Cardiovascular News - Issue 65 - May 2022 (US) by BIBA Publishing

May 2022 | Issue 65

www.cardiovascularnews.com

The best TAVR vs. SAVR durability data yet. CoreValve™ and Evolut™ TAVR systems are the only platforms to demonstrate a durability benefit over SAVR at five years.†1 Valve durability is important to you and your patients. It’s important to us too.

SVD cumulative incidence

Surgery RCT (N = 971)

4.38%

CoreValve/Evolut RCT (N = 1128)

P = 0.0095 (Fine-Gray)

2.57%

2% 1%

Years post-procedure

† ‡

In pooled analysis of intermediate and high-risk patients. Devices used: CoreValve 88.5%/Evolut R 11.5%. Structural valve deterioration (SVD) was defined as an increase in mean gradient ≥ 10 mm Hg over five years with a mean gradient ≥ 20 mm Hg at last echo OR new onset/increase of central AR of ≥ moderate in severity.

Medtronic TAVR platforms demonstrated significantly lower rates of structural valve deterioration (SVD)‡ vs. SAVR at five years.

Reardon M. 5-Year Incidence, Timing and Predictors of Structural Valve Deterioration of Transcatheter and Surgical Aortic Bioprostheses: Insights from the CoreValve US Pivotal and SURTAVI Trials. Presented at ACC 2022.

Indications The Medtronic CoreValve™ Evolut™ R, CoreValve™ Evolut™ PRO, and Evolut™ PRO+ systems are indicated for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be appropriate for the transcatheter heart valve replacement therapy. The Medtronic CoreValve Evolut R, CoreValve Evolut PRO, and Evolut PRO+ systems are indicated for use in patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (e.g., STS predicted risk of operative mortality score ≥ 8% or at a ≥ 15% risk of mortality at 30 days). Contraindications The CoreValve Evolut R, CoreValve Evolut PRO, and Evolut PRO+ systems are contraindicated in patients who cannot tolerate Nitinol (titanium or nickel), an anticoagulation/antiplatelet regimen, or who have active bacterial endocarditis or other active infections. Warnings General Implantation of the CoreValve Evolut R, PRO, and PRO+ systems should be performed only by physicians who have received Medtronic CoreValve Evolut R, PRO, or PRO+ training. This procedure should only be performed where emergency aortic valve surgery can be performed promptly. Mechanical failure of the delivery catheter system and/or accessories may result in patient complications. Transcatheter aortic valve (bioprosthesis) Accelerated deterioration due to calcific degeneration of the bioprostheses may occur in: children, adolescents, or young adults; patients with altered calcium metabolism (e.g., chronic renal failure or hyperthyroidism). Precautions General Clinical long-term durability has not been established for the bioprosthesis. Evaluate bioprosthesis performance as needed during patient follow-up. The safety and effectiveness of the CoreValve Evolut R, PRO, and PRO+ systems have not been evaluated in the pediatric population. The safety and effectiveness of the bioprosthesis for aortic valve replacement have not been evaluated in the following patient populations: Patients who do not meet the criteria for symptomatic severe native aortic stenosis as defined: (1) symptomatic severe high-gradient aortic stenosis — aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient ≥ 40 mm Hg, or a peak aorticjet velocity ≥ 4.0 m/s; (2) symptomatic severe low-flow, low-gradient aortic stenosis — aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient < 40 mm Hg, and a peak aortic-jet velocity < 4.0 m/s; with untreated, clinically significant coronary artery disease requiring revascularization; with a preexisting prosthetic heart valve with a rigid support structure in either the mitral or pulmonic position if either the preexisting prosthetic heart valve could affect the implantation or function of the bioprosthesis or the implantation of the bioprosthesis could affect the function of the preexisting prosthetic heart valve; patients with liver failure (Child-Pugh Class C); with cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support; patients who are pregnant or breastfeeding. The safety and effectiveness of a CoreValve Evolut R, Evolut PRO, or Evolut PRO+ bioprosthesis implanted within a failed preexisting transcatheter bioprosthesis has not been demonstrated. Implanting a CoreValve Evolut R, Evolut PRO, or Evolut PRO+ bioprosthesis in a degenerated surgical bioprosthetic valve (transcatheter aortic valve in surgical aortic valve [TAV-in-SAV]) should be avoided in the following conditions: The degenerated surgical bioprosthetic valve presents with: a significant concomitant paravalvular leak (between the prosthesis and the native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g., wire form frame fracture); partially detached leaflet that in the aortic position may obstruct a coronary ostium; stent frame with a manufacturer-labeled inner diameter < 17 mm. The safety and effectiveness of the bioprosthesis for aortic valve replacement have not been evaluated in patient populations presenting with the following: Blood dyscrasias as defined as leukopenia (WBC < 1,000 cells/mm3), thrombocytopenia (platelet count < 50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states; congenital unicuspid valve; mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation [3-4+]); moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation; hypertrophic obstructive cardiomyopathy; new or untreated echocardiographic evidence of intracardiac mass, thrombus, or vegetation; native aortic annulus size < 18 mm or > 30 mm for Evolut R/ Evolut PRO+ and < 18 mm or > 26 mm for CoreValve Evolut PRO per the baseline diagnostic imaging or surgical bioprosthetic aortic annulus size < 17 mm or > 30 mm for CoreValve Evolut R/Evolut PRO+ and < 17 mm or > 26 mm for Evolut PRO; transarterial access unable to accommodate an 18 Fr sheath or the 14 Fr equivalent EnVeo InLine™ sheath when using Model ENVEOR-US/ENVPRO-14-US/D-EVPROP2329US or transarterial access unable to accommodate a 20 Fr introducer sheath or the 16 Fr equivalent EnVeo InLine sheath when using Model ENVEOR-N-US/ENVPRO-16-US or transarterial access unable to accommodate a 22 Fr introducer sheath or the 18 Fr equivalent Evolut PRO+ InLine sheath when using Model D-EVPROP34US; prohibitive left ventricular outflow tract calcification; sinus of Valsalva anatomy that would prevent adequate coronary perfusion; significant aortopathy requiring ascending aortic replacement; moderate to severe mitral stenosis; severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20%; symptomatic carotid or vertebral artery disease; and severe basal septal hypertrophy with an outflow gradient.

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Before Use Exposure to glutaraldehyde may cause irritation of the skin, eyes, nose, and throat. Avoid prolonged or repeated exposure to the vapors. Damage may result from forceful handling of the catheter. Prevent kinking of the catheter when removing it from the packaging. The bioprosthesis size must be appropriate to fit the patient’s anatomy. Proper sizing of the devices is the responsibility of the physician. Refer to the Instructions for Use for available sizes. Failure to implant a device within the sizing matrix could lead to adverse effects such as those listed below. Patients must present with transarterial access vessel diameters of ≥ 5 mm when using Model ENVEOR-US/ENVPRO-14-US/DEVPROP2329US or ≥ 5.5 mm when using Model ENVEOR-N-US/ENVPRO-16-US or ≥ 6 mm when using Model D-EVPROP34US, or patients must present with an ascending aortic (direct aortic) access site ≥ 60 mm from the basal plane for both systems. Implantation of the bioprosthesis should be avoided in patients with aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) of > 30° for right subclavian/axillary access or > 70° for femoral and left subclavian/axillary access. For subclavian access, patients with a patent left internal mammary artery (LIMA) graft must present with access vessel diameters that are either ≥ 5.5 mm when using Models ENVPRO-14-US/ENVEOR-L-US/D-EVPROP2329US or ≥ 6 mm when using Models ENVPRO-16-US and ENVEOR-N-US or ≥ 6.5 mm when using Model D-EVPROP34US. Use caution when using the subclavian/axillary approach in patients with a patent LIMA graft or patent RIMA graft. For direct aortic access, ensure the access site and trajectory are free of patent RIMA or a preexisting patent RIMA graft. For transfemoral access, use caution in patients who present with multiplanar curvature of the aorta, acute angulation of the aortic arch, an ascending aortic aneurysm, or severe calcification in the aorta and/or vasculature. If ≥ 2 of these factors are present, consider an alternative access route to prevent vascular complications. Limited clinical data are available for transcatheter aortic valve replacement in patients with a congenital bicuspid aortic valve who are deemed to be at low surgical risk. Anatomical characteristics should be considered when using the valve in this population. In addition, patient age should be considered as long-term durability of the valve has not been established. During Use After the procedure, administer appropriate antibiotic prophylaxis as needed for patients at risk for prosthetic valve infection and endocarditis. After the procedure, administer anticoagulation and/or antiplatelet therapy per physician/clinical judgment. Excessive contrast media may cause renal failure. Prior to the procedure, measure the patient’s creatinine level. During the procedure, monitor contrast media usage. Conduct the procedure under fluoroscopy. Fluoroscopic procedures are associated with the risk of radiation damage to the skin, which may be painful, disfiguring, and long-term. The safety and efficacy of a CoreValve Evolut R, Evolut PRO, or Evolut PRO+ bioprosthesis implanted within a transcatheter bioprosthesis have not been demonstrated. Potential adverse events Potential risks associated with the implantation of the CoreValve Evolut R, CoreValve Evolut PRO, or Evolut PRO+ transcatheter aortic valve may include, but are not limited to, the following: • death • myocardial infarction, cardiac arrest, cardiogenic shock, or cardiac tamponade • coronary occlusion, obstruction, or vessel spasm (including acute coronary closure) • cardiovascular injury (including rupture, perforation, tissue erosion, or dissection of vessels, ascending aorta trauma, ventricle, myocardium, or valvular structures that may require intervention) • emergent surgical or transcatheter intervention (e.g., coronary artery bypass, heart valve replacement, valve explant, percutaneous coronary intervention [PCI], balloon valvuloplasty) • prosthetic valve dysfunction (regurgitation or stenosis) due to fracture; bending (out-of-round configuration) of the valve frame; underexpansion of the valve frame; calcification; pannus; leaflet wear, tear, prolapse, or retraction; poor valve coaptation; suture breaks or disruption; leaks; mal-sizing (prosthesis-patient mismatch); malposition (either too high or too low)/malplacement • prosthetic valve migration/embolization • prosthetic valve endocarditis • prosthetic valve thrombosis • delivery catheter system malfunction resulting in the need for additional recrossing of the aortic valve and prolonged procedural time • delivery catheter system component migration/embolization • stroke (ischemic or hemorrhagic), transient ischemic attack (TIA), or other neurological deficits • individual organ (e.g., cardiac, respiratory, renal [including acute kidney failure]) or multiorgan insufficiency or failure • major or minor bleeding that may require transfusion or intervention (including life-threatening or disabling bleeding) • vascular access-related complications (e.g., dissection, perforation, pain, bleeding, hematoma, pseudoaneurysm, irreversible nerve injury, compartment syndrome, arteriovenous fistula, or stenosis) • mitral valve regurgitation or injury • conduction system disturbances (e.g., atrioventricular node block, left bundle-branch block, asystole), which may require a permanent pacemaker • infection (including septicemia) • hypotension or hypertension • hemolysis • peripheral ischemia • General surgical risks applicable to transcatheter aortic valve implantation: • bowel ischemia • abnormal lab values (including electrolyte imbalance) • allergic reaction to antiplatelet agents, contrast medium, or anesthesia • exposure to radiation through fluoroscopy and angiography • permanent disability. Please reference the CoreValve Evolut R, CoreValve Evolut PRO, and Evolut PRO+ Instructions for Use for more information regarding indications, warnings, precautions, and potential adverse events.

Caution: Federal Law (USA) restricts these devices to the sale by or on the order of a physician. The commercial name of the Evolut™ R device is Medtronic CoreValve™ Evolut™ R System, the commercial name of the Evolut™ PRO device is Medtronic CoreValve™ Evolut™ PRO System, and the commercial name of the Evolut™ PRO+ device is Medtronic Evolut™ PRO+ System.

©2022 Medtronic. All rights reserved. Medtronic, Medtronic logo, and Engineering the extraordinary are trademarks of Medtronic. ™*Third-party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. UC202215810a EN 04/2022

May 2022 | Issue 65

Featured in this issue:

www.cardiovascularnews.com

Save A Child’s Heart Sagi Assa

CX spotlights aortic challenges:

“Transformational” TAVI turns 20 “We have come a long way now,” Eberhard Grube (University Hospital, Bonn, Germany) told delegates at CRT 2022 (26 February–1 March, Washington DC, USA), in his presentation titled “What is next for transcatheter aortic valve implantation (TAVI)”.

Analysis of data pooled from the CoreValve US Pivotal and SURTAVI trials, two of the largest clinical trials to date to study transcatheter aortic valve implantation (TAVI) suggests that patients undergoing TAVI with a supra-annular self-expanding valve had less structural deterioration after five years compared with patients receiving a biologic valve implanted surgically.

page 18

page 17

Latest data show encouraging performance of TAVI on valve deterioration, further benefit seen for low-risk patients

hese significant findings, delivered by Michael J Reardon ( Houston Methodist DeBakey Heart and Vascular Center, Houston, USA), pictured above, during a late-breaking trial session at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA) came hot on the heels of fouryear data from the Low Risk TAVR trial, presented at CRT 2022 (27 February–1 March, Washington DC, USA) which are also seen as significant when balancing the merits of TAVI in low-risk patients. Delivering his findings at ACC 2022, Reardon told attendees that overall, patients with structural valve deterioration in their artificial valve were about twice as likely to die or need to be rehospitalised as those who did not. The study met its primary endpoint—showing that the incidence of structural valve deterioration was significantly lower in patients who received TAVI than in those who received surgical aortic valve replacement (SAVR). “Heart surgeons tend to worry that in younger, lower-risk patients, replacement valves inserted using TAVI may fail more quickly than surgically inserted valves,” Reardon said. “The results of this study suggest exactly the opposite—that at five years, the TAVI-inserted valve has less structural deterioration than the surgically inserted one.” The study is the largest to assess structural valve deterioration in patients who participated in randomised trials comparing TAVI and SAVR and the first to show less structural valve deterioration after five years among patients treated with TAVI compared with SAVR, Reardon said. Bioprosthetic valves are typically made from porcine or bovine tissue, with their main advantage over mechanical valves seen to be that patients do not require lifelong anticoagulation to prevent thrombosis. Previous studies suggest that younger patients are at higher risk for structural valve deterioration because their valves fail more quickly and because they have a longer potential life span. Previous

Profile: Vijay Kunadian

studies have not clearly established whether the risk of structural valve deterioration is higher with TAVI or with SAVR. “Durability of the replacement valve becomes increasingly important in younger patients,” he said. In the current study, Reardon and his colleagues analysed data from 1,128 patients who underwent TAVI and 971 patients who underwent SAVR in the two large, randomised trials—both of which used the CoreValve and Evolut TAVI systems (Medtronic)—to determine the frequency of structural valve deterioration at five years using Doppler echocardiography. The researchers also examined the factors that predicted deterioration in the same patient cohort plus an additional 2,663 patients who were treated with TAVI in a non-randomised registry of the two trials. They found that 2.6% of the patients treated with TAVI had structural valve deterioration at five years, compared with 4.4% of those treated with SAVR. Patients in both groups who developed structural valve deterioration were at about 50% greater risk of death or hospitalisation for valve-related disease or heart failure as patients who did not have structural valve deterioration, the researchers found.

The results of this study suggest…that at five years, the TAVI-inserted valve has less structural deterioration than the surgically inserted one” Michael J Reardon

HIS COMMENTS CAME JUST WEEKS before the 20th anniversary of the first-inman TAVI procedure, performed by Alain Cribier at the University Hospital of Rouen, France, on 16 April 2002, a date that is recognised as one of the most significant in the history of the development of TAVI, and the advance of transcatheter heart valve treatments more widely. Grube’s presentation covered what he sees a some of the potential future directions for TAVI, including a possible role in the treatment of asymptomatic aortic stenosis or severe aortic regurgitation. Other presentations at CRT 2022 recognised the continuing evolution of TAVI, and included four-year data from the LRT—Low Risk TAVR—trial, demonstrating that TAVI in low-risk patients with symptomatic severe aortic regurgitation yields low adverse event rates and excellent haemodynamics, as well as two-year outcomes of TAVI in patients with bicuspid aortic stenosis. These data at CRT were followedup by the presentation of a five-year analysis of the CoreValve US Pivotal and SURTAVI trials, at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA), where attendees learned that patients receiving a self-expanding TAVI valve had less structural deterioration after five years compared with patients who received a biologic valve surgically. To mark the 20 years since the first TAVI procedure, Cardiovascular News has spoken to a number of the important figures involved in TAVI research to date, discussing the impact of the procedure, some of the important unanswered questions, and where it could go next.

We have come a long way now” Continued on page 6

Continued on page 4

May 2022 | Issue 65

Top Stories

Heart team approach points to mortality benefit in complex cardiac patients Consultation by a heart team led to an observed benefit in objective patient outcomes, a prospective analysis of patients treated at a single centre in Winnipeg, Canada has concluded.

he authors of the study, which was published in the American Journal of Cardiology, claim that theirs is the first such research to provide results of the mortality benefit of the heart team approach to patients. Joel A Scott-Herridge (University of Manitoba, Winnipeg, Canada) et al, add that they hope that this finding will translate into faster adoptation and greater use of heart team consultation. Scott-Herridge and colleagues note that the use of a team-based healthcare approach is a relatively recent development in the management of cardiovascular disease, with heart team consultation now a class I recommendation in guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and the European Society of Cardiology (ESC) for the management of patients with complex cardiac disease. However, despite the class I guideline recommendation, the study team notes that there is

Heart team discussion

a paucity of data to support whether this approach impacts patient outcomes. Researchers assessed patients aged 18 years or older who were reviewed by the heart team at their centre between 10 November 2013 and 15 May 2019, during which time 342 patients were enrolled. Cases required the presence of the referring cardiologist or surgeon, in addition to a heart team panel consisting of a general cardiologist, interventional cardiologist, cardiac surgeon, cardiac anaesthetist, intensive care unit physician and cardiac imaging technologist. Patients were followed to if recommendations were adhered to, with medical records examined at 30 days and six months to monitor clinical outcomes including cardiac death, non-cardiac death, cerebrovascular accident, ST-segment elevation myocardial infarction (STEMI) and non-STEMI. The primary outcome was the relation between whether advice was followed and cardiac death. Of the 342 cases reviewed by the heart team, six were removed as a conclusion could not be reached. Among the 342 remaining cases, 287 were treated according to the heart team recommendation, whereas 49 were not. The researchers note that when analysing the differences between cardiac death in patients for whom the recommendations were followed compared with those for whom they were not, cardiac death occurred less frequently at 6.3% vs. 15.3% (p=0.04). Noting that they believe this is the first study to show a mortality benefit through adoption of the heart team approach, the researchers ascribe this to the presumption that improved outcomes were due to the

NACMI registry finds reducing rates of death among STEMI patients with COVID-19 Latest results from the North American COVID-19 STEMI (NACMI) registry reported a 25% reduction in early mortality in 2021 compared to 2020 among patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection and zero deaths for patients vaccinated against SARS-CoV-2. THE STUDY’S PRINCIPAL investigator, Santiago Garcia (Christ Hospital, Cincinnati, USA) delivered the findings at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA), reporting that the availability of vaccines significantly reduced COVID-19 hospitalisations and deaths among patients who had a STEMI. “We observed a reduction in inhospital mortality, our primary endpoint, from 33% in 2020 to 23% in 2021—a 25% decline after adjusting for age, sex, race, diabetes or other factors that could have played a role,” said Garcia. “We also saw a decline in our secondary endpoint—a composite of death, stroke or a repeat heart attack—from 35% in

2020 to 25% in 2021.” The registry is a collaboration between Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC) and the Canadian Association of Interventional Cardiology (CAIC). The registry was established in 2020 with the aim to define baseline characteristics and management strategies and outcome data for COVID-positive patients with STEMI. A total of 64 medical centres

2020

ability to more accurately identify the most suitable therapeutic option via the team-based model. However, Scott-Herridge et al note that the same differences were largely not observed within the secondary outcomes other than unanticipated cardiac hospital admissions and composite cardiac outcomes. “Unanticipated cardiac hospitalisations were almost three times higher in patients in whom recommendations by the heart team were not followed compared with the patients in whom the recommendations were followed,” the researchers document in their paper. Similarly, it is reported that the composite cardiac outcome was increased by two times in patients compared with those in whom recommendations by the heart team were not followed. “These differences cannot directly be attributed to a causal effect of the heart team because of the nature of this observational trial but are highly suggestive of the improved therapeutic plan provided by the heart team,” ScottHerridge et al add. Despite pointing towards a mortality benefit achieved through use of the heart team strategy, the study’s authors note that their research is limited by its design, and to unequivocally determine if the heart team is the cause for the positive results would require a randomised clinical trial.

These differences cannot directly be attributed to a causal effect of the heart team because of the nature of this observational trial but are highly suggestive of the improved therapeutic plan provided by the heart team”

contributed data to the registry. In the patients’ risk of dying. Yes, they had initial findings, it was reported that 33% had a severe type of heart attack, but of patients with both COVID-19 and a they did not necessarily die from the STEMI died in the hospital. heart attack—they died from severe Vaccination data was available for COVID-19. In 2021, however, the 193 (54%) of the patients treated in availability of vaccines significantly 2021. Of these, 22 patients (11%) had reduced hospitalisations and deaths been vaccinated, and none due to COVID-19 infection, of these patients died while including among patients who in the hospital. By contrast, had a STEMI.” 37 of the 171 unvaccinated In total, 586 patients patients (22%) died in the were examined, 227 who hospital—an in-hospital death were treated in 2020 before rate considerably above the Santiago Garcia vaccinations were made expected rate of about 4–6% available and 359 in 2021 for patients who have had a STEMI. after emergency use authorisation “In 2020, before vaccines were (EUA) from the US Food and Drug available for COVID-19, we saw Administration (FDA). Of the patient significantly more patients presenting to population, more than 70% were male the hospital with shortness of breath as and nearly 75% were aged 55 and their primary symptom, over. Close to 70% had high blood rather than with the pressure and nearly 45% were diabetic. more typical heart-attack Compared to 2020, the proportion of symptom of chest Caucasian patients was higher, and pain,” Garcia said. patients presented more frequently “Having shortness with typical ischaemic symptoms, the of breath, having investigators report. an abnormal chest When looking at outcomes in 2021, X-ray and needing the research team found that survival to be on a ventilator was significantly better when compared were all factors to 2020 with mortality dropping from that increased 33% in 2020 to 23% in 2021.

In-hospital mortality

33%

23% 2021

May 2022 | Issue 65

TAVI at 20

“Transformational” TAVI turns 20 Continued from page 1

Lars Søndergaard

(The Heart Centre, Rigshospitalet, Copenhagen, Denmark)

What impact has the advent of TAVI had on the treatment of aortic stenosis? The groundbreaking concept of TAVI was developed in 1989 by Henning Rud Andersen who demonstrated its feasibility in an animal model. This has led to a paradigm shift in not only treating patients with aortic stenosis ineligible for surgical aortic valve replacement (SAVR) but also patients at low surgical risk and younger age.

Since the first TAVI procedure in 2002, what in your view has been the biggest development in the treatment? The combination of evidence for the therapy, device iterations, and increased operator experience. With the expansion of TAVI into intermediate- and low-surgicalrisk patients, how reassured can we be about the durability of the valves into the long term? Eight-year data from the NOTION-1 trial demonstrate that TAVI with self-expanding technology is superior to SAVR with regards to durability. However, this may not apply for all transcatheter bioprosthetic

Establish a heart team to select the right patients for TAVI” Megan Coylewright

aortic valves as data from the PARTNER-2 trial show than the Sapien (Edwards Lifesciences), balloon-expandable platform is inferior to SAVR.

What have been the most impactful trials to shape our understanding of TAVI, and are there any that you anticipate doing so in future? All seven randomised controlled trials (RCTs) between TAVI and SAVR have changed both guidelines and clinical practise for patients with severe symptomatic aortic stenosis. I am looking forward to the results of NOTION-2 (TAVI versus SAVR in patients at younger age and low surgical risk) next year. Also, ongoing and planned trials on TAVI in asymptomatic patients with severe aortic stenosis, and patients with moderate aortic stenosis and heart failure may potentially improve the treatment of patients.

What questions about TAVI would you like to see answered? The possibility of TAVI-in-TAVI, and RCTs between TAVI and SAVR in patients with bicuspid aortic valves. What is your advice to interventional cardiologists and cardiac surgeons who are starting to perform TAVI? Establish a heart team in order to select the right patients for TAVI based on clinically and anatomically criteria.

(Erlanger Health System, Chattanooga, USA)

What impact has the advent of TAVI had on the treatment of aortic stenosis? Prior to the advent of TAVI, there were many patients who were suffering from the symptoms of severe aortic stenosis who were not offered aortic valve replacement because the only option was surgery and it was deemed to be too high risk for many patients. It

has been a gamechanger in the respect that we are able to offer therapies to a much broader group of patients and truly impact their quality of life and quantity of life. It has also really changed the way that we think about what is possible in the treatment of heart disease. Prior to 2002 and the advent of the earliest experience with TAVI we were tackling most of the structures

Toby Rogers

(MedStar Heart & Vascular Institute, Washington, USA)

What impact has the advent of TAVI had on the treatment of aortic stenosis? Transformational is the way to describe it. It has taken a disease for which there was only one solution, open heart surgery, and made it almost a day-case procedure. That is fundamentally enabling, as it means that it is not only people who are very sick with multiple comorbidities, which is where we started with TAVI, to have the procedure because they would never have been offered surgery. It allows people at the other end of the spectrum, who lead an active lifestyle, who do not want to take six weeks out to recover from a sternotomy, to have a procedure and get back to their activities of daily living within days. So, having that option available has widened the population to whom we can offer treatment in both directions. We are at a stage where patients come expecting TAVI. I spend more time convincing people not to have TAVI than I have to spend convincing them to have TAVI. We have to think not just about this first procedure but what we do in 10 years’ time, if that valve degenerates, which is inevitable. Since the first TAVI procedure in 2002, what in your view has been the biggest development in the treatment? There are only two valves in the USA that have real presence in the market, that is the balloonexpandable valve and the selfexpanding valve. They have the lion's share of the market, and it is going to be difficult for other valves to really get a big foot in

in the heart with surgery. Now, 20 years later we have so many choices for patients from the treatment of valvular heart disease, to treating congenital heart disease to preventing stroke for example, that we can do through minimally invasive procedures and send patients home the same day. Since the first TAVI procedure in 2002, what in your view has been the biggest development in the treatment? When we first started TAVI in the USA, it was in trials in the late 2000s. We were still approaching it as a surgical procedure in

there. We are on to our thirdgeneration devices, and everything has got smaller. I think that from the TAVI devices [we have], it is probably going to be little steps and small iterations and improvements on what is there. Are there important unanswered questions for TAVI that need answering? There are trials that I wish we could do and trials that are likely to be done. For example, we still do not have a randomised trial of TAVI versus surgery for younger bicuspid patients. I think we would all wish there was this trial, because we see these patients, they all come wanting TAVI, and we do not have good data to say this is better than surgery.

What lessons can be applied from the TAVI space into mitral/tricuspid transcatheter interventions? One thing that TAVI has taught us is that most of the benefit comes from the fact it is not surgery, meaning it is not invasive. A lot of the early mitral devices, because they were very bulky, were done through a surgical incision through the chest wall, and although we can get the valve into the patient, they would spend a long time in hospital afterwards. One of the key lessons of TAVI is that 'less is more', and that clearly applies to mitral. There is a reason all of the mitral devices are pivoting to transvenous, transfemoral and transseptal delivery. If we can avoid surgical incisions in the chest, and avoid surgery, that is where the biggest bang for the buck in terms of getting the benefit for the patient.

many ways. We would do a cardiac catheterisation before the procedure, and we would stent all of the arteries that we thought would normally be bypassed. We had fairly large tools, so we were doing surgical cutdowns at the femoral artery site. As time has gone on there has been two shifts, one has been that we do not need to fix everything at the time. We can treat the patient as we could for any other transcatheter therapy. Use the same guidelines with regards to the appropriateness of percutaneous coronary intervention (PCI). Also, over time the tools have

Issue 65 | May 2022

Michael J Reardon

TAVI at 20

(Academic Institute Methodist DeBakey Heart & Vascular Center, Houston, USA)

What impact has the advent of TAVI had on the treatment of aortic stenosis? TAVI has led to a revolution in the treatment paradigm for aortic stenosis rather than the incremental evolution we typically see as we advance in medicine. It has transformed the way that both physicians and patients think about aortic stenosis.

Since the first TAVI procedure in 2002 , what has been the biggest development in the treatment? TAVI has seen a rapid progression from a procedure fraught with both morbidity and mortality to a safe and reproducible procedure. The development of smaller devices and access methods leading to almost complete elimination of access requiring a transthoracic approach has allowed a minimalist approach without intensive care unit (ICU) stay and a common one-day hospital stay. With the expansion of TAVI into intermediate- and low-surgical risk patients, how reassured can we be about the durability of the valves into the long-term? The data suggest that TAVI valves have a durability similar to surgical tissue valves. Longer follow-up beyond 10 years will be needed to confirm this. Surgical tissue valve durability is often discussed as if all surgical tissue valves have

Durability beyond ten years is the last remaining question”

changed and become much smaller, which has really increased the safety profile of the procedure. There is a very low risk of stroke or vascular complications today compared to the earlier experience. I think that is an important message to continue to emphasise. I think that some clinicians outside of cardiology may still think of aortic valve replacement as a risky procedure, and what we are learning more and more is that the risk of not treating the valve far outweighs the risk of treating it. What questions about TAVI would you like to see answered?

similar durability and this is not true. How durability plays out between the different TAVI valves remains to be seen.

What have been the most impactful trials to shape our understanding of TAVI, and are there any that you anticipate doing so in future? The Partner and CoreValve/ Evolut (Medtronic) randomised trials have had the largest impact on the field. Of these trials, the Partner 3 and Evolut low-risk trials have had the most impact and they led to removal of risk as an isolated factor in the current valve guidelines

What questions about TAVI would you like to see answered? Pacemaker need and paravalvular leak continue to improve. The largest remaining question for me will be the durability beyond 10 years for these valves. Both balloon-expandable and selfexpandable valve intermediaterisk and low-risk trials will now be followed for 10 years—I would suggest they be followed permanently as we are unlikely to ever have an opportunity to follow randomised trials like this again. What is your advice to interventional cardiologists and cardiac surgeons who are starting to perform TAVI? Learn the imaging. Especially for surgeons, you should not do this procedure if you cannot do your own computed tomography (CT) analysis and valve plan. Learn the valve you use and if you add a second valve remember that each valve has its own use characteristics.

There are a number of research studies that are going on around TAVI today. Some are focused on optimising the procedure that we are familiar with. That is reducing the risk of stroke with cerebral protection devices or reducing the risk of pacemakers with different implanting techniques. There is research also in the timing of aortic valve replacement, and there is increasing focus on ensuring access to transcatheter therapies across a diverse patient population. We know that in the USA there are marked health disparities that impact how long people live. That the life

Kimberly Skelding

(Confluence Health, Tuscaloosa, USA)

What impact has the advent of TAVI had on the treatment of aortic stenosis? TAVI has been revolutionary. In the early days when we were treating the extreme-risk patients, we were treating patients whose option was either TAVI or die. So, being able to give people a new lease on life was phenomenal. My very first TAVI patient was 89 when we did his procedure and he died at 98, and TAVI was so transformational and life changing for him that he had a picture of the TAVI treatment team at his funeral ceremony, along with his family, because he felt that we were part of his family and had really changed his life, which is unbelievable.

Since the first TAVI procedure in 2002, what in your view has been the biggest development in the treatment? I started TAVI at the very beginning and was the first woman in the USA and the first female PI in the USA, so we had the early devices, and every iteration has made it a little easier and a little safer. I cannot say that with the current generation devices there have been these astronomical changes, because the devices were really pretty good to begin with. But, as we did the trials, we as a group noticed something that could be done better and could be improved. As it was a small group of us at the beginning, we knew each other well and we could sit down together and talk about it and make changes. You have done a lot of research about outcomes of TAVI in women, can you discuss the differences in understanding of the procedure in women?

expectancy of patients who are African American or Latino are much less because of many of the social determinants of health that are impacted by items such as structural racism.

What is your advice to interventional cardiologists and cardiac surgeons who are starting to perform TAVI? I think that it is really important the we recruit and retain the top talent in cardiology and cardiac surgery. For me personally, when I found out as a medical intern in 2005 that someone had replaced a heart valve through a tube in the leg, that is

Women have been demonstrated to be at high risk for bleeding in PCI and so their vasculature is always an issue with TAVI. This is not so much the case now as it was in the earlier days because the devices have become smaller. They also have smaller annulus sizes, and that is certainly a challenge. Some devices are better at small valve areas than others and as we move forward into a continuum of treating aortic stenosis throughout a lifetime we are going to have to be more cogniscant of that. I think we have to get better devices and more options for small annulus sizes, so that we have better haemodynamics up front, of course, but then we have better options for them to treat throughout their lifetime. Right now, I think, younger women with smaller annulus sizes are going to be a challenge to treat throughout their lifetime.

Are there important unanswered questions for TAVI that need answering? There are a number of valves that are coming onto the market and trying to expand on what we have already, expanding the pros and diminishing the cons. I do not see any valve that is really revolutionary, but is expanding on improvements in the current valves that we have and that is a testament to the people who designed the first valve. Often generation one is such a poor product that there are hundreds of iterations, and the fact that the iterations are small and the changes are incremental, I think, speaks to the elegant design initially.

what led me to cardiology. One of the things that we are working on when we recognise that both women and people of colour are under-represented in clinical trials is the recruitment of women and people of colour into our workforce where we have had marked disparities. In structural heart disease, for example, only about 3% of TAVI operators are women and that has broad implications when we think about who has access to the therapy, who is included in clinical trials and whether or not our research is as evidence based for our diverse population as we would like it to be.

May 2022 | Issue 65

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TAVI valve durability under the microscope Due to the growth of transcatheter aortic valve implantation (TAVI) in recent years—initially available to patients at high surgical risk, then more recently to those deemed to be at moderate risk, and now increasingly offered to patients who would be considered at low risk for surgery—the question of valve durability becomes ever more important.

“I

t is not only important for TAVI, but it is also important for surgical aortic valve replacement [SAVR], because we now speak about low-risk patients, [and] younger patients,” Hendrik Treede (University Hospital Mainz, Mainz, Germany) tells Cardiovascular News. This focus has changed, Treede acknowledges, as TAVI is now moving towards younger patients—those with a longer life expectancy. From that perspective, he comments, it is highly important to have long-term durability data available for patients who have had TAVI and SAVR, which is seen to be central to the question of which patients may be suitable for a transcatheter valve and which may be more likely to gain benefit from a surgical bioprosthesis. However, the same questions are also relevant when it comes to choosing the appropriate therapy in older and higher risk patients. “The questions we have to answer today, are ‘what is the journey of the patient?’ and ‘what kind of valve will they have?’,” he notes. “We now speak about patients who will definitely see structural

valve deterioration (SVD) during their lifespan. And then the discussion starts on which valve to start with.”

Signals of structural valve deterioration

Understanding the signs and impact of SVD are fundamental to any decisionmaking process when it comes to setting a strategy for each patient, and predicting whether a transcatheter or surgical approach will give them the greatest benefit. “If you have SVD it means you have irreversible morphological change of the structure of your valve,” says Treede. “That, of course, has an impact on your future life because you may have either aortic stenosis or aortic regurgitation, or even a combination of both. That basically makes you a sick patient again, and you may see all the effects related to it.” Morphological changes to the valve, caused by SVD, may be hard to detect, Treede comments, but haemodynamic changes may be more straightforward to identify, and indicative of the presence of SVD. Findings of a study presented at the American College of

EvolutTM PRO+ TAVI System

Cardiology’s annual scientific sessions patients with smaller (≤23mm) annuli (ACC 2022, 2–4 April, Washington (5.86% surgery vs. 1.39% TAVI; DC, USA) are among the latest data p=0.049), but a trend was also found in available that offer some indication of patients with larger (>23 mm) annuli the relative performance of TAVI when (3.96% surgery vs. 2.48% TAVI; it comes to valve durability. p=0.067). The study, a pooled analysis from “It is pretty significant, especially the CoreValve US Pivotal High Risk in the light of the use of the very early and SURTAVI randomised trials, CoreValve generation at the time,” says evaluated the five-year incidence and Treede, commenting on the data. “That predictors of haemodynamic valve leaves room for the idea that the data deterioration and clinical outcomes at might have even been better if they had five years among patients who had been used the latest generation,” he adds. randomised to undergo TAVI—using Among the important messages to either the CoreValveTM or EvolutTM take away from the data are, according to (Medtronic) platforms, both Treede, the fact that there is a low supra-annular, self-expanding likelihood of developing SVD valves—or SAVR. after five years, and that this For the purposes of may be at least competitive the study, investigators with, and, if not better than defined SVD as moderate or surgery. Longer-term followgreater haemodynamic valve up, and more data in lowerdeterioration, determined as Hendrik Treede risk patients will also be key. an increase in mean gradient ≥10mmHg from discharge and a mean Are all valves gradient ≥20mmHg at the last available created equally? echo, or the new onset or increase of Could the findings also be extrapolated intraprosthetic aortic regurgitation. across the full gamut of devices currently In total, the study evaluated 1,484 available? Treede suggests possibly not. intermediate risk (792 TAVI, 692 Asked whether he thinks all valves are SAVR) and 615 high risk (336 TAVI, equal when it comes to valve durability, 279 SAVR) for SVD. Headline findings he responds: “This is a very important presented at ACC showed that in question. It is definitely not true for patients with symptomatic severe aortic surgical valves, and we know this, but it stenosis at intermediate or high surgical may also be different with TAVI valves, risk, the five-year rate of SVD was because SVD very much depends on 4.38% in patients undergoing surgery, haemodynamic function.” versus 2.57% in patients undergoing In particular, the use of supraTAVI using the Evolut and CoreValve annular, self-expandable valves may platforms (p=0.0095). Furthermore, be even more advantageous when it the risk of death and rehospitalisation comes to durability than, for example, for aortic valve disease or heart failure balloon-expandable valves, Treede goes doubles in patients that develop SVD, on to suggest. according to the study investigators. “We know self-expanding valves Furthermore, the difference in SVD have larger opening areas due to the was observed to be more profound in supra-annular valve position,” he explains. “It seems very likely that then they may have a longer durability than balloon expandable valves, which sit intra-annular and have, in comparison, higher gradients and smaller, effective opening areas. “So, there is a clue and I think we have some evidence that the durability of certain self-expanding valves might be a bit better than the balloonexpanding valves. But we also have to say that there is no comparative trial with long enough follow-up to really show this in a proper scientific way,” Treede adds. Returning to the question of lifetime management, Treede acknowledges that the findings of the analysis may have a bearing on the choice of TAVI as a first approach, particularly in younger patients for whom a reintervention may be required further down the line. “We have to make sure that the second procedure is also safe, and also related to very good long-term outcomes, to speak about TAV-in-TAV options,” Treede comments, adding that, as more younger patients get TAVI as the first choice in many centres, this will be an increasing area of focus.

We know selfexpanding valves have larger opening areas due to the supraannular valve position. It seems very likely that then they may have a longer durability than balloon expandable valves, which sit intraannular and have, in comparison, higher gradients and smaller, effective opening areas”

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October 2021 Issue 01 www.renalinterventions.net

In this issue:

Twelve-month Wrapsody results at CIRSE 2021 page 4

Alexandros Mallios page 12

Dialysis:

Latest debates in dialysis care page 17

Transplantation:

Healthcare disparities in the spotlight page 20

Renal community reckons with removal of race variable in kidney disease diagnosis

Bioartificial device receives KidneyX award after reaching preclinical testing AN IMPLANTABLE BIOARTIFICIAL kidney device (iBAK) has moved closer to becoming a reality after being awarded a US$650,000 prize from KidneyX. The device’s creator, the Kidney Project, received this award following the first ever demonstration of its functional prototype. The Kidney Project is a US-wide collaboration led by Shuvo Roy (University of California San Francisco [UCSF], San Francisco, USA) and William Fissell (Vanderbilt University Medical Center, Nashville, USA). In the past few years, it has successfully tested the two essential components that make up its artificial kidney technology—a haemofilter, which removes waste products and toxins from blood, and a bioreactor, which replic ates other kidney functions, like the balance of electrolytes in blood—in separate experiments. To secure KidneyX’s Artificial Kidney Prize, the team married these two units in a scaled-down version of the artificial kidney that is roughly the size of a smartphone and evaluated its performance in a preclinical model following successful implantation. The units worked in tandem, powered by blood pressure alone, to provide continuous renal replacement therapy without the need for blood thinning or immunosuppressant drugs. This technology, which is intended to provide patients with improved mobility and physiological outcomes compared to dialysis, will now be upscaled for more rigorous preclinical testing and, eventually, clinical trials. For the latest step forward in the development of this device, the Kidney Project team was awarded KidneyX’s Phase 1 Artificial Kidney Prize—becoming one of six winning teams selected from a field of innovators across Canada, Israel, Japan, The Netherlands, Portugal, Singapore, South Korea, the UK, and the USA. Other recipient technologies included a wearable, lightweight, dialysate-free artificial kidney (US Kidney Research Corporation) and genetically engineered pig kidneys designed to increase supplies of transplantable organs (Makana Therapeutics).

Proﬁle:

iBAK device

(Credit: UCSF)

Follow Renal Interventions on all our social media platforms for the latest news, insight and events in kidney care

The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) have jointly released a report outlining a new race-free approach to diagnosing kidney disease. In its report, the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recommends the adoption of the new estimated glomerular filtration rate (eGFR) 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation that estimates kidney function without a race variable.

and subsequent treatment of kidney diseases,” said ASN president Susan Quaggin. “By recommending the CKD-EPI creatinine equation refit without the race variable, the task force has taken action and demonstrated how nephrology continues to lead the way in promoting healthcare justice. It is time for other medical specialties to follow our lead, and NKF and ASN stand ready to help however we can.” In the USA, more than 37 million adults have kidney diseases and 90% are not aware they have diminished kidney function, the NKF-ASN statement adds, with a disproportionate number of these patients being Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, and Native Hawaiian or other Pacific Islander. These patient groups also face “unacceptable” health disparities and inequities in healthcare delivery.

he task force has also recommended the increased use of the protein cystatin C—a commonly used biomarker of kidney function—combined with serum (blood) creatinine as a confirmatory assessment of GFR or kidney function. The final report, which has been published online in the American Journal of Kidney Diseases (AJKD) and the Journal of the American Society of Nephrology (JASN), was drafted with “considerable input” from hundreds of patients and family members, medical students and other trainees, clinicians, scientists, healthcare professionals, and other stakeholders, to “achieve consensus for an unbiased and most reasonably accurate estimation of GFR”, according to a joint statement from the NKF and the ASN. “This recommendation by the NKF-ASN task force is an important step forward in assuring health and healthcare equity,” said NKF president Paul Palevsky. “We commend the task force for the time, thought, thoroughness and effort it took to explore this issue deeply, and recommend the best path forward for us all. The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race. While the work of the task force is an important initial path forward, both of our organisations are committed to continuing to work to eliminate disparities in the diagnosis and treatment of kidney disease.” “As the largest organisations representing kidney patients and health professionals, NKF and ASN are committed to eliminating health disparities that harm kidney patients, and ensuring that racial bias does not affect the diagnosis

Developing race-free recommendations Over a 10-month period, the NKF-ASN task force organised its work into three phases. The first involved clarifying the problem and evidence regarding eGFR equations in the USA; the second involved evaluating different approaches to address the use of race in GFR estimation; and the third involved providing recommendations based on this. In April 2021, the task force published its interim report on reassessing the inclusion of race in diagnosing kidney diseases in AJKD and JASN, asserting that race modifiers should not be included in equations used to estimate kidney function, and that current, race-based equations should be replaced by a substitute that is “accurate, representative, unbiased and provides a standardised approach

“The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race.” Paul Palevsky Continued on page 2

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May 2022 | Issue 65

10 The TAVI Story

“TAVI was my baby, now it is a teenager” In the history of transcatheter aortic valve implantation (TAVI), 16 April 2002 is a landmark date, with the implant of the first transcatheter aortic valve in a patient at the University Hospital of Rouen, Rouen, France, by Alain Cribier and his team. However, the story of TAVI goes back much further, driven largely by the ingenuity and tenacity of its creator, Henning Rud Andersen (Aarhus University Hospital, Aarhus, Denmark). To mark the 20 years since the first implanted valve, Andersen, regarded by many as the ‘Father of TAVI’, speaks to Cardiovascular News about his development of the early transcatheter valve, the decades-long mission to bring the technology to fruition, where he sees TAVI going next and his advice for budding physician-inventors.

he story begins in 1989. Andersen was attending an interventional conference in Phoenix, USA, where he saw a talk by the developer of the balloon-expandable stent, Julio Palmaz, when he first chanced upon the idea of using a balloon-expandable device to implant a heart valve percutaneously. “It suddenly came out, just while I was sitting there, it took me one second to think 'why not use the same technology, use the balloon and the stents and build a heart valve with a metal frame’,” recalls Andersen. On return from his US trip, Andersen started work on what would become his prototype aortic valve, though he admits that, at the time, it was seen as being an outlandish concept. “When I went back to my professor and I told him that I have got this idea, he said to me that I was crazy. But he also told me to give it a shot,” he says. Colleagues too were less than optimistic about his prospects of bringing the idea to reality. As a result, Andersen set about without funding or industry support to work on the proof-of-concept valve. “What I built was a metal stent which had a valve inside. If you look at what is going out today, there is a metal stent, there is a foldable valve, and there is a balloon,” remarking that the concept is largely consistent with that of balloonexpandable valves that are still in use today. “When I am out presenting, I am still pointing at the engineers sitting

The original valve design

there and saying 'what the hell have you done within the last 30 years, nothing new has happened!’” he jokes. Initial experiments with the device involved implantations into adult pigs, which were performed via retroperitoneal access to the abdominal aorta. The first such implant was successfully performed on 1 May 1989, less than three months after his initial spark of the idea in Phoenix. After the first successful procedure, Andersen performed a series of implantations to attempt to refine the procedure. “After five to ten animal implantations I was completely sure that this would be a revolution within interventional cardiology,” says Andersen. “Of course, I was turned down for many years, but my belief at that time was that this would be a technology that would develop and would be there for many years.” Despite his own certainty, which had

I was completely sure that this would be a revolution within interventional cardiology”

moment that PVT gained the licence to the idea that it took flight. “He [Stanton Rowe] established a budget of around US$20 million to start the development of my idea. I was in close contact with him, and they started to do all of the technical things down in Tel Aviv in Israel,” Andersen recalls. Further animal experiments were conducted in Paris, led by Cribier and Henning Rud Andersen undertakes an with the support of Leon who would animal implantation travel in from the USA. Andersen’s own led him to invest in patents to protect story then circles back to the beginning, his own financial interests and to secure when in 2002 Cribier performed the funding to develop the idea, it was an first in-human TAVI procedure. In uphill struggle to convince others that fact, the circularity in Andersen’s story his successful concept could turn into continues when his own father, aged 86 the transformational procedure that it in 2011 underwent TAVI due to severe has become today. His initial attempts to symptomatic aortic stenosis, and went publish the findings of his early studies on to live for a further nine years. were rebuffed by several well-known “My dad was nearly dying from his journals, before finally being accepted aortic stenosis. He was living outside for publication in the European Heart the city, and he had a small farm, but Journal in 1992, now more than three he could not do anything anymore,” years after the start remembers of the story. Andersen. Though The initial not involved in Henning Rud Andersen's publication was the procedure TAVI timeline followed by the directly, which presentation of a was performed by poster at the 65th his colleagues in Early 1989 American Heart Aarhus, Andersen Initial idea of using a balloonAssociation (AHA) recognises the role expandable device to implant Scientific meeting that his innovation a heart valve percutaneously in New Orleans, played in extending USA in 1992, his father’s life. though Andersen “He lived until he admits that the idea was 95 and he had May 1989 did not gain huge no symptoms from Experimental device implanted traction at this time. his heart for the rest into an adult pig via retroperitoneal Although he felt of his life,” he says. access to the abdominal aorta colleagues were “He had a very slow to recognise good life. Normally the value of the I would never say 1992 concept, Andersen that I saved my The successful concept is finally had secured dad's life! I am very accepted for publication in the some financial frequently asked European Heart Journal backing from about it, but I could Stanford Surgical never claim that I Technologies (SST), did!” based in California. Andersen says 2002 Despite working he still follows Alain Cribier performs the first with SST for a the developments in-human TAVI procedure number of years in in the technology, a bid to develop his and is proud of his research, Andersen contribution to the said that his efforts had ground to a halt, field. He says: “This was my baby, I and the company had instead opted to created it, now it has grown up and it focus on the development of a technique is a teenager. But it is a strong teenager for less invasive surgical aortic valve and it will mature and mature.” replacement (SAVR). He believes that the expansion of Andersen says he began to see the TAVI, first in patients at extreme risk idea gathering pace when it caught the from surgery, and then latterly out attention of Stanton Rowe, a former into lower-risk populations, has been director of development with Johnson the right approach.” We started with & Johnson, and who had secured the the very fragile, very old patients licence for the coronary stent pioneered who cardiac surgeons would not offer by Julio Palmaz, the initial spark for treatment to,” he comments. “It was the Andersen’s TAVI idea, on behalf of the right place to start, because remember company. When he saw the value in the that this is a completely new, unproven idea, Rowe had formed Percutaneous procedure, maybe all the devices would Valve Technologies (PVT) in a bid have failed after six months. Nobody to pursue the concept, with partners knew.” including Marty Leon and Alain Cribier. To conclude the conversation, The company acquired the license Andersen offers a quote from Albert agreement for the idea, which was later Einstein about shifting paradigms. “If purchased by Edwards Lifesciences in at first the idea is not absurd, then there 2004 for US$125 million. is no hope for it.” This, he says, applies Andersen recognised that it was the exactly to the development of TAVI.

CMY

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12 Advertorial THIS ADVERTORIAL IS SPONSORED BY SIEMENS HEALTHINEERS

Cath lab technologies for medicine in the precision age In the modern cath lab, having a suite of tools to treat coronary artery disease all the way through the patient journey is key to optimising outcomes among an increasingly diverse population of patients. In this advertorial, Cardiovascular News speaks to three interventional cardiologists—Daniel Duerschmied (University Hospital of Mannheim, Mannheim, Germany), Joost Daemen (Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands) and Francisco Fernández-Avilés (Hospital General Universitario Gregorio Marañón, Madrid, Spain)—all of whom offer different perspectives on how new technologies are shaping their approach to care in the modern age.

or Duerschmied, having access to non-invasive these technologies is the Naeotom Alpha (Siemens technologies for the diagnosis and riskHealthineers), the world’s first photon-counting CT stratification of coronary artery disease patients system. As part of the interdisciplinary cardiovascular is of paramount importance. “It is critical not to imaging center together with the Department of subject the patient to further risk that is not necessary,” Radiology and Nuclear Medicine Duerschmied’s he tells Cardiovascular News. “That is one of the institution began using the system —which uses primary goals of being a doctor: do what needs to be cadmium telluride crystals, converting X-ray photons done but do not do harm.” directly into electrical signals to overcome the loss of That is where technologies such as coronary information encountered in conventional CT—since computed tomography angiography (cCTA) have early 2022. The introduction of the new technology has become a vital component in his practice. “At present, been “very exciting”, he tells Cardiovascular News. we use CT according to risk prediction,” he explains. “The huge step forward is in spatial resolution,” “We either decide to have patients transferred to the he explains. In addition, Naeotom Alpha is also a cath lab for direct invasive coronary dual source system (two tubes, two angiography followed by PCI detectors, quite unique to Siemens [percutaneous coronary intervention], Healthineers) which offers fast or have examination by a CT, nontemporal resolution (66 ms) and this invasively to exclude coronary artery is needed to freeze cardiac motion. disease.” “The heart is a beating organ, that There are many cases in which also moves due to breathing. So we cCTA is essential, he notes, including have really sharp images that are quite patients with chronic coronary impressive to see and to discuss with symptoms, but there are limitations— the patient.” including for example, when heavy This is one element where the Daniel Duerschmied calcification is present. “We see a lot photon-counting system offers a truly of patients with calcifications, due to unique experience for the patient, which we are not able to tell whether Duerschmied adds. “Just today, I was the degree of stenosis is severe or not looking at images from a patient that significant and if this lesion needs had a previous stent implanted, and to be further treated via by a PCI for reported new problems. This has been example,” he says. “So, this of course, a major issue before, but with the is a limitation.” Naeotom Alpha, it has been easier to The presence of blooming artifacts exclude stent thrombosis or in-stent when using CT in severely calcified restenosis in this patient, and it was vessels, which can distort the overall quite convincing to show the images to Joost Daemen picture of the level of calcification, the patient.” is a big challenge in clinical practice, This example demonstrates how Duerschmied says. He uses the example Naeotom Alpha has changed the of a patient who may be typical of decision-making process, Duerschmied those he sees regularly in practice, comments, noting that previously he describing a middle-aged male, who would have opted to send the patient would be considered at high-risk due to coronary angiography, rather than to being a smoker, presence of arterial opting for CT. The ability to offer a hypertension and dyslipidaemia, with solution that exposes the patient to elevated LDL cholesterol. less harmful radiation is a “clear step “Imagine the patient coming to Francisco Fernández-Avilés forward”, he says. me and reporting his symptoms. I The new system also offers benefits then transfer him to CT and then he comes back with when it comes to heavily calcified vessels, adds an image with heavy calcification, [with] blooming Duerschmied. He says: “I know that before I would artifacts. I cannot really tell whether his symptoms have just seen blooming and not been able to tell if are really related to his coronary artery disease, and this is severe stenosis or just minor narrowing with I would still need to perform coronary angiography heavily calcified, but mostly externalised plaque.” to decide on whether medical treatment alone would Because of the increased spatial resolution, the be sufficient, or whether stenting would be more blooming is already reduced compared to conventional adequate.” CT. In addition, Naeotom Alpha brings another unique These are all examples, according to Duerschmied, feature, called PureLumen. This application identifies where new technologies are turning the dial. Among just the calcium in the coronary arteries and simply

May 2022 | Issue 65 removes it, letting physicians see behind the curtain of calcium. Importantly, Duerschmied says, the technology offers new opportunities for clinical research and to improve diagnostics for patients in future, as well as opening doors to work more closely with colleagues in radiology. “There are a number of completely new applications that this new technology brings to the table. For the first time, for example, we are thinking of using different contrast agents in one CT examination,” Duerschmied describes. “With photon-counting CT, we can part from the iodine-based contrast agents and also use gadolinium, which we usually only use for magnetic resonance tomography.” Overall, the technology “will enable a huge step forward in research of coronary or cardiological imaging of the heart,” Duerschmied concludes.

vFFR: Making lesion assessment easier and faster*

When the decision is made that the patient should be transferred to the cath lab, this new cutting-edge technology on making lesion assessment easier and faster comes into play. Measuring fractional flow reserve (FFR)—evaluating the haemodynamic relevance of a coronary stenosis by determining the ratio between the maximum achievable blood flow in the diseased segment and the theoretical maximum flow under normal conditions—is one such step. Traditional, invasive FFR includes the usage of a guidewire to measure pressure differences across a coronary stenosis. Drawbacks of this technique can include length of the procedure as well as potential discomfort to patients due to the administration of hyperaemic agents. “There is a growing interest in physiological lesion assessment, however people refrain from doing it because of technical limitations and a perceived increase in cost,” says Daemen, principal investigator in the FAST (Fast assessment of stenosis severity) study programme, investigating the use of vFFR—a non-invasive, angiography-based method for calculating FFR values. It is hoped that vFFR, which is derived from routine coronary angiography, could eliminate some of the drawbacks inherent in invasive FFR, as well as being a cost-saving, simpler approach. The technology requires two orthogonal angiographic projections that allow a 3D reconstruction of the vessel, combined with an input boundary condition for the pressure, which in this case is the aortic root pressure. Taken together these provide an instantaneous calculation of the vFFR over the specific segment of interest based on simplified computational fluid dynamics embedded in the algorithm. The technology was validated first in the FAST I and FAST EXTEND clinical studies—retrospective single centre studies in which investigators demonstrated a positive correlation to invasive, pressure wire-based physiology, then in the prospective, multicentre FAST II study, comparing core lab-based vFFR assessment to invasive FFR. “With FAST II we concluded that there was a very good correlation between vFFR and FFR as well as an excellent diagnostic accuracy in identifying lesions with an FFR below 0.80,” says Daemen. “We were able to report positive and negative predictive values, and sensitivity and specificity figures of 90%, 90%, 81% and 95% respectively.” “Though FAST II adds to the growing body of evidence validating vFFR, there is still work to do to drive adoption of angiography-based FFR in the cath lab,” comments Daemen, who says there are three important components needed to change this picture. “One is the need for dedicated trials showing the superiority of angiography-driven physiology versus angiography-guided PCI, as well as studies that demonstrate the non-inferiority of angiography-

Issue 65 | May 2022 derived FFR to conventional FFR or iFR.” A second requirement is a need for consensus on the cost efficacy of the technology, and its impact on reimbursement models. Finally, says Daemen, the most important requirement is seamless connectivity between the angio-based FFR and fluoroscopy systems. “I think there is a huge interest in having everything seamlessly integrated, but the fact of the matter is that a lot of the technologies we use are thirdparty solutions,” he adds, noting that this is where the partnership between Siemens Healthineers and Pie Medical Imaging, developer of the vFFR software, bears fruit, allowing speedier integration into cath lab systems. The two companies together took a first step by launching QuantWeb vFFR, which offers vFFR integrated in the application software of the newest Siemens Healthineers imaging platform ARTIS icono. The next step in the FAST study chain is the multicentre randomised outcome trial FAST III. Enrolment began in November 2021 involving 35 sites in The Netherlands, Ireland, UK, Germany, Italy, Spain and France, with an aim to include 2,228 coronary artery disease patients randomised 1:1 to either vFFR-guided revascularisation, or an FFR-guided strategy. Primary endpoints include a composite of all-cause death, any myocardial infarction, or any revascularisation at one year. “The trial was set up as a non-inferiority trial, in which we hope to show non-inferiority of a vFFR versus an FFR-guided treatment strategy,” says Daemen. However, he adds, the interesting part of the study will be in the secondary endpoints, in which investigators will assess procedure times and cost. “We notice that doing vFFR really makes the physiological lesion assessment easier and faster as compared to a hyperaemic, physiologically-guided invasive approach,” he comments. “We hope that the procedures will become shorter, and it could also be that we find differences in contrast usage and fluoroscopy time, because of the shorter procedures.”

Robotics: Medicine in the precision era

The combination of precision imaging, like the ARTIS icono imaging system, and new technologies, like the CorPath GRX Vascular Robotic System, is a symbol of the modern era of medicine, which is described by Fernández-Avilés. Not only does this offer healthcare providers with the opportunity to streamline the delivery of PCI procedures, but there are huge benefits in terms of the health and wellbeing of the cath lab team in adopting these technologies, he explains. “We are now in a precision medicine era, and in this era robotic management is particularly important in general medicine, cardiovascular medicine and in PCI,” Fernández-Avilés tells Cardiovascular News, adding that “high-quality imaging and the robotic precision, protection, and automation are essential for the treatment of our patients”. According to Fernández-Avilés, robotic-assisted PCI presents a “clear opportunity” due to the structure of the coronary arteries. Since creating a robotic PCI programme in his own institution, which has been running since mid-2021, he comments that the safety features offered in terms of potential reduction in radiation exposure for the cath lab team, as well as the precision when stenting in combination with the integrated automated movements increase efficiency and prove to be very beneficial. “We realised that, in principle, there are no lesions which are not amenable to be treated with robotics, and that the benefits on the reduction of injuries derived from radiation are very clear,” he comments. “Everybody knows that the cath lab is a dangerous workplace because of the deleterious effects of radiation. Young interventionalists in particular are facing a very long period of strong exposure to radiation with a clear risk of injuries which could include different types of tumours, degenerative diseases like

Advertorial 13

Robotic PCI in action

cataracts, and also orthopaedic problems derived from the use of protective lead to avoid radiation,” Fernández-Avilés explains. “The possibility to perform robotic intervention in a remote way is one of the reasons why we decided to start the programme.” Reflecting on his own experience of implementing a robotics programme in his practice, FernándezAvilés comments that buy-in from the team, including interventional cardiologists, and also nursing staff, is the most important component, even before choosing the technology platform. “In robotic PCI, the most important thing, the key of success, is the commitment of the team. Physicians need to realise the benefits of the change,” he explains, adding that nurses also play an important role. “We started training a few doctors and nurses, first with simulators, then with animal models and then with patients, with the support of expert proctors,” he reflects. “This started with a small number of people and two nurses, each performing 10 procedures, and then we were certified and able to train the rest of the

High-quality imaging and the robotic precision, protection, and automation are essential for the treatment of our patients” group. Now we have seven interventionalists able to perform complex robotic procedures, and we have all the nurses of the group, at least 15, able to assist.” The CorPath GRX platform is intuitive and straightforward to use, according to FernándezAvilés, who explains that, in his eyes, compatibility between the robotic unit and the angiographic imaging system are the fundamental elements of success in robotic PCI. The angiographic system should be a high-quality imaging system and should be capable of being manipulated outside the operating room in combination with the robot, he says. “You can manipulate the guiding catheter and the guidewire, which is the most important part of the procedure, and you can advance different types of devices, including balloons, stents and other devices, by the manipulation of the three controls

you have at the workstation,” Fernández-Avilés explains, describing the operation of the platform. “These controls can be manipulated manually, or can be helped by automatic movements. There are five different automatic movements that help you with guidewire navigation, lesion crossing or anatomy measurement inside the coronary tree, and can help to navigate complex anatomies and severe lesions.” Recent research by Campbell et al has shown that more than 60% of coronary lesions lengths are inaccurately estimated leading to suboptimal stenting and bad prognosis. A further strength of the robotic system is the accuracy of measurement that the platform enables, allowing the operator to precisely measure the length of the diseased anatomy and then to select exactly the length of the stent that this particular lesion needs, according to Fernández-Avilés. “This is very important because it reduces the number of stents you will need,” he says. Wiring assistance also helps to save time and resources during a PCI procedure, he says. When you are pushing the controls of the robot, you can move your stent with a constant speed that you are not able to do manually, he adds. “This allows you to position the stent precisely in landing zone, exactly where you want, what is extremely important in complex situations, like ostial lesions or bifurcations.” Though Hospital General Universitario Gregorio Marañón is a high-volume centre, performing more than 2,000 manual PCI procedures per year, Fernández-Avilés believes that there are benefits to be found in lower volume centres employing a robotic system. He explains: “In our experience, we need no more than five cases to be familiar with the robot. No more. I think that you can really improve efficiency by using the robot.” Asked if he sees robotics as the future of PCI, Fernández-Avilés tells Cardiovascular News: “I think that you should not avoid robotic PCI if you have the possibility to do it.” *Cases which can be assessed with vFFR are stable coronary syndrome and non-ST elevation acute coronary syndrome. The statements by Siemens Healthineers customers described herein are based on results that were achieved in the customer's unique setting. There can be no guarantee that other customers will achieve the same results.

May 2022 | Issue 65

14 Outreach

Cardiologists without borders “When I was one year old, my father died in the war between Israel and Egypt and I was left with a broken heart, which has no good treatment in the cath lab or the operating room,” says Sagi Assa (Wolfson Medical Center, Holon, Israel) telling Cardiovascular News the driving force behind his career in paediatric interventional cardiology.

his early trauma is perhaps one motivating factor that led Assa to become one of around 140 physicians working with the Israelbased humanitarian organisation Save a Child’s Heart, which, over its 25-year existence, has helped to deliver more than 6,000 interventional and surgical cardiac procedures to children from 63 countries, including some of the most impoverished and politically challenging regions of the world. Through Save a Child’s Heart, children suffering with congenital heart disease—who would otherwise struggle to access treatment—are offered cuttingedge care, with costs including travel, accommodation and treatment, funded entirely by the charity. Much of this work extends to Africa, where Save a Child’s Heart has treated children from 28 countries to date. But, it is the organisation’s work with children closer to home, in the disputed territories of Gaza and the West Bank—making up around 50% of the overall intake—that has garnered the most attention. “Every Tuesday, we have a Palestinian clinic running, no matter what the political situation,” Assa tells Cardiovascular News. These sessions typically involve screening between 20 and 25 children who are assessed for potential care. Assa and his colleagues work with doctors on the ground in Gaza, where there are no centres for interventional cardiac treatment, to identify possible urgent cases. “Even if a child is born and needs urgent intervention, they can be referred to us. The local physicians in Gaza have my phone number and they can call me even in the middle of the night to refer the child. In a few hours they can be in our hospital and treated just like any Israeli child,” Assa explains. Despite the volatile situation in the region, Assa says that the important work that he and colleagues are carrying out helps to build bridges between populations that would otherwise be separated across the political divide. “The first meeting can be a very intense meeting,” he says, reflecting on the initial interaction with young patients— and their parents—who may be travelling into unfamiliar, and what they may perceive as hostile territory for the first time. “They can be afraid to meet us. I think it is very natural if you come to an Israeli hospital as a Palestinian, with the intense atmosphere between Israelis and Palestinians.” However, Assa is a firm believer that projects like Save a Child’s Heart are furthering the cause of peace in the

region. “Once they leave, they hug you, they smile, they laugh with you. It is like becoming a family. They feel very close,” he says. “This is a privilege we have as doctors. Despite all that is going on here around us, we really get attached to each other, and I think that this is the beautiful thing about Save a Child's Heart. We all become ambassadors of peace, and these are seeds that I really believe in the future are going to help these two countries get closer to each other.” For 11-year-old Mazen, Save a Child’s Heart’s 6,000th patient, the strong ties between Gazan doctors and Assa’s team has proven to be lifechanging. During the first few weeks of his life, doctors in Gaza diagnosed Mazan with a congenital heart condition which required surgery. As he grew older, Mazan’s defect made it more difficult for him to breathe, and in late 2021 it was decided he needed emergency intervention—something that is not available to him in his home territory. Gazan doctors Abdalraheem Said and Hany Al Faleet referred Mazan to the Save a Child’s Heart programme in the hope that he could receive the care needed. Swiftly transferred to the Israeli team, Mazen was treated at the Save a Child’s Heart International Pediatric Cardiac Care Center at the Sylvan Adams Children’s Hospital at the Wolfson Medical Center in Holon. First he was screened by Alona Raucher Sternfeld, the centre’s director of paediatric

cardiology, before he was treated in of course in Africa, who without getting the hospital’s new hybrid cath lab, in a this intervention are dying. Our aim procedure performed by Assa. was always to grow, and to save more “When he was referred to us there children.” was a question if it was possible to treat One branch that the organisation him in the cath lab, or if he would need looks set to expand is its training a second surgery. We have to remember offering, which has already contributed that reoperating on a child who has to training several physicians in already had open chest surgery means Tanzania, Zambia and more recently a much more complicated operation,” Ethiopia to deliver care for paediatric says Assa. “The defect Mazan had congenital heart patients. Save a Child’s was very near to his aortic valve, and Heart has also recently announced I am happy that due to very a new partnership between advanced technology in the with Israel's Ministry of new cath lab we were Foreign Affairs (MFA), able to offer him better through its Africa treatment. Instead of Division and Agency being operated on he for International was catheterised.” Development Speaking to Cooperation Cardiovascular News (MASHAV), which in early 2022, Assa says will bring 25 children he has been encouraged from 25 African countries by Mazan’s swift recovery to Israel for care. The from the procedure. “The partnership will expand the beautiful thing about cath labs Save a Child's Heart geographical reach of the in Africa is that the children can enter charity to help children from very sick, and half an hour an additional 11 African after [the procedure] they have no scar, nations—South Sudan, Democratic they are back to their normal life and Republic of Congo, Chad, Sierra Leone, feel much better. Mazan had really big Liberia, Cameroon, South Africa, problems before with breathing, with Angola and Mozambique—in receiving exercising, and the day after he was care. fine,” Assa explains. Reflecting on his affiliation with Save Now marking its 25th year in a Child’s Heart, which has lasted for existence, Save a Child’s Heart has 20 of the organisation’s 25 years, Assa its sights on expanding its reach to sees a personal humanitarian mission offer care further afield. “We have to running in step with that of the charity. remember that eight of every 1,000 “It was probably destiny for me to children are born with a congenital become a cardiologist and to heal and heart defect,” says Assa. “Half of them save children with heart problems. I am will need some intervention. It means very proud and very happy for every there are so many children here in child that we are able to save. I go back Israel, in the West Bank, in Gaza, and home very satisfied,” he reflects. “I have friends and colleagues in the USA and in Europe, and some of them cannot treat patients because they do not have the right insurance, or because there is not the right facilities to treat them. So, being able to help children, not only Israelis but from other countries, it is a big privilege.”

Our aim is always to grow, and to save more children”

Mazen, Save a Child's Heart's 6,000th patient, with Sagi Assa

Issue 65 | May 2022

Cardiovascular surgery VISION study concludes troponin is a benchmark for cardiac surgery risk Levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury, a study in the New England Journal of Medicine has concluded.

On-pump and offpump CABG confer similar outcomes over 10 years A 10-year study monitoring patients receiving “on-pump” or “off-pump” coronary artery bypass grafting (CABG) has concluded that outcomes between the two forms of surgery are not much different.

he study by Laurie Shroyer (Stony Brook University Renaissance School of Medicine, Stony Brook, USA) and colleagues monitored the postCABG outcomes of patients enrolled in the Department of Veterans Affairs (VA) Randomized on/off bypass (ROOBY) trial. The phase IV clinical trial represents the largest US-based, multicentre, randomised clinical trial comparing off-pump versus on-pump patients. The findings have been published in JAMA Surgery. On-pump surgery is the more conventional approach and uses a heart-lung machine to circulate the blood while the heart is stopped enabling surgeons to more easily complete CABG. Off-pump CABG eliminates complications potentially caused by the heart lung machine yet makes the procedure more technically difficult. The researchers tracked more than 1,000 veterans for each group—those treated by way of on-pump and those with off-pump procedures over 10 years. These veterans are a national cohort from 18 VA centres. The average age at the time of surgery for both groups was around 63. According to the authors, no significant 10-year treatment-related differences were documented for any primary or secondary post-CABG endpoint rates. Endpoints included repeat CABG, other heart revascularisation procedures, and changes in cardiac symptoms. The death rates at 10 years were 34.2% for the off-pump group and 31.1% for the on-pump group. Although the 10-year outcome rates were not different, researchers did document a slightly shorter revascularisation-free survival period among patients in the off-pump group. Additionally, the median time to death in the off-pump patients was 5.6 years, and the median time to death in the on-pump patients was 6.1 years. Across all study outcomes no off-pump advantages were found. The analyses for cardiac outcomes for these two groups were completed from May 2017 to December 2021. “While our findings may not settle the ongoing debate about on-pump versus off-pump advantages with CABG, the data is strong to support the notion that for patients

who are viable candidates for either procedure, no benefits were found for using an off-pump procedure,” says Shroyer, the study’s lead author. “As these veterans were nearly all men, the findings should not be generalised to women or non-veterans. Thus, surgeons should choose the best CABG method based each individual patient’s risks and in light of the surgeon’s own technical CABG expertise and post-CABG outcome experiences. In summary, each CABG patient’s care should be customised to meet their unique needs.” “I congratulate the authors for their diligence to follow this group of veterans, who represent the first wave of an operation that has since evolved greatly,” said Thomas V Bilfinger (Renaissance School of Medicine, Stony Brook, USA) who was not involved in the study. “These operations were performed at a time when this revascularisation approach was considered novel, and it served as an impetus for a few dedicated surgeons to advance it further to become a minimally invasive robotic and often hybrid operation. While it is good to know there is no difference in the long-term outcomes between off and on pump groups, the lasting importance of this research is that it provides a seed to newer procedural developments that will lead to long-lasting beneficial outcomes for today’s patients.”

The lasting importance of this research is that it provides a seed to newer procedural developments that will lead to long-lasting beneficial outcomes for today’s patients”

INVESTIGATORS DESCRIBED THE finding as a “landmark” for care of patients following cardiac surgery, as it provides a marker that is fast and reliable for monitoring their recovery and could help timing procedures to improve outcomes. The VISION, international prospective cohort study, assessed patients undergoing cardiac surgery, measuring troponin levels were obtained three to 12 hours after surgery and on days one, two, and three after their procedure, and assessing death and the incidence of major vascular complications. The research team, which was led by PJ Devereaux (McMaster University, Ontario, Canada), performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex. The study involved 15,984 patients with an average age just over 63 years undergoing cardiac surgery. Patients were from 12 countries, more than a third of which were outside of North America and Europe. Investigators found that by 30 days after heart surgery, 2.1% of patients had died, and 2.9% had experience a major vascular complication, such as heart attack, stroke, or life-threatening blot clot. “We found that the levels of troponin associated with an increased risk of death within 30 days were substantially higher—200 to 500 times the normal value—than troponin levels that surgical teams are currently told defines the risk of a patient having one of the most common complications after heart surgery—myocardial injury, a heart muscle injury associated with increased deaths,” said Devereaux. “This study is a landmark for the health teams taking care of patients after cardiac surgery. For the first time, we have a marker that is fast and reliable for the monitoring of these patients after cardiac surgery,” said André Lamy, a study investigator. “Our findings will help further studies look at the timing of treatments and procedures to improve patient outcomes after heart surgery,” said investigator Richard Whitlock.

May 2022 | Issue 65

Cardiovascular surgery New technique outperforms manual assessment of thoracic aortic aneurysm growth Researchers have developed a novel method of measuring growth of thoracic aortic aneurysm, which they claim could significantly improve the accuracy and reliability of aortic measurements compared to standard-of-care measurement techniques. THE TECHNIQUE, WHICH IS KNOWN AS vascular deformation mapping, measures changes in the thoracic aorta, using computed tomography (CT) imaging to calculate changes in the aortic wall. The technique outperforms the standard manual rating methods performed by experts, according to the research team behind the technique, Zhnangxing Bian (University of Michigan, Ann Arbor, USA) and colleagues, writing in a paper published in Radiology and Medical Physics. “The technique used in this algorithm has been around for a while, but no one has ever used it to see threedimensional growth of an aneurysm of the thoracic aorta,” said Nicholas Burris (University of Michigan, Ann Arbor, USA), corresponding author of the paper. “This is a promising step towards having technology that pushes the accuracy of measurement past what human raters can achieve, allowing clinicians to have the best possible picture of a patient’s condition.” Currently, the standard practice to measure growth is done with human “raters” who line up two images and draw a line at two points to find the change. “The challenge we are faced with clinically is that a typical aneurysm in the aorta is going to grow only a fraction of a millimetre every year, and the process of manually drawing diameters that precise is very hard to reproduce,” Burris said. “You have a lot of variability in standard measurements relative to a very small amount of actual aneurysm growth. Basically, you rarely end up getting a confident assessment of growth, which can make it difficult to know what the patient’s actual risk is and how closely they need to be followed with repeat CT scans.” The vascular deformation mapping technique developed by Burris’ team relies on an image analysis technique which aligns the anatomy shown in multiple CT scans by taking any pixel on the first scan and relating its exact position to the pixel on the second scan. When they are all aligned, a map of the aorta shows the growth. Researchers used scans from nearly 50 aortic aneurysm patients and 75 reference models with variable growth of the aortic wall. They tested the automated programme against two expert manual raters and found the vascular deformation mapping outperformed the humans with higher accuracy and lower variability in the growth measurements. Vascular deformation mapping achieved an accuracy of less than 1mm in all cases when even the most experienced human analysts had measurements with errors of up to 3mm, they report. While these reports show vascular deformation mapping may be more useful than human rating to inform whether surgery is necessary on an aortic aneurysm, researchers say the approach must be studied further in large groups of patients in a clinic. Burris says, the vascular deformation mapping technique can be performed on routine CT scans of the aorta, making performing larger research studies easier.

Ross procedure “associated with better long-term outcomes” for aortic valve replacement The “Ross procedure” may be a more favourable option for aortic valve replacement among patients under 50 years old than more standard mechanical or biological replacements, according to a study published in the Journal of the American College of Cardiology (JACC).

he research, authored by Ismail El-Hamamsy (Icahn School of Medicine at Mount Sinai, New York, USA) is the first to compare the Ross procedure to the other options, and shows that it leads to improved survival and better outcomes in younger adults, the study team suggests. “Not only was survival better than after biological or mechanical aortic valve replacement, it was also identical to the matched US general population. To this day, this is the only operation that has ever been shown to restore survival after aortic valve replacement in young adults,” says El-Hamamsy. “This is a huge deal because it demonstrates the impact of valve choice in the long-term. However, there is an important word of caution: the Ross procedure is a more complex operation and should only be performed in Ross centres of excellence. When done in that setting, this represents a major breakthrough for young patients with aortic valve disease, including young women contemplating pregnancy.” The standard open-heart procedures for aortic repair include mechanical valve replacement— which uses a manufactured valve that requires patients to take life-long blood thinners to prevent stroke, as well as make some lifestyle modifications such as avoiding contact sports that may lead to falls and bruising—or a biological aortic valve replacement from a human or animal donor, which may last up to 20 years, but requires earlier reoperation in younger patients than a mechanical valve. The Ross procedure is a more complex operation where a surgeon replaces the diseased aortic valve with the patient’s own living pulmonary valve, which is a mirror image of a normal aortic valve. This is the fundamental difference between the Ross procedure and a biological or mechanical valve replacement, which is a critical factor for successful long-term outcomes in patients. Researchers analysed records of 1,302 patients between 18 and 50 years old who underwent first-time elective aortic valve replacement surgery in California and New York State between 1 January 1997 and 31 December 2014. Patients were equally divided into three categories using propensity-matched analysis to eliminate any baseline differences; one-third of them had the Ross procedure, one-third had biological valve replacement, and the rest had mechanical valve replacement. The retrospective Ismail study compared the long-term El-Hamamsy survival and risk of valve-related

complications (including stroke, major bleeding, reoperation, and acute endocarditis) according to the surgical procedure. Investigators looked at outcomes 15 years post-procedure and found that patient survival was significantly better after the Ross procedure. At 15 years, overall mortality was more than twofold higher if the patients received a biological or mechanical aortic valve versus a Ross procedure. Furthermore, survival after the Ross procedure (93% survival at 15 years) was identical when compared to people of the same age and sex in the US general population who did not have aortic valve replacement surgery. In terms of valve-related complications, the Ross procedure was associated with a significantly lower risk of stroke or major bleeding than a mechanical valve (3.8% after a Ross procedure versus 13% after a mechanical valve at 15 years). Similarly, the Ross procedure was associated with significantly fewer reoperations (17% versus 30% at 15 years) and endocarditis—an infection of the heart tissue—than a biological valve (2.3% versus 8.5% at 15 years). At 15 years, however, the risk of reoperation was higher after a Ross procedure than after mechanical valve replacement (17% versus 7.4% at 15 years). The study also looked at 30-day mortality after the occurrence of any valve-related complication, including stroke, major bleeding, endocarditis, or reoperation. Researchers found the lowest mortality was linked to reoperation (1%), whereas if patients had a stroke, major bleeding, or endocarditis, the associated mortality was at least three times higher (5.6% after a stroke and 13.5% after endocarditis). “This study demonstrates that while there is a definite risk of reoperation after the Ross procedure, the associated risk is low. In other words, this should be seen as a bump on the road, rather than the end of the road. In contrast, if patients suffer a stroke, haemorrhage, or infection, the consequences are much more dire,” adds El-Hamamsy. “Patients should be given all this data so they can make truly informed decisions about these major life events. Ultimately, the Ross procedure is associated with better survival and fewer complications.” The authors hope that this will further encourage the development of regional Ross centres of excellence to improve patient access and safety. Furthermore, ElHamamsy’s team are working on further improving the durability of the Ross procedure so that even fewer patients ever need a reoperation.

Issue 65 | May 2022

CX 2022

Aortic arch and radiation challenges under the spotlight at CX 2022 Leaders from the cardiac, vascular and endovascular surgery specialties convened at the 2022 Charing Cross International Symposium (CX 2022, 26–28 April, London UK and broadcast) which featured a comprehensive programme highlighting pressing aortic challenges—spanning the thoracic, abdominal and juxtarenal aorta. DELEGATES TO THE SYMPOSIUM, WHICH made a much-anticipated return to the in-person format for the first time since the beginning of the pandemic, also heard some of the latest challenges relating to radiation reduction, as well as advancements in the aortic field. The full programme, which includes sessions covering challenges to practice in all vascular domains—including peripheral arterial, venous, acute stroke and vascular access—is available to view on demand for registered users. Highlights from the Arch Aortic Challenges programme, which took place on the final day of the three-day symposium, included presentations from Joseph Coselli (Baylor College of Medicine, Houston, USA) who gave attendees an overview of challenges relating to reoperation of the aortic arch, and Joseph Bavaria (University of Pennsylvania, Philadelphia, USA) who offered insights into a novel technique combining surgical ascending and arch repair with a thoracic single side branch device. Bavaria and Coselli also took part in a session highlighting challenges relating to thoracic aortic dissection, during which Bavaria discussed management of the aortic arch during type A aortic dissection. “Do we have a problem with the distal aorta after repair of acute type A dissection?” asked Bavaria during his presentation, commenting that acute type I dissection is “a total aortic catastrophe”. In his presentation, Bavaria argued that this issue must be addressed with thoracic endovascular aortic repair (TEVAR)-enabling solutions in order to improve outcomes, later summarising that the ultimate approach will be dependent on the life-expectancy and indication of the patient. Depending on these factors, suitable strategies could include a classic hemi-arch procedure, frozen elephant trunk (FET) technique, or sequential arch branch TEVAR—which is likely to be the case for the majority of patients, Bavaria commented. This theme was re-examined during a debate session in which Coselli argued for the motion that FET should be used rather than branched and fenestrated arch procedures for chronic type A aortic dissection.

Coselli faced off against Tilo Kölbel (University Heart Center Hamburg, Hamburg, Germany) who argued against the motion. Coselli put forward the case that FET combines the benefits of a traditional open total arch replacement, and prepares for the subsequent open or endovascular repair of the downstream aorta. The CX audience vote was split after hearing of Kölbel’s argument that EVAR is a valid alternative to open surgery in patients with increased surgical risk.. In a later session, speakers considered the need to reduce radiation dose to patients and providers. Bijan

Modarai (King’s College London, London, UK) set the scene by offering evidence of radiation exposure induced chromosomal aberrations in endovascular operators. Modarai highlighted the cumulative lifetime burden of chronic low-dose exposure and also outline work, carried out in conjunction with collaborators at UK Health Security Agency and Brunel University, examining high-volume endovascular operators for evidence of chronic DNA damage. “It is really frightening,” session anchor Markus Steinbauer (Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany) said in response to Modarai’s presentation, adding that it is important to “face the reality” of this issue. In the same session, Maria Antonella Ruffino (Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Turin, Italy) delivered a presentation detailing radiation dose exposure in patients undergoing complex revascularisation procedures for aortoiliac occlusive disease (AIOD), in which she noted that endovascular procedures for complex AIOD decrease risks and patient discomfort, shortening both the in-hospital stay and recovery period, but may be associated with high radiation exposure for patients. The emergence of new technologies for the treatment of aortic disease were also addressed at CX 2022. In a Podium 1st presentation—one of 15 to take place across the three-day symposium—Tom Carrell (Cydar Medical, Barrington, UK) offered detail on the future direction of tools for planning, guiding and reviewing endovascular surgery. The company’s current product uses “virtual guidewires”, Carrell explained. “We use [virtual guidewires] for planning, but the main function is to identify where you are going to be operating, so that your planning is rendered in the form of a map and overlaid on a live fluoroscopy. As your real guidewires deform the anatomy, the virtual guidewires deform the map so that you have an overlay that reflects the realtime anatomy.” Carrell provided some details on where the software is headed: “What we are doing with Intelligent Maps is taking that capability with the virtual guidewires and the AI that we have in the system and the data from all the thousands of patients who have been treated with Cydar EV Maps and building tools to analyse anatomy.”

Failure to rescue may complement mortality as an outcome measure for aortic surgery Failure to rescue may act as a suitable quality assessment marker for open aortic repair and endovascular aneurysm repair (EVAR). THIS WAS THE MESSAGE of Kevin Mani (Uppsala University, Uppsala, Sweden), who delivered a Podium 1st presentation examining the volume-outcome relationship in aortic surgery and its association with failure to rescue. Mani and collaborators studied intact abdominal aortic aneurysm (AAA) repairs performed in a multinational registry dataset, assessing complications after aortic repair, failure to rescue complications, and the relation to surgical volume, assessing more than 60,000 intact AAA repairs

performed in eight countries. The study team noticed that complications occurred after 4‒5% of all endovascular aneurysm repair EVAR procedures, and the frequency of any complication was three times higher after open repair. Whilst the frequency of complications was reduced after open repair with increasing volume, this trend was not present after adjustment for patient characteristics, Mani said.

Overall, the adjusted risk of developing a complication after aortic repair did not decrease with increasing volume, he said. Failure to rescue occurred in 10‒12% of the patients suffering a complication. When looking at the relationship between volume and failure to rescue, it was clear that increasing volume resulted in a lower failure to rescue rate, Mani told the CX audience. “In conclusion, the current analysis suggests that the volume-outcome relationship in aortic surgery is driven at least in part by the preparedness to promptly recognise and manage complications,” Mani said. “As such, failure to rescue is a quality assessment marker that reflects processes of care in aortic surgery for both open repair and EVAR, and complements Kevin mortaltity as Mani an outcome.”

May 2022 | Issue 65

18 Interview

PROFILE

Vijay Kunadian

Vijay Kunadian (Newcastle University and Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK) tells Cardiovascular News about her early career in interventional cardiology, the need for more concerted effort to improve outcomes among women with cardiovascular disease, and her research among elderly patients suffering from acute coronary syndromes.

I really loved science when I was in school, always coming top of the class, and at around 13 years of age I decided I wanted to be a doctor. Throughout medical school I absolutely loved everything about the heart— heart murmurs and structures really fascinated me—and wanted to be a cardiac surgeon. One of my first junior doctor jobs was in cardiothoracic surgery, but I did not enjoy that very much, so I switched gear. After medical training I took up post as a junior doctor in cardiology, and loved everything about it, particularly having great mentors who supported and encouraged me. My MD research project was all about coronary angiography and coronary artery blood flow, involving in-depth analysis of hundreds of coronary angios. I absolutely loved analysing the angios and I recall staying behind very late in the research office to make sure I was upto-date with all my analysis. Then, as a clinical research fellow, I became interested in interventional cardiology. At the time we were not doing primary percutaneous coronary intervention (PCI) in the UK, but we were leading projects on rescue angioplasty. I was fascinated every time I was in the cath lab and I would always be welcomed by consultants and the cath lab staff that I did not feel any different as a woman in that environment. I was presenting work in nearly every cardiology congress, nationally and internationally, which sparked my enthusiasm for interventional cardiology. You could not get a consultant post in a tertiary cardiac centre in the UK at the time without an international overseas fellowship, and, as I was well ahead in my clinical training, I applied and was accepted to undertake an academic fellowship at Brigham and Women’s Hospital, Harvard Medical School (Boston, USA) which ignited my passion for academia.

Who were the biggest influences on your early career?

My dad has been the number one influence throughout my life, encouraging me to keep moving forwards, and break barriers. In my professional life, I am fortunate to have had great mentors from the early stages of my career. I learnt all about intervention and academia when I worked as a clinical research fellow under the supervision of Mark de Belder, and that is where it all started for me. I also had an absolutely incredible time in Boston as an academic research scholar with Mike Gibson. There was a very steep learning curve, but it was worth it. His attention to detail in everything—angiographic analysis, manuscript writing and reviewing, forward thinking—is so inspiring to me, and I still cherish everything I learn from him. I also got connected to Roxana Mehran as a Society for Cardiovascular Angiography & Interventions (SCAI) Women in Innovations (WIN) mentor. She is a truly remarkable person and an absolute honour to collaborate with. When such giants in interventional cardiology are supporting you, you really want to do the very best you can to provide outstanding care to patients through direct clinical care and research.

What has been the most important development in interventional cardiology during your career?

Having worked during the rescue PCI era, it is so amazing to see how primary PCI has transformed the way we deal with patients with ST-elevation myocardial infarction (STEMI). It is incredible to see the difference with lives being saved and very low complication rates. I was a trainee when we first performed transcatheter aortic valve implantation (TAVI) in Newcastle. That really was a memorable moment in my career. It is absolutely amazing how TAVI has evolved over the years and gives hope to patients who would normally have been turned down from open heart surgical procedures, particularly in the context of an ageing population with multi-morbidities.

What has been the biggest disappointment? Something you hoped would change practice but did not? I am really so disappointed that we have not made much progress in the best care of women with cardiovascular disease. We have been talking about the fact that women are undertreated and have worse outcomes for decades, but have not really seen much change to improve outcomes. Even in 2022, papers are being published showing that women are undertreated for the various cardiovascular conditions leading to worse outcomes. The pandemic has not helped progress either, perhaps pushing the health and wellbeing of women backwards. This is why, as a commissioner on The Lancet Commission to reduce the global burden of heart disease in women by 2030, I am determined

It is amazing to see how primary PCI has transformed the way we deal with patients with STEMI” to see this mission realised through raising awareness and new clinical research projects. I was also chosen by the British Heart Foundation (BHF) as their panel member for the Bias and Biology campaign, and have campaigned on national media to improve the care of patients with heart disease, in particular women. I was an invited keynote speaker at the United Nations Commission on Status of Women event in 2021 discussing gender equality and equity in healthcare.

What are your current research priorities?

I have been leading on several research projects in Newcastle to improve the outcomes in older adults with acute coronary syndromes (ACS). Although 50% of myocardial infarctions (MIs) happen in over 70s, there is very sparse evidence on the best care of older adults. Hopefully our studies will help address the evidence gap in this cohort of patients.

Andy Watt/NB Illustration

Why did you choose to become a doctor and why, in particular, did you choose to specialise in interventional cardiology?

What have recent studies taught us about treatment of elderly patients with ACS, and are there areas where research in this population is lacking?

In the last decade, there have been many drug and device studies which have increased the evidence base in older adults. For example, we can now safely give short duration dual antiplatelet therapy (DAPT) with latest generation drug-eluting stents for older patients without an increase in ischaemic events, but with reduced bleeding events. But, we still do not know if interventional strategies such as PCI or coronary artery bypass grafting (CABG) are of benefit equally in younger and older adults with ACS. We are studying this in the SENIOR RITA trial and hopefully we will have the results soon which will impact clinical practice worldwide. Although there is lack of evidence, it is also a challenge recruiting older patients to research studies.

Issue 65 | May 2022

Interview 19

What are the current challenges facing women seeking to enter the interventional cardiology field, and how would these be best overcome? Looking at the my own career, all of the barriers that women currently report have always existed, but it has not always been something I have taken to hamper my progress personally. I always sought out support and guidance from great leaders which helped refine and shape my career. I think the key for success is to shut out the negatives, keep seeking, and not to give up, because there are some remarkable leaders who would be willing to help and support you. In cardiology, and in medicine in general, there is no shortcut. Sometimes you might think ‘I am not going anywhere’, but these are times of growth and development. The bottom line is to make the most of opportunity and support from mentors, work hard, be proactive, always be willing to learn, be grateful, be respectful of others, and go with your passion. It is crucial that trainees are nurtured to strengthen the future workforce in our amazing specialty where there is much need for dedicated professionals.

Looking back over your career, what has been your most memorable case?

I have many memorable cases, but I always remember the history and story from female patients. The recurring theme is that women themselves, or their doctors, do not think they are having a heart attack, but in the end it is always the heart. I often present the case of a 50-plus woman who did not seek help for 12 hours. Her husband came home from work and saw her not looking well and then called for help. She was brought to the cath lab, where, en route, she had multiple cardiac arrests, was in cardiogenic shock, had a large thrombus in left main stem extending to the circumflex artery. When we aspirated the thrombus, there was no evidence of a lesion. But, an intravascular ultrasound (IVUS) showed plaque rupture in the ostium of the left main which needed to be fixed with stenting to save her life. You can see how we could have easily lost her if we did not undertake the right investigations and treatment.

Outside of medicine, what are your hobbies and interests?

I have many interests and hobbies outside of medicine and cardiology. To name a few, I am a keen gardener, growing all sorts of flowers, fruits and vegetables in my garden. I love to cook and having family and friends around. I love hiking, and live in the stunning North East of England countryside and love long walks in the moors and up the hills. I love taking photographs of the stunning beautiful scenery during my walks.

Fact file Current appointments

Personal Chair, Professor of Interventional Cardiology, Newcastle University Honorary Consultant Interventional Cardiologist, Freeman Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust Lead Supervisor: MRes Cardiovascular Science, Newcastle University

Education & training

General and Interventional Cardiology, Northern Deanery, UK Postgraduate Diploma in Clinical Trials, University of London, UK Research Scholar, Brigham and Women's Hospital, Harvard Medical School, USA Research Registrar, The James Cook University Hospital, Middlesbrough, UK

Memberships

British Cardiovascular Society British Cardiovascular Intervention Society European Society of Cardiology European Association of Percutaneous Cardiovascular Interventions Royal College of Physicians

Editorial positions

European Heart Journal Digital Health, Associate Editor Heart, Associate Editor, Education in Heart Circulation Cardiovascular Interventions, Editorial Board

May 2022 | Issue 65

20 Gender Disparities

“We have work to do here”: Studies pinpoint lack of representation of women in senior positions on cardiovascular trials and at scientific meetings

changing trial results at scientific meetings.” Walsh said that increasing the number of women on trial steering committees needs to start at a deeper level. Mentorship in early career is crucial as is knowledge of clinical trial committee structure. “We are starting to see work being done to close the gap in representation, but more needs to be done,” Walsh said. “Scientific sessions and meeting planners only have so much influence over who is presenting at conferences. This comes down to senior clinical trialists relinquishing the podium and giving a leg up to others.” Walsh laid out steps to increase representation in clinical trial leadership, including that sponsors The number of female principal investigators falls well below the number of clinical trials need to insist on diversity of of males leading similar cardiovascular clinical studies, despite attempts the trial steering committee; investigators to improve the number of women at the helm of such trials, according to asked to lead clinical trials must consider research presented at the American College of Cardiology’s annual geographic, institutional and trial site scientific sessions (ACC 2022, 2–4 April, Washington DC, USA). diversity, along with a diverse slate of experienced investigators in leadership hese findings add to the conclusions of a review do here.” positions; institutions, department chairs published in the Journal of the American The study took a broad view of and division chiefs need to encourage College of Cardiology (JACC) in February, cardiovascular clinical trials conducted women to serve as site principal highlighting a lack of gender diversity among from 2010 to 2019 and assessed whether investigators; the informal, or formal, presenters at scientific meetings. Authors of both female-led studies varied by funding pecking order of cardiovascular trial studies suggest that the findings point to the fact that type and subject. Overall, the proportion leadership needs to be reworked, and; huge strides are needed to improve the representation of female principal investigators did not women should not be tapped for clinical of new drug of women in the field of cardiovascular health. significantly change over the 10-year trial leadership, and late-breaking results research Presenting at ACC, Aashana Suvarna (University period. reporting, solely if the trial is pertinent of California, Berkeley, USA) told delegates that The researchers also found a only to a female patient population. compared with their male counterparts, female correlation between female-led clinical “There will be no room at the top principal investigators led fewer drug and device trials and female patient enrolment. for new and innovative investigators trials—18.9% of new drug research and 9.6% of Compared with studies conducted by to shine if those who have already device trials. Suvarna and team and team came to this a male principal investigator, studies achieved success do not make finding after conducting a consecutive review of 620 with a female principal investigator room,” Walsh said. cardiovascular National Institutes of Health (NIH) were associated with a 7% mean higher The lack of representation of women, and industry or pharmaceutical-funded studies on enrolment of female subjects, with both at a leadership and patient level of device ClinicalTrials.gov. an average of 44.9% female subjects in cardiovascular medicine has been trials for female-led studies vs. an average of increasingly in the spotlight in recent 37.9% female subjects for male-led studies. months. Cardiovascular News recently “The field of cardiology has long struggled reported on discussions at the European with the inclusion of women in clinical trials as well Society of Cardio-Thoracic Surgery annual meeting as the underrepresentation of women in the profession (EACTS 2021; 13–16 October; Barcelona, Spain itself,” Suvarna said. “Current clinical trials rely on and virtual) where speakers considered current data a majority of male subjects, and the generalisation of concerning women undergoing coronary artery these results [to women] may be inaccurate. Improving bypass grafting (CABG) or percutaneous coronary Aashana representation of women in trials will yield more intervention (PCI). Panellists at the session concluded Suvarna meaningful results by significantly improving clinical that the underrepresentation of women in clinical outcomes.” coronary revascularisation trials on a patient level may Suvarna’s findings paint a similar picture to those encourage treatment that favours outcomes in men, of the February JACC paper authored by Mary despite the presence of significant differences in the Norine Walsh (Ascension St Vincent Heart Center, clinical characteristics between women and men. Indianapolis, USA) suggesting that underrepresentation of women in cardiovascular trials also corresponds with underrepresentation and a lack of gender diversity among presenters at scientific meetings. A previous analysis of cardiovascular trials published over the last four years found that women comprised only 10.1% of clinical trial leadership committees, and more than half of the trials had no women as part of the trial leadership team. Other research has also found a Mary Norine correlation between women leading clinical trials and Walsh the number of women participating in clinical trials. Historically, clinical trials have largely enrolled white men, and participation has been low among women, Aashana Suvarna older adults and racial/ethnic minorities. The current review highlights gender diversity of Of these, only about one in five studies (18.4%) panellists and session chairs at the recent American were led by a female principal investigators. Women College of Cardiology (ACC) Scientific Sessions, but were more likely to lead “other investigations,” which demonstrates that 93% of the clinical trial results were included behavioural, surgery or rehabilitation studies. presented by men. Women were also more likely to lead trials funded “These problems are, unfortunately, cyclical in by the NIH rather than industry sponsors, 28.9% vs. nature. A lack of women in leadership positions on 14.7%, respectively, Suvarna detailed. clinical trials results in fewer women participating in “I was rather surprised that despite efforts to improve the trials. The fewer women participating in studies female representation in clinical trial leadership, there means that medications and other therapies are not was barely an increase in recent years,” Suvarna, an ensured to be safe and effective for everyone,” said undergraduate studying molecular and cellular biology, Walsh. “Fewer women leading clinical trials also Mary Norine Walsh said. “This confirms how much more work we have to means fewer women presenting pivotal, practice-

Female leadership

18.9% 9.6%

I was rather surprised that despite efforts to improve female representation in clinical trial leadership, there was barely an increase in recent years”

Fewer women leading clinical trials means fewer women presenting pivotal, practice-changing trial results”

Issue 65 | May 2022

Gender Disparities 21

Female representation in interventional cardiology remains low, but there is cause for hope Suzanne Baron and Ki Park Comment & Analysis

any female interventional cardiologists tell the story of being the only woman in their interventional fellowship or the only female physician in the catheterisation laboratory at their institution. Unfortunately, this narrative extends beyond just anecdotes. Indeed, despite 50% of medical students being women, the proportion of females in cardiology and cardiology sub-specialties remains low with only 14.9% of practicing cardiologists identifying as women1. The number becomes even more dismal when one looks at the percentage of practicing interventional cardiologists who are female – a mere 8%1, and the numbers decline even further when assessing gender diversity of structural operators2. The aetiology for such poor gender representation amongst interventional cardiologists appears to be multifactorial. Yong and colleagues surveyed 574 cardiology fellows in an attempt to identify those factors that may affect a trainee’s decision to pursue a career in interventional cardiology3. Compared with males, females were significantly more likely to be deterred

from interventional cardiology due to concerns regarding radiation exposure during childbearing years, sex discrimination and harassment, an “old boys club” culture, and a lack of female interventional role models. Coupled with the well documented disparities in salary and academic advancement between male and female cardiologists4, it is not surprising that women remain sorely underrepresented in the interventional cardiology sphere. Recruiting more women into the field of interventional cardiology is important not just to improve diversity, but also to potentially address sex-specific disparities in patient care. Studies have shown that female patients with a wide variety of cardiovascular conditions tend to be under-diagnosed, undertreated and have worse outcomes when compared with men5–7. Additionally, there are several female-specific or female-predominant cardiac disease entities (e.g. coronary microvascular dysfunction, MINOCA [myocardial infarction in non-obstructive coronary arteries], spontaneous coronary artery dissection), which have been historically under-recognised8,9. While there are

SCAI publishes expert consensus statement on sex-specific considerations in myocardial revascularisation The Society for Cardiovascular Angiography & Interventions (SCAI) has announced the release of an expert consensus statement on sex-specific considerations in myocardial revascularisation, which it said aims to summarise available literature on myocardial revascularisation in women and identify important gaps in evidence. The document was published in JSCAI, the Society’s recently-launched official journal. IN A PRESS RELEASE, SCAI said that utilisation of cardiovascular procedures is far lower in women than men, and women continue to be underrepresented in cardiovascular clinical trials, severely limiting the opportunity to better understand sex

differences in cardiovascular drug or device outcomes. Current practice guidelines do not address sex-based differences and fail to highlight when insufficient evidence exists regarding cardiovascular outcomes in women, resulting in overall poorer outcomes.

many contributing factors to these disturbing trends, the historically low enrollment of women in cardiology trials has likely contributed to a poorer understanding of the best methods to diagnose and treat women with cardiac disease10. Since some studies have suggested that physician-patient gender concordance may influence outcomes11, it is possible that increasing female representation in the field of cardiology, both at the patient-provider level as well as in clinical trial leadership, may translate to improved patient care through increased female participation in clinical trials and through a better understanding of disease presentation and management of the female patient. The gender imbalance within interventional cardiology and cardiology in general has been recognized over the last several years, due in no small part to a handful of iconic female trailblazers in cardiology, who have shown a bright light on this issue. With this recognition has come the growth of formal women’s groups and mentorship programs within national cardiology societies (e.g. Society for Cardiovascular Angiography and Interventions - Women In Innovations; American College of Cardiology - Women In Cardiology), increased involvement of female

Improving female representation within the ranks of cardiology will require a continued focus from academic institutions, industry and national societies”

“This consensus is an international collaborative effort that highlights the knowns, the gaps and ambiguities in evidence related to sex-specific revascularisation,” says Alexandra Lansky, professor of medicine in the section of Cardiology at the Yale School of Medicine and a practicing cardiologist at Yale-New Haven Hospital, New Haven, USA. “As a companion to the recent percutaneous coronary intervention (PCI) guidelines, it will inform clinicians on best practices most relevant to our female patients and draws attention to areas in need of additional evidence.” The paper explores gaps in evidence in several areas including the epidemiology of ischaemic heart disease, diagnostic tools to guide coronary revascularisation, revascularisation for chronic coronary syndromes, revascularisation for non-

cardiologists as faculty at conferences, greater education on radiation safety in the catheterization lab, and industry commitment to improve involvement of women in clinical trials, both at the patient and physician level. And these efforts appear to be bearing fruit as evidenced by the fact that the pipeline is expanding - 13% of U.S. interventional cardiology trainees were women in 2019 - a 50% increase from 2015 (1,12). While these statistics are certainly encouraging, the absolute numbers are modest, thereby underscoring the fact that much work remains to be done. Indeed, improving female representation within the ranks of cardiology will require a continued focus from academic institutions, industry and national societies alike, for it is only with this communal effort that the true benefits of gender diversity can be recognised for our patients. References 1. Association of American Medical Colleges. Physician Specialty Data Report Washington, DC, 2020. 2. Simpson TF, Atkinson TM, Chadderdon S et al. Gender Disparity Among Transcatheter Aortic Valve Replacement Operators in the United States. Circ Cardiovasc Interv 2021;14:e010659. 3. Yong CM, Abnousi F, Rzeszut AK et al. Sex Differences in the Pursuit of Interventional Cardiology as a Subspecialty Among Cardiovascular Fellows-inTraining. JACC Cardiovasc Interv 2019;12:219-228. 4. Jagsi R, Biga C, Poppas A et al. Work Activities and Compensation of Male and Female Cardiologists. J Am Coll Cardiol 2016;67:529-41. 5. Bugiardini R, Ricci B, Cenko E et al. Delayed Care and Mortality Among Women and Men With Myocardial Infarction. J Am Heart Assoc 2017;6. 6. Skelding KA, Boga G, Sartorius J et al. Frequency of coronary angiography and revascularization among men and women with myocardial infarction and their relationship to mortality at one year: an analysis of the Geisinger myocardial infarction cohort. J Interv Cardiol 2013;26:14-21. 7. Dewan P, Rorth R, Jhund PS et al. Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women. J Am Coll Cardiol 2019;73:29-40. 8. Hayes SN, Kim ESH, Saw J et al. Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association. Circulation 2018;137:e523-e557. 9. Berry C, Duncker DJ. Coronary microvascular disease: the next frontier for Cardiovascular Research. Cardiovasc Res 2020;116:737-740. 10. Cho L, Vest AR, O'Donoghue ML et al. Increasing Participation of Women in Cardiovascular Trials: JACC Council Perspectives. J Am Coll Cardiol 2021;78:737-751. 11. Lau ES, Hayes SN, Volgman AS et al. Does PatientPhysician Gender Concordance Influence Patient Perceptions or Outcomes? J Am Coll Cardiol 2021;77:1135-1138. 12. Association of American Medical Colleges. Physician Specialty Data Report. Washington, DC, 2016.

ST-elevation myocardial infarction (MI) and ST-elevation MI, and revascularisation consideration for specific patient populations, vascular access in women, and more. “Physicians can use this consensus document to inform their discussions with female patients on the risks and benefits of coronary revascularisation,” said J Dawn Abbott, co-chair of the document and professor of Medicine and director of the Interventional Cardiology Fellowship Training Program at Brown Medical School, Providence, USA. “An understanding of the limitations of the data is important in this regard,” Abbott concluded. Authors of the paper state that while the evidence supporting clinical decisions in women is lacking, these findings are important to guide prospective investigation and establish research priorities.

May 2022 | Issue 65

22 Conference Coverage

FAME 3 shows FFR-guided PCI leads to a faster recovery versus surgery Percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) leads to a faster improvement in quality of life, with similar outcomes at 12-month follow-up compared with coronary artery bypass graft (CABG) surgery.

his was the conclusion of an analysis of the FAME 3 (Fractional flow reserve versus angiography for multivessel evaluation) trial, presented by Frederik Zimmermann (Catharina Hospital Eindhoven, Eindhoven, The Netherlands) during the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA) and published simultaneously in Circulation. William Fearon (Stanford University, Stanford, USA) presented primary results of the trial at the 2021 Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA), where he revealed that FFR-guided PCI for three-vessel coronary artery disease had failed to meet non-inferiority for one-year adverse events compared to CABG. The finding led Fearon to remark that in

patients with more complex, three-vessel coronary The proportion of patients with Canadian artery disease, CABG remains the treatment of choice. Cardiovascular Class 2 or greater angina—the study’s The latest analysis focuses on the impact of FFR secondary endpoint—were also broadly similar guidance used in conjunction with current generation, between the groups at 12 months. Younger patients zotarolimus drug-eluting stents on quality of life after (<65 years-old) also had higher odds of working at 12 PCI compared to CABG. months in the PCI group (3.9, CI 1.7 to 8.8) FAME 3 was a multicentre, international, Writing in Circulation, Fearon and colleagues note randomised, controlled non-inferiority trial in which the analysis shows earlier improvement in quality patients with three-vessel CAD warranting of life after FFR-guided PCI with current revascularisation were randomly assigned to generation drug-eluting stents compared with PCI or CABG. CABG, as shown in previous studies, but A total of 1,500 patients were randomised also shows similar quality of life and degree 1:1 to either CABG based on coronary of angina at one year, as well as improved angiogram or FFR-guided PCI in all lesions working status after FFR-guided PCI. with an FFR ≤0.80 at 48 centres in Europe, “Although FFR-guided PCI did not meet Frederik North America, Australia, and Asia. For Zimmermann the criterion set for non-inferiority regarding inclusion in the trial, patients had three-vessel major adverse clinical events at one year CAD, defined as ≥50% diameter stenosis by visual compared with CABG, the difference was smaller than estimation in each of the three major epicardial vessels, in previous studies,” the authors write. “In this setting, but not involving the left main coronary artery, and other factors like quality of life, degree of angina and amenable to revascularisation by both PCI and CABG returning to work can be important considerations as determined by the heart team. A total of 757 patients for both patients and physicians when evaluating underwent FFR-guided PCI and 743 received CABG. revascularisation strategies.” For the latest analysis, quality of life was measured using the European Quality of Life-5 Dimensions (EQ5D-3L) questionnaire at baseline, one, and 12 months. The primary objective of the study was to compare EQ-5D summary index at 12 months. Results of the study, presented by Zimmermann, showed that the EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference=0.001, confidence interval (CI) -0.016 to 0.017). The trajectory of EQ-5D differed (p<0.001) between PCI and CABG: at one month, EQ-5D was 0.063 (CI 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ visual analogue scale.

FFR-guided PCI non-inferior to IVUS for intermediate coronary stenosis

A head-to-head comparison of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) in patients with intermediate coronary artery stenosis found that FFR was non-inferior to IVUS for adverse clinical outcomes at a two-year follow-up. THIS WAS THE CONCLUDING finding of the FLAVOUR study, an investigator-initiated, prospective, randomised open-label multinational trial, which sought to assess which of the two adjunctive tools could bring about better clinical and patient-reported outcomes, presented in a late-breaking trial session at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA) by Bon-Kwon Koo (Seoul National University Hospital, Seoul, South Korea). “Our study shows that in patients with intermediate levels of coronary arterial blockage, determining the need for a stent by measuring blood flow to the heart, rather than by the extent of arterial blockage, resulted in similar clinical outcomes, similar patient quality of life and reduced use of medical resources,” said Koo, the principal investigator for the study. FLAVOUR’s findings should encourage interventional cardiologists to consider an FFR-guided PCI first strategy for patients with intermediate

coronary stenosis, Koo went on to state. Patients were enrolled in the study if they had de novo intermediate (40–70%) and were eligible for PCI. This group of patients is most likely to need evaluation of their need for stenting, Koo said. In his presentation, Koo described FFR as an invasive physiologic index to define ischaemia-causing stenosis, whereas IVUS is an invasive imaging tool to evaluate anatomical severity and plaque characteristics, and to optimise PCI. An outcome-based comparison trial is needed, he said, to unravel the clinical relevance of the conceptual difference between physiology-guided—FFR— and imaging-guided—IVUS—PCI. Previous studies, including some conducted in patients with intermediate coronary stenosis, had shown that both FFR-guided and IVUS-guided PCI produced better patient outcomes than angiography-guided PCI, said Koo. However, FFR-guided and IVUS-guided PCI had not been compared head-tohead. The study enrolled 1,682 patients with intermediate coronary stenosis. The

Other factors like quality of life, degree of angina and returning to work can be important considerations for both patients and physicians when evaluating revascularisation”

average age of patients was 65 and 71% were men. Just over half had blockages in multiple arteries supplying blood to the heart and about one-third had diabetes in addition to heart disease. Six percent of the patients had previously had a heart attack and 30% were at high risk for one. All patients were randomly assigned to undergo evaluation for PCI using either FFR or IVUS. The decision to proceed with PCI was based on each technique’s standard criteria for doing so. In accordance with standard care after PCI, patients who received PCI took two antiplatelet medications for six to 12 months after their procedure to reduce their risk of adverse events. Patients who did not receive PCI continued to manage their heart disease with medication. The study met its primary endpoint—a composite of death from any cause, myocardial infarction (MI) or revascularisation after two years of follow-up. Compared with patients who were evaluated by IVUS, significantly fewer patients evaluated by FFR underwent PCI (65.3% vs. 44.4%, respectively). After two years, 8.1% of the patients evaluated by FFR had died, had an MI or needed a repeat stenting procedure, compared with 8.5% of those evaluated by

IVUS, a non-statistically significant difference. In addition, when the investigators compared patients who received PCI with those who remained on medical therapy, they found no statistically significant differences in the rates of death, heart attacks or repeat procedures in either the FFR or IVUS group. “Despite the fact that FFR-evaluated patients received significantly fewer stents than IVUS-evaluated patients, they were no more likely to experience adverse events,” Koo said. “The rates of adverse outcomes and patients’ quality of life were similar in both groups. These results support considering FFR-guided PCI first for patients with intermediate coronary stenosis, as it is associated with a reduced use of medical resources.” The study has some limitations, Koo said. Its findings apply only to patients with intermediate coronary stenosis and not those with more severe blockages of the coronary artery. Also, the study examined only FFR guidance compared with IVUS guidance. Additional studies are needed to comparatively evaluate other technologies for evaluating patients’ need for PCI. The study was funded by a grant from Boston Scientific.

Bon-Kwon Koo

Structural Heart Interventions 23

Issue 65 | May 2022

Structural Heart Interventions “Promising” one-year results for Pascal device in CLASP-TR trial

Patients with tricuspid regurgitation (TR) who received a Pascal transcatheter valve (Edwards Lifesciences) experienced significant improvements in blood flow through the heart and in quality of life at one year, research presented during a late-breaking trial session at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA) has concluded. The research was also published in the journal Circulation.

“A

t one year of follow-up, the repair procedure appears to be safe and significantly reduced the severity of patients’ tricuspid regurgitation and improved their ability to function in daily life, maintaining gains that we previously saw at 30 days of follow-up,” said Adam B Greenbaum (Emory University School of Medicine, Atlanta, USA). The study offers further validation for transcatheter edge-to-edge repair, a minimally invasive approach to the treatment of patients with the disease, Greenbaum said. Patients with tricuspid regurgitation are commonly treated with diuretics, drugs that are also used to treat high blood pressure. Surgery to repair or replace a poorly functioning tricuspid valve is often done at the same time a patient undergoes surgery for a problem on the left side of the heart. Minimally invasive options are needed to treat tricuspid regurgitation, Greenbaum said, as most patients are older and may have comorbidities that make them poor candidates for open surgery. The CLASP-TR study is a feasibility study of the investigational Pascal system. The device consists of a central spacer and adjacent paddles and clasps that attach to the native leaflets to reduce regurgitation. The spacer fills the regurgitant orifice and minimises stress on the leaflets. The clasps can be actuated either simultaneously or independently when clasping the leaflets. The study endpoints included a composite of major adverse events at 30 days (death due to cardiovascular disease, heart attack, stroke, kidney failure, severe bleeding); evidence on an echocardiogram of a reduction in backward blood flow; and death from any cause, distance walked in six minutes and scores on two measures of heart failure severity. A preliminary report found that, at 30 days of follow-up, the repair system substantially reduced TR, produced few adverse events, and

significantly improved patients’ ability to function, exercise capacity and quality of life. The current study reports results after one year of follow-up. A total of 65 patients (average age 77, 55% women) received the investigational device, 70% of whom had tricuspid regurgitation that was rated “massive” or “torrential” (the two highest grades of severity on a fivepoint scale) despite treatment with diuretics. In addition, most had other health problems that made them poor candidates for surgery, including atrial fibrillation (AF), liver or kidney disease and pulmonary hypertension. The COVID-19 pandemic affected the researchers’ ability to obtain one-year follow-up data for all treated patients, Greenbaum said. For example, some patients completed follow-up questionnaires that could be done remotely but did not complete tests that had to be done at the hospital, such as the echocardiogram and six-minute walk test. In addition, several patients died (although none died because of the repair procedure). In a few patients, the procedure was unsuccessful because the device failed to attach to the flaps in the tricuspid valve; and a few patients were lost to follow-up. Ultimately, one-year follow-up results were available for 49 patients. Seven patients (10.8%) died and 12 (18.5%) were rehospitalised for heart failure. These results compare with an expected one-year mortality rate of about 30% for patients with tricuspid regurgitation, Greenbaum said. Among 36 patients with available data at one year, all achieved a reduction of at least one grade in the severity of their tricuspid regurgitation; 75% saw a reduction of at least two grades; and 86% achieved an overall grade of moderate or less. Eleven patients (16.9%) experienced a major adverse event. Improvements were seen in heart failure severity, Adam B the six-minute walk test and Greenbaum patient-reported quality of life.

Novel transfemoral mitral valve repair technology wins CRT 2022 innovation competition A novel transcatheter system designed for transfemoral mitral valve repair—the NeoChord Nexus system— won the CRT Best Innovation Competition, taking place at the CRT 2022 annual meeting (27 February–1 March, Washington DC, USA)

AZEEM LATIB (MONTEFIORE Medical Center, New York, USA) presented the results of first-in-man experience with the valve, involving a 55-year-old male patient with a history of coronary artery disease, atrial fibrillation (AF) and prostate cancer. The patient presented with severe mitral regurgitation (MR)

and New York Heart Association (NYHA) class 3 heart failure. According to Latib, 30 days after implantation, it was shown to be mimicking native construction of the papillary muscle and physiological function of the mitral valve. The investigational NeoChord Nexus transcatheter mitral chordal repair device is designed to restore function in patients with severe symptomatic primary MR due to ruptured native chords and the mitral valve’s inability to close properly.

SURPASS registry shows low rate of adverse events associated with Watchman FLX

Results from a new analysis assessing real-world outcomes with the Watchman FLX (Boston Scientific) left atrial appendage closure (LAAC) demonstrated a low rate of major adverse events at seven days following the procedure. THE SURPASS ANALYSIS, WHICH included data from more than 16,000 patients with non-valvular atrial fibrillation (AF) within the National Cardiovascular Data Registry (NCDR) were presented during a late-breaking trial session at CRT 2022 (26 February–1 March, Washington DC, USA) by Samir Kapadia (Cleveland Clinic, Cleveland, USA). The data demonstrated a 0.37% rate of major adverse events at seven days following Watchman FLX implant or the time of hospital discharge, whichever was later. This safety endpoint was defined as a composite of all-cause death, ischaemic stroke, systemic embolism or device/procedure-related events requiring open cardiac surgery or major endovascular intervention. Additional outcomes measured at the 45day follow up after a Watchman FLX implant included a 0.51% rate of pericardial effusion requiring either surgical or percutaneous intervention, with only 0.03% of patients requiring cardiac surgery. “This analysis includes the largest number of real-world Watchman FLX patients to date and provides evidence that this stroke reduction therapy is associated with a low incidence of adverse events and peri-device leak through 45 days,” said Kapadia. “SURPASS represents the experience of more than 2,000 physicians using this therapy in routine clinical practice.” In the analysis, the WATCHMAN FLX device was successfully implanted in 97.6% of patients, and data also demonstrated low rates of ischaemic stroke (0.28%) and device embolisation (0.03%) in patients at 45 days. The SURPASS study is ongoing and will continue to collect outcomes through at least two years post-implant on all patients in the NCDR-LAAO Registry treated with Watchman FLX between August 2020 and August 2022. The key effectiveness endpoint of occurrence of ischaemic stroke or systemic embolism will be evaluated after 24 months. “The strong safety and efficacy profile of the Watchman FLX device demonstrated in the SURPASS analysis reinforces many of the safety and effectiveness results seen in the pivotal PINNACLE FLX trial, while representing a high-risk, real-world patient population and wide variety of patient anatomies,” said Ian Meredith, global chief medical officer, Boston Scientific. “We look forward to further analyses from this large, representative study of patients with NVAF treated by physicians with a broad range of implanting experience.”

24 Structural Heart Interventions

May 2022 | Issue 65

TAVI patients treated with edoxaban see fewer incidences of leaflet thrombosis compared to DAPT Patients treated with edoxaban for six months after a transcatheter aortic valve implantation (TAVI) procedure experienced fewer incidences of leaflet thrombosis compared to patients receiving dual antiplatelet therapy (DAPT), data presented during a late-breaking trial at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA) has revealed.

owever, compared with those in the antiplatelet therapy group, patients in the edoxaban group saw no reduction in risk for strokes or transient ischaemic attacks (TIAs), cerebral thromboembolism, or neurological and neurocognitive dysfunction during the six months after the valve replacement procedure. Although the study’s primary endpoint—the incidence of subclinical leaflet thrombosis (SLT) at six months after the valve replacement procedure— was lower in patients treated with edoxaban than in those treated with DAPT, it did not achieve statistical significance, the study’s investigators, including principal investigator DukWoo Park (Asan Medical Center, Seoul, South Korea), who presented the findings at ACC 2022, report. The trial also failed to meet its secondary endpoint, a causative association of SLT with thromboembolism and problems with thinking or memory, Park detailed. “The key messages from this study

are that SLT has not been proven to affect clinical outcomes for patients undergoing valve replacement and that in patients in whom SLT causes no symptoms or complications, its presence should not dictate the type of antithrombotic therapy that patients receive following the implantation of an artificial heart valve,” Park said. “Additionally, these findings do not support the routine use of computed tomography (CT) scans to detect SLT.” At the time of enrolment in the study, most patients undergoing TAVI received treatment with DAPT (consisting of aspirin and clopidogrel) for six months after the procedure to reduce the risk of

Duk-Woo Park

“Reassuring” twoyear outcomes for bicuspid TAVI reported at CRT 2022 Two-year findings from the Low-risk TAVI (LRT) Trial, assessing clinical outcomes after transcatheter aortic valve implantation (TAVI) in low-risk patients with symptomatic, severe bicuspid aortic stenosis have yielded “reassuring” results, attendees at CRT 2022 (26 February–1 March, Washington DC, USA) have heard. TOBY ROGERS (MEDSTAR HEART & Vascular Institute, Washington, USA) presented the two-year bicuspid outcomes from LRT and commented that improvements in valve haemodynamics seen shortly after the TAVI procedure were maintained out to the two-year follow-up. LRT is a prospective, multicentre registry, with a primary outcome of all-cause mortality (VARC-II defined). Secondary outcomes include safety and

thromboembolism. Despite this drug therapy, however, some patients develop SLT that can be detected on a CT scan. Previous studies had suggested that as many as 38% of patients undergoing TAVI could develop SLT and that SLT might increase their risk for a stroke or TIA caused by a cerebral thromboembolism. Prior studies also suggested that treatment with an anticoagulant rather than DAPT after TAVI might reduce patients’ risk for a stroke or TIA. The ADAPT-TAVR study was designed to overcome the deficiencies of prior studies and resolve these uncertainties, Park said. The study enrolled 229 patients (average age of 80 and 58% women) who had undergone TAVI and did not have any heart conditions or other disorders that required long-term treatment with anticoagulants. The patients were randomly assigned to receive either edoxaban or DAPT for six months. To detect cerebral thromboembolism or brain damage likely to cause problems with cognitive function, patients received magnetic resonance imaging (MRI) scans and tests of thinking and memory within one week of their TAVR procedure and again at six months. About 95% of patients in the study completed all scans and cognitive function tests. At the six-month mark, patients received CT scans to detect SLT. Ten patients in the edoxaban group (9.8%) developed SLT that was detectable on the CT scan, compared with 20 (18.4%) of those in the DAPT group; however, this difference was not statistically significant. Rates of death, stroke, TIA, cerebral thromboembolism and problems with thinking or memory were similar in the two groups.

efficacy (New York Heart Association, NYHA), clinical outcomes (VARC II), valve haemodynamics by echocardiography, and subclinical leaflet thrombosis evaluation by computed tomography (CT). Patients were enrolled between 2016 and 2020. Interim, 30-day findings from the LRT trial were presented at CRT 2020 by Ron Waksman (Georgetown University and MedStar Heart & Vascular Institute, Washington DC, USA), and Rogers presented the oneyear findings from the study virtually at CRT 2021. Researchers enrolled a total of 72 bicuspid patients, all of whom were confirmed as low-risk for surgery, with an STS Score <3%, and who were eligible for transfemoral TAVI. The patient cohort had a mean age of 68.1 ±7.7 years, were majority women (54.2%), and 15 (20.8%) had NYHA classification III or IV. These were compared to the tricuspid aortic stenosis cohort from the LRT trial. Bicuspid patients were on average six years younger than the patients with tricuspid aortic stenosis enrolled in the trial, Rogers explained, noting that consequently they had a lesser burden of comorbidities. Rogers presented two-year data from 64 available patients, noting that eight had been lost to follow-up during the COVID-19 pandemic. “At two years, for the 64 patients that we know about, they were all alive, and other key outcomes such as stroke and MI were very similar to patients with

“We saw no correlation between the number of occurrences of detectable SLT and the number of new signs of blood clotting in the brain or changes in cognitive function,” Park said. The study has several limitations, Park added. It was not blinded, meaning both patients and their doctors knew which medication they were receiving. The number of patients enrolled was also too small to identify any correlation between findings on MRI or CT scans and adverse events. Finally, the sixmonth follow-up period was too short to determine the long-term effects of SLT or whether edoxaban or DAPT had any effect on the durability of a patient’s replacement heart valve. Park and his colleagues are planning future studies to address some of these questions. This study was simultaneously published online in the journal Circulation at the time of presentation. The study was an investigator-initiated trial funded by the CardioVascular Research Foundation of Seoul, South Korea, and Daiichi Sankyo Korea (a subsidiary of the Japan-based maker of edoxaban).

We saw no correlation between the number of occurrences of detectable SLT and the number of new signs of blood clotting in the brain or changes in cognitive function”

tricuspid aortic stenosis,” Rogers said. “Reassuringly there was no endocarditis and no aortic valve reintervention among bicuspid patients and no patient required pacing after that initial 30-day period.” He added: “Based on these two-year data I think we are getting reassuring outcomes in low-risk bicuspid aortic stenosis patients are equivalent to low-risk tricuspid aortic stenosis patients, with excellent valve haemodynamics maintained at two years.”

Based on these two-year data I think we are getting reassuring outcomes in low-risk bicuspid aortic stenosis patients are equivalent to low-risk tricuspid aortic stenosis patients, with excellent valve haemodynamics maintained at two years”

Issue 65 | May 2022

Conference Coverage 25

Final BIOFLOW-V results “affirm durability” of Orsiro out to five years Final five-year results from the BIOFLOW-V trial, presented during a late-breaking trial session at CRT 2022 (27 February–1 March, Washington DC, USA), affirm the durability of longer-term outcomes with the ultrathin Orsiro coronary drug-eluting stent (DES) compared to Xience (Abbott). BIOFLOW-V US PRINCIPAL INVESTIGATOR, David Kandzari (Piedmont Heart Institute, Atlanta, USA) who presented the results at CRT 2022, told attendees that through the five-year follow-up, significant differences in the individual outcomes of target vessel myocardial infarction (MI) and late stent thrombosis persisted, favouring treatment with Orsiro over Xience. However, Kandzari also revealed that though previously identified significant differences in target lesion failure (TLF) and target lesion revascularisation (TLR) seen at one-, two- and three-year follow-up remained numerically lower, they were no longer statistically significant, indicating some catch-up over the longer term between the two devices. New iterative coronary stent development has included new metal alloys, changes in stent architecture and bioresorbable polymers, Kandzari told the CRT audience, noting that both individual trials and meta analysis have demonstrated significant improvements in both safety and efficacy outcomes with ultrathin strut drug-eluting stents compared with alternative designs. The trial randomised 1,334 patients undergoing elective percutaneous coronary intervention in a 2:1 fashion David between the Orsiro versus the Xience Kandzari

stent in 13 countries spanning North America, Europe, Israel, New Zealand and Asia. The primary endpoint was target lesion failure, defined as a composite of cardiovascular death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation at one year, but with prespecified planned follow up through five years. Previously the trial has demonstrated superiority of the Orsiro stent at one-, two- and three-year follow-up with regard to the primary endpoint, a composite of TLF, as well as target vessel MI. Further, at two- and three-year follow-up, superiority with the Orsiro compared to the Xience stent was identified with regard to TLR. Detailing the results, Kandzari commented that completeness of follow-up was identical for both groups, with a total of 884 patients initially randomised to the Orsiro group, 807 (91.3%) of whom were still active at five-year follow-up, and 450 were enrolled in the Xience group, with 411 (91.3%) active at the five-year timepoint. The baseline characteristics, and angiographic and procedural characteristics were broadly similar between the two groups. “Now, today through five years

COBRA-REDUCE findings do not support routine use of nanocoated stent with shortduration DAPT

of follow-up in a Kaplan Maier analysis, the rate of target lesion failure is 15.3% for the Xience cohort, and 12.3% for the Orsiro cohort, an approximate 3% absolute difference, but with a p-value of 0.11.” No significant differences in TLR were identified at five years, although rates were similar at one year and began to diverge after two years, achieving statistical significance at two and three years, he explained. “Although the differences remained numerically lower through five years, they no longer remained significantly different,” he said. Alternatively, stent thrombosis did remain significantly different through five years, favouring the Orsiro stent, particularly with regard to both late and very late stent thrombosis, Kandzari noted. In his concluding remarks, Kandzari said: “Altogether, these findings confirm the durability of longer-term comparative outcomes with an ultrathin strut bioresorbable polymer sirolimus-eluting stent, demonstrating continued differences in late ischaemic events.”

Altogether, these findings confirm the durability of longer-term comparative outcomes with an ultrathin strut bioresorbable polymer sirolimus-eluting stent, demonstrating continued differences in late ischaemic events”

risk patients in particular. Investigators hypothesised that in patients undergoing PCI who were receiving oral anticoagulation, with or without dose reduction, a 14-day duration of DAPT after stenting with Cobra PzF, versus three to six months duration of DAPT after stenting would provide superior Final findings from the COBRA-REDUCE randomised trial outcomes in terms of bleeding and assessing 14-day dual antiplatelet therapy (DAPT) after non-inferior outcomes in the composite percutaneous coronary intervention (PCI) with the Cobra PzF of death, MI, stent thrombosis and (CeloNova BioSciences) nanocoated stent have shown that the ischaemic stroke. device did not meet its non-inferiority criteria with respect to During his presentation, Byrne noted thrombotic ischaemic events compared to standard drug-eluting that patients were typically older with stents with three to six months of DAPT. a mean age of around 74 years. Over a third of patients had diabetes, and THIS WAS THE CONCLUSION oral anticoagulants”, he said that the comorbidities were “relatively well presented by Robert Byrne (RSCI investigational device may benefit represented” in the patient population. University of Health Sciences, Dublin, selected patients with high bleeding risk All patients had at least one major Ireland) who detailed the trial findings or those with whom an early interruption criterion for high bleeding risk, and during a late-breaking trial session of DAPT for surgery is likely. about 40% of patients had greater than at CRT 2022 (27 February–1 March, The study randomised 996 two major criteria, according Washington DC, USA). high-bleeding-risk patients to the Academic Research Further to the headline finding, Byrne across 59 global sites to Consortium for high bleeding detailed that at 12 months the trial’s receive either the Cobra PzF risk (ARC-HBR) criteria. composite ischaemic endpoint of allstent (n=495) with 14-day Oral anticoagulation dose cause death, myocardial infarction (MI), DAPT or a US Food and Drug intensity could be reduced at definite or probable stent thrombosis, (FDA)-approved drug-eluting the discretion of the treating Robert Byrne ischaemia-driven target lesion stent (n=501) with three or physician, Byrne explained, revascularisation (TLR) or ischaemic six months DAPT. Byrne described noting that patients with dose reduction stroke was significantly higher in Cobra PzF as a drug-free stent coated were seen more frequently than in patients treated with the Cobra PzF with a polyzene-F polymer, which is patients who had drug-eluting stent stent, primarily driven by an increased “thromboresistant, non-inflammatory implantation, which was associated with rate of ischaemia-driven TLR. and pro-healing”. The thin-strut stent a longer duration of DAPT. Byrne commented that while the has a thickness of 71μm and is made of Byrne reported that the primary results “do not support a routine cobalt-chromium alloy. endpoint, incidence of BARC level strategy of Cobra PzF stenting with The COBRA-REDUCE trial looked 2‒5 bleeding after 14 days was seen 14 days DAPT in patients receiving at the use of the device in high-bleeding in 7.79% of patients with the Cobra

PzF stent, compared to 9.75% with the standard strategy. Furthermore, the thrombotic coprimary endpoint of all-cause death, MI, stent thrombosis or ischaemic stroke was seen in 7.52% with the Cobra PzF strategy compared to 4.9% in the drugeluting stent group. “Non-inferiority was not declared,” Byrne commented. Secondary bleeding endpoints were statistically similar between the two groups, Byrne noted. Noting some limitations of the study, Byrne acknowledged that it was an open-label design, and added that there was a difference in anticoagulation dose intensity reduction, which was at the discretion of the operator, “confounding somewhat the comparison of bleeding events between the groups”. In his concluding remarks, Byrne told the CRT audience that in patients undergoing PCI for acute or chronic coronary syndromes who are receiving oral anticoagulation, stenting with Cobra PzF stents with 14 days DAPT did not reduce bleeding and did not meet non-inferiority criteria with respect to thrombotic ischaemic events compared to standard drug-eluting stents with three to six months of DAPT. “At 12 months the rate of the composite ischaemic endpoint was significantly higher in patients treated with the Cobra PzF stent and that was a difference that was driven mainly by an increase in the rate of ischaemia-driven TLR,” Byrne said.

May 2022 | Issue 65

26 Advertorial THIS ADVERTORIAL IS SPONSORED BY ADEPT MEDICAL

Advancing radial ergonomics Outlining Adept Medical’s process for identifying and solving ergonomic issues in the cath lab.

ith technological advancements over the last 10 years rapidly changing the scope of atrial treatment, radial has quickly become the access point of choice for clinicians globally. Between 2011 and 2018, radial access adoption for diagnostic angiograms increased from 17.5% to 60.4%, and from 14% to 51.8% for percutaneous coronary intervention (PCI) procedures1, and this trend is set to rise. This change of technique has led to clinicians having to adapt the interventional lab environment, making improvements to patient set-up for the radial approach, protecting the clinician, and considering workspace ergonomics. As designers of advanced patient supports, Adept Medical has been collaborating with industryleading experts to address identified needs in improving the interventional lab working environment. Adept Medical first launched the STARBoard as part of the STARSystem in 2013. After seeing the need for a device to facilitate ease of radial access during interventional cardiology procedures, the company developed a solution alongside experts in the interventional cardiology field, allowing for quick, effective presentation of the patient’s wrist for radial access. Since its launch in 2013, Adept Medical has successfully placed upwards of 2,600 units of the STARBoard in market globally and experienced a positive uptake for a device to provide ongoing procedural repeatability in the cath lab. After surveying existing users, spanning from New Zealand to the UK, Adept Medical has gathered insight into the benefits the STARSystem has provided clinicians in the cath lab, when compared to their previous way of working.

Wire/device manipulation and security

When first witnessing procedures without a device to manage radial access, Adept Medical noticed that often the equipment and wires would be placed over the patient, causing concern of the wires kinking during advancement, or dislodgement of wires from the access site completely. When using the Adept Medical STARSystem, clinicians can easily position and place the wire for ease of manipulation on the work surface of the STARTable. In a recent study, completed by Adept Medical, the company found that users of the STARSystem had an 87% satisfaction rate with the ergonomic

eliminating the need of having to bend over the patient and consequently causing back issues. In a recent study conducted by Adept Medical, it was discovered that users of the STARSystem have an 81% satisfaction rate in the ergonomic procedural position of back straightness using the device, compared to when not using it.

Managing patient restlessness and movement

The Adept Medical STARSystem handle design provides reassurance for the patient, limiting movement during radial access procedures

procedural position of wire/device manipulation and an 83% satisfaction rate with wire/device security when using the STARSystem, compared to not using it.

Ergonomic procedural position for the clinician

Without correct positioning of the patient, the clinician is often left having to bend over to gain radial access and complete wire manipulation, particularly in instances when leftarm access is required. Using a rigid arm board or rolled towels offers little flexibility when considering patient management, and often leaves the clinician restricted in movement throughout the procedure. The STARSystem has been designed to improve the clinician’s posture by having a rotatable arm board that can be positioned correctly to their working preferences. The left arm support allows radial access to be gained on the left-hand side, with the patient's arm then able to be draped across the abdomen so the clinician can continue to work as normal on the right-hand side. This allows for better working ergonomics for the clinician,

During procedures where the patient is under conscious sedation, the risk of restlessness and movement is a concern for clinicians who manage patient safety and imaging outcomes. After understanding the requirements of the clinician, Adept Medical noticed that patients often need a security reminder to avoid excess restlessness and movement. The handle design of the STARSystem allows the patient to grip an object which provides reassurance throughout the procedure and therefore limits movement compared to not using any methods of patient security. The concaved channel also assists with forearm containment preventing it rolling sideways. In Adept Medical’s recent study, the company found that clinicians had a 81% satisfaction rate in the STARSystem’s ability to control patient restlessness and movement when compared to their previous method.

the device, when compared to their previous method.

Product set-up time when performing left and right arm radial access

Having to create custom solutions for each procedure to set the patient up for radial access is less than ideal. Rolling towels for support, or taping patients to homemade arm boards is a lengthy process for the clinical team, affecting the time to set-up and procedural repeatability. These solutions offer less procedural flexibility, which can also cause delays in gaining access to begin the procedure. The length of the STARSystem adapts to each patient's size once they grip the handle. Adept Medical designed the STARBoard to allow for multiple levels of adaptability to comfortably suit most patient sizes. Clinicians in Adept Medical’s study rated their level of satisfaction with product set-up time when performing right arm and left arm radial approach at 77% and 75% respectively using the STARSystem compared to their previous method.

Gaining hyperextension of the wrist for access

One of the STARSystem’s key features is its ability to present the patient’s wrist quickly and effectively for proximal radial access when hyperextension is required for ease of puncture. The STARSystem handle is designed to be manipulated to rotate the patient’s wrist from a medially rotated position to a hyperextended position, allowing the radial artery to be presented for puncture. This can often be a cumbersome process without having the degree of manipulation and rotation that the STARSystem provides. In Adept Medical’s recent study, clinicians had an 85% satisfaction rate in the STARSystem’s ability to hyperextend the patient’s wrist using

The Adept Medical STARSystem offers an ergonomic procedural position for safe wire/device manipulation

The Adept Medical STARSystem presents the patient’s wrist effectively for proximal radial access when hyperextension is required for puncture

The solution

Adept Medical’s development journey of designing a complete radial solution for left and right access has been one derived from strong clinical input. With Adept Medical adopting a solution when radial access was first gaining traction, it allowed the company to understand pain points and offer benefits to a technique that was novel for many clinicians. According to the company, its findings show that the STARSystem forms a complete and effective ergonomic solution that offers benefits to the clinician during radial access for both patient management and clinician workflow and comfort. All of Adept Medical’s patient positioning equipment and operator supports are proudly designed and manufactured at the company’s site in New Zealand. References: 1. Doll, J, Beaver, K, Naranjo, D, et al. 2022. Trends in Arterial Access Site Selection and Bleeding Outcomes Following Coronary Procedures, 2011–2018. Circulation: Cardiovascular Quality and Outcomes.

Issue 65 | May 2022

Technology 27

Portsmouth Hospital: How tech is guiding decision-making in the cath lab Peter Haworth Comment & Analysis Peter Haworth (Portsmouth Hospitals University NHS Trust, Portsmouth, UK) documents how computer-derived fractional flow reserve (FFRct) has been instrumental in optimising care in the cath lab at his institution, despite the challenges created by the COVID-19 pandemic.

ince it was mandated by NHS England last year, many cardiologists will be aware of, or are actively using, FFRct to help diagnose coronary artery disease (CAD). It is technology we have been using within our service at Portsmouth for some time now, having initially adopted it in 2018 to support our computed tomography (CT)-first approach. For those unfamiliar, FFRct is a non-invasive, artificial intelligence (AI)-enabled diagnostic test that takes data from a coronary CT to create a 3D digital model of a patient’s coronary arteries. The technology uses sophisticated algorithms to calculate the severity with which arterial stenoses may be impacting blood flow. Clinicians are given FFRct values alongside the model so they can quickly understand if CAD is present, where blockages may be and whether invasive intervention is required. For many cases, the insights

provided by FFRct give us confidence that patients can be treated with medication alone. But it is also a tool I use increasingly to support procedural planning in the cath lab, and it has been invaluable in helping to minimise patient contact whilst prioritising the most urgent cases during the pandemic.

In the cath lab

Once patients are scheduled for the cath lab, I have increasingly been using FFRct to aid interventional procedures. In fact, since I am able to view the entire coronary tree non-invasively with the FFRct model, I am often able to plan out a complete strategy for the patient before they are on the table. Using the data and modelling available, I can assess the type of revascularisation required—for example, is more complicated bifurcation stenting needed or can we opt for a simpler intervention? I also use the technology to plan the angles of the procedure—it shows us where to position the C-arm to get the best angiographic images of the vessels as we are working. This has meant less time searching for the best angles and potentially less radiation exposure and time on the table for the patient. And when it comes to explaining our plans to patients, having a well-rounded

strategy before the procedure and a visual 3D digital model on hand during conversations is particularly useful in helping them feel fully informed about their condition and comfortable with the next steps. Despite the disruption of the pandemic, our cath lab is now as busy as it has ever been. But due to the clarity gained through FFRct the patients we see arrive in the cath lab have anatomical, plaque composition and physiological information which allows us to optimise their treatment. Our need for diagnostic angiograms has dramatically reduced and as we continue to grow increasingly confident in using technologies such as these, it is likely to fall even further. As a result, we have freed up time and space in the cath lab for other essential services such as electrophysiology and pacing. FFRct has also been instrumental in identifying patients who could be considered for clinical trials. FFRct has been integral to streamlining the diagnostic process and improving patient experience. For me, it speaks to the value of embracing new technologies to optimise delivery of care and continue to improve patient experience. Peter Haworth reports no relevant financial disclosures.

Triaging patients

The more we know about a patient’s CAD severity, the better we are able to plan the best course of action. A CT-first approach often gives us what we need, but FFRct really comes into its own for those scans where disease or the nature of a blockage is unclear. The technology gives us both anatomical and physiological insights which have been instrumental in significantly reducing the number of patients we send to the cath lab at Portsmouth. This has been especially useful during the COVID-19 pandemic, where we have had limited bed spaces and

Deep learning tool could predict future myocardial infarction Researchers have detailed the use of an artificial intelligenceenabled tool for atherosclerotic plaque quantification from coronary CT angiography (CCTA), which they claim may make it easier to predict whether a person will have a heart attack. THE TOOL, DESCRIBED IN A paper published in The Lancet Digital Health by Andrew Lin, Damini Dey (both Cedars-Sinai Medical Center, Los Angeles) et al provides rapid measurements of plaque volume and stenosis severity from CCTA that agree closely with expert readers and intravascular ultrasound (IVUS), and could have prognostic value for future myocardial infarction (MI) the researchers suggest.

restrictions on the number of people we can bring into the department. In these circumstances, it is essential we bring in the right patients who will get the most benefit from further investigation or revascularisation. It has also allowed us to be as efficient as possible with the care we are delivering, reducing the time our patients spend in the hospital.

Dey and colleagues analysed CTA images from 1,196 people who underwent a coronary CTA at 11 sites in Australia, Germany, Japan, Scotland and the USA. The investigators trained the AI algorithm to measure plaque by having it learn from coronary CTA images, from 921 people, that had already been analysed by trained doctors. The algorithm works by first outlining the coronary arteries in 3D

New technologies have been "integral" to streamlining the diagnostic process

images, then identifying the blood and plaque deposits within the coronary arteries. Investigators found the tool’s measurements corresponded with plaque amounts seen in coronary CTAs. They also matched results with images taken by two invasive tests considered to be highly accurate in assessing coronary artery plaque and narrowing: IVUS and catheter-based coronary angiography. Finally, the investigators discovered that measurements made by the AI algorithm from CTA images accurately predicted heart attack risk within five years for 1,611 people who were part of a multicentre trial, the SCOT-HEART trial. “More studies are needed, but it is possible we may be able to predict if and how soon a person is likely to have a heart attack based on the amount and

composition of the plaque imaged with this standard test,” said Dey. Detailing some limitations of the study, the authors note that data on patient race or ethnicity were not uniformly available for all sites; however, they add that the training dataset drew from diverse and geographically distinct populations. “Despite these limitations, our study represents the first validation of a deep learning approach for atherosclerotic quantification from CCTA using invasive reference standards, and is the first demonstration of the predictive value of deep learning-based plaque measurements for risk of cardiac events,” they write. Dey and colleagues are continuing to study how well their AI algorithm quantifies plaque deposits in patients who undergo coronary CTA.

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Issue 65 | May 2022

Technology 29

3D printing to support physician training and coronary device testing The donation of new 3D printing technology to the Visible Heart Laboratories at the University of Minnesota (Minneapolis, USA) will aid the training of future cardiologists and medical device development by producing anatomic models that replicate a patients’ heart anatomy and pathology.

tratasys is sponsoring the University of Minnesota Visible Heart Laboratories with a donation of Stratasys J750 Digital Anatomy 3D printers, as well as MakerBot Method X and MakerBot Sketch 3D printers. The Visible Heart Laboratories are a research lab located that supports medical research, student and physician education, and medical device product development and testing. Stratasys’ Digital Anatomy 3D printers produce anatomic models that mimic the feel, responsiveness, and biomechanics of human anatomy. Models can be punctured, sutured, cut, and physically manipulated like human tissue. During their education, all University of Minnesota medical students pass through the Visible Heart Laboratories to learn about the benefits of 3D printing technology and how anatomic models can

3D-printing could aid device development

assist them in their future practice. The Visible Heart Laboratories also are committed to providing outreach education about cardiac anatomy and device therapy to students from school age to clinical cardiologists. “The Visible Heart Laboratories are driven to train the next generation of medical device developers and provide them with the abilities to 3D print prototypes and/or virtually placed devices within real heart anatomies, as today these are considered essential skills,” said Paul Iaizzo, professor Visible Heart Laboratories, University of Minnesota Medical School. In addition to medical student, patient, and physician education, the 3D printing technology in the Visible Heart Laboratories supports medical device research across a variety of coronary medical device applications. 3D printing technology allows physicians,

SCAI aims to minimise risks in medical proctoring of new techniques and technologies The Society for Cardiovascular Angiography & Interventions (SCAI) has released an official position statement aimed at providing recommendations to minimise the potential risks involved with medical proctoring. THE DOCUMENT, “SCAI POSITION statement on best practices for clinical proctoring of new technologies and techniques,” was published in the Journal of the Society for Cardiovascular Angiography & Interventions (JSCAI). Clinical proctoring is the culmination of an educational process to disseminate new technologies and procedures in the cath lab. Operators seeking privileges after completing training are proctored or monitored by an experienced peer, while performing the procedure for which privileges are requested. “This document addresses a process that has been integral to advancing the skillsets of interventional cardiologists,” stated Sunil Rao (Duke University, Durham, USA), chair of the writing group and SCAI president-elect. “It is focused on protecting patients and interventionalists and ensuring the best outcomes for all stakeholders.” As new technologies emerge, this position statement recommends best practices to reduce the potential for adverse events, misunderstandings,

conflicts of interest, and unexpected medicolegal liability, SCAI said in a press release. Writing group vice-chair Arnold Seto (University of California, Irvine, USA), added: “Some patients, operators, and proctors approach the proctored procedure as though nothing can go wrong, whereas new procedures with new operators and facilities have some inherent risks. This document will help set expectations for all parties and support effective communication, preparation, and oversight of the proctoring experience.”

This document will help set expectations for all parties and support effective communication”

researchers, and medical device product developers to iterate, create, and test existing and new medical devices in anatomic models that mimic actual anatomy and pathology. “We believe that widespread use of 3D-printed anatomic models in healthcare would translate into better and more cost-effective patient care and shorter time to market for new medical device innovations. This sponsorship allows us to support the world-class education and medical device research happening right here in Minnesota,” said Rich Garrity, president, Americas for Stratasys. “At Stratasys, we recognise the importance of supporting the communities in which we live and work, and we are proud to support the University of Minnesota Visible Heart Laboratories and the work they are doing.”

Expert group sets out principles for device-led hypertension trials A consensus document outlining design principles and outcome definitions for device-based therapies for hypertension has been published in the journal Circulation. THE DEVELOPMENT OF THE document has been led by the Hypertension Academic Research Consortium (HARC), which aims to create consensus among experts developing device-based therapies for hypertension, following the process defined in the Academic Research Consortium (ARC). Its drafting brought together clinicians, trialists, regulators, and industry. According to HARC, despite its recognition worldwide as the leading cause of death and disability, awareness, treatment and control of blood pressure have plateaued, if not “moderately declined”. Recent randomised clinical trials have demonstrated clinical benefits of more intensive blood pressure reduction, the authors note, which has led to revision of guideline-directed treatment goals. “Countering evidence-based efforts to improve blood pressure with a broad spectrum of pharmaceutical therapies are routine challenges in clinical practice that include patient intolerance of medication-related adverse effects, general non-adherence with prescribed therapy, and physician inertia for treatment of an illness that remains largely silent until onset of clinically irreversible conditions,” authors of the consensus paper write. “The advancement of device-based approaches to hypertension has been motivated by clinical implications associated with a persistently high prevalence of both uncontrolled blood pressure and medication non-adherence. The expansion of device technologies and emerging clinical trials imparts the need for consistency in trial design, conduct and definitions of clinical study elements to allow for trial comparability and data poolability,” the authors add. “The HARC programme represented an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspective on clinical trial design and methodology. From this programme, clinical trial design and principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies were established, and standardisation of blood pressure assessment, effectiveness measures beyond blood pressure, and safety outcomes have been proposed,” they add.

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Issue 65 | May 2022

Market Watch 31

Product News Translumina announces launch of dual drug polymer-free coated stent

FDA approves coronary use of XO Cross support catheter system

Transit Scientific has announced US Food and Drug Administration (FDA) clearance of its XO Cross support catheter platform to include coronary use. The platform is indicated to guide and support a guidewire during access of the peripheral or coronary vasculature, allow for wire exchanges, and provide a conduit for delivery of saline solutions or diagnostic contrast agents. Support catheters are used to help navigate guidewires through complex lesions and facilitate guidewire exchanges during interventional procedures in patients with coronary or peripheral artery disease. Legacy technologies often fail to provide sufficient guidewire support, are prone to kinking, and lack the pushability needed to successfully cross severe calcifications and plaque. The XO Cross support catheter platform is designed to deliver new levels of pushability, trackability, flexibility, and torque response for access in challenging lesions and tortuosity, Transit Scientific said in a press release. The non-tapered metal-alloy and polymer construction delivers high fatigue-resistance against tough complex lesions found in advanced coronary artery disease (CAD), peripheral artery disease (PAD), and critical limb ischemia (CLI). “We need better, more controllable, and more durable microcatheters and technology for use in complex coronary lesions and chronic total occlusions (CTO),” said Vasili Lendel (Arkansas Heart Hospital, Little Rock, USA). “The trackability and high-torque response of the XO Cross platform will help us gain wire access in challenging coronary tortuosity and worst-case calcium and plaque. We’ve seen great results with XO Cross in our peripheral vascular procedures, so we look forward to using this platform for percutaneous coronary interventions.” Transit Scientific will launch the 2Fr coronary XO Cross 014 Microcath for use with standard 0.014″ guidewires in 90cm, 135cm, 150cm, and 175cm working lengths. The non-tapered shaft and tapered polymer tip offer a low crossing profile and facilitate coaxial use through any 035 compatible coronary guiding catheter.

Translumina has announced the launch of Vivo Isar, its latest generation dual drug polymer-free coated stent, in various international markets including Europe. According to a company press release, Vivo Isar is the first dual drug polymer-free coronary stent technology, which brings together a stent with a superior safety profile without compromising the drug release kinetics. Vivo Isar is the first technology that uses Probucol, an antioxidant and lipidlowering drug, as a carrier for releasing Sirolimus and thus creates a polymerfree drug-eluting stent platform with uncompromised safety and efficacy. In 2020, Translumina published 10-year follow-up data on its dual drug polymer-free coated stent, which were released in the Journal of the American College of Cardiology (JACC). “The ten-year outcome of Vivo Isar is a major breakthrough in drug-eluting stent technology as it proves that synthetic polymers can be removed from a drug-eluting stent without compromising the efficacy of the drug-eluting stent. The excellent safety profile demonstrated in the 10-year follow-up study is especially notable as it provides a powerful new technology for treating complex coronary artery disease in high-risk patient subsets. This drug-eluting stent technology carries the great potential of significantly shortening the duration of dual antiplatelet therapy,” said Adnan Kastrati, (German Heart Center, Munich, Germany) and the lead investigator of ISAR TEST 5, the trial that compared Vivo Isar to Endeavour Resolute (Medtronic).

VenusP-Valve gains CE mark

Venus Medtech’s transcatheter pulmonic valve replacement (TPVR) system—VenusP-Valve—has received CE mark under the Medical Devices Regulation (MDR). Designed to treat patients with moderate to severe pulmonary regurgitation with or without right ventricular outflow tract (RVOT) stenosis, the device is designed with both flared ends, to provide stable anchoring and easy delivery, with no need for pre-stenting. Following its first clinical implantation in 2013 by Ge Junbo (Zhongshan Hospital, Fudan University, Shanghai, China) the valve has been used in nearly 300 cases for humanitarian reasons, spanning more than 20 countries in Asia, Europe, North America, and South America, Venus Medtech says. In March 2021, VenusP-Valve received special use authorization from the UK Medicines

and Healthcare products Regulatory Agency (MHRA) for use in designated medical institutions. Moderate to severe pulmonary regurgitation is common after surgical correction of congenital heart disease. It leads to right ventricular volume overload and may cause arrhythmia and even sudden death in the long term. The traditional thoracotomy approach to pulmonic valve replacement is difficult and carries high mortality, while existing TPVR products in the European market, due to their balloonexpandable design, apply to patients with particular anatomic structures only and require pre-stenting, Venus Medtech adds VenusP-Valve is undergoing review and approval of registration with the Chinese National Medical Products Administration (NMPA) and is expected to be marketed within 2022. Venus Medtech is preparing for its investigational device exemption (IDE) application to the US Food and Drug Administration (FDA).

Teleflex catheters and coronary guidewires cleared for CTO PCI

Teleflex has announced that the US Food and Drug Administration (FDA) has cleared an expanded indication for its specialty catheters and coronary guidewires for use in crossing chronic total occlusion percutaneous coronary interventions (CTO PCI). CTOs are longstanding complete blockages in coronary arteries that result in profound ischaemia. Importantly, clinically significant CTOs are found in nearly 20% of patients undergoing diagnostic coronary angiography for suspected ischaemic heart disease. Often a source of limiting symptoms, CTOs may also contribute to cardiac dysfunction and are associated with poor prognosis. Devices receiving the expanded indication include the Teleflex GuideLiner V3 catheter, TrapLiner catheter, Turnpike catheters, Spectre guidewire, Raider guidewire, Bandit guidewire, Warrior guidewire, and R350 guidewire. These products were evaluated as part of the CTO-PCI study, a peer-reviewed, prospective, single-arm IDE study that enrolled 150 patients across 13 investigational centres across the USA. In this cohort, technical success (defined as successful guidewire recanalisation) was achieved in 93.3% of cases, and procedural success (i.e., free of major adverse cardiovascular events, MACE) was achieved in over 75% of cases, Teleflex said in a press release. David Kandzari, (Piedmont Heart Institute, Atlanta, USA) was one of the study’s principal investigators. He commented: “Considering the complexity of both anatomy and procedural strategy in this

study, the very favourable success achieved underscores the need for an ‘interventional toolbox’ that features an array of enabling device technologies that include guidewires, guide catheter extensions and microcatheters. Given the challenging patient population, the high technical success rate in this most demanding PCI environment is particularly notable.”

Japanese and US regulatory approvals granted for BioFreedom stent Biosensors International Group has announced both the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) approval for BioFreedom Ultra and US Food and Drug Administration (FDA) approval for BioFreedom. BioFreedom is Biosensors’ novel polymer and carrier-free drugcoated stent with their proprietary limus drug Biolimus A9 (BA9). BA9 is Biosensors’ proprietary highly lipophilic anti-restenotic drug, developed specifically for use in coronary vascular applications. BioFreedom Ultra also features thin (84µmβ) Cobalt Chromium (Co/Cr) struts. BioFreedom will give physicians in the USA the opportunity to reduce dual antiplatelet therapy (DAPT) to one month in patients post-PCI who are at high-Risk of bleeding..

FDA approval granted for Mitris Resilia mitral valve replacement

Edwards Lifesciences has received approval from the US Food and Drug Administration (FDA) for the Mitris Resilia valve, a tissue valve replacement for the mitral position. The Mitris Resilia valve has a saddle-shaped sewing cuff that mimics the asymmetric shape of the native mitral valve. It also features a low-profile frame that helps avoid obstruction of the left ventricular outflow tract by stent posts and is visible under fluoroscopy, to facilitate potential future transcatheter interventions for patients. Resilia tissue is bovine pericardial tissue and serves as the platform for Edwards’ new class of valves, the company said in a press release. Resilia tissue has been studied in two premarket clinical trials, the COMMENCE trial comprised of 694 patients enrolled in an aortic arm and the EU Feasibility trial comprised of 133 patients enrolled who were followed for five years. These studies together represent outcomes on 904 patients and more than 3,800 patient years of follow-up. “For patients who need mitral valve replacement, the advanced Mitris Resilia valve is based on a trusted pericardial valve platform, designed to mimic the native valve and incorporating tissue with integrity-preservation technology that will potentially allow the valve to last longer,” said Kevin Accola (AdventHealth, Orlando, USA).

May 2022 | Issue 65

32 Market Watch

Product News

Artis icono

Siemens introduces “integrated” cath lab imaging system, Artis icono biplane

Siemens Healthineers has announced the launch of Artis icono biplane—an angiography system with detectors optimised in size for integrated use in the cath lab. The system offers new features for diagnosing and treating coronary heart disease, structural heart disease and cardiac arrhythmia that simplify clinical workflows and provides excellent image quality at a low radiation dose, the company said in a press release. For complex cardiovascular diseases and their interventional treatment, Artis icono biplane allows for simple positioning of the C-arm—particularly for displaying images at steep angulations. In addition, images can be acquired simultaneously from different angles. This helps saving time and for patients has the potential to result in a lower contrast agent dose, Siemens Healthineers adds in its release. Artis icono biplane provides a type of X-ray exposure regulation that considers contrast-to-noise ratios to maintain the same high level of image quality, regardless of patient size and angulation. According to the company, the result is excellent image quality at a low radiation dose for physicians and patients. In the case of coronary heart diseases, an integrated quantification feature of Artis icono biplane does away with the need for a preliminary examination with a pressure wire to determine stenosis relevance and subsequently, if a stent has to be placed, Siemens explained in a press release. A new feature “angio-derived vFFR”2 (Fractional Flow Reserve), means two images are needed to provide three-dimensional visualisation of the affected vessel and to obtain the necessary information. According to Siemens Healthineers, this image-guided method offers a couple of advantages: Even though using a pressure wire for diagnosis is a routine intervention, patients are still at risk for vascular injury. Furthermore, the administration of medications needed for the procedure can make patients feel unwell and also requires

a certain amount of time to induce cardiac stress which is needed for the pressure wire examination. For interventions in patients with structural heart disease, such as transcatheter aortic valve implantation (TAVI), left atrial appendage closure (LAAC), or transcatheter mitral valve implantation (TMVI), Artis icono biplane provides the option of performing fusion imaging. Angiography images can be overlaid with live ultrasound images These fused images help to ensure effective communication among treating interventional cardiologists and ecocardiographer.

SafeCross

SafeCross transseptal balloon gets first commercial use

East End Medical has announced the first commercial use of its SafeCross transseptal radiofrequency (RF) puncture and steerable balloon introducer system. The system is designed to provide a predictable and safe solution for performing structural heart and electrophysiology interventions requiring left atrial access, the company said in a press release. The first commercial devices were implanted during left atrial appendage closure (LAAC) and transcatheter mitral valve edge-to-edge repair (TEER) procedures at New York Presbyterian Hospital -Columbia, performed by Martin Leon (Columbia University Medical Center, New York, USA), Torsten Vahl and Rebecca Hahn. “Accessing the left atrium in a safe and precise manner is critical for optimal patient outcomes in left atrial procedures. Depending on the anatomy, achieving safe and precise transseptal access frequently leads to decreased overall left atrial procedure times,” stated Vahl. “In using SafeCross, I particularly liked how the balloontipped sheath allowed me to safely glide across the septum in small and precise adjustments to enable me to position on the exact pre-determined location of the transseptal puncture.” The system consists of a bidirectional steerable introducer sheath and a radiofrequency puncture dilator, and is designed with an atraumatic contrastfilled positioning balloon on its distal

end. The introducer sheath is ultravisible under echocardiography and X-ray to facilitate precise puncture site selection, while its bidirectional steerability allows for safe manoeuvring and perpendicular placement on the septum. The RF puncture dilator delivers electrical energy quickly and predictably to puncture the atrial septum. “As a structural heart interventional echocardiographer who helps guide these procedures, the steerable balloon sheath and needle-less RF system provides for a very visible, precise, and safe transseptal experience,” says Hahn. “The precision and efficiency with which the interventionalist can now perform the transseptal puncture is remarkable and will likely shorten procedure times and improve procedural success.” “With the increasing number of left atrial procedures, it is imperative to have a left atrial access device that helps physicians safely and predictably cross the septum,” commented Leon, “The SafeCross system represents a novel tool for successful left atrial procedures including LAAC, transcatheter mitral valve repair (TEER), and AF ablation procedures among others. I look forward to collecting clinical evidence on the performance of the SafeCross system and to focusing on training initiatives to improve the safety and efficacy of left atrial procedures.”

FEops Heartguide receives FDA clearance for LAAO planning capabilities

FEops has announced that it received authorisation from the US Food and Drug Administration (FDA) for the use of FEops Heartguide pre-operative planning of left atrial appendage occlusion (LAAO) in conjunction with Abbott’s Amplatzer Amulet and Boston Scientific’s Watchman FLX device. FEops Heartguide is a cloud-based procedure planning solution in the structural heart space, based on digital twin technology. With the US introduction for the LAAO workflow, FEops Heartguide will enable US physicians to virtually model clinical scenarios with different implant positions and sizes of these FDA cleared LAA devices, helping the physician to select the optimal size and position for every individual patient, the company said in a press release. “FEops Heartguide is the new generation preoperative planning allowing operators to enter the procedure room with increased confidence for sizing and position for LAAO interventions,” said Devi Nair (St Bernard’s Heart & Vascular Center, Jonesboro, USA). “The platform is easy to use, very intuitive and provides critical data on how the device will interact with the LAA anatomy. The software provides implanting physicians high-quality images that enhance pre-procedure planning for proper sizing of the

LAAO device and implant depth. It gives the operator the best chance to choose and implant the correct device with confidence and get it right the first time.” “FEops enabled me to select the appropriate device size and optimal device position upfront, resulting in an efficient, trouble-free, and successful ICE-guided LAAO procedure,” said Matthew Price (Scripps Clinic, La Jolla, USA).

Health Canada approval granted for Savvywire TAVI guidewire

OpSens has announced that it has received Health Canada approval for the Savvywire, its new guidewire for transcatheter aortic valve implantation (TAVI) procedures. The SavvyWire, a third-generation, intelligent, pre-shaped, structural guidewire with integrated pressure monitoring, aims at improving procedural efficiency and clinical outcomes by allowing multiple steps over the same device without exchange. The device is designed to support the growing minimalist TAVI approach. With the Savvywire, physicians can expect to implant the percutaneous valve over the same device while obtaining continuous and accurate haemodynamic measurements to assist their diagnosis, OpSens said in a press release.

First patient in Japan treated with Impella 5.5 with SmartAssist Abiomed has announced that the first patient in Japan has been treated successfully with Impella 5.5 forward flow heart pump with SmartAssist. Additionally, the number of patients treated globally has surpassed 5,000. The first Impella 5.5 with SmartAssist procedure in Japan took place at Osaka Police Hospital when an 82-year-old man was treated for cardiogenic shock. “Our facility is proud to be the first in Japan to treat patients using Impella 5.5 with SmartAssist,” said Yoshiki Sawa, director at Osaka Police Hospital (Osaka, Japan). “We are excited to utilise this innovative technology and look forward to providing a minimally invasive surgical option for our acute heart failure patients.” The milestone 5,000th procedure was performed by Tamer Attia at Emory University Hospital, Atlanta, USA on a 41-year-old woman with cardiomyopathy. “Impella 5.5 with SmartAssist has completely changed how we are able to support our cardiogenic shock and cardiomyopathy patients,” said Mani Daneshmand, chief of the section of thoracic transplant and mechanical circulatory support surgery at Emory University Hospital, Atlanta, USA. “Given the safety and efficacy of Impella 5.5 with SmartAssist, Attia and his team are able to treat patients who otherwise would not have had other options for heart recovery.”

Issue 65 | May 2022

Market Watch 33

Clinical News

Symplicity

Three-year data show “durable blood pressure reductions” through renal denervation

Long-term data from the first 80 patients in the SPYRAL HTN-ON MED trial have been presented during a featured clinical research session at the American College of Cardiology’s annual scientific sessions (ACC 2022, 2–4 April, Washington DC, USA). The data, which were simultaneously published in The Lancet, “underscore confidence” in renal denervation (RDN) as a treatment for hypertension, according to Medtronic, the sponsor of the study. In the first 80 patients of the SPYRAL HTN-ON MED trial, the data demonstrated that patients who were prescribed anti-hypertensive medications and treated with the Symplicity Spyral (Medtronic) RDN system continued to show durable, clinically significant blood pressure reductions through three years. The results demonstrated an 18.7mmHg reduction in RDN patients versus 8.6mmHg in sham for 24-hour systolic ambulatory blood pressure (ABPM), as well as 20.9 mmHg reduction in RDN patients versus 12.5mmHg in the sham arm for office systolic blood pressure (OSBP). “Across the latest trials, consistent blood pressure reductions have been observed in patients with uncontrolled hypertension treated with the Medtronic Symplicity Spyral RDN system,” said Felix Mahfoud (Saarland University Hospital, Homburg, Germany) and member of the SPYRAL HTN executive committee. “For the first time, we now have randomised data that demonstrates that in a typical patient population—hypertension patients who are on anti-hypertensive medications and treated with RDN— we are seeing the continued, longterm blood pressure lowering effect. Lowering blood pressure can have meaningful clinical results for patients, including a decrease in the risk of cardiovascular events.”

First patient enrolled in BIOMICS study for CTO-PCI Biosensors International has announced the enrolment of the first patient in the BIOMICS study, a prospective,

multicentre evaluation of the safety and effectiveness of the Biosensors Microcatheter in patients undergoing percutaneous coronary intervention (PCI) for the treatment of chronic total occlusions (CTO). Biosensors are conducting BIOMICS as part of their product development activities for the new coronary microcatheter. The trial will include up to 10 sites in the UK and is being conducted under the leadership of Margaret McEntegart (Golden Jubilee National Hospital, Glasgow, UK) and James Spratt (St George’s Hospital, London, UK). Margaret McEntegart and Aadil Shaukat enrolled the first BIOMICS patients at the Golden Jubilee National Hospital in Glasgow. “We are very excited to have performed the first in human cases with the new microcatheter from Biosensors as part of the BIOMICS study here at GJNH. The new microcatheter was successful in crossing the CTO with no complications. We look forward to recruiting more patients in coming weeks.”

Clínico San Carlos, Madrid, Spain. The prospective single-arm study assesses the safety and clinical performance of Dreams 3G resorbable magnesium scaffold (RMS). “Based on my extensive experience with resorbable magnesium scaffolds, Dreams 3G represents a very promising evolution for resorbable technology. With its larger size matrix, thinner struts and improved mechanical performance, Dreams 3G has the potential to provide a broader range of clinical benefits than previously available scaffolds,” said Haude. “The BIOMAG-I study is investigating whether these design improvements will translate into the expected clinical benefits. The study has now achieved a major milestone by completing the enrolment, primary endpoint data on in-scaffold late lumen loss at six-month follow up are intended to be presented later this year.” A total of 14 clinics in eight European countries are taking part in the BIOMAG-I clinical trial. The patient cohort includes 116 patients aged between 18 and 80 years with single de novo lesions in up to two coronary arteries. The study will run for a total of three years, assessing the primary endpoint of in-scaffold late lumen loss at six months, with followups at 12, 24 and 36 months.

First-in-human study paves way for further clinical trials of Valvosoft

Cardiawave has announced the success of its first-in-human I (FIH I) safety and feasibility clinical trial for Valvosoft its breakthrough technology that allows for the remote application of a focused therapeutic ultrasound beam to restore valve function in patients with aortic stenosis (AS). This intense beam decreases the stiffness of the aortic valve and improves its functional opening to allow sufficient oxygenated blood to reach the brain and the rest of the body. This non-invasive therapy is a new treatment option for aortic stenosis, as the only current medical response is to replace the aortic valve with open heart surgery, or with a transcatheter aortic valve implantation (TAVI). The purpose of the FIH I study was to assess the safety, and operating system of the first generation of Valvosoft as well as the clinical effects of softening calcific aortic valve tissues with a beating heart. Thirty patients (average age 84 years, with nine patients over 90) have now been successfully treated in France and The Netherlands, the last being in late 2021.

Enrolment in BIOMAG-I trial of resorbable magnesium scaffold completed

Biotronik has announced final enrolment in the BIOMAG-I clinical trial by Michael Haude (Rheinland Klinikum, Neuss, Germany) the study’s coordinating clinical investigator and the principal investigator Javier Escaned (Hospital Universitario

PiCSO therapy

First patient enrolled in PISCO-AMI-V study

Miracor Medical has announced the first patient enrolled in the PICSOAMI-V study to evaluate PiCSO— pressure-controlled intermittent coronary sinus occlusion—therapy as an adjunct to conventional primary percutaneous coronary intervention (PCI) for patients presenting with inferior ST-Elevation Myocardial Infarction (STEMI). The first patient enrolled was treated at the University Hospital of Toulouse (Toulouse, France) by the team of Didier Carrié. “Our team started using the PiCSO therapy for anterior STEMI patients in 2021. We are delighted to explore new indications and now start using PiCSO for inferior STEMI patients in the context of the PiCSO-AMI-V study,” says Carrié. The principal investigator of the study is Adrian Banning, Oxford Heart Center, Oxford, UK. “We are pleased to be initiating the PiCSO-AMI-V study. It will explore the potential for PiCSO therapy to improve the outcomes of patients with heart attacks affecting the inferior side

of the heart. The study builds upon the data from the First-InMan study that we published in 20213. We know that improving outcomes for patients with large heart attacks remains an important unmet need, especially because these patients often progress to develop heart failure,” says Banning. PICSO-AMI-V is a prospective, randomised, multicentre feasibility study and will enrol 75 inferior STEMI patients presenting with TIMI 0 & 1 flow, at up to 10 clinical sites in Europe. In the study, patients will be randomised 2:1 to a group receiving PiCSO as an adjunct to their primary PCI procedure versus a conventional strategy of primary PCI alone. Adverse Device Effect (ADE) rate at 30 days post index procedure will be assessed as the primary endpoint. In addition, cardiac function and clinical safety endpoints – including death, heart failure-related hospitalisation, new onset or worsening of heart failure— will be assessed.

Enrolment for EXPAND TAVR II trial begins

Medtronic has announced the first patient enrolment in the EXPAND TAVR II pivotal trial, the first randomised clinical trial evaluating the self-expanding, supra-annular Evolut transcatheter aortic valve implantation (TAVI) platform in patients with moderate, symptomatic aortic stenosis, a population currently outside of guidelines and indications for TAVI. The first patient in the EXPAND TAVR II pivotal trial was enrolled by the team led by Shigeru Saito and Tomoki Ochiai at Shonan Kamakura General Hospital in Kamakura, Japan. The EXPAND TAVR II Pivotal Trial is a multicentre, international, prospective trial to be conducted in USA, Canada, Japan, EMEA regions, Australia, and New Zealand. Investigational Device Exemption (IDE) approval was received in October 2021 from the US Food and Drug Administration (FDA) and clinical trial approval was received from the Japan Pharmaceutical and Medical Device Agency (PMDA) in February 2022. The trial will evaluate the safety and effectiveness of the Medtronic Evolut PRO+ TAVI system and guidelinedirected management and therapy (GDMT) compared to GDMT alone in moderate, symptomatic aortic stenosis patients. The data may be used to support future regulatory submissions to expand indications for the platform. “There are many patients living with varying levels of aortic stenosis, including moderate symptomatic, who may benefit from the less invasive TAVI procedure even though they fall outside of the current indications,” said Paul Sorajja (Minneapolis Heart Institute Foundation, Minneapolis, USA) and principal investigator in the study. “We are excited to add to the growing body of clinical evidence to support the safety and benefits of TAVI in new patient populations.”

May 2022 | Issue 65

34 Market Watch

Industry News Medtronic names Laura Mauri as new chief scientific, medical and regulatory officer

Medtronic has announced that Laura Mauri has been appointed as the company’s chief scientific, medical and regulatory officer. This appointment adds to Mauri’s prior responsibilities as chief clinical and regulatory officer, aligning and integrating the company’s scientific, medical, clinical research and regulatory affairs under her leadership, according to a Medtronic press release. It also intends to leverage her deep expertise and understanding of the interaction between patients and medical technology to accelerate innovation that puts patients first, the release states. Mauri will continue to serve as a member of the Medtronic Executive Committee as well. “With this appointment, we are enabling a patient-centred approach to healthcare technology innovation at every stage of the product lifecycle,” said Geoff Martha, chairman and CEO, Medtronic. “Dr Mauri’s expertise and leadership connects medical and scientific intelligence, ensuring we have a clear appraisal of the medical and scientific landscape as we make investment decisions, and helping to deliver effective and reliable innovations for patients and healthcare providers.” The release adds that priorities for Mauri include delivering a transformative approach to both patient safety and patient engagement. She recently hired Olaf Hedrich—a patient safety, risk and analytics industry expert—to serve as the company’s chief medical safety officer, responsible for leading an independent medical safety organisation that will provide expert input to assure patients safety and quality across Medtronic products. Mauri will also lead the integration of robust and independent medical expertise into the company’s business processes, including investment decisions, business development, exploration of therapeutic areas, and development of novel technologies. “Medtronic is fortunate to have world-leading experts across diverse scientific and medical fields

who provide unique insights and breakthrough discoveries,” said Mauri. “I am excited to integrate this expertise across our company, to connect technology innovation with better health outcomes for patients. A strong scientific and patient-centred mindset across all stages of device development will enable innovation that saves and improves lives.” Prior to joining Medtronic, Mauri was a practising interventional cardiologist at the Brigham and Women’s Hospital in Boston, USA for 15 years, and an internationally renowned investigator and professor of medicine at Harvard Medical School. She succeeds Richard Kuntz as chief medical and scientific officer, who previously announced his retirement, effective 29 April.

Cobra PzF stent

CeloNova to seek medical device partnerships

CeloNova BioSciences has announced the strategic decision to focus its core business on creating partnership and co-development opportunities with medical device manufacturers seeking to optimise implant interaction within the body. The company’s nanocoated innovation is the result of years of rigorous scientific research and engineering and has been extensively published in numerous academic articles to date, CeloNova said in a press release. “We are pleased to offer leading medical device manufacturers access to the unique clinical advantages of our Polyzene-F nanocoated technology that has clinically demonstrated low thrombosis, restenosis and inflammation with rapid healing effects,” stated Carl St Bernard, president and chief executive officer of

Calendar of events

CeloNova. “This technology offers a significant benefit to companies seeking to improve the clinical performance of their implant technologies.” “I fully support CeloNova’s new strategic direction which allows medical device manufacturers to benefit from long-term biocompatibility and thromboresistance of Polyzene-F,” stated Michael Grunze (RuprechtKarls-University, Heidelberg, Germany) and co-inventor of Polyzene-F. “When my students and I set out to study the haemocompatibility of this inorganic polymer in our lab in Heidelberg Germany, we soon realised its potential to significantly limit a wide range of implant complications and being broadly applied in the human body and in biomedical devices.”

Viz.ai raises US$100 million in Series D funding to expand AI technologies

Viz.ai has raised a US$100 million funding round at a US$1.2 billion valuation, as per a company press release. The Series D round, which comes as the number of hospitals using the Viz platform surpasses the 1,000 mark, and with patients served in the millions, was led by Tiger Global and Insight Partners. Also joining the round were several of the company’s early backers, including Scale Ventures, Kleiner Perkins, Threshold, GV (formerly Google Ventures), Sozo Ventures, CRV, and Susa. These new funds will be used to support Viz.ai’s significant growth trajectory, expand the Viz platform to detect and triage additional diseases, and grow its customer base globally, the release adds. The company continues to expand its reach and innovation in additional disease states. Through its vast network of hospital and health system customers, Viz.ai claims to assist in the care of one patient every 32 seconds. Over the past year, Viz.ai has launched artificial intelligence (AI)driven solutions for aortic disease, pulmonary embolism, cerebral aneurysms, and is US Food and Drug Administration (FDA) 510(k)-pending for subdural haematoma. The company was also awarded its first five CE marks in 2021, followed by contracts with several leading hospitals. “Viz.ai is committed to helping patients get better, faster and more equitable access to life-saving treatments,” said Chris Mansi, Viz.

ai co-founder and CEO. “We will continue to invest heavily in cuttingedge technology and services to integrate deeply into the clinical workflow, allowing us to automate disease detection, increase diagnostic rates, and enhance workflows across the entire hub and spoke health system. More patients receive the right treatment, resulting in better patient outcomes and improved financial efficiency for the health system.”

Corindus relocates Massachusetts headquarters to accommodate company growth

Corindus, a Siemens Healthineers company, announced today the opening of its new headquarters at 275 Grove Street in Newton, USA. Siemens Healthineers relocated the Corindus headquarters from its previous location in Waltham, USA to accommodate company growth, doubling the size of the current location from 35,000 to 77,000 square feet, according to a company press release. The headquarters will serve as the global ‘Centre for Excellence’ for Siemens Healthineers’ endovascular robotic technologies—encompassing development, manufacturing, and administration, the release adds. “Our new facility is a testament to the commitment Siemens Healthineers

A robotic-assisted procedure

has made to metro Boston and Massachusetts as a hub for innovative talent,” said Wayne Markowitz, executive vice president and head of Corindus. “As we continue to advance our robotic-assisted platform, the new facility will support our mission to elevate the standard of care and increase access to cutting-edge treatment for coronary artery and neurovascular disease.” The new facility marks the first of 15 new offices or major facility expansions that Siemens Healthineers has planned in the USA.

Please be advised that the events listed below are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

17–20 May EuroPCR 2022 Paris, France

8–11 June TVT 2022 Chicago, USA

27–30 August ESC Congress 2022 Barcelona, Spain

5–8 October EACTS 2022 annual meeting Milan, Italy

19–22 May SCAI 2022 Scientific Sessions Atlanta, USA

19–21 June Joint Interventional Meeting (JIM) 2022 Milan, Italy

16–20 September TCT 2022 Boston, USA

27–29 November PCR London Valves

pcronline.com/courses/europcr

scai.org/scai2022

crf.org

jim-vascular.com

escardio.org

crf.org

eacts.org/annual-meeting/

London, UK

Issue 65 | May 2022

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Performance goal derived from contemporary 1-month DAPT trials, including ZEUS, LEADERS FREE, and SENIOR trials. Kandzari DE, Kirtane AJ, Windecker S, et al. One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients. Circ Cardiovasc Interv. November 2020;13(11):e009565. 2 Kandzari, et al. Complex PCI with 1-month DAPT in High Bleeding Risk Patients: Analysis from the Onyx ONE Clear Study. Presented at TCT Connect 2020. 3 Resolute Onyx DES IFU. The safety and effectiveness of the Resolute Onyx™ stent have not yet been Resolute Onyx™ Zotarolimus-eluting Coronary Stent System established in the following patient populations:  Patients with target lesions Indications or the use of brachytherapy to treat The Resolute Onyx™ Zotarolimus-eluting Coronary Stent System is indicated that were treated with prior brachytherapy in-stent restenosis of a Resolute Onyx™ stent  Women who are pregnant or for improving coronary luminal diameters in patients, including those with lactating  Men intending to father children  Pediatric patients  Patients with diabetes mellitus or high bleeding risk, with symptomatic ischemic heart coronary artery reference vessel diameters of < 2.0 mm or > 5.0 mm  Patients disease due to de novo lesions of length ≤ 35 mm in native coronary arteries with evidence of an acute ST-elevation MI within 72 hours of intended stent with reference vessel diameters of 2.0 mm to 5.0 mm. In addition, the ™ implantation  Patients with vessel thrombus at the lesion site  Patients with Resolute Onyx Zotarolimus-eluting Coronary Stent System is indicated for lesions located in a saphenous vein graft, in the left main coronary artery, ostial treating de novo chronic total occlusions. lesions, or bifurcation lesions  Patients with diffuse disease or poor flow distal Contraindications to identified lesions  Patients with three-vessel disease ™ The Resolute Onyx Zotarolimus-eluting Coronary Stent System is ™ contraindicated for use in:  Patients with a known hypersensitivity or allergies The safety and effectiveness of the Resolute Onyx stent have not been established in the cerebral, carotid, or peripheral vasculature. to aspirin, heparin, bivalirudin, clopidogrel, prasugrel, ticagrelor, ticlopidine, Oral Antiplatelet Therapy drugs such as zotarolimus, tacrolimus, sirolimus, everolimus, or similar drugs Dual antiplatelet therapy (DAPT) using a combination treatment of aspirin or any other analogue or derivative  Patients with a known hypersensitivity with a P2Y12 platelet inhibitor after percutaneous coronary intervention to the cobalt-based alloy (cobalt, nickel, chromium, and molybdenum) or ™ (PCI), reduces the risk of stent thrombosis and ischemic cardiac events, platinum-iridium alloy  Patients with a known hypersensitivity to the BioLinx but increases the risk of bleeding complications. The optimal duration of polymer or its individual components DAPT (specifically a P2Y12 platelet inhibitor in addition to aspirin) following Coronary artery stenting is contraindicated for use in:  Patients in whom DES implantation is unknown, and DES thrombosis may still occur despite antiplatelet and/or anticoagulation therapy is contraindicated  Patients who are judged to have a lesion that prevents complete inflation of an angioplasty continued therapy. It is very important that the patient is compliant with the post-procedural antiplatelet recommendations. balloon or proper placement of the stent or stent delivery system Per 2016 ACC/AHA guidelines,1 a daily aspirin dose of 81 mg is recommended Warnings indefinitely after PCI. A P2Y12 platelet inhibitor should be given daily for at  Please ensure that the inner package has not been opened or damaged least 6 months in stable ischemic heart disease patients and for at least 12 as this would indicate the sterile barrier has been breached.  The use of months in patients with acute coronary syndrome (ACS). Consistent with the this product carries the same risks associated with coronary artery stent 2 implantation procedures, which include subacute and late vessel thrombosis, DAPT Study, and the 2016 ACC/AHA guidelines, longer duration of DAPT may be considered in patients at higher ischemic risk with lower bleeding risk. The vascular complications, and/or bleeding events.  This product should not Academic Research Consortium (ARC) proposed a standardized definition for be used in patients who are not likely to comply with the recommended identifying patients at high bleeding risk (HBR).3 Additionally, evidence from a antiplatelet therapy. dedicated study of Resolute Onyx in HBR patients and those who are unable Precautions to tolerate long term DAPT after PCI has been published.4  Only physicians who have received adequate training should perform Based on the Onyx ONE Clear Analysis, Resolute Onyx is safe and effective in implantation of the stent.  Subsequent stent restenosis or occlusion may patients at high risk of bleeding treated with one month of DAPT. The patients require repeat catheter-based treatments (including balloon dilatation) of evaluated in the Onyx ONE Clear Analysis met the pre-defined criteria for the arterial segment containing the stent. The long-term outcome following high bleeding risk and were those whom in the opinion of their physician, the repeat catheter-based treatments of previously implanted stents is not well potential benefit of 1-Month DAPT outweighed the potential risk. In addition characterized.  The risks and benefits of the stent implantation should be to at least one HBR risk factor, enrollment included 48.6% ACS patients assessed for patients with a history of severe reaction to contrast agents.  Do (unstable angina 22.8%, Non-STEMI 21.7% and STEMI 4.2%). not expose or wipe the product with organic solvents such as alcohol.  The Decisions about duration of DAPT are best made on an individual basis and use of a drug-eluting stent (DES) outside of the labeled indications, including should integrate clinical judgment, assessment of the benefit/risk ratio, and use in patients with more tortuous anatomy, may have an increased risk of patient preference. Premature discontinuation or interruption of prescribed adverse events, including stent thrombosis, stent embolization, MI, or death.  Care should be taken to control the position of the guide catheter tip during antiplatelet medication could result in a higher risk of stent thrombosis, MI, or death. Before PCI, if premature discontinuation of antiplatelet therapy is stent delivery, stent deployment, and balloon withdrawal. Before withdrawing anticipated, physicians should carefully evaluate with the patient whether a the stent delivery system, confirm complete balloon deflation using DES and its associated recommended DAPT regimen is the appropriate PCI fluoroscopy to avoid arterial damage caused by guiding catheter movement into the vessel.  Stent thrombosis is a low-frequency event that is frequently choice. associated with myocardial infarction (MI) or death. Data from the RESOLUTE Following PCI, if elective noncardiac surgery requiring suspension of antiplatelet therapy is considered, the risks and benefits of the procedure clinical trials have been prospectively evaluated and adjudicated using the should be weighed against the possible risk associated with interruption of definition developed by the Academic Research Consortium (ARC). *

antiplatelet therapy. Patients who require premature DAPT discontinuation should be carefully monitored for cardiac events. At the discretion of the patient’s treating physician(s), the antiplatelet therapy should be restarted as soon as possible. Potential Adverse Events Other risks associated with using this device are those associated with percutaneous coronary diagnostic (including angiography and IVUS) and treatment procedures. These risks (in alphabetical order) may include but are not limited to:  Abrupt vessel closure  Access site pain, hematoma, or hemorrhage  Allergic reaction (to contrast, antiplatelet therapy, stent material, or drug and polymer coating)  Aneurysm, pseudoaneurysm, or arteriovenous fistula (AVF)  Arrhythmias, including ventricular fibrillation  Balloon rupture  Bleeding  Cardiac tamponade  Coronary artery occlusion, perforation, rupture, or dissection  Coronary artery spasm  Death  Embolism (air, tissue, device, or thrombus)  Emergency surgery: peripheral vascular or coronary bypass  Failure to deliver the stent  Hemorrhage requiring transfusion  Hypotension/hypertension  Incomplete stent apposition  Infection or fever  MI  Pericarditis  Peripheral ischemia/ peripheral nerve injury  Renal failure  Restenosis of the stented artery  Shock/pulmonary edema  Stable or unstable angina  Stent deformation, collapse, or fracture  Stent migration or embolization  Stent misplacement  Stroke/transient ischemic attack  Thrombosis (acute, subacute, or late) Adverse Events Related to Zotarolimus Patients’ exposure to zotarolimus is directly related to the total amount of stent length implanted. The actual side effects/complications that may be associated with the use of zotarolimus are not fully known. The adverse events that have been associated with the intravenous injection of zotarolimus in humans include but are not limited to:  Anemia  Diarrhea  Dry skin  Headache  Hematuria  Infection  Injection site reaction Pain (abdominal, arthralgia, injection site)  Rash Please reference appropriate product Instructions for Use for more information regarding indications, warnings, precautions, and potential adverse events. CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician. For further information, please call and/or consult Medtronic at the toll-free numbers or websites listed. 1 Levine GN, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016; doi:10.1016/j. jacc.2016.03.513. For full text, please refer to the following website: http:// content.onlinejacc.org/articleaspx?doi=10.1016/j.jacc.2016.03.513 2 Mauri L, et al. Twelve or 30 months of dual antiplatelet therapy after drugeluting stents. N Engl J Med. 2014; 371:2155–66. 3 Urban P, Mehran R, Colleran R, et al. Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention. Circulation. 2019;140:240–6. 4 Windecker S, Latib A, Kedhi E, et al. Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk. N Engl J Med. 2020:10.1056/NEJMoa1910021.

medtronic.com/OnyxOneProgram UC202115622a EN ©2021 Medtronic. All rights reserved. Medtronic and the Medtronic logo are trademarks of Medtronic. All other brands are trademarks of a Medtronic company. For distribution in the USA only. 05/2021

Medtronic Tel: 707.525.0111

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Resolute Onyx™ DES

PROVEN SAFE AND EFFECTIVE WITH 1-MONTH DAPT IN HBR PATIENTS The Onyx ONE Clear Analysis Included the Most Complex High Bleeding Risk (HBR) Patients for Greater Confidence in Short DAPT Decisions1

Complex Patients

Complex Lesions

50%

Nearly

years average age

50%

ACS patients

39%

diabetes

moderate to severe calcified lesions

79%

B2/C lesions

Event Rates 1–12 months (%)

average stented length

patients with > 60 mm stented length2

Onyx ONE Clear Analysis p < 0.001

37 mm 225

n = 1,491/1,506

9.7

PERFORMANCE GOAL*

MONTH DAPT

7.0 2.6 Primary Endpoint Cardiac Cardiac Death/MI Death

4.8 MI

3.4

0.7

TLR

Def/Prob ST

DAPT duration decisions are best made on an individual basis. Premature discontinuation or interruption of prescribed antiplatelet medication could result in a higher risk of ST, MI, or death.

Resolute Onyx DES is indicated for HBR patients and labeled for 1-month DAPT.3