias.

Awareness of inequality. And in this last year, awareness of the importance of the sense of belonging.

I have to step down by the end of this year, because my term is over. I am enthusiastic, and I would really like to thank EACTS for their commitment. I always approach it from a

very positive and proud attitude. I am proud that I am a cardiac surgeon, I am a head of department, but I am also a mother and a woman.

What we do not want to see, and this was often the case in the past, is that women are chairs in sessions about the soft issues and not in the plenary session on surgical techniques, for example. I mentioned this topic of unconscious bias, and we all have our biases.

We as female surgeons also have biases.

What can be done differently to attract the next generation of physicians into the field of cardiothoracic surgery?

This is an interesting and important question, that I really struggle with. There is a real difference in the expectations of young people today than in previous generations. Generally, they do not necessarily want to be in the hospital during nights, they do not want to be on call, they do not want to work for 80 hours.

The generation before mine, especially, lived for hundreds of hours in the hospital every week, and that is not good. The change is very

“I put a lot of effort into team building and people management, so that everyone goes to the hospital with a smile and delivers the best that he or she can.”

fast. But, I do not see how you can become a very good surgeon when you only work 30 hours a week.

We have to involve the next generation when we have these discussions. I sometimes sit around the table when we ask how to make them enthusiastic for the job, and there is often someone missing, and that is the new generation. We think about them, but we should involve them to know what they need.

Outside of medicine what are your hobbies and interests?

I am a mother of four children, and a lot of my time at home goes to the children. On Saturday I am at the hockey pitch or the football pitch the entire day. My husband is a nature photographer, so photography is my biggest hobby outside of work. I cannot do something for any less than 100%, so when we are on holiday I am fanatic about photography, because I really love it. If you do that you enter a completely different world, when you enter this small environment with, for example, butterflies, it is fascinating.

November 2023 | Issue 71

16 TCT 2023 Round-Up

TCT 20 2 3

Swedeheart registry analysis allays concerns about mortality signal for iFR-assisted PCI

A longitudinal analysis from the National Swedeheart Quality Registry of more than 42,000 patients undergoing percutaneous coronary intervention (PCI) supported by instant wave-free ratio (iFR) or fractional flow reserve (FFR), showed no difference in major adverse cardiac events (MACE) between the two modalities.

THE ANALYSIS, PRESENTED BY MATTHIAS Götberg (Lund University, Lund, Sweden) during a late-breaking clinical science session at TCT 2023 (23–26 October, San Francisco, USA) compared long-term patient outcomes following coronary revascularistion using iFR or FFR guidance. Fiveyear data from the DEFINE-FLAIR trial presented at EuroPCR 2023 (16–19 May, Paris, France) had shown a signal of higher mortality with iFR, which prompted the analysis of data from the Swedeheart registry. iFR is a pressure-derived index used to assess coronary blockages during interventional procedures, which avoids the use of hyperaemic agents, a class of drugs that maximise blood flow but have an impact on the patient experience.

In previously published analysis of the randomised trial iFR-SWEDEHEART, results found iFR and

FFR to be equally safe and effective with respect to risks for MACE. The cumulative MACE risks for each group differentiated by 1.6% (iFR: 21.5%, FFR: 19.9% at five years).

The results presented at TCT by Götberg revealed that patients in the iFR group had more risk factors compared with the FFR group but when adjusted for known confounders there was no difference in five-year MACE between patients who underwent iFR or FFR-guided revascularisation (32.2% vs.

31.3%). Furthermore, the outcome was similar in the individual components of MACE (death, myocardial infarction (MI), or new revascularisation) as well as in both deferred and treated subgroups.

“These new findings once again confirm the safety of iFR. We continue to see that iFR-guided treatment offers consistent outcomes, reduces costs, and

Pressure controlled coronary sinus occlusion does not reduce myocardial infarct size in STEMI patients A multicentre, prospective randomised trial of pressure controlled intermittent coronary sinus occlusion (PiCSO) therapy used in conjunction with primary percutaneous coronary intervention (pPCI)—PiCSO-AMI-I— found that it did not reduce myocardial infarct size in patients with anterior ST-segment elevation myocardial infarction (STEMI).

GIOVANNI LUIGI DE MARIA (JOHN Radcliffe Hospital, Oxford, UK) presented the findings of the trial, evaluated whether PiCSO therapy can further reduce myocardial infarct size in STEMI patients undergoing pPCI, during a TCT clinical trial session.

Primary PCI has improved clinical outcomes in patients with STEMI, but as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis which adversely affects long-term clinical outcomes, he said. Novel pharmacological and device-based therapies have been developed to limit infarct size in STEMI patients, largely unsuccessfuly.

PiCSO is used as an adjunctive procedure after epicardial flow has been restored during the primary PCI procedure. The mechanism of action, of intermittently occluding the coronary sinus outflow, redistributes venous blood-flow to the peri-infarct zone and enhances the coronary microcirculation viability by washing-out debris and other noxious agents of the infarct process.

The trial took place between July 2019 and August 2022, randomising 145 patients with anterior STEMI presenting within 12 hours of symptom onset and angiography demonstrated TIMI flow Picso catheter 0–1 of the left anterior

descending coronary artery 1:1 to PiCSOassisted pPCI (n=72) or conventional pPCI (n=73) at 16 centres throughout Europe. The PiCSO Impulse (Miracor Medical) catheter was inserted via femoral venous access after antegrade flow restoration of the culprit vessel prior to inserting a stent.

The primary endpoint was the difference in infarct size (expressed as a percentage of left ventricular mass) at five days by cardiac magnetic resonance imaging. Secondary endpoints were the extent of microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) at five days and infarct size at six months.

The study found no differences in infarct size at five days or six months. In addition, there were no differences between PiCSOtreated and control patients related to the occurrence of MVO (67.2% vs. 64.6%, p=0.85) or IMH (55.7% vs. 60%, p=0.72).

PiCSO use was safe with no device-related adverse events.

“Randomised trials like PiCSO-AMI-I play a crucial role in advancing our understanding of how to minimise infarct size,” said De Maria. “These results contribute to the ongoing body of research, offering valuable insight and stressing the importance of refining patient selection to better define the phenotype of STEMI patients who can benefit from additional therapies on top of primary PCI.”

Matthias Götberg

provides a better patient experience,” said Götberg.

“The data from this new analysis provide additional confidence in the safety of iFR for physicians.”

The data from this new analysis provide additional confidence in the safety of iFR for physicians.”

Orsiro wins out over Xience at five years in BIOSTEMI trial FIVE-YEAR-DATA FROM THE BIOSTEMI TRIAL confirmed the superiority of the Orsiro (Biotronik) drug-eluting stent (DES) over Xience (Abbott) DES in patients with acute ST-segment elevation myocardial infarction (STEMI).

Juan F Iglesias (Geneva University Hospitals, Geneva, Switzerland) presented the final study data in a late-breaking clinical science session at TCT 2023, and the results were published simultaneously in The Lancet.

BIOSTEMI is an investigator-initiated, multicentre, superiority trial, using a Bayesian design, to compare biodegradable-polymer, sirolimus-eluting Orsiro stent to the durable-polymer, everolimus-eluting Xience stent in 1,300 patients with acute myocardial infarction.

The ultrathin-strut Orsiro DES demonstrated superiority in the clinical primary endpoint of target lesion failure (TLF) at 12 months, which was further confirmed at 24 months with an incidence of 5.1%. In comparison, the Xience DES, showed an incidence of 8.1% at 24 months.

For the clinical primary endpoint of TLF at five years, Orsiro demonstrated superiority with an incidence of 7.7% compared to Xience with an incidence of 11.1% (posterior probability of superiority, 98.8%). The difference was mainly driven by a numerically lower risk for ischaemia-driven target lesion revascularisation for the Orsiro ultrathin strut DES, investigators reported.

“The BIOSTEMI ES study is truly unique as it is the first head-to-head randomised trial with a superiority design and long-term follow-up demonstrating significant differences between two contemporary DES for the treatment of patients with STEMI,” Iglesias said. “Another unique characteristic of this trial is the absence of late catch-up phenomenon with newer-generation biodegradable polymer DES after complete degradation of the polymer coating.”

Caused by a complete thrombotic occlusion in a coronary vessel, STEMI is the most acute manifestation of coronary artery disease, with substantial rates of morbidity and mortality. STEMI patients represent about 30% of all primary percutaneous coronary intervention (PCI) cases.

Issue 71 | November 2023

TCT Round-Up 17

Highlights from TCT 2023

Interventional cardiologists, cardiac surgeons and industry came together in California for TCT 2023. Here is a roundup of stories from around the congress.

MedTech Innovation Forum addresses global challenge of health inequity

CLASP IID trial and registry report favourably at one year for Pascal mitral repair system

Opportunities to improve access across society to new advances in medical device technologies were the focus of the opening session of the MedTech Innovation Forum at TCT 2023.

High-level speakers from the interventional cardiology, digital technology, medical devices and regulatory communities joined the panel to probe the current trends in cardiovascular disease across the developed and developing worlds, which hinted at widening gaps in health outcomes based upon income and educational status.

“We are developing amazing technologies,” Juan Granada, Cardiovascular Research Foundation (CRF) chief executive officer and president said, cautioning that many of these technologies may not be reaching those who need them the most. “I feel that when I go to different regions, most technologies are not making it to patients.”

Disparities in care are a particular problem for those living in rural communities, it was noted, who may not have easy access to healthcare facilities. The role of digital technologies and remote monitoring were touted as being potential solutions to this disparity, speakers agreed, but equitable access to these technologies will be required.

US Food and Drug Administration (FDA) commissioner Robert M Califf highlighted that this is a key area of focus for his organisation, but said that many challenges exist that may be preventing access to care. “The average population is not getting access [to new technologies] as long as the driver is the profit margin,” Califf remarked.

One-year results of the CLASP IID randomised registry affirm mitral transcatheter edge-toedge repair (TEER) in with degenerative mitral regurgitation (DMR) at prohibitive risk for surgery, investigators shared at TCT 2023.

Results from the CLASP IID randomised trial, comparing the Pascal (Edwards Lifesciences) and Mitraclip (Abbott) TEER therapies, showed that the Pascal system achieved a freedom from major adverse events (MAE) rate of 84.7% and significant and sustained reduction in mitral regurgitation (MR), with 95.8% of patients achieving MR ≤2+ at one year.

“These data from the CLASP IID randomised trial and registry further advance mitral edge-toedge repair as an important treatment option for a wide range of very sick patients who suffer with debilitating symptoms,” said Firas The PASCAL Zahr (Oregon Health & Precision Science University, Portland, transcatheter valve repair USA), CLASP IID study system investigator.

Technological solutions drift into society’s penthouses, diseases seep into its cracks.”

Robert M Califf US FDA Commissioner

Eliminating long-term aspirin for acute coronary syndrome patients is safe, effective, and reduces bleeding complications A joint analysis of the TWILIGHT and TICO trials has shown that a strategy of ticagrelor monotherapy, instead of the standard dual antiplatelet therapy (DAPT) of ticagrelor plus aspirin after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome significantly reduced total bleeding events without increasing total adverse cardiac events.

“This strategy of short dual antiplatelet therapy (ticagrelor plus aspirin) followed by ticagrelor monotherapy is associated with less bleeding without any compromise in ischaemic events,” said investigator Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA).

According to researchers, these data challenge the convention paradigm of using DAPT in all patients after an acute coronary syndrome, and offer a safe and effective option for physicians Roxana Mehran seeking to reduce bleeding risk in their patients.

Japanese registry finds use of IVUS in coronary interventions reduces mortality and need for coronary bypass surgery A Japanese multicenter registry including data from 8,721 patients undergoing percutaneous coronary intervention (PCI) has demonstrated that the use of intravascular ultrasound (IVUS) led to reduced mortality and need for coronary artery bypass graft (CABG) surgery.

The analysis revealed a reduced incidence of major adverse cardiac events, and improved long-term clinical outcomes in patients who underwent IVUS-guided procedures.

Toshiki Kuno (Montefiore Medical Center, New York, USA), said: “Our study provides robust evidence supporting the use of IVUS in coronary interventions. By visualising the coronary arteries in realtime, physicians can accurately assess the severity of the disease and optimise stent placement, ultimately leading to better patient outcomes.”

Research highlights inequities in access to mechanical circulatory support New research presented at TCT 2023, evaluating the presence of racial, ethnic, and socioeconomic inequities in access to mechanical circulatory support in the USA among patients with cardiogenic shock, revealed stark disparities, particularly among Black patients, that further highlight systemic inequities in access to lifesaving therapies, according to investigators.

“The magnitude of the inequities that we identified in this project are the largest that we have seen within the literature and demonstrate a critically important and urgent issue that needs to be immediately addressed in the care of patients with acute heart failure,” said Ashwin Nathan (Hospital of the University of Pennsylvania, Philadelphia, USA).

November 2023 | Issue 71

18

Structural Heart Interventions TCT 20 2 3

TAVI system for aortic regurgitation shows promise in ALIGN AR trial

Positive results from the ALIGN AR pivotal trial, investigating the use of the Trilogy (JenaValve) transcatheter aortic valve implantation (TAVI) system in high-risk patients with symptomatic, severe aortic regurgitation (AR), were presented during a late-breaking clinical trial session at TCT 2023 (23–26 October, San Francisco, USA).

VINOD THOURANI (PIEDMONT HEART Institute, Atlanta, USA), who presented the results of the study, said that the device is “well positioned to become the preferred therapy” for patients with moderate-to-severe or severe aortic regurgitation who may be at high risk for surgery.

Untreated, severe, symptomatic aortic regurgitation is associated with high mortality, Thourani explained in his presentation, adding that while surgery is only recommended in patients with native severe aortic regurgitation, there are a multitude of high-risk patients who are not offered therapy.

The self-expanding Trilogy valve is the first TAVI system designed to address this patient population, for whom treatment options are currently limited. 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.

ALIGN AR, which enrolled a total of 180 patients at 20 sites, is a landmark prospective, single-arm investigation device exemption (IDE) study designed to assess the safety and efficacy of the Trilogy system within high-risk patients with symptomatic aortic regurgitation and is intended to support a premarket approval submission to the US Food and Drug Administration (FDA). Clinical evaluation, echocardiography, functional and quality-of-life

assessments are scheduled at 30 days, six months, one year and annually up to five years.

On safety—assessed against a composite of 30-day all-cause mortality, stroke, life-threatening or major bleeding, major vascular complications, acute kidney injury (AKI), valve intervention, new permanent pacemaker or moderate or greater paravlavular regurgitation (PVR)—Thourani reported that the valve met 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%.

Simarly, the efficacy of the device—which was measured by the rate of all-cause mortality at one-

Vinod Thourani

year—also came in favourably, with a rate of 7.8% reported by investigators, compared against a 25% prespecified non-inferiority margin.

Thourani also reported the rate of new pacemaker implantations seen throughout the trial, divided into the first, second and third group of 60 patients enrolled, which stood at 30%, 28% and 14% respectively. He attributed this improvement toward the later stage of the trial as likely being due to the insertion technique, placing locators above the nadir of the native valve cusp, a reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities.

Alongside these findings, Thourani noted that there were further positive indicators of the valve’s performance, with large effective orifice area (EOA) and low transvalvular gradients, as well as low PVR at one year. In addition, echocardiography demonstrated improvements in left ventricular (LV) remodelling, and patients reported sustained improvement in quality of life and heart failure functional status through to one year.

“In a population of symptomatic patients with moderate to severe, or severe aortic regurgitation at higher surgical risk, TAVI using the Trilogy THV [transcatheter heart valve] achieved safety outcomes that met the 30-day performance goal, achieved an efficacy outcome of all-cause mortality that met the 12-month performance goal and among safety endpoints the rate of new pacemaker implantation was 24% and declined during the course of the trial due to changes in implant technique and oversize strategy,” Thourani said in his concluding remarks.

“The Trilogy THV performance was excellent, with a large EOA and low transvalvular gradients. There was 0 moderate or greater than moderate PVR at one year and echocardiography demonstrated significant improvement in LV remodelling.”

convenience and safety,” said lead for the use of a direct oral anticoagulant, patients undergoing TAVI plus LAAO No difference author Samir Kapadia (Cleveland Clinic, warfarin or no blood thinners, based compared to TAVI plus medical therapy.

Cleveland, USA). “If patients can get on the physician’s discretion. One third In the trial, the Watchman patients in outcomes both procedures done at the same time, of patients who were in the medical received blood thinners for 45 that eliminates the need to be on blood therapy control group were not on blood days followed by dual antiplatelet for AF patients thinners, which can have significant side thinners at two years. therapy (DAPT) until six months. effects. In addition, many patients can The primary endpoint, a composite Anticoagulation was based on the undergoing not take the medications due to high risk of all-cause death, stroke and major treating physician’s preference for of bleeding.” bleeding at two years, showed that patients randomised to TAVI plus LAAO and TAVI Patients with AF undergoing TAVI there were no differences in outcomes medical therapy. an increased risk of death, stroke for patients when getting TAVI plus At baseline, 85.4% of patients were at the same time have and rehospitalisation compared to LAAO compared to getting TAVI plus taking blood thinners and 71.3% of

Patients with atrial fibrillation (AF) undergoing a transcatheter aortic valve implantation (TAVI) at the same time as a left atrial appendage occlusion (LAAO) procedure using the Watchman (Boston Scientific) device had similar outcomes when compared to patients getting TAVI in addition to medical therapy or blood thinners.

RESULTS FROM THE WATCH TAVR trial were presented during a late-breaking clinical trial session at the 2023 TCT meeting and simultaneously published in the journal Circulation.

“WATCH TAVR is a novel study where two devices were used in order to combine the TAVI procedure for patient

those without AF. The multicentre, randomised WATCH-TAVR trial set out to investigate the safety of implantation of the Watchman 2.5 device at the time of TAVI and to compare the efficacy of Watchman LAAO with contemporary medical therapy in this population of patients with an increased risk of bleeding and stroke.

The trial enrolled 349 patients with severe aortic stenosis and AF. Of these, 177 patients received TAVI plus the LAAO procedure and 172 patients received TAVI plus medical therapy.

The trial took place between December 2017 and November 2020 at 34 centres in the USA. The mean age was 81 years old.

Patients in the TAVI plus medical therapy control group were managed by their treating physician, which allowed

medical therapy. However, there was a higher rate of blood clots, mainly more frequent blood clots in the veins, in

If patients can get both procedures done at the same time, that eliminates the need to be on blood thinners, which can have significant side effects.”

patients were on antiplatelet therapy.

After 24 months, 82.5% compared to 50.8% of patients were on any antiplatelet therapy, and 13.9% compared to 66.7% of patients were on any blood thinner therapy in the TAVI plus LAAO group compared to TAVI plus medical therapy group, respectively.

“Although the findings showed similar outcomes, the increased complexity and risks of the combined procedure should be considered when LAAO is viewed as an alternative to medical therapy for patients with atrial fibrillation undergoing TAVI,” said Kapadia.

The trial was coordinated by the Cleveland Clinic Coordinating Center for Clinical Research and funded by a research grant from Boston Scientific.

Structural Heart Interventions 19

Issue 71 | November 2023

Initial phase of TRISCEND II trial of Evoque transcatheter replacement for severe tricuspid regurgitation meets primary endpoints A RANDOMISED TRIAL comparing transcatheter tricuspid valve replacement (TTVR) with the Evoque system (Edwards Lifesciences) to medical therapy in patients with severe tricuspid regurgitation (TR)— TRISCEND II—has demonstrated “meaningful improvements in functional status and symptoms” at six months.

This was the headline finding delivered by Susheel Kodali (Columbia University Medical Center, New York, USA) during a late-breaking clinical trial session at the 2023 TCT meeting (23–26 October, San Francisco, USA), in which he presented the first tranche of data from 150 patients.

Kodali previously presented sixmonth findings from TRISCEND—the single-arm study of the device—at TCT 2021 where he reported a significant reduction in TR severity as well as significantly improved functional and quality-of-life outcomes among patients

(KCCQ), New York Heart Association (NYHA) classification and six-minute walk test (6MWD).

Kodali reported that the valve was successfully implanted in 95.8% of enrolled patients and that the trial met its primary endpoints with an MAE rate at 27.4% at 30 days, as well as a significant TR grade reduction with 98.8% of patients achieving ≤ moderate who received the therapy.

TR and 93.8% achieving TRISCEND II, the ≤ mild TR at six months. multicentre, randomised Additionally, Kodali relayed pivotal trial comparing the that there were superior device to medical treatment, quality-of-life and functional has enrolled a total of 400 outcomes at six months patients and was designed as for the composite endpoint a two-part study with initial including KCCQ, NYHA safety and efficacy endpoints and 6MWD for the Evoque presented at six months. system plus medical therapy Susheel Kodali Full echocardiographic and over medical therapy alone. clinical data will be analysed at one year “We are excited by the safety and including the full patient cohort, and effectiveness data from the first 150 Kodali said that these data are expected patients of the TRISCEND II pivotal in the coming year. trial,” said Kodali. “With no predicate Kodali’s presentation detailed the study of a novel transcatheter tricuspid initial phase of the US Food and Drug valve replacement, these data and Administration (FDA) breakthrough outcomes give us great hope in the device trial, including a primary safety Evoque system as an option to treat endpoint of major adverse events patients who are very sick and have few (MAE) at 30 days, and an effectiveness effective therapeutic options.” endpoint comprising TR grade reduction An FDA advisory committee meeting and including changes in Kansas of the Evoque system is expected City Cardiomyopathy Questionnaire in January 2024, followed by an

TRILUMINATE quality-of-life data point to benefit for patients with severe TR undergoing TEER Analysis of health status and quality-oflife data from the TRILUMINATE pivotal trial, presented at TCT 2023 indicates that patients undergoing transcatheter edgeto-edge-repair (TEER) for severe tricuspid regurgitation (TR) provides “substantial” benefits for symptoms, functional status and quality of life compared to medical therapy, investigators have reported.

S

uzanne Arnold (Saint Luke’s Mid America Heart Institute/UMKC Kansas City, Kansas City, USA) presented the data, which investigated the use of the TriClip (Abbott) device, during a late-breaking clinical trial session at the TCT meeting.

Primary results of the trial were presented at the 2023 American College of Cardiology (ACC) annual scientific session (4–6 March, New Orleans, USA), where it was reported that the transcatheter device was

effective in reducing TR and led to improvements in quality of life at one year. However, the results did not show any significant difference in survival or heart failure hospitalisation between patients treated with the interventional approach or with medical therapy, the study’s control arm, with the superiority of the device in meeting its composite primary endpoint mainly driven by improvements in quality of life for patients.

Investigators performed an in-depth analysis of the health status outcomes to describe the timing, magnitude, and consistency of the health status benefits and to estimate the biologic correlates of health status after the procedure and the clinical relevance of the health status benefit.

The trial randomised patients with severe TR to TEER (n=175) or medical therapy alone (n=175).

Health status was assessed at baseline as well as at one, six, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and at baseline, one and 12 months with the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey.

The primary health status endpoint was the KCCQ overall summary score (KCCQ-OS; range 0–100; higher=better) which was compared between treatment groups using mixed effects linear regression. Alive and well at one year was defined as KCCQ-OS greater than or equal to 60 and no decline from baseline greater than 10 points.

Compared with medical therapy alone, TEER resulted in a significantly greater improvement in the KCCQ-OS at one month (mean Suzanne Arnold

anticipated US approval in mid-2024, Edwards Lifesciences has stated. The device received FDA breakthrough designation in 2019, and received CE mark for the transcatheter treatment of eligible patients with TR in October 2023 (see page 25).

With no predicate study of a novel transcatheter tricuspid valve replacement, these data and outcomes give us great hope in the Evoque system as an option to treat patients who are very sick and have few effective therapeutic options.”

between-group difference 9.4 points, 95% confidence interval [CI] 5.3–13.4) with a small additional improvement at one year (mean between-group difference 10.4 points, 95% CI 6.3–14.6), Arnold reported. Improvements in quality of life were greater among those with the most severe symptoms.

Interaction analyses demonstrated that the benefit of TEER diminished as baseline KCCQ-OS increased.

TEER patients were also more likely to be alive and well at one year compared to those who received medical therapy alone (74.8% vs. 45.9%, p<0.001) with a number needed to treat of 3.5 to derive benefit.

“As with any medical procedure, the impact on a patient’s quality of life is an important factor in assessing its success,” said Arnold. “Compared with medical therapy alone, TEER resulted in substantially better health status at one month that was sustained through one year. These findings support the use of TEER with the transcatheter tricuspid valve repair system for improvement in the symptoms, functional limitations, and quality of life in patients with severe TR.”

Compared with medical therapy alone, TEER resulted in substantially better health status at one month that was sustained through one year.”

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Issue 71 | November 2023

Advertorial 21

THIS ADVERTORIAL IS SPONSORED BY MEDTRONIC

NOTION trial results crystallise long-term thinking on TAVI versus SAVR

least as good up to 10 years.”

Further, Abdel-Wahab notes that these results, while reflecting a positive long-term picture for the durability and outcomes with the CoreValve cannot be applied across all TAVI platforms. “It depends on several factors, but one key factor that affects durability is haemodynamics and we know from a lot of studies, this valve has the best in class With transcatheter aortic valve implantation (TAVI) now increasingly being considered haemodynamics, and it appears that this has an impact as an option for younger patients who may be at low risk for surgery, the need for on durability,” he comments. long-term data charting the durability of transcatheter valves, as compared to those Also important to consider is that the NOTION trial implanted during a surgical procedure, becomes ever more important. results reflect experience using the first-generation CoreValve devices, which have now been replaced by he recent presentation of 10-year data from the valve dysfunction). the newer-generation Evolut™ (Medtronic) family of NOTION trial—the longest-running randomised In the trial, structural valve deterioration was TAVI valves. Abdel-Wahab suggests that importantly clinical study to compare outcomes among considered to be present if the patient had a as it relates to current practice, the design of the lower-risk patients undergoing TAVI using the first transprosthetic mean gradient ≥20mmHg, an increase leaflets of the supra-annular device, which contributes generation CoreValve™ (Medtronic) device versus of 10mmHg from three months, or more to its durability, remain consistent between surgical aortic valve replacement (SAVR)—is seen as than mild intraprosthetic aortic regurgitation. the earlier generation and the currently a milestone moment in the continuing development The NOTION investigators found the risk of available devices. Changes between the of the TAVI procedure. Reported by Troels Hojsgaard structural valve deterioration was increased generations have focused on the stent frame Jorgensen (Copenhagen University Hospital, in patients with a surgical bioprosthesis at and the delivery of the device, which he Rigshospitalet, Copenhagen, Denmark) at the 2023 37.7%, when compared to patients with a suggests mean that durability is likely to be European Society of Cardiology (ESC) congress transcatheter heart valve, whose risk was similar with the newer systems.

(25–28 August, Amsterdam, The Netherlands), the 10around 20.2%.

“Other endpoints may be favourably Mohamed Abdel-Wahab affected by the newer-generation device, year NOTION trial data offer important insights into Detailing findings on the composite risk long-term outcomes among lower surgical risk patients of bioprosthetic valve failure, comprising the because you have fewer acute complications receiving either a TAVI or SAVR valve. risk of valve-related death, the need for aortic valve with this device compared to the previous one,” The data presented by Jorgensen at the ESC meeting Abdel-Wahab speculates. “You can position it more paint a reassuring picture for TAVI in the long-term, precisely for example, [and] you have fewer leaks or with patients undergoing TAVI demonstrating a similar pacemakers. The delivery catheter is smaller so you risk of all-cause mortality, stroke and myocardial may have less vascular and bleeding complications. infarction (MI) as those treated surgically. What is All of these acute complications affect long-term perhaps more important to learn from the 10-year outcome as well.”

NOTION data is the relative performance of the Considering how these results will impact his valves in terms of structural valve deterioration practice, Abdel-Wahab says that his institution and bioprosthetic valve failure of the CoreValve is already “progressive” in considering TAVI as (Medtronic) TAVI valves when compared to those a treatment option for patients considered at low implanted during surgery. risk for surgery, but the latest data help to focus “The data we have on 10-year durability of TAVI discussion, particularly if more long-term data confirm CoreValve™ are very scarce and what we had before NOTION the findings seen within NOTION. Importantly, TAVI platform were just registry-based analyses describing durability he says, the trial can change thinking about the of TAVI not compared to surgery, so this is really the lifetime management of younger patients who may first time we see such a long-term outcome assessment be considered for TAVI, and face the possibility of from a randomised trial,” Mohamed Abdel-Wahab needing a further procedure later down the line.

(Leipzig Heart Center, Leipzig, Germany) tells “If you think that the patient will need a second Cardiovascular News, commenting on the significance valve then you need a plan, and you need to be sure of these latest data. that it will be anatomically possible. This is the way Abdel-Wahab praises the quality of the execution things should be discussed in the heart team,” he says, of the trial, which was conducted at sites in Denmark commenting that if a patient may be suitable for either and Sweden between 2009–2013, and in particular TAVI or surgery, then the decision may be based on he praises the availability of 10-year follow-up data, the possibility for reintervention later down the line. collected from 27 patients from an initial cohort of Asked how future iterations of practice guidelines 120 in the trial’s SAVR arm, and 34 of an initial 130 could take these results into account, Abdelpatients who underwent TAVI. Wahab offers the view that a simple “age-based” “We know from experience that it is extremely recommendation for TAVI or SAVR may not be hard to get such long-term follow-up in a population sufficient to identify the patients who are most suitable of patients that are elderly and usually have multiple for either strategy. comorbidities,” he comments. “It is not that easy to “We are learning a lot on how to decide which get them back to do an echocardiographic follow-up strategy to use, and it should not be an age cut-off, but which is the cornerstone of having a good durability it should be an anatomical decision-making process assessment.” reintervention, or the development of severe structural for patients, based on the expected acute result and the The definition of structural valve deterioration valve deterioration, NOTION trial investigators expected possibilities for reintervention in the future,” as used in the NOTION trial is an important point reported a failure rate of 15.1% in the surgical arm, he concludes. to reflect on, says Abdel-Wahab, as this has been a compared to 10.8% in the transcatheter arm, with no The 10-year NOTION data add to the growing significant area of debate. Since the commencement significant differences between the two groups overall, body of evidence to support decision-making when of the trial a consensus document on valve durability or for the individual endpoints apart from severe weighing up the best choices for treating aortic from the European Association of Percutaneous structural valve deterioration. stenosis. This continues to evolve, with the release Cardiovascular Interventions (EAPCI) was published According to Abdel-Wahab, these findings lead to of four-year results from the Evolut Low Risk trial at in 2017 in the European Heart Journal, defining valve an important takeaway message from the trial: that TCT 2023 (23–26 October, San Francisco, USA; see durability using both bioprosthetic valve dysfunction TAVI valves perform at least as well as their surgical cover story), and the first anticipated data release from (comprising of structural valve deterioration, nonequivalents when it comes to durability. the SMART post-market trial, a randomised, headstructural valve deterioration, and bioprosthetic “If you want to interpret the results in a more or less to-head study comparing the Evolut PRO and PRO+ valve thrombosis/endocarditis) and bioprosthetic neutral way, we do not have any reason to believe that systems with the Sapien 3 and Sapien 3 Ultra valve failure (valve-related death, aortic valve TAVI with the CoreValve device will have a durability valves (Edwards Lifesciences), helping to guide reintervention, and severe haemodynamic structural issue compared to surgery,” he comments. “It is at physicians further.

T

We do not have any reason to believe that TAVI with the CoreValve device will have a durability issue compared to surgery.

It is at least as good up to 10 years.”

November 2023 | Issue 71

22 Coronary Intervention

because most previous research did not consider changes in smoking habits SMOKING CESSATION before and after PCI, leaving the effects of quitting smoking after PCI largely unexplored.

He said: “From the beginning of this study, my colleagues and I, as clinical researchers, suspected that there could be a threshold for irreversible harm resulting from smoking. Yet, the revelation that this threshold lies around 20 pack years—not like just five or 10 pack years—was an encouraging discovery. It suggests that smokers undergoing percutaneous coronary intervention, who have not reached a cumulative smoking exposure of 20 pack years, may still have an opportunity to evade the lasting detrimental effects on their cardiovascular outcomes caused by smoking.

“Patients undergoing percutaneous coronary intervention should be encouraged to quit smoking as soon as possible, and smoking cessation may improve their cardiovascular outcomes even within a relatively short period of time. This emphasises the paramount importance of clinicians’ attention to their patients’ smoking status, along with the combined efforts of clinicians, patients, and policymakers in promoting smoking higher rate of cessation.”

MACCE among The study also contributes to smokers after PCI de-bunking what is known as the “smokers’ paradox”; some previous Patients who quit smoking after undergoing percutaneous coronary intervention (PCI) for studies seemed to suggest that narrowed arteries have similar outcomes as non-smokers during four years of follow-up after the smokers who had a heart attack had a procedure, according to a large study published in the European Heart Journal. However, if they better prognosis after PCI. had been heavy, long-term smokers, no improvement was seen.

“A sub-group analysis of our study, which included 28,266 patients with he study of 74,471 patients who had current smokers had a 19.8% higher smoking exposure of 20 pack years, had myocardial infarction, refuted this a PCI between 2009 and 2016 is the rate of MACCE than people who had cardiovascular risks similar to those paradox by demonstrating that current first, large population-based study never smoked, and ex-smokers had a of non-smokers. Notably, this finding smokers had a significantly higher to examine the impact of smoking comparable rate as never-smokers. was observed within a relatively short rate of adverse cardiovascular events on cardiovascular outcomes, such as Additionally, they also analysed data interval after smoking cessation—a compared to non-smokers. Notably, the death, heart attacks, and strokes, since from 31,887 patients with information median of 628 days between pre- and positive impact of smoking cessation drug-eluting stents (DESs) were first on their smoking habits before and post-PCI-health check-ups.” in patients with myocardial infarction approved for use in PCIs in Europe in after PCI to further assess the impact One of the reasons Han and his was not as pronounced as in the overall 2002 and in the USA in 2003. of quitting smoking after PCI. They colleagues conducted the study was study population. This may be due The researchers, led by Jung-Kyu Han assessed how much patients smoked to insufficient numbers of patients (Seoul National University Hospital, by placing them in four groups: less and events in the subgroup analyses, Seoul, South Korea), analysed data than 10 pack years, between 10 and 19 or because the synergistic effects of from the Korean National Health pack years, between 20 and 29 pack heart attack and smoking resulted Insurance System nationwide database years, and over 30 pack years. ‘Pack in more irreversible damage to the to investigate patient outcomes over years’ indicates a person’s accumulated myocardium,” said Han. four years following PCI. They looked exposure to tobacco; this was reached A strength of the study is that itis at major adverse cardiovascular and by multiplying the number of cigarettes based on the Korean National Health cerebrovascular events (MACCE), smoked a day by the number of years Insurance System, which covers 97% a composite of all-cause death, the person had smoked. of the Korean population, and is one myocardial infarction (MI), coronary Quitters who stopped smoking of the most comprehensive sources of revascularisation, and stroke. after PCI and who had smoked less data on people’s health. Limitations As well as collecting information on than 20 pack years had a comparable include: whether or not a person smoked factors that could affect the results, such rate of MACCE as people who had and how much was self-reported in a as age, sex, diabetes, blood pressure, never smoked. However, those who questionnaire and may not reflect the alcohol drinking, exercise, body had smoked more than 20 pack years true status; other, unknown factors mass index (BMI), medications and before quitting had a 20% higher rate might affect the findings; the findings socioeconomic status, they also gathered of MACCE, similar to the rate for cannot be generalised to all races; and information on whether or not the persistent smokers. pack years cannot differentiate between patients were current smokers, neverHan said: “Patients who quit smoking the impact of long-term smoking at smokers, or ex-smokers. after undergoing percutaneous coronary low doses from short-term smoking During four years of follow-up, intervention, with a cumulative at high doses.

Smokers who quit after a PCI have similar outcomes to non-smokers

19.8%

T

Patients who quit smoking after undergoing percutaneous coronary intervention, with a cumulative smoking exposure of 20 pack years, had cardiovascular risks similar to those of nonsmokers.”

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November 2023 | Issue 71

24 Market Watch

Intellistent multi-lumen stent system for pulmonary arterial hypertension wins TCT 2023 Shark Tank innovation prize

with preserved right ventricle function provides a novel alternative as a ‘bridge-to-transplant’ or as an alternative to destination therapy in infants and children with advanced left ventricle dilated cardiomyopathy.

Seth Bogner, chairman and CEO of Heartpoint Global said: “We are deeply honoured to be bestowed Heartpoint Global was named winner in the Shark Tank innovation competition at the with this prestigious award. TCT stands as a pinnacle 2023 TCT conference (23–26 October, San Francisco, USA). The company received the platform for highlighting innovation in cardiovascular award for its novel multi-lumen stent system for interventional adjustment of pulmonary medicine. Having our technology acknowledged by blood flow in congenital heart disease, Intellistent. such a distinguished panel of judges is truly humbling.

We are eager to forge ahead eartpoint Global’s pioneering approach to and allows for the adjustment with Heartpoint Global’s intreating pulmonary arterial hypertension of blood flow in the heart-lung human trials and anticipate its caused by congenital heart disease and system. Patients with severe substantial clinical impact in pulmonary arterial hypertension (PAH-CHD) stood PAH can become surgical the future.” out due to its potential to address a significant unmet candidates after Intellistent The TCT Shark Tank clinical need,” said Juan F Granada, CEO and president treatment (bridge-to-surgery). innovation competition has of the Cardiovascular Research Foundation (CRF), The embedded technology partnered with the Jon DeHaan organiser of the TCT conference. “It was selected will be used to treat many Foundation for six years to as the winner by a distinguished panel of judges, other indications. provide a US$200,000 award including physician innovators, physician investors, Previous successful prefor the winner. The Shark Intellistent wins the Shark Tank prize and experts actively involved in building companies clinical tests of the implant Tank Innovation Competition and developing innovative, high-impact therapies.” system studied the direct aims to identify and showcase Intellistent is described by Heartpoint Global placement of the device in the main pulmonary groundbreaking concepts in modern cardiovascular as a groundbreaking multi-lumen stent system for artery and bilateral delivery in the left and right medicine. This year, six companies were chosen interventional adjustment of pulmonary blood flow pulmonary arteries and branches. Research presented to present at TCT. The Jon DeHaan Foundation to treat PAH-CHD. It reproduces the effects of the at TCT by Elena K Amin (University of California, supports those working to advance cardiac medicine validated surgical therapy, pulmonary artery banding, San Francisco, San Francisco, USA), a member of and provides grants and awards to individuals and and is patented in over 20 regions, including the USA, Heartpoint Global’s advisory board, demonstrated companies who focus on innovative developments European Union, and China. The device is placed in first proof-of-concept results showing that reversible in cardiovascular medicine, including research, the main pulmonary artery and the arterial branches pulmonary artery banding in left ventricle failure prevention, diagnosis, treatment, or rehabilitation.

“H

Industry News MedAlliance acquired by Cordis

MedAlliance has been acquired by Cordis for a 2022 investment of US$35 million and an upfront closing payment of US$200 million, together with regulatory achievement milestones of up to US$125 million and commercial milestones of up to US$775 million through 2029, for a total consideration of up to US$1.135 billion.

Cordis is a developer and manufacturer of interventional cardiovascular and endovascular technologies. MedAlliance’s sustained sirolimus drug-eluting balloon (DEB) programme, Selution SLR, has provided a flagship product family which complements Cordis’ existing product portfolio, together with its sales, marketing and distribution expertise, the companies said in a press release. Cordis customers will benefit from the extensive clinical study programme and publication plan that have been executed by MedAlliance to further Cordis’ heritage of bringing innovative products to patients, the press release states.

“The Cordis acquisition will accelerate access to this breakthrough technology for patients around the globe suffering from coronary and peripheral disease,” said Jeffrey B Jump, founder, chairman and CEO of MedAlliance. “I want to thank our entire MedAlliance team—including physicians, distributors and clinical patients—who have succeeded in disrupting the coronary and peripheral markets to provide a safe and effective

new technology. The arsenal of Selution SLR DEB clinical data is designed to change medical practice and improve patient outcomes.”

“We are excited to report on the positive Selution SLR data to date, with first-hand experience of the impressive clinical outcomes from patients treated with Selution SLR in Japan, India, Europe, and South America. We are now leading the effort to emulate these results in the USA. This technology has the distinct opportunity to change the treatment paradigm for patients suffering from cardiovascular and peripheral vascular disease,” commented George Adams (Cardiovascular and Peripheral Vascular Research, Rex Hospital, Raleigh, USA), Steering Committee member of both the US SELUTION4SFA and SELUTION4BTK IDE studies.

Nick West appointed to associate CMO role at Shockwave Medical

Shockwave Medical has announced that Nick West has joined the company in the role of associate chief medical officer (CMO). He reports to current CMO Keith Dawkins, and will be based in Santa Clara (USA) with plans to succeed Dawkins in mid-2024.

“Dr West brings to Shockwave a wealth of expertise in the interventional cardiology space,” said Dawkins.

“Having known Nick for many years, I am confident that his expertise will be highly influential in further developing intravascular lithotripsy (IVL) as

the standard of care for calcium modification, and will also be a valued asset in the evaluation and development of novel transformational technologies to augment our portfolio in the years to come.”

West joins Shockwave from Abbott Vascular, where he served as CMO and divisional vice president of global medical affairs for the past four years.

Prior to his time with Abbott, West served as an attending cardiologist at the Royal Papworth Hospital NHS Foundation Trust (Cambridge, UK).

“There is no denying the exceptional job Shockwave has done to generate significant momentum behind IVL in a relatively short period of time.

I am extremely excited to utilise

Nick West

everything I have learned from my time both in industry and previously as an interventional cardiologist to help continue to propel Shockwave forward as one of the most innovative players in the cardiovascular space,” said West.

OpSens and Haemonetics enter into acquisition agreement OpSens has entered into a definitive arrangement agreement with

Haemonetics Corporation that will see Haemonetics indirectly acquire all of the issued and outstanding common shares in the capital of OpSens.

OpSens’ board of directors unanimously approved the transaction and has recommended that shareholders vote in favour of the deal.

OpSens’ products include the OptoWire, a guidewire designed to help in the diagnosis and treatment of fractional flow reserve (FFR), and SavvyWire, a minimalist approach guidewire for transcatheter valve implantation (TAVI) procedures.

Haemonetics believes that these products will provide significant synergies with its own device portfolio, which includes Vascade and Vascade MVP, catheter-based vascular access site closure devices generally used in interventional cardiology, electrophysiology, and peripheral vascular procedures.

“This transaction will create value for our shareholders and is a testament to the quality of the team’s work over the years, the added value of our products, and the potential for the years to come,” said Louis Laflamme, president and chief executive officer of OpSens. “The integration within Haemonetics should enhance the benefits for OpSens’ products with access to a world-class sales network, while capitalising on the specialised production and R&D expertise of OpSens. From design to production, OpSens’ expertise and knowledge are recognised by clinicians, hospitals and device industry suppliers and OpSens’ innovative products will be a valuable addition to Haemonetics’ existing product line.”

Issue 71 | November 2023

Market Watch 25

Product News

Mitris Resilia

Evoque

Edwards Lifesciences gains CE mark for mitral surgical valve and transcatheter tricuspid systems

“The Evoque system is able to fully replace the tricuspid valve, virtually eliminating TR in a wide range of anatomies,” said Philipp Lurz (University of Mainz, Mainz, Germany), European principal investigator for the TRISCEND II study. “The significant improvements in patients’ quality of life are remarkable, now offering a therapy to many patients who previously had no treatment options.”

Edwards Lifesciences has received CE mark for the Mitris Resilia tissue valve replacement specifically designed for the mitral position as well as the Evoque tricuspid valve replacement for the transcatheter treatment of eligible patients with tricuspid regurgitation (TR).

The Mitris Resilia valve is made with bovine pericardial tissue technology that is designed to reduce calcium build-up on the valve. According to the company, this technology enables the valve to potentially last longer than conventional bioprosthetic valves.

Recent data on the Resilia tissue from the COMMENCE aortic trial reported encouraging results with low rates of structural valve deterioration (99.3% freedom from structural valve deterioration), clinically stable gradients and freedom from reoperation (97.2%) through seven years.

Additionally, the COMMENCE mitral trial demonstrated clinically stable haemodynamics and freedom from structural valve deterioration (98,7%) at five years.

“Mitral valve disease is prevalent and patients experience the disease in various ways. For patients who need mitral valve replacement, the advanced Mitris Resilia valve, designed to mimic the native valve, is based on a trusted pericardial Perimount,” said Daniel Pereda Arnau (H Clínic de Barcelona, Barcelona, Spain). “As valve durability is becoming increasingly important, the integrity-preservation technology incorporated in the Resilia tissue that will potentially allow the valve to last longer is critical.”

The Mitris Resilia valve received US Food and Drug Administration (FDA) approval in 2022, and its introduction into the portfolio demonstrates Edwards’ continuous investment in innovation for the benefits and the quality of life of patients, a press release states.

The company also announced that the Evoque tricuspid valve replacement system received CE mark for the transcatheter treatment of eligible patients with TR. The Evoque system is comprised of a nitinol self-expanding frame, intra-annular sealing skirt, and tissue leaflets made from the same bovine pericardial tissue as the company’s current heart valves. The Evoque valve will be available in three sizes, all delivered through a lowprofile transfemoral 28Fr system.

Boston Scientific gains US FDA clearance for AVVIGO+ multimodality guidance system

Boston Scientific has announced US Food and Drug Administration (FDA) clearance of the AVVIGO+ multimodality guidance system, a nextgeneration intravascular ultrasound (IVUS) and fractional flow reserve (FFR) system.

The system features advanced software and hardware features designed to provide high-quality IVUS vessel imaging and physiology experience during percutaneous coronary intervention (PCI) procedures, the company said in a statement.

Building upon the AVVIGO guidance system II, the technology helps to inform treatment decisions and enable faster, more efficient treatment procedures such as angioplasties and atherectomies for patients with coronary artery disease, Boston Scientific adds. The company also received CE mark for the system, with launch anticipated early next year.

“We are pleased to introduce US clinicians to the next-generation AVVIGO+ multi-modality guidance system, which builds upon the AVVIGO guidance system II and provides fast, intuitive and accurate vessel and lesion assessment capabilities for percutaneous coronary interventions,” said Lance Bates, president, Interventional Cardiology Therapies, Boston Scientific. “Coming on the heels of the updated American College of Cardiology (ACC) guidelines recommending intracoronary imaging during PCIs, we believe this enhanced and automated tool will help physicians optimise these procedures to provide better outcomes for their patients with coronary artery disease.”

Medtronic receives CE mark for Evolut FX TAVI system to treat severe aortic stenosis

Medtronic has received CE mark for the Evolut FX transcatheter aortic valve implantation (TAVI) system, the newest

generation of its CoreValve/Evolut TAVI platform.

In a press release, Medtronic states that the Evolut FX system is designed to enhance ease-of-use and provide greater precision and control throughout the procedure for clinicians treating patients with severe aortic stenosis. The CoreValve/Evolut platform is the only TAVI platform to demonstrate a durability advantage over SAVR at five and 10 years in a randomised trial.

The Evolut FX system incorporates the same supra-annular, self-expanding valve design as the CoreValve/Evolut platform which has shown to have a superior haemodynamic performance compared to surgical aortic valve replacement (SAVR) at one year across three separate, large-scale, randomised controlled trials.

The fourth-generation Evolut technology is equipped with gold markers built into the frame to provide implanters with direct visualisation of depth and valve leaflet orientation during implant. In addition, the Evolut FX system incorporates a redesigned catheter for a smoother insertion profile and a more flexible delivery system for a stable, predictable deployment.

“With the latest Evolut FX system,

Evolut FX

we are elevating the precision, control and predictability of transcatheter aortic valve replacement procedures for patients with severe aortic stenosis,” said Danny Dvir (Shaare Zedek Hospital Canter, Jerusalem, Israel).

“The system provides physicians with an innovative solution to meet the needs of a patient population desiring to get back to their active lifestyles sooner.”

The Evolut FX system is indicated for severe aortic stenosis in adult patients across all risk categories (extreme, high, intermediate, and low) in the European Union (EU) and is indicated for symptomatic severe aortic stenosis patients across all risk categories in the USA. The Evolut FX system is expected to be commercially available across Europe as teams and physicians are trained on the new technology.

Recor Medical gains first US FDA renal denervation approval

Recor Medical has become the first company in the USA to have a device-based therapy approved for the treatment of hypertension, after it was announced that the US Food and Drug Administration (FDA) has approved the company’s Paradise ultrasound renal denervation system.

The Paradise system is intended as

an adjunctive treatment option when lifestyle changes and medications have not adequately controlled a patient’s blood pressure. The Paradise catheter features the HydroCooling system, which circulates sterile water through the balloon catheter during the procedure to help protect the renal artery wall.

Approval of the Paradise system follows Recor’s positive FDA Advisory Committee Panel in August 2023. Earlier this year, results from Recor’s US pivotal study, the RADIANCE II randomised clinical trial, were published in the Journal of the American Medical Association (JAMA). In the study, the Paradise system met both the primary safety and effectiveness endpoints without any major adverse events.

“Despite the longstanding availability of dozens of affordable anti-hypertensive medications, blood pressure control rates in the USA are alarmingly low and falling. Given the significant blood pressure reductions seen in the ultrasound renal denervation trials, the Paradise ultrasound renal denervation system offers a much-needed advancement in our currently available options to control hypertension,” said site principal investigator Naomi Fisher (Brigham and Women’s Hospital, Boston, USA).

“Ultrasound renal denervation has proven efficacy in patients with truly resistant hypertension, a population for whom medication therapy often fails. It is also effective in patients with mildto-moderate hypertension who cannot tolerate enough medication to control their blood pressure.”

The Paradise system previously received CE mark and has been successfully introduced in Europe and is an investigational device in Japan.

Elixir Medical submits approval for DynamX coronary bioadaptor in Japan

Elixir Medical has announced submission to Japan's Pharmaceutical and Medical Device Agency (PMDA) for the approval of the DynamX coronary bioadaptor for the treatment of coronary artery disease.

DynamX was developed to overcome the limitations of drug-eluting stent (DES) and bioresorbable scaffold (BRS) technologies.

The device is a novel coronary implant designed to unlock the scaffold, uncage the vessel, and provide the essential dynamic support after uncaging to return normal vessel motion and function after percutaneous coronary intervention (PCI).

“Drug-eluting stents have served an important role in the treatment of coronary artery disease, but have yet to overcome many challenges, including restricting vessel motion and function, mechanical failure, and progression of plaque,” said Shigeru Saito (Shonan Kamakura General Hospital, Kamakura, Japan), principal investigator of the BIOADAPTOR RCT trial.

November 2023 | Issue 71

26 Market Watch

Clinical News First patients treated with Laguna Tech’s Zeta transcatheter valve system for aortic regurgitation

Laguna Tech USA has announced that the first-in-human clinical case was completed with the Zeta balloonexpandable aortic valve system, while additional patients have been successfully treated in the feasibility clinical study of its investigational Alpha self-expanding aortic valve system to treat aortic regurgitation.

To date, two patients have been successfully treated in the Alpha aortic valve study, with both achieving complete resolution of aortic regurgitation immediately following the procedure, which has been maintained at the 30-day follow-up examination.

The Alpha transcatheter aortic valve implantation (TAVI) system is a one-piece self-expanding transcatheter valve engineered with a low profile valve and delivery system, with six support arms for positioning within the aortic annulus and cusps.

The Zeta system is a novel balloonexpandable transcatheter valve with six expanding arms and a low profile covered delivery system. The six expanding arms allow for positioning of the valve into the aortic annulus and cusps.

The feasibility study is being conducted at the Instituto Nacional de Torax in Santiago, Chile, and Tbilisi Heart and Vascular Clinic in Tbilisi, Georgia.

Scott Lim (University of Virginia, Charlottesville, USA), the primary investigator in the study, commented: “The Laguna Tech USA Alpha selfexpanding aortic valve and Zeta balloon-expandable aortic valves performed as designed, allowing us to successfully and percutaneously treat these first patients at high surgical risk with severe aortic regurgitation, and in one case, with concomitant significant calcific aortic stenosis.

“I look forward to these novel transcatheter aortic valves being further investigated in larger studies, as this initial experience is quite encouraging toward helping us address a significant unmet patient need in those with complex aortic valve disease.”

Site-less model helps to improve diversity in PREVUE-VALVE study

Researchers behind a trial to quantify the true prevalence of valvular heart disease within the USA say their use of cloud-based software has markedly boosted the diversity of the trial population, with the trial currently reaching over three times the average for target demographics compared to other research.

The PREVUE-VALVE study is being led by the Cardiovascular Research Foundation (CRF) and investigators from the Columbia Presbyterian Medical Center (New York, USA), with participation from Hawthorne Effect, a company that specialises in decentralised clinical trials, University of Michigan (Ann Arbor, USA), Vanderbilt University Medical Center (Nashville, USA) and the retail health company CVS Health, and has been designed as a “site-less” clinical trial.

Around 5,000 participants aged 65–85 years, intended to be demographically representative of the US population, are expected to be enrolled in the study, and investigators expect to carry out a number of clinical assessments including in-home echocardiograms (ECG), 12-lead ECG, blood draws and quality-of-life assessments either in the patients’ home, at community practices or at retail sites, with an aim to reduce barriers and increase participation among traditionally underrepresented groups.

The study is supported by the Hawthorne Cloud software platform, a digital interface that delivers real-time clinical data from multiple sources.

In addition to handling scheduling, logistics and digital enrolment, the system’s algorithm links patients with a network of medical professionals to carry out the assessments.

After the recruitment of over 1,000 participants in the trial, the organisers say that the study marks a “new standard for inclusive medicine”, with the recruitment for target demographics reportedly reaching more than three times the industry average when compared against figures from the Association of Clinical Research Professionals (ACRP).

This includes recruitment of 15% African Americans compared to the industry standard of <5%, 10% Hispanic compared to the industry standard of <1% and 3% Asian compared to the industry standard of 2%.

“This is a major accomplishment for the medical research industry,” said David Cohen, director of clinical and outcomes research at CRF, and an investigator in the trial. “For a disease that impacts so many in the USA, it is critical to gather data that are actually representative of our diverse population. With our partnership with Hawthorne Effect, CRF is paving the way for the development of advanced treatments to keep everyone healthy.”

compromising normal flow in the sinuses and hindering coronary access.

The device enables the pre-existing valve leaflets to be split, facilitating a safer valve-in-valve procedure and potentially broadening the TAVI market’s reach to younger patients.

“We are excited to have been able to complete enrolment in such a groundbreaking study so efficiently,” said Kodali. “It clearly demonstrates the unmet need for ShortCut and how excited the sites were to learn and perform the procedure. I look forward to the commercial launch of ShortCut in the USA in the near future.”

RELIEF clinical study of PFO closure for migraine relief begins randomisation

Pi-Cardia has announced the successful completion of its ShortCut pivotal study enrolment. ShortCut is designed to split the leaflets of pre-existing valves to enable safe transcatheter aortic valve replacement (TAVI) in patients at risk of coronary obstruction.

The study was conducted across 20 of the world’s leading TAVI centres in the USA and Europe and was led by Susheel Kodali (New York Presbyterian/Columbia University, New York, USA), Didier Tchétché (Clinique Pasteur, Toulouse, France) and Danny Dvir (Sha’are Zedek, Jerusalem, Israel).

It included 60 patients undergoing valve-in-valve procedures, in whom ShortCut was used as a preceding step to TAVI implantation. Data were independently analysed by central echo and computed tomography (CT) corelabs and baseline data were presented at the recent TCT meeting (23–26 October, San Francisco, USA).

The ShortCut device is designed to address a fundamental challenge in TAVI: that the leaflets of preexisting valves are pushed sideways,

Patients have passed through the multi-month enhanced screening process and have begun entering the final randomisation phase of the Gore RELIEF clinical study, an investigational study to evaluate the safety and efficacy of transcatheter closure of patent foramen ovale (PFO) for the relief of migraine headaches utilising the Gore Cardioform septal occluder, WL Gore has announced.

“The RELIEF clinical study investigates whether PFO closure may reduce the number of monthly migraine headache days for select patients. No previous PFO closure migraine trial has yet included such clearly defined selection criteria designed to identify those patients expected to most likely respond to this potential, PFO-mediated mechanism,” said Robert Sommer (Columbia University Irving Medical Center, New York, USA), national principal investigator for the RELIEF clinical study. “Clinical experiences have suggested a platelet-based connection between migraine and PFO, and there may be a correlation between PFO closure responsiveness and thienopyridine responsiveness.

PFO closure may offer a mechanical method to reduce or eliminate this trigger factor.”

WL Gore has been actively screening patients in the USA since initiating the trial in November of 2022. The enhanced screening process identifies the targeted 150 patients found responsive to the study drug, with a documented PFO and history of more than one migraine headache day per week.

21–23 March JIM GISE Congress Milan, Italy

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

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

14–17 May EuroPCR 2024 Paris, France

A TAVI valve is implanted

Pivotal study of ShortCut leaflet splitting device completes enrolment

Conference calendar 2023 19–21 November PCR London Valves 2023 London, UK

9–12 March Cardiovascular Research Technologies (CRT) 2024 Washington, DC, USA

2024 27–29 January Society of Thoracic Surgery (STS) Annual Meeting San Antonio, USA

14 March Global Cardiovascular Awards London, UK

www.pcronline.com/courses

www.sts.org/meetings

www.crtmeeting.org

www.globalcardiovascularawards.com

www.jimgise2024.it

www.expo.acc.org

www.cxsymposium.com

www.pcronline.com/Courses/EuroPCR

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