Cardiovascular News - Issue 63 - November 2021 (US) by BIBA Publishing

November 2021 | Issue 63

Featured in this issue:

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EACTS 2021 Left main revascularisation in focus

Profile Mirvat Alasnag

HBR patients irrespective of clinical presentation—for example in those with stable coronary artery disease or acute coronary syndrome—to six months or less, or potentially as short as one month. However, the recommendation is classed as level C evidence, indicating that it reflects the expert opinion and further evidence is needed. Studies investigating one-month DAPT after stent implantation have suggested that this regimen has potential to mitigate bleeding without compromising safety but have either been non-randomised or not specific to HBR patients, Valgimigli explained. MASTER DAPT sought to assess whether one month of DAPT preserved the benefit in relation to cardiovascular events, while mitigating bleeding outcomes, compared with longer treatment durations. The trial was a non-inferiority study with sequential superiority testing. Patients were candidates for the trial if they had an acute One month of dual antiplatelet or chronic coronary therapy (DAPT) following syndrome, underwent percutaneous coronary successful PCI of all intervention (PCI) using the coronary artery stenosis, Ultimaster (Terumo) sirolimusand fulfilled one or eluting stent in patients at more HBR criteria. high bleeding risk (HBR) Patients free from preserves ischaemic benefit ischaemic and reduces bleeding risk and bleeding according to the findings of events and who the MASTER DAPT study. adhered to a DAPT regimen he results of the trial were were screened The panel (l-r): presented during a Hot Line trial for inclusion 30 to Marco Valgimigli, Jean-Philippe Collet, Robert session at the European Society of 44 days after PCI. Cardiology’s 2021 congress (ESC 2021, 27–30 Byrne, Davide Capodanno Participants were and Roxana Mehran August, virtual), and published in the New randomised 1:1 to receive England Journal of Medicine. open-label abbreviated or standard DAPT. Patients in the “In patients at high bleeding risk who had undergone abbreviated treatment group immediately discontinued implantation of a biodegradable polymer Ultimaster DAPT and continued single antiplatelet therapy until study sirolimus-eluting stent, the discontinuation of DAPT at completion—except for those receiving clinically indicated a median of 34 days, compared with a continuation of oral anticoagulation, who continued single antiplatelet treatment for a median of 193 days after PCI, was nontherapy up to six months after PCI. inferior for the incidence of net adverse clinical events, Those allocated to the standard treatment group non-inferior for the incidence of major cardiac or cerebral events, and associated with a lower incidence of major or clinically-relevant non-major bleeding,” study author Marco Valgimigli (Cardiocentro Ticino Foundation, Lugano, Switzerland) told ESC 2021 attendees. The findings were described as “game-changing” by panellists at ESC 2021 in terms of their implication for the use of a shorter-duration DAPT regimen following stent implantation in HBR patients, however Valgimigli cautioned against extrapolating the trial’s results across all stent platforms, due to the prevalent use of Ultimaster during the study. DAPT—the dual-use of aspirin and a P2Y12 receptor inhibitor after PCI—is known to reduce recurrent ischaemic events, but comes at the expense of an increased risk of major bleeding in some patients. Recent clinical trials on newer generation drug-eluting stents (DESs) have shown an acceptable safety profile with a short course of DAPT, but the optimal DAPT duration in HBR patients undergoing PCI remains a topic of study. Guidelines recommend shortening DAPT duration in Continued on page 4

page 18

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MASTER DAPT “game changing” for onemonth dual antiplatelet therapy

Marco Valgimigli

Discontinuation of DAPT…was noninferior for the incidence of net adverse clinical events, non-inferior for the incidence of major cardiac or cerebral events, and associated with a lower incidence of major or clinically-relevant nonmajor bleeding.”

Konstantinos Tsioufis Renal denervation

CX AORTIC VIENNA

Multidisciplinary working vital for the next generation of aortic surgeons Building and maintaining expertise in both open and endovascular surgical techniques will play an important role in training the next generation of surgeons in order to optimise outcomes in patients with aortic disease. This is among the messages to have emerged from CX Aortic Vienna 2021 (5–7 October, broadcast), in which speakers discussed training in aortic procedures, and stressed the need for multidisciplinary teamwork between the cardiac and vascular surgery specialties. THE THREE-DAY CX AORTIC VIENNA symposium highlighted the latest developments in the comprehensive treatment of aortic disease—discussing treatment techniques and latest research from the aortic valve to the iliac arteries. Speakers from the fields of cardiac, vascular and endovascular surgery all provided perspectives on advances in aortic care, and cross-disciplinary working was a common theme throughout the programme. In particular, attendees to the event heard the importance of offering patients a choice between open and endovascular approaches for aortic conditions. During a session covering training and teamwork for optimal aortic patient outcomes, Eric Roselli, chief of adult cardiac surgery, and director of the Aorta Center at the Cleveland Clinic (Cleveland, USA), presented a view on the future of training for surgeons who will specialise in the aorta. Roselli commented that aortic disease “knows no boundaries” and offered the opinion that there is a need to “think smarter about how we offer care for this complex disease”. Both open and endovascular approaches should be complimentary, he added, and said that the focus has to be on what the patients’ needs are, based around the details of aortic disease and the interplay of comorbidities. Roselli added that aortic care requires a mixed skillset, combining both cognitive and technical attributes, and said that overlapping training programmes involving specialists from cardiology, vascular surgery, and cardiothoracic surgery are important components in the future Continued on page 9

November 2021 | Issue 63

Diversity

ACC survey points to discrimination, inequity in cardiovascular workforce

were similar to their peers. Along the same lines, 85% of underrepresented racial and ethnic minority respondents were satisfied with their family lives outside of work. These results are at odds with previous research and data showing underrepresented racial and ethnic minorities are at a disadvantage for job and financial advancement. The researchers said that prior studies have focused on advancement and leadership in academic settings, whereas this study included cardiologists in private practice and academics who may have different experiences. However, over half (52.3%) of underrepresented racial and ethnic minority respondents reported experiencing Underrepresented racial and ethnic minorities discrimination, compared with 36.4% of white respondents. in the cardiovascular workforce continue to Women of all racial and ethnic groups were more likely than experience a lack of representation and face men to report discrimination (57‒69.2% compared with discrimination, inequitable job negotiations 13.9‒44.6%, respectively). When broken down, men were and burnout in their professional lives, more likely to report race and religion-based discrimination, according to an analysis of the Professional whereas nearly all women reported gender discrimination, Life Survey conducted by the American and underrepresented racial and ethnic minority women College of Cardiology (ACC). The analysis has in addition reported frequently experiencing race-based been published in the Journal of the American discrimination in the workplace. College of Cardiology (JACC). Compared with white cardiologists, underrepresented racial and ethnic minority cardiologists were less espite calls for racial and ethnic likely to negotiate or prioritize salary, benefits and diversification in medicine or work hours in their first job (white cardiologists cardiology, there has been little reported 20.6%, 23.3%, 31.3% in each category change. Putting into place methods to support respectively, versus 13.6%, 10.9%, 19.3% those who are underrepresented in medicine is respectively from underrepresented racial and ethnic critical moving forward,” said Kevin Thomas, minority cardiologists). associate professor of medicine at the Duke As their careers advanced, underrepresented University Research Institute, Durham, USA and racial and ethnic minority respondents placed Kevin Thomas lead author of the study. more emphasis on salary, benefits and work The ACC’s third decennial Professional Life hours compared with white cardiologists, which Survey was conducted by the ACC Women in according to researchers is potentially a marker that Cardiology Section and on behalf of the ACC Diversity and underrepresented racial and ethnic minorities are placed Inclusion Task Force to assess the professional experience at a disadvantage in these categories at the start of their of cardiologists. careers and showcasing there is a greater need to overcome The survey included 2,245 respondents who provided systemic barriers. racial/ethnic data. Of the respondents, 1,447 identified as white, 564 as Asian or Pacific Islander and 37 as multiracial. Underrepresented racial and ethnic minorities, those identifying as Black, Hispanic or Native American, counted for 197 of the respondents. The researchers looked at the 197 underrepresented racial and ethnic minority respondents to assess career satisfaction and advancement, personal and family issues, discrimination, mentoring, job negotiations and burnout rates compared with the other racial and ethnic groups. “This particular group has never been singled out in White cardiologists were more likely than those in analysing the data from the 2015 Professional Life Survey, minority groups to report higher rates of burnout, however and the results are very revealing about how much work underrepresented groups experienced more isolation and there is still left to do,” said Thomas. non-inclusive work environments. Over 91% of underrepresented racial and ethnic The researchers said greater learned resiliency over their minority respondents were satisfied with their career and lifetime from underrepresented racial and ethnic minorities felt their level of advancement and career opportunities may contribute toward reporting lower rates of burnout.

“D

Despite calls for racial and ethnic diversification in medicine or cardiology, there has been little change.”

News in brief

The latest stories from the world of Cardiology

n ADVERTORIAL: Chronic total occlusion (CTO) treatment has been described as the “last frontier” in interventional cardiology. In this advertorial, sponsored by Roberto Garbo iVascular, Roberto Garbo (Turin, Italy) details his experience with the Navitian microcatheter, a new entrant into the field designed to improve the success of CTO treatment.

For more on this story go to page 6. n EACTS 2021: Top stories from the European Society of Cardio-Thoracic Surgery annual meeting (EACTS 2021; 13–16 October; Barcelona, Spain and virtual), where speakers discussed the lack of female patients enrolled Nick Freemantle in cardiac surgery trials, and continuing controversies around coronary revascularisation.

For more on this story go to page 10. n FUTURE OF IMAGING IN THE CATH LAB: Philips’ chief business leader for Image Guided Therapy, Bert van Meurs, tells Cardiovascular News his vision for the future of imaging in the cath lab. Reducing radiation is an important goal, he says, detailing some of the emerging technologies that may allow this to happen.

For more on this story go to page 24. Bert van Meurs

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2022

Stroke is underdiagnosed. It can happen to any TAVR patient. No matter their age. No matter their background. Even minor cognitive events can represent life-changing effects for your patients and their families. It’s time to take another look at the effects of every stroke.

Get the Facts on Cerebral Embolic Protection BostonScientific.com/StrokeAwareness

SENTINEL™ Cerebral Protection System (CPS) - INDICATIONS FOR USE: The Sentinel Cerebral Protection System is indicated for use as an embolic protection device to capture and remove thrombus/debris while performing transcatheter aortic valve replacement procedures. The diameters of the arteries at the site of filter placement should be between 9.0 – 15.0 mm for the brachiocephalic and 6.5 – 10.0 mm in the left common carotid. CONTRAINDICATIONS: • Do not use in patients for whom anticoagulant and antiplatelet therapy is contraindicated. • Do not use in patients with a known hypersensitivity to nickel-titanium. • Do not use in vessels with excessive tortuosity. • Do not use in patients with uncorrected bleeding disorders. • Do not use in patients with compromised blood flow to the right upper extremity. • Do not use in patients who have arterial stenosis >70% in either the left common carotid artery or the brachiocephalic artery. • Do not use in patients whose brachiocephalic or left carotid artery reveals significant stenosis, ectasia, dissection, or aneurysm at the aortic ostium or within 3 cm of the aortic ostium. WARNINGS: • The appropriate antiplatelet/anticoagulation therapy should be administered pre- and post-procedure in accordance with standard medical practice. • It is recommended that the patency of the right radial or brachial artery be assessed prior to the introduction of the Sentinel System. • It is recommended that the patient be tested for occlusion of the radial or brachial artery prior to device introduction. • Do not use the device in left radial or left brachial access. • Do not use the Sentinel System to deliver any type of fluid to the patient e.g. contrast media, heparinized saline, etc. due to risk of air embolization and comprise to device performance. Excessive movement of filters may lead to embolization of debris, vessel and/or device damage. • Do not deploy the filters within a previously repaired artery, an artery that has been used for dialysis purposes, or an AV fistula. • Indwell time of the Sentinel System is not to exceed 90 minutes as occlusion could occur, resulting in slow or no flow. • Do not undersize or oversize the filters in relation to the selected vessel diameter. This may result in inadequate vessel wall apposition or incomplete deployment of the filters. (Refer to Sizing Guide, Table 1 in the DFU). PRECAUTIONS: • Do not forcefully bend or reshape the Articulating Sheath of the Sentinel System. • Use of TAVR delivery systems other than those designed to cross the aortic arch with a valve frame in a sheathed or crimped configuration may result in device interference or entanglement. ADVERSE EVENTS: • Possible adverse events associated with Sentinel System use and application procedure include, but are not limited to, the following: • Access site complications • Angina • Aortic dissection • Arrhythmia • Arteriovenous fistula • Atelectasis • Bleeding, operative or post-operative • Cardiac Tamponade • Cardiogenic Shock • Conduction system injury • Congestive Heart Failure (CHF) • Death • Endocarditis • Embolism, including air • Gastrointestinal (GI) bleed • Hematoma • Ischemia (coronary, limb, carotid) • Infection (local or systemic) • Myocardial Infarction (MI) • Nerve injury • Pericardial effusion • Pneumonia • Pulmonary edema • Pulmonary embolism • Respiratory failure • Respiratory insufficiency • Stroke • Vessel injury (e.g., dissection, rupture, perforation, pseudoaneurysm). CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician. Rx only. Prior to use, please see the complete “Directions for Use” for more information on Indications, Contraindications, Warnings,Precautions, Adverse Events, and Operator’s Instructions. 92329606 B All cited trademarks are the property of their respective owners. All photographs taken by Boston Scientific. To order product or for more information, contact customer service at 1.888.272.1001.

November 2021 | Issue 63

Antithrombotics

COVER STORY

DAPT in HBR patients who undergo PCI and that is based to a large extent on stent trials, LEADERS FREE to name one, SENIOR, to name another, that have given us confidence, but definitive or more robust evidence was lacking until now, I would say,” he said. “I think this study tells us that an abbreviated DAPT in this setting seems to be safe, and by safe I mean that we see absolutely no signal of an increase in ischaemic complications with the abbreviated DAPT regimen, and also that bleeding in line with expectations, is significantly reduced.” Byrne also raised the point of the

“I would like to stick to numbers, and I would like to try to respond to this point by sharing some numbers with you. We have had a total of 18 definite stent thromboses in the entire study, 99.8% of patients received the Ultimaster stent, 0.2% of patients received other kinds of stent. Sixteen stent thromboses occurred the findings as “game changing”, Davide in the Ultimaster stent, whereas two Capodanno (University of Catania and stent thromboses occurred in 19 nonG Rodolico-San Marco, Catania, Italy) Ultimaster stents.” said he believed that the findings could Byrne also commented that the study have major significance for clinical team did not observe a significant practice and the development of future reduction in the most serious types guidelines—however, he questioned the of bleeding—BARC 3–5—and he replicability of the results in other stent questioned whether Valgimigli had platforms. expected to see a stronger “HBR patients represent effect for abbreviated DAPT 30‒40% of the patients that in this regard. are commonly referred to “Yes, we have been our cath labs, so it is a quite surprised not to see Net adverse Major adverse Major or relevant proportion of a significant difference clinical cardiac and clinically relevant for BARC 3,” Valgimigli patients, and in this field events cerebral events non-major we have seen some trials, responded, adding: “We (NACE) (MACCE) bleeding but these were comparing were expecting both BARC stents on a background 2 and 3 to be reduced, of short DAPT regimen,” at least that was a signal Capodanno commented. “Here coming from the single-arm they investigated a totally studies done before. different question, which “The explanation may Standard DAPT Standard DAPT Standard DAPT is that of the duration of come from the fact that we the DAPT using the same did not compare a short % % % or different stents, versus DAPT regimen versus one Short DAPT Short DAPT Short DAPT standard DAPT. We have year of DAPT, as it has already seen some studies been performed in these % % % in this domain but they single-arm studies with were single arm, with historical historical comparison. Here comparators. So, this is perhaps the first replicability of the study’s results across we were comparing one-month DAPT adequately powered, active controlled, other stent platforms, commenting that with a relatively short duration, even if randomised trial in all-comers patients,” many interventional cardiologists will called standard DAPT, which was at least not have this particular stent available on six months. That could at least explain their cath lab shelves. why the BARC 3 was not significantly To this point, Valgimigli cautioned reduced per se.” against interpreting the study’s results Asked by the session chair Mehran to too widely. “We are transitioning from sum up the findings, Capodanno said that evidence, which is the study just being the results reflect a vote of confidence for presented and published, and opinions,” short-duration DAPT. “I will feel better he responded. “I can only share with when I stop DAPT, Capodanno said. “I you my opinion, which is of course had no data before and now I have data completely irrelevant for our colleagues! to back up this action.” he continued. Capodanno described MASTER DAPT as a first-of-its-kind study, the results of which support the abbreviated DAPT regimen, and apply to a broad cohort of HBR patients undergoing PCI. “I think these results will inform practice and MASTER DAPT investigator Marco Valgimigli spoke to also the guidelines, but the challenge will Cardiovascular News about the background to the trial, and be how to phrase the recommendations, considers the implications of the study’s results. because as you know there was no upper High bleeding risk (HBR) patients are a heterogenous group of patients in whom the limit for the duration of DAPT in this predicted risk of bleeding events up to one year after having a coronary intervention is much higher than average. trial and we have seen that the triple Recently the Academic Research Consortium (ARC) has provided a clear cut-off. therapy regimen was longer than what is If the major bleeding risk is at least 4% at one year, this is the point at which that currently recommended,” he said. specific patient population should be labelled as HBR. The reason why we need to Panellist Robert Byrne (Mater Private identify them up front is because, of course, we may want to modulate treatment Hospital, Dublin, Ireland) said that there duration and intensity so that the bleeding risk will also be lower. had been a large number of trials of The rationale for setting up and conducting the MASTER DAPT study comes from antithrombotic therapy after the fact that until now we did not have any randomised evidence informing us of the PCI in recent years, many optimal duration of dual antiplatelet therapy (DAPT) specifically in patients at high of which have made bleeding risk. Actually we already had two one-month DAPT studies in the past, important contributions however these were not addressing specifically HBR patients in whom the price to pay for bleeding complications is much higher than average, or they were selecting to the field, but he patients at relatively low ischaemic risk. described MASTER The results of the MASTER DAPT study are very clear and clear cut. I think oneDAPT as a “standout” trial. month DAPT now is becoming the new standard of care in patients undergoing PCI “We have in whom a high bleeding risk feature is present. We have shown that there is no become more penalty to pay with respect to ischaemic events by reducing DAPT duration down to comfortable one month and in fact there is only benefit with respect to the bleeding risk. with using abbreviated

MASTER DAPT “game changing” for one-month dual antiplatelet therapy Continued from page 1

continued DAPT for at least five additional months (six months after PCI)—or, for those receiving clinically indicated oral anticoagulation—for at least two additional months (three months after PCI) and continued thereafter on single antiplatelet therapy. Three ranked primary endpoints were chosen for the study, namely: net adverse clinical events (NACE, the composite of all-cause death, myocardial infarction [MI], stroke, and major or clinically relevant non-major bleeding); major adverse cardiac or cerebral events (MACCE, the composite of all-cause death, MI and stroke); and major or clinically relevant non-major bleeding (MCB, the composite of BARC type 2, 3 and 5 bleeding). The two first primary endpoints were to be tested for noninferiority in the per-protocol population, and only if both were met could the study team proceed to test the third in the intention-to-treat population. A total of 4,579 patients in 30 countries were randomised to abbreviated or standard DAPT at a median of 34 days after PCI. The mean age was 76 years, 69.3% were men, 36.2% were receiving concomitant oral anticoagulation, and 48.3% underwent PCI for acute coronary syndrome. There was a mean of 2.1 HBR criteria per patient, Valgimigli told ESC 2021 delegates. Complete follow-up data at 335 days were available for 4,547 (99.3%) patients, and showed that a shortened DAPT regimen was non-inferior to standard DAPT in terms of NACE and MACCE, and superior in terms of MCB. Net adverse clinical events occurred in 165 (7.5%) patients in the abbreviated DAPT group and 172 (7.7%) patients in the standard DAPT group (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.78–1.20) in the per-protocol population, for a difference in risk of -0.23 percentage points (95% CI -1.80– 1.33; p<0.001 for non-inferiority). A total of 133 (6.1%) patients in the abbreviated DAPT group had a major adverse cardiac or cerebral event vs. 132 (5.9%) patients in the standard DAPT group (HR 1.02; 95% CI 0.80–1.30) in the per-protocol population, for a difference in risk of 0.11 percentage points (95% CI -1.29– 1.51; p=0.0014 for non-inferiority). Major or clinically relevant non-major bleeding was lower in the abbreviated versus standard DAPT group (148 [6.5%] vs. 211 [9.4%]; HR 0.68; 95% CI 0.55–0.84; p<0.001 for superiority) in the intention-to-treat population, for a difference in risk of -2.82 percentage points (95% CI -4.40–-1.24). During a discussion session following the presentation of the results at ESC 2021, chaired by Roxana Mehran (Icahn School of Medicine, New York, USA), who described

Robert Bryne

MASTER DAPT in numbers

7.7

6.1

9.4

7.5

5.9

6.5

I think this study tells us that an abbreviated DAPT in this setting seems to be safe.”

One month DAPT “is becoming the standard of care” in HBR patients

navitian ad

navitian ad AF.indd 1

14/10/21 18:47

November 2021 | Issue 63

Advertorial

THIS ADVERTORIAL IS SPONSORED BY iVASCULAR

Chronic total occlusion: The last frontier in the cath lab Treatment of a chronic total occlusion (CTO)—a complete obstruction of the coronary artery that has persisted for more than three months—is one of the major challenges in the cath lab. A CTO consists of a proximal and distal cap, separated by an occluded segment, and due to the complexity involved in CTO percutaneous coronary intervention (PCI), the approach is seen as being so challenging that some have described it as the last frontier in interventional cardiology. In this advertorial, sponsored by iVascular, Cardiovascular News considers the challenges of treating CTOs, and details the features of the Navitian microcatheter, which has been designed specifically for the treatment of complex lesions and CTOs.

he literature has suggested a varying in procedural success. In such complex prevalence of CTOs in coronary scenarios, microcatheters are essential tools and artery disease patients, with data high-quality performance is required.” pointing towards an incidence rate of Deployment of a microcatheter is one of the anywhere up to 30% of cases,1 with an essential techniques for successful CTO PCI, even greater prevalence in diabetic or and the device can be used for a number of heart failure patients.2 Furthermore, functions, including to increase the support of a 13% of cases exhibit more than one guidewire, to advance through tortuous vessels, CTO. Historically, the vast majority of Roberto Garbo to gain access to side branches, facilitating patients with a CTO are not treated using a parallel wiring, and plaque modificiation.3 percutaneous technique largely due to increased failure In their 2018 paper in Vessel Plus,4 Lazzaro Paraggio rates, technical complexity, cost and procedure length— and Francesco Burzotta (Institute of Cardiology, with medical management or coronary artery bypass Università Cattolica del Sacro Cuore, Rome, Italy) grafting (CABG) having been the favoured approaches document the important functions of microcatheters in the bulk of cases. in the successful deployment of PCI for CTOs. They However, this balance is gradually shifting, as percutaneous approaches continue to develop, and as new techniques, devices, and knowledge enter the field. Significant advances have been made in recent years that have led to increases in the success rate of PCI for CTO—advancing from close to 70% to more than 90%—which potentially open out the percutaneous option to a wider subset of patients. This picture is summed up by EuroCTO board member Roberto Garbo (Maria Pia Hospital, Turin, Italy) who tells Cardiovascular News: “CTOs are the most complex coronary interventions, in which operator expertise and dedicated devices play a fundamental role

CTOs are the most complex coronary interventions, in which operator expertise and dedicated devices play a fundamental role in procedural success.”

Chronic total occlusion (CTO) in focus A CTO is defined as the complete obstruction of a coronary artery, exhibiting TIMI 0 or TIMI 1 flow, with an occlusion duration of three months or more. The prevalence has been described as high as 30%, and 13% of cases exhibit more than one CTO.

Benefits of Navitian Optimal pushability due to a unique design with a proprietary braiding technology High penetration capacity with low profiles to cross the most challenging lesions Excellent visibility due to a c-cut radiopaque marker and radiopaque charged polymers Excellent trackability due to a proprietary hydrophilic coating Hydrax plus Antegrade and retrograde approach: 135 and 150cm

note that the key role of the microcatheter in CTO procedures can be summarised in three essential steps. Namely, these are: to safely place the CTO guidewire just in front of the lesion, to increase support and precision, and to allow guidewire exchange once the lesion has been crossed. “All these steps could be used even in complex PCI procedures when a CTO-dedicated guidewire is used to cross a heavily calcified and/or narrowed lesion as explained before or when a workhorse guidewire should be manipulated more precisely which facilitates torque in the tip response,” Paraggio and Burzotta write. Finally, they add that microcatheters could be very useful in reducing guidewire kinking and prolapse while trying to cross a lesion immediately after a large side branch.

Navitian: A new entrant in the microcatheter market

As approaches to CTO PCI have developed, so has microcatheter technology. The latest entrant to the evolving coronary microcatheter market is Navitian from iVascular. iVascular is a fast-growing company founded in 2010 in Barcelona, Spain with the aim of developing advanced medical devices and therapies for the treatment of cardiovascular system disorders. Thanks to know-how and investment in technology, iVascular has achieved the vertical integration of all the processes of their products. Navitian has been designed specifically with complex lesions and CTOs in mind. The Navitian coronary microcatheter has a single lumen from the proximal end to the distal end, and it is used for support, passage of a guidewire and for the delivery of contrast media or saline solution. Features that have been targeted for CTOs in particular include a unique proprietary braiding technology, intended to optimise the pushability of the device and featuring a high penetration capacity, with low profiles and external conical transition to cross the most challenging lesions. Furthermore, the tip of the Navitian device is completely adaptable thanks to its design, which features a c-cut radiopaque marker and radiopaque charged polymers, which are intended to aid the visibility of the device. The distal body of the catheter is coated with a

Issue 63 | November 2021

proprietatry hydrophilic coating, Hydrax plus, which is durable and helps with catheter navigation through tortuous arteries and is designed to facilitate excellent trackability. The useful length of the catheter can be 135cm or 150cm, for antegrade and retrograde approach respectively. The product is compatible with 0.014” guidewires can support a maximum pressure of 2070kPa (300psi) with the distal end open.

The performance of Navitian was really good both in antegrade and retrograde, the overall performance of the device in terms of profile, crossability and support was at high-quality level.” On the right and below, Garbo describes real case experience using the Navitian microcatheter in both antegrade and retrograde approaches. He describes the performance of the device as being at a “highquality level”. “The performance of Navitian was really good both in antegrade and retrograde, the overall performance of the device in terms of profile, crossability and support was at high-quality level,” Garbo says. “In the retrograde approach, after balloon dilatation over stent struts, the Navitian 150 easily crossed the septal giving us good feedback for the rest of the procedure.” References 1. Lombardi W, Banerjee S. Chronic Total Occlusions [Internet]. The Cardiology Advisor. 2021 [cited 27 September 2021]. Available from: https://www. thecardiologyadvisor.com/home/decision-support-in-medicine/cardiology/ chronic-total-occlusions/ 2. Konstantinidis N, Werner G, Deftereos S et al. Temporal Trends in Chronic Total Occlusion Interventions in Europe. Circulation: Cardiovascular Interventions. 2018;11(10). 3. Vemmou E, Nikolakopoulos I, Xenogiannis I et al. Recent advances in microcatheter technology for the treatment of chronic total occlusions. Expert Review of Medical Devices. 2019;16(4):267-273. 4. Paraggio L, Burzotta F, Aurigemma C et al. Usefulness of chronic total occlusion devices and techniques in other complex lesion subsets. Vessel Plus. 2019.

Advertorial

Navitian: Simplifying complex CTO cases

Two case studies involving the use of the Navitian microcatheter were recently presented at the EuroCTO congress (17–18 September; Florence, Italy) demonstrating the performance of the device in challenging CTO cases. Presented by Roberto Garbo, board member of EuroCTO club, details of the cases are presented below.

Case 1: Complex calcified CTO supported by a new microcatheter Patient profile: Patient is a 74-year-old male, whose risk factors include diabetes and hypertension. In December 2020 he presented with effort angina, and an exercise test was positive at a low threshold. Lesion: Mid left anterior descending (LAD) CTO (Figure 1) with diffuse disease was scheduled for treatment on 26 March 2021. Procedure: The LAD/diagonal branch presented with a severely calcified CTO, which was treated using the antegrade approach. The first soft polymeric wire (Fielder XTR) was advanced (Figure 2), with a subsequent step-up using Navitian (Gaia 2nd) and then a final successful crossing with Fielder XTR (wire de-escalation technique). Navitian showed very good behaviour in this case (Figure 3). Garbo’s conclusion: “In this complex antegrade CTO case, Navitian microcatheter had very good performance in crossing the calcified CTO lesion.”

Figure 2: Fielder XTR is advanced

Figure 1: Presence of the mid-LAD CTO is detected

Figure 3: The final case result

Case 2: Complex RCA CTO from antegrade to retrograde approach achieved with Navitian Patient profile: The patient is a 64-year-old male, with risk factors including a history of smoking, hypertension and dislipidaemia. In December 2020 he presented an anterior non-ST segment elevation myocardial infarction (NSTEMI). Lesion: Right coronary artery (RCA) CTO post-stent was detected. In February 2021 he presented with angina for minimal effort, so an RCA CTO PCI was scheduled for 26 March 2021. Procedure: An antegrade approach with intravascular ultrasound (IVUS) guidance for entry failed due to calcification at the proximal cap. A retrograde approach was needed, which was attempted using Navitian 150cm and Sion black (Asahi). This achieved good crossing in the septal branch over a stented LAD. The connection between the two wires (ante and retro) was obtained with the Reverse CART technique. Garbo’s conclusion: “The performance of Navitian was really good both in antegrade and retrograde, the overall performance of the device in terms of profile, crossability and support was at highquality level. In retrograde approach, after balloon dilatation over stent struts, the Navitian 150 easily crossed the septal giving us good feedback for the rest of the procedure.”

Figure 1: RCA CTO post-stent

Figure 2: Navitian 150 and Sion black are advanced into the lesion

Figure 3: Crossing the septal branch using Navitian

Figure 4: Reverse CART procedure is employed

Figure 5: External view of the Navitian microcatheter in use

Figure 6: The final case result

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Issue 63 | November 2021

Cardiovascular surgery CX AORTIC VIENNA

Multidisciplinary working vital for the next generation of aortic surgeons

of bringing everyone together to wrap around the aorta in a 360-degree fashion, with a multidisciplinary approach involving people with different skillsets.” He also stressed the importance of having a range of options open to patients—echoing earlier comments of the need for open and endovascular expertise. “You have to go into the patient’s room with the idea that you have multiple ideas available, and that you are going to be— especially in complex conditions like type A dissection or type B dissection—operating until the entire aorta is Continued from page 1 replaced if they live long enough,” he said. landscape for developing Following the two the next generation of aortic discussions, the audience was surgeons. asked to vote upon the desire Asked by the session’s to see more multidisciplinary moderator, German aortic teams. There was Vascular Society (DGG) total support in favour of the president Markus Steinbauer multidisciplinary philosophy. (Krankenhaus Barmherzige Later in the session Brüder, Regensburg, Maani Hakimi (Luzerner Germany), if he thought Kantonsspital, Luzern, training in both endovascular Switzerland) offered the and open techniques should be audience a view on treatment a requirement, Roselli said: “I of abdominal aortic aneurysm think you have to know how (AAA) from the perspective to do both. How much endo[vascular] of a training centre for vascular and Clockwise from top left: Roger Greenhalgh (London, UK), Markus and how much open anyone will do in endovascular surgery. Steinbauer (Regensburg, Germany), any one particular centre I think will Hakimi commented that aortic Stéphan Haulon (Paris, France), evolve. surgery is a highly specialised area of Joseph Bavaria (Philadelphia, USA) “You cannot come out of training medicine. He added that there should and Eric Roselli (Cleveland, USA) and promote yourself as an aorta be no dogma regarding treatment specialist only. You have to come out modalities and that future training of training and be able to do whatever the group that you should be a fusion of traditions. join needs you to do, and if it is a big aortic practice … Following his presentation, Hakimi was asked by cothere is going to be someone taking on a lot of those cases moderators Steinbauer and Stéphan Haulon, chairman and they are going to ask you to handle certain parts of it.” of the Aortic Centre at Hôpital Marie Lannelongue, Roselli then detailed the Cleveland Clinic philosophy for Université Paris Sud (Paris, France), about whether aortic surgery training, which involves crossover between trainees in his centre are offered the opportunity to the cardiac and vascular surgery teams. participate in courses to learn either open or endovascular Roselli said: “We have cardiac surgery-trained personnel approaches, subsidising their caseload within the centre. who are doing aortic fellowships that spend time with “I think that in addition to our case numbers such the vascular team and then we have the vascular surgery courses are very important—on the one hand to learn fellows spending time with the cardio-aortic team. It techniques and get in touch with other people, and the is something that has evolved, but it comes from the other hand to build up your own network because I think leadership.” that the academic exchange is also very important.” The session also saw a presentation from the Society of However, Hakimi highlighted that restrictions on travel Thoracic Surgeons (STS) past president Joseph Bavaria, brought about by the pandemic, mean that there are limited vice chief of the division of cardiovascular surgery at opportunities for trainees to visit high-performing centres the University of Pennsylvania (Philadelphia, USA). to learn from experts in the field, for example. Bavaria’s presentation zeroed-in on the importance of “Our young trainees would like to go abroad,” he said, having a multidisciplinary thoracic aortic team, including before adding that it is now more challenging for centres collaboration across the boundaries of both vascular and to permit such travel. cardiovascular surgery. Bavaria touched upon how the two specialisms can work together, and said that collaboration between vascular and cardiac surgery has been a longstanding theme within the Penn Medicine healthcare system, a collaboration that is ultimately ‘embedded within the culture of the organisation’. The goal of this type of collaboration is to move towards an “aortic centre”, which combines the expertise of both specialties, as well as other fields such as genetics, Bavaria said, describing this type of set-up as the multidisciplinary “holy grail”. During discussion following his presentation, Bavaria offered further comment on how this principle could work in practice. He said: “The way this is going to end up, certainly in the large centres, is that we are going to be going to the aortic centre concept. That concept is a way

We have cardiac surgery-trained personnel who are doing aortic fellowships that spend time with the vascular team and then we have the vascular surgery fellows spending time with the cardio-aortic team.”

New technologies will simplify and shorten aortic surgical procedures while reducing radiation In a session on “Reduction of radiation challenges” at CX Aortic Vienna 2021 (5–7 October, broadcast), experts highlighted new technologies with the potential to make aortic surgical procedures simpler and shorter, reducing radiation exposure to patients and care teams. A PRESENTATION BY TOM CARRELL (Cydar Medical, Barrington, UK) on intelligent maps for surgery and an edited case by Tilo Kölbel (University of Hamburg, Hamburg, Germany) were among the programme highlights to emphasise this message. Opening the session, Carrell outlined the applications of Cydar EV Maps, which recently received regulatory clearance in the European Union. This software includes integrated planning, navigation and review, offering a dynamic, three-dimensional (3D) map of the current state of a patient’s anatomy, he informed viewers. Carrell relayed that the technology offers more accurate device positioning and better overall outcomes with a reduced radiation dose, and that each new patient’s plan and surgery is informed by all previous similar cases. Audience polling following Carrell’s talk revealed that 82% of voters in the audience believe intelligent maps for surgery are a useful concept. In an edited case, Kölbel presented a branched endovascular repair for a type IV thoracoabdominal aortic aneurysm using FORS laser light guidance. He concluded that the procedure is feasible, with a low radiation dose and short fluoroscopy time, and that the 3D visualisation FORS offers enhances target vessel catheterisation. Kölbel summarised that FORS provides a “new, precise and low-radiation visualisation tool for complex endovascular aortic repair”. Moderator Joost van Herwaarden (UMC Utrecht, Utrecht, The Netherlands) was keen to know what the learning curve is for this novel technology, with Kölbel responding that FORS is “very intuitive”. Also in the “Reduction of radiation challenges” session, Michele Antonello (University of Padua, Padua, Italy) spoke about an off-the-shelf endograft with four inner branches to treat thoracic aortic aneurysm, which, used in conjunction with intravascular ultrasound (IVUS), has resulted in shorter procedural times.

November 2021 | Issue 63

Cardiovascular surgery EACTS 2021

Panel urges action over lack of representation of women in coronary revascularisation trials The underrepresentation of women in clinical coronary revascularisation trials may encourage treatment that favours outcomes in men, despite the presence of significant differences in the clinical characteristics between women and men. This is according to speakers at the European Society of Cardio-Thoracic Surgery annual meeting (EACTS 2021; 13–16 October; Barcelona, Spain and virtual) in a panel session which considered current data concerning women undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

“W

e as women are not small men, and there are a lot of pathobiological differences in how we present, what the anatomy looks like and how we respond to different therapeutic regimens or revacsularisation strategies,” said interventional cardiologist Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA) who opened the session with a presentation detailing the differences between women and men undergoing PCI. “I think it is really important to think about how myocardial ischaemia could be very different in its presentation, in its lesion and vessel characteristics, between men and women,” Mehran added. Detailing some potential differences that may be present between women and men, she listed smaller vessel size, higher risk of restenosis, lower plaque burden, diffuse disease, more slow flow mediated dilation, and higher fractional flow reserve (FFR). Mehran told EACTS attendees that women presenting to the cath lab are often a lot older than men, and are more likely to have more comorbidities such as diabetes, hypertension and hypolipidemia. Furthermore, Mehran said that women may be at a higher risk for bleeding complications than men, sharing data from her centre suggesting that high bleeding risk criteria are seen in around 56% of women, compared to 40% of men coming to the cath lab.

Guidelines not reflective of gender differences But, despite these characteristic differences, treatment guidelines do not reflect any difference in terms of recommendations for treatment between men and women, she added. “The strategies are not tailored according to sex, and I wonder if we should be having an entire section in our guidelines that relates to the sex

differences. I think the time has come for us to think about that,” Mehran commented. Women have made up around 20–25% of the patient population in major drug-eluting stent studies, Mehran said, later commenting that “there is no question we have to be better represented”. Mehran’s comments regarding differences in outcomes for women undergoing PCI painted a similar picture to those of cardiac surgeon Sigrid Sandner (Medical University of Vienna, Vienna, Austria), who discussed the differences in CABG outcomes between women and men. The proportion of women in the CABG population is between 20–30% , Sandner said, adding that women tend to present at a more advanced age than men, and they present more frequently in urgent or emergency status. They tend to come with a higher burden of comorbidities such as hypertension, diabetes, peripheral vascular disease and renal dysfunction, and are more likely to present with heart failure symptoms, despite actually having better left ventricular systolic function than men. “We know that women tend to have smaller calibre coronary artery targets and also smaller arterial grafts,” she added, as well as noting that women frequently face delayed diagnosis and delayed referral for surgery. She continued: “Women are, as Dr Mehran said, underrepresented in clinical trials of cardiovascular care, and particularly in clinical trials of cardiovascular surgery. The participation prevalence ratio also for women in CABG trials has consistently been between 0.5–0.6 and this reflects a very poor representation of women in CABG trials. It raises the question of the applicability of the trial results to both sexes, and it also raises the question of whether there are potentially differential

sex-based treatment effects.” She then turned to differences in outcomes between men and women undergoing CABG, commenting that there are likely to be a multitude of factors influencing these disparities. “We know that women have a higher burden of comorbidities, but even after we adjust for this and for presentation these differences in outcome remain, so there may be an underlying biological mechanism,” Sandner said. “What we also see is that there are disparities in operative technique, particularly as they relate to the use of arterial grafts, the use of cardiopulmonary bypass and the completeness of revascularisation.” Sandner cited the findings of a study, first presented at the 57th Annual Meeting of The Society of Thoracic Surgeons (STS 2021, 29–31 January, virtual) which analysed detailed demographic, clinical, and procedural data from more than 1.2 million patients, using data from the STS Adult Cardiac Surgery Database. The study closely examined the correlation between female sex and the likelihood of receiving one of the three different CABG surgical techniques that are recommended in official US and European guidelines—grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, complete revascularisation, and multiarterial grafting. Results showed that women were 14‒22% less likely than men to undergo CABG procedures with these revascularisation strategies. “Although the evidence is conflicting on the effect on outcomes there is observational evidence that has shown that women do derive the same survival benefit from multiple arterial grafting as men,” Sandner commented.

Echoing Mehran’s call for a greater capture of female-specific data and clinical trials, in her concluding remarks Sandner commented: “We definitely need strategies to improve the outcomes after CABG in women, [and] we need better evidence of the surgical use of techniques and this includes multiple arterial grafting and off-pump CABG, and we may need sex-specific risk assessment scores. We definitely need a greater involvement of women in clinical trials, or clinical trials that are specifically designed to study outcomes in an exclusively female CABG population.” Though speakers had criticised the lack of clinical trials focused specifically on treatment and outcomes specifically in women, later in the session Mario Gaudino (New York-Presbyterian and Weill Cornell Medicine, New York, USA) offered attendees a glimpse of what he described as the first cardiac trial dedicated to women.

20%

Female population in cardiac surgery trials 2000–2019

“It is really important to think about how myocardial ischaemia could be very different in its presentation, in its lesion and vessel characteristics, between men and women.”

ROMA Women

ROMA Women—a spin-off of the ROMA (Randomization of Single vs Multiple Arterial Grafts) study—is a global trial that will seek to randomise over 2,100 female patients undergoing primary isolated non-emergent CABG to either single or multiple arterial grafts. Gaudino’s presentation noted that most of the data on CABG are based upon studies taken from an overwhelmingly male population, with women representing around 20% of the patients enrolled in cardiac surgery trials between 2000 and 2019, commenting that this number is “too small to derive estimates of treatment effects”. His presentation also noted that the proportion of women studied had dropped significantly during this period. Study taking place exclusively among women is justified as there are surgical and biologic reasons to believe that the treatment effect may be different by sex and current recommendations may not be applicable to women. “The reality is that we have no solid information to inform our clinical decision-making for women undergoing coronary artery bypass surgery,” Gaudino commented. He later added: “Everything is telling us that there are important differences between sexes and you as a community should better try to investigate those differences, rather than to rely on studies that have been performed in an overwhelmingly male population.”

Issue 63 | November 2021

EACTS speakers consider controversies in left main revascularisation

inferiority is rejected for PCI, but also PCI is found to be worse than CABG.” Furthermore, Dayan noted that the five-year results of the NOBLE trial have shown that PCI was worse for the primary outcome. “PCI was associated with more MI and new revascularisation, and this was especially true in the low SYNTAX Score group, which was a matter of concern for the authors that they are given an equal level of recommendations either for PCI or Speakers at the European Society of Cardio-Thoracic Surgery annual meeting (EACTS CABG,” he said. 2021; 13–16 October; Barcelona, Spain and virtual) addressed the thorny topic of left Speaking after Dayan, interventional cardiologist main revascularisation, with discussion focusing on the controversy surrounding the Patrick Serruys (National University of Ireland, EXCEL trial and the reflection of the data in current clinical guidelines. Galway, Ireland) offered a perspective on left main randomised controlled EACTS ATTENDEES WERE SHOWN disease, Dayan argued in trials at five and 10 years. previously unpublished data from EXCEL during favour of new guidelines Serruys commented that a presentation by Nick Freemantle, director of the incorporating the latest data. regarding randomised Comprehensive Clinical Trials Unit at University ESC and EACTS trials of left main College London (London, UK), pointing towards initiated a review of the revascularisation there are a higher incidence of death, stroke or myocardial available evidence for the essentially “three debates infarction (MI) among patients randomised treatment of patients with in one”, including on to percutaneous coronary intervention (PCI), left main coronary artery the definition of pericontradicting the trial’s initial finding, that was stenosis in September 2020 procedural MI (PMI) and ultimately used to inform guidelines on left main after EACTS withdrew its impact on composite revascularisation. its support for the left endpoints; all-cause Freemantle discussed methodological challenges main recommendations mortality or major with composite primary outcome measures in of the societies’ joint adverse cardiovascular revascularisation trials in general, but highlighted guidelines on myocardial events (MACE) in PCI EXCEL as a “beautiful textbook example” of a revascularisation. This versus CABG in patients composite endpoint “going spectacularly wrong”. followed an investigation with left main coronary EXCEL was an international, open-label, into the EXCEL trial by the artery disease; and multicentre, randomised trial that compared PCI BBC which cast doubt upon appropriateness of PCI or using an everolimus-eluting stent (Xience, Abbott) the conclusions of the trial. CABG in the treatment Nick and coronary artery bypass grafting (CABG) for the Making the case in favour of patients with left main Freemantle composite endpoint of death, myocardial infarction of new guidelines covering and three-vessel disease. (MI), and stroke in patients with left main disease. The left main coronary artery “Definition of PMI trial concluded that there was no significant difference disease, Dayan made a has a major theoretical between the procedures, though the study’s findings number of points including impact on time to event have been subject to intense debate, in particular due to arguing that there is a lack curve, and a composite questions over the definition of MI used in the trial. of evidence supporting the endpoint at five years,” During his presentation at EACTS 2021, Freemantle use of the SYNTAX Score said Serruys. singled out the primary composite endpoint used in to support decision-making Serruys also EXCEL as being “not fit for purpose” and showed in left main revascularisation commented on the 10a comparison of the published trial results in which and that left main disease year PCI versus CABG PCI and CABG exhibited comparable rates of a should not be considered as a data from the perspective of primary composite endpoint of death, stroke and separate clinical or statistical average treatment effect EXCEL: Rate of PMI according to UDMI MI, based upon the study’s definition of procedural entity to multivessel disease. analysis. He argued that MI, contrasted with an analysis in which the same Furthermore he argued that from this standpoint, the outcomes were assessed based upon the third universal five-year data from the NOBEL and EXCEL decision to opt for either treatment strategy definition of MI (UDMI). In the data shown by trials both point to a higher rate of mortality for PCI. should be viewed on an individualised basis. Freemantle, PCI was shown to be non-inferior to “Based on the average treatment effect should you CABG for the composite primary endpoint, putting it SYNTAX Score evidence send all your patients to surgery? The answer is of at odds with the trial’s initial findings. On the SYNTAX Score, Dayan argued that both course: no. We are moving from average treatment EXCEL and NOBLE found no interaction between effect to individualised prognosis. We are creating EXCEL outcomes in focus the SYNTAX Score and the primary outcome. “How decision tools to improve personalised care. We are “I think this is a real problem,” Freemantle reproducible is the SYNTAX Score if we are to use moving the heart of medicine towards science,” he commented. “I would say that the EXCEL composite it as a way to make recommendations for left main commented. outcome is not fit for purpose. The UDMI is a wellrevascularisation?” Dayan posited. Presenting data detailing the average treatment effect established definition that is used in many trials. If the “This was evaluated by the EXCEL authors, and assessed in clinical trials, he noted: “You have a mixed authors’ version of the outcome measure of MI, which they found that in 50% of cases the SYNTAX Score bag of patients, some expected to derive benefit from is new for this trial, gives us a completely different reported at site was lower than reported at core lab, the alternative treatment, [some] expected to have result, then what should we believe?” which suggests that interventional cardiologists at equivocal response, and [some] expected to be harmed The EXCEL data shared by Freemantle were site underestimate the SYNTAX Score. the risk score by the treatment, and an estimation of the average brought into focus a second time during the meeting, according to core lab was high, which actually is a treatment effect. on the second occasion by the president of the Latin class III recommendation for revascularisation in the “We have to identify the heterogeneous response American Association of Cardiac and Endovadcular left main.” to the treatment. We have to segregate the patient Surgery (LACES) Victor Dayan (Universidad de la Turning to the EXCEL data presented by population based on treatment response, see who is República, Montevideo, Uruguay). In his presentation Freemantle, Dayan commented: “When you use the going to by harmed in the trial, who is going to benefit covering new evidence in left main coronary artery universal definition of MI, you see that not only is non- in the trial, and who is going to be equivocal.”

4% 2.2% PCI

CABG

November 2021 | Issue 63

12 Conference Coverage

Fractional flow reserve assessment at the time of diagnostic “has no advantage” The routine use of fractional flow reserve (FFR) alongside coronary angiography for the assessment of vessel-specific ischaemia at the diagnostic stage confers no benefit compared to performing angiography alone.

his was findings of the RIPCORD 2 trial, presented during a Hot Line session at the European Society of Cardiology’s 2021 congress (ESC 2021, 27–30 August, virtual). Results were presented by Nicholas Curzen (University Hospital Southampton NHS Foundation Trust, Southampton, UK) who described the routine use of FFR of all major epicardial vessels at the diagnostic angiogram stage as “neither necessary or beneficial”. RIPCORD2 is the first randomised trial to examine whether systematic FFR assessment of all relevant coronary arteries at the stage of the diagnostic angiogram would provide superior resource utilisation, quality of life and clinical outcomes when compared to angiographic assessment alone. In patients with chest pain, coronary angiography alone does not accurately determine whether or not there is reversible myocardial ischaemia. The RIPCORD concept proposes routine pressure wire assessment of all epicardial vessels amenable to revascularisation at the stage of diagnostic angiography, and thus before triage to medical therapy alone, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). Curzen told ESC 2021 attendees that randomised trials looking at FFR versus angiographic assessment in patients already committed to PCI—including DEFER,

FAME and FAME 2—had exhibited positive results for the use of FFR in this setting. Furthermore the original 200 patient proof-ofconcept RIPCORD study previously showed that when systematic FFR data were added to information from coronary angiography in patients with stable chest pain, the management plan changed in 26% of the population. “The data raise a logical and clinically plausible question, which represents a knowledge gap for us,” Curzen said. “If we were to use routine systematic assessment using FFR of all the epicardial vessels at the stage of the diagnostic angiogram, would that translate into the same degrees of benefit in terms of significantly lower resource utilisation and improved patient experience that was shown in the FAME study in patients who had already been allocated to PCI?” The open-label RIPCORD 2 trial enrolled 1,100 patients undergoing invasive coronary angiography for the investigation of angina or non-ST elevation myocardial infarction (STEMI). Patients had a mean age of 64 years and 75% were men. All participants had a stenosis of 30% or greater in at least one coronary artery suitable for either PCI or a bypass graft. Once enrolled, patients were randomised to systematic pressure wire–derived FFR after angiography

STOPDAPT-2 ACS does not support clopidogrel monotherapy one-month after acute coronary syndrome Findings of the STOPDAPT-2 ACS trial presented during a hot line session at the European Society of Cardiology’s 2021 congress (ESC 2021, 27–30 August, virtual), do not support the use of one month of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients undergoing stent implantation. THE STOPDAPT-2 TRIAL previously demonstrated that among patients undergoing percutaneous coronary intervention (PCI), one month of DAPT followed by clopidogrel monotherapy resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, compared with 12 months of DAPT with aspirin and clopidogrel. In that trial, 62% of patients had stable coronary artery disease and 38% had ACS.

To generate sufficient statistical power to compare the effect of the two treatments in ACS patients alone, the STOPDAPT-2 ACS trial enrolled 2,988 ACS patients and pooled the results with the 1,148 ACS patients in STOPDAPT-2—for a total of 4,136 patients. Both trials used the same protocol. Participants were randomly assigned in a 1:1 ratio to one-month DAPT followed by clopidogrel monotherapy or 12-month DAPT after

or angiography alone. FFR measurement was performed in all coronary arteries of sufficient calibre for PCI or CABG unless Thrombolysis in Myocardial Infarction (TIMI) grade flow was less than 3. The recommended management plan—which consisted of (a) optimal medical therapy, (b) optimal medical therapy alongside PCI, or (c) optimal medical therapy and CABG—was reported for all patients. Pre-specified secondary endpoints included clinical events—all-cause mortality, non-fatal stroke, non-fatal myocardial infarction (MI) and unplanned revascularisation. Detailing the results, Curzen noted that the median total hospital cost over the one-year period of the study was similar in the two groups: £4,510 (interquartile range [IQR] 2,721–7,415) for FFR plus angiography versus £4,136 (IQR 2,613–7,015) for angiography alone (p=0.137). Furthermore, there were no differences between groups in quality of life and angina status at one year. Regarding secondary endpoints, there were a similar number of deaths, strokes, MIs, and unplanned revascularisations in both groups. Nor were there significant differences between groups in the distribution of the selected management plan. However, in the FFR group, the strategy was chosen immediately after the cath lab procedure in more than 98% of patients whereas a further test was required in 14.7% of patients in the angiography alone group. In his concluding remarks, Curzen said: “Routine systematic FFR assessment at the time of diagnostic angiography is cost neutral compared to angiographic guidance and is not associated with significant differences in terms of quality of life or angina status at one year. Nor did this strategy significantly alter the clinical event rate, or the distribution of management in terms of medical therapy versus PCI versus CABG, but it was associated with a longer procedure with more radiation and contrast and more complications compared to angiography alone. “We have to conclude that a strategy of routine FFR assessment of all the vessels at the time of diagnostic angiography has no overall advantage and therefore no place in routine clinical practice.”

PCI with cobalt-chromium everolimuseluting stents. The primary outcome was a composite of cardiovascular and bleeding outcomes at one year: death from cardiovascular causes, myocardial infarction, definite stent thrombosis, ischaemic or haemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. The two major secondary endpoints were: a cardiovascular composite outcome (death from cardiovascular causes, myocardial infarction, definite stent thrombosis, ischaemic or haemorrhagic stroke); and TIMI major or minor bleeding. The primary outcome occurred in 65 patients (3.2% one-year cumulative incidence) assigned to one-month DAPT and 58 patients (2.83%) assigned to 12-month DAPT (hazard ratio [HR] 1.14; 95% confidence interval [CI] 0.80–1.62; p=0.06 for noninferiority). The major secondary cardiovascular outcome occurred in 56 (2.76%) patients in the one-month DAPT group and 38 (1.86%) patients in the 12-month DAPT group (HR 1.50; 95% CI 0.99–2.26). The major secondary bleeding outcome occurred in 11 (0.54%) patients allocated to one-month DAPT and 24 (1.17%)

Nick Curzen

patients allocated to 12-month DAPT (HR 0.46; 95% CI 0.23-0.94). Study author Hirotoshi Watanabe of Kyoto University, Kyoto, Japan, said: “One-month DAPT and subsequent clopidogrel monotherapy failed to achieve non-inferiority for net clinical benefit compared with standard 12-month DAPT after ACS. There was a trend toward an increase in cardiovascular events despite a reduction in major bleeding events.”

One-month DAPT and subsequent clopidogrel monotherapy failed to achieve noninferiority for net clinical benefit compared with standard 12-month DAPT after ACS.”

November 2021 | Issue 63

14 Interview

PROFILE

Mirvat Alasnag Mirvat Alasnag is the Gulf region’s first female interventional cardiologist. Currently the director of the Catheterization Laboratory at King Fahd Armed Forces Hospital (Jeddah, Saudi Arabia), she serves on a number of councils including the American College of Cardiology (ACC) Interventional Leadership, Society for Cardiovascular Angiography & Interventions (SCAI) Board of Trustees, and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Women’s Steering Committee. She talks to Cardiovascular News about her career in medicine and the challenges for women in the interventional cardiology field.

Early on in my life my father struggled with heart disease. We are a very close-knit family and lived through his surgeries and hospitalisations. I quickly realised how fascinating medicine and cardiology can be by offering a lifeline to someone. When I started my cardiology fellowship, my intent was to focus on imaging. As soon as I started my cath lab rotation I found myself seduced by the instant gratification of opening closed vessels. I could not imagine myself specialising in anything else. But, I understood the intimate relationship between imaging and interventions.

Who have been your career mentors?

What are the key unanswered questions around the field that future research should prioritise?

Artificial intelligence (AI) has certainly shown promise in smaller scale studies. I am very interested in evaluating its performance in the evaluation of the functional significance of stenoses—fractional flow reserve (FFR), instant flow reserve (iFR) nonhyperemic indices. I am also interested to see if it has a role in the as the assessment of plaque morphology obtained through intracoronary imaging—intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The CLARITY trial examined the role of machine learning and AI in the evaluation of plaque determined by cardiac computed tomography (CCT) and compared it to results reported by expert readers.

I was fortunate to have many mentors who have encouraged and supported me. The chief resident in my early training years was an incredible anchor and support as I was ploughing through residency and personal loss. She was also an important source of inspiration. Later in my career I had many cardiologists both on social media, and during my career, guide and encourage me. Each had his or her own impact. To name a few: Khaled Al-Shaibi, Waqar Ahmed, Mamas Mamas, Roxana Mehran, Ted Shreiber, Marie Claude Morice.

What do you foresee is the next practice-changing step forward in cardiovascular imaging?

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

What has been the most important paper published in the past year?

Imaging has taken huge leaps in the last decade facilitating novel procedures particularly in the structural arena. As imaging technologies and acquisition protocols became more streamlined the procedures have expanded to a higher risk population and included more complex interventions. Imaging is an important tool to predict complications and strategise the safest approach.

What has been the biggest disappointment? Something you hoped would change practice but did not?

Sadly, we still do not seek quality of life in the therapies we offer. Much of our discussions revolve around hard endpoints like death, myocardial infarction (MI) and stroke. However, quality of life matters to patients and this becomes increasingly important with advanced age—a population often excluded from research. The definition of quality of life is subjective and this makes it difficult to capture. The only way to understand it is to have patients be a part of the conversation early on.

What are your current research interests?

I am very interested in generating local research. We need to understand the landscape of regional practices and identify areas for improvement. We need to learn about the population we treat and their response to therapies, and create predictive models for our region. In this respect, Khalid AlHabib at King Saud University (Riyadh, Saudi Arabia) has been a pioneer.

I believe artificial intelligence is the next big thing in this space. It will permit population studies and adoption of algorithms that are time efficient, precise, and reproducible. Although this is still a developing technology, I believe once the evidence is generated, it will soar. Its utility will largely aid in prevention programmes, but I could see it streamline cost efficiency.

There have been several, but I would say the ISCHEMIA trial for chronic coronary syndromes and the COAPT trial for percutaneous repair of the mitral

It becomes a daily struggle for women to assert themselves in this field in particular.” valve have been practice changing or reaffirming. The selection of patients is central to better outcomes.

What are the current challenges facing women seeking to enter the interventional cardiology field, and how would these be best overcome?

The difficulties facing women are multi-layered. There are the expectations set by society to have an older man perform delicate procedures. Historically, men have directed centres and been the principal investigators of landmark trials. Most women were hidden in the shadows. This has posed a challenge for women in the field of interventional cardiology to assume leadership positions, whether as researchers, administrators, mentors or operators. It is not uncommon for staff to listen to the men in the cath lab. It becomes a daily struggle for women to assert themselves in this field in particular.

Andy Watt/NB Illustration

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

Have you found the switch to digital learning during the pandemic a positive or a negative development? Digital learning permitted us to travel the world several times in the same day. Suddenly, the world felt connected like a small village and the science became more accessible to everyone. However, we lost the human interaction. Digital meetings also snatched opportunities for mentees and trainees to interact and engage with their mentors and experts. Traditionally, in-person meetings allowed side meetings for trainees, investigator meetings, and hands-on training. A lot of those smaller round table meetings were lost.

What value does social media add to practice and how important has it been in your career?

Social media has been a force that propelled my career forward. I met virtual mentors and collaborators. I found

Issue 63 | November 2021

Interview 15

like-minded colleagues to discuss techniques, cases and research projects. Today, I enlist collaborators and faculty for scientific webinars and meetings from social media. I am able to understand their train of thought, areas of expertise, and reach out to them unofficially to gauge their availability and interests. There are of course drawbacks to social media. The most important is that these are public platforms that are not regulated. Patient privacy and operator critique can take unpleasant turns.

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

It was an older woman who came with critical left main disease and pulmonary oedema. I had to go, as a young petite woman with little experience, and explain to her family (tall men, many of whom were older than me) that I would need to put in a mechanical circulatory device and stent her left main artery. I will never forget how difficult it was to impress them and gain their trust. But, it was that case that taught me to be self-confident. It paid off and I learned how to assert myself when discussing complicated management plans. She did well and was my patient for many years later.

What can interventional cardiology do to better attract young physicians into the field?

Training in interventional cardiology generally focuses on two key areas: skill and judgement development. As the cath lab volume drops globally, integrating simulation and research in the core training can overcome the issue of volume. More importantly, it is important to instil in trainees the principle of lifelong learning. This is integral as the field is always evolving with new data, and new and more refined devices and techniques. As for the judgement, I find this is an area that requires meticulous effort. Trainees need to attend mortality and morbidity rounds, heart team meetings and assume leadership roles in order to exercise judgment. Judgment is critical—not only in decision making but in the basic communication with patients, families and colleagues. At some point during their training, candidates should be given the opportunity to be the primary communicator with the families and to lead care team discussions. This is how empathy and wisdom grow, both integral to a field that deals with life and death situations on a daily basis.

Outside of medicine, what are your hobbies and interests?

Before the pandemic, I enjoyed travel and exploring new cultures, cuisines, and visiting historic sites. I now enjoy some quiet time with a good book or some uninterrupted family time with the kids. They are a wonderful source of energy and fun.

Fact file Memberships

American College of Cardiology (ACC) Asia Pacific Society of Interventional Cardiology (APSIC) European Society of Cardiology (ESC) European Association of Percutaneous Cardiovascular Interventions (EAPCI) Society for Cardiovascular Angiography & Interventions (SCAI) Society of Cardiovascular Computed Tomography (SCCT)

Appointments

Director, Cardiac Catheterization Laboratory, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia ACC Interventional Leadership Council ACC Women In Cardiology (WIC) International Working Group Chair SCAI Board of Trustees Circulation: Cardiovascular Interventions Editorial Board PCROnline Editorial Board

Education

Wayne State University Loma Linda University King AbdulAziz University Dubai Medical College

November 2021 | Issue 63

16 COVID-19

Waiting list mortality for coronary procedures exacerbated during pandemic Patients awaiting coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) procedures during the COVID-19 pandemic were at higher risk of dying while waiting for their procedure than prior to the pandemic. This is according to an analysis of healthcare data from Ontario, Canada, which found a significant decline in referrals and procedures performed for common cardiac interventions after the onset of the pandemic.

he study underscores the importance of timely recognition of symptoms and treatment in patients at high risk for cardiovascular disease, researchers observed in the Canadian Journal of Cardiology. “In the first wave of the COVID-19 pandemic, we kept hearing stories from patients and other doctors that

there were delays in care for patients with heart disease,” waiting for coronary bypass surgery or stenting were at explained lead investigator Harindra C Wijeysundera higher risk of dying while waiting for their procedure (Institute of Health Policy, Management and Evaluation, compared to before the pandemic, the researchers University of Toronto, Toronto, Canada). “We decided reported. Surprisingly, mortality rates increased to look into these claims using the Ontario database that even though wait times did not during the pandemic, keeps track of wait lists and wait times for individuals suggesting patients may have delayed in presenting to with heart disease who require a procedure or surgery.” their doctors with symptoms. The researchers were linked multiple population“We found that the increase in wait list mortality was based administrative data sources and clinical consistent across patients with stable coronary registries housed at the Institute for Clinical artery disease, acute coronary syndrome, or Evaluative Sciences (ICES), Canada’s largest emergency referral,” said Wijeysundera. health services research institute. “Coupled with reduced referrals, this raises The study looked at patients over the age of concerns of a care deficit due to delays in 18 who were referred for PCI; isolated CABG; diagnosis and wait list referral.” valve surgery (aortic, mitral, or tricuspid); or The researchers suggest a number of transcatheter aortic valve implantation (TAVI) potential explanations for the decline in from 1 January 2014 to 30 September 2020. referrals during the pandemic, from patient Harindra C For the purposes of the study, the onset of the Wijeysundera factors such as fear of contracting COVID-19 COVID-19 pandemic was defined as 15 March in the hospital or concerns about missing work, 2020, when Ontario health authorities issued a directive to system factors including delays in testing and hospital that cancelled elective surgical procedures. Outcomes bed and staffing pressures. were defined as death while awaiting procedure and This research suggests that any reduction in cardiac hospitalisation while waiting for procedure. procedural capacity to accommodate critically ill A total of 584,341 patients were identified, of COVID-19 patients must be balanced against the real whom 37,718 were referred during the pandemic. As risk for wait list mortality observed in this study. anticipated by the researchers, a decline in referrals was “We believe this is highly relevant to the recovery observed at the outset of the pandemic, although those phase of the pandemic,” commented Wijeysundera. numbers steadily increased throughout the pandemic “Efforts must target not only increasing capacity to treat period. patients on the wait lists, but also efforts must be made Similarly, researchers observed an initial decline to identify upstream barriers that have prevented patients in the number of procedures performed. Individuals from getting on the wait list.”

Cardiothoracic surgery trainees report disruption, mental health impact of pandemic Education of trainees in cardiothoracic surgery has been significantly disrupted by the COVID-19 pandemic data from a survey of surgeons carried out in the UK have suggested. However, disruption to cardiothoracic surgery training was more acute in the first wave of the pandemic compared to the second wave, researchers found. THE FINDINGS OF THE SURVEY were presented by junior doctor Kornelija Maceviciute (St Bartholomew’s Hospital, London, UK) at the European Society of Cardio-Thoracic Surgery annual meeting (EACTS 2021; 13–16 October; Barcelona, Spain and virtual) during which she documented some of the challenges faced by cardiothoracic trainees during the pandemic. Notably, Maceviciute told EACTS attendees that disruption caused by the pandemic had reduced junior doctors' access to time in the operating theatre, time in outpatient clinics, as well as having increased workload and negatively impacting mental health. Training time is essential for junior cardiothoracic surgeons for both career progression and the quality of healthcare delivery, Maceviciute said in her presentation, noting that the COVID-19 pandemic has had a major impact on junior surgeon training. From February to March 2021, Maceviciute and colleagues from St Bartholomew’s Hospital instigated a 23-question survey to gather data on the impact among cardiothoracic surgery trainees.

Kornelija Maceviciute

Respondents were asked for their experience regarding the COVID-19 approximately impact on multiple 75%. Operating aspects of their time reductions training such as were reported redeployment, time in to be less face-to-face the operating theatre, time in pronounced during teaching during outpatient clinics, workload, the second wave, with teaching cancellation, wellbeing the first wave, 38% of respondents reporting compared to time reduction of 50‒75%. and career progression the second Additionally, only 21.6% of Respondents included 58 wave doctors across 27 hospitals, respondents reported the presence of whom 94% felt COVID-19 of face-to-face teaching during the had affected their surgical experiences. first wave, compared to 47.3% during the Within the first pandemic wave, 53% second wave. Virtual teaching did not of junior surgeons reported that they change significantly during both waves, were redeployed to other departments with 72.2% of respondents reporting compared to only 10% of senior virtual classes and 71.4% during the surgeons. In the second wave, a similar first and second waves, respectively. pattern occurred, with 25% and 37% Access to teaching sessions reportedly of junior surgeons, fully and partially increased from the first to the second redeployed respectively. Additionally, wave, increasing from 38.5% to 78.6% of only 30% of senior surgeons were respondents accessing teaching. Despite redeployed with 62% not redeployed. this, approximately 90% of respondents Time in the operating theatre reduced reported disturbance to teaching events during both pandemic waves, with 33% such as exams. of respondents reporting reduced time by In contrast to teaching access, 33

21.6%

vs.

47.3%

(54.1%) of respondents reported a reduction to their annual leave during the first wave, with 24 (39.3%) during the second, as a result of the pandemic. The pandemic was reported to negatively impact mental health of with 51% of respondents reported burnout, lowmood or reduced motivation, with 60.3% reporting concerns over career progression. Overall, it is evident the COVID-19 pandemic had numerous impacts on the training of junior cardothoracic surgeons, with improvements seen in the second wave across different areas, Maceviciute reported. Further research is required to fully understand the extent to which better preparation is needed for training, she said. Suggestions for future training include increased flexibility in learning with more digital and virtual learning. There remain queries regarding a standardised approach across teaching hospitals to ensure all junior cardiothoracic surgeons receive sufficient training before qualifying, she concluded.

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November 2021 | Issue 63

18 Hypertension

RENAL DENERVATION

Position paper highlights renal denervation as a third option for hypertension management European Society of Hypertension (ESH) presented an updated position paper on renal denervation during the eighth pre-ESH congress satellite symposium (10–11 September; Athens, Greece). The paper was recently published in the September issue of the Journal of Hypertension.

enal denervation is a minimally invasive procedure intended to regulate overactivity of nerves that lead to and from the kidney, which play an important role in controlling blood pressure. In recent sham-controlled randomised trials and registries, clinically favourable effects of renal denervation have been consistently demonstrated across a wide spectrum of patients with uncontrolled hypertension, in the absence and presence of prescribed anti-hypertensive medications. The position paper confirms that renal denervation is considered a safe endovascular procedure without significant short-term or long-term adverse effects based on data available up to three years. “In light of the recent publication of several secondgeneration sham-controlled clinical trials, we thought it was important to provide an updated position paper on

renal denervation and its role in treating uncontrolled hypertension,” said Roland Schmieder, professor of Internal Medicine, Nephrology and Hypertension at the University Hospital Erlangen, Erlangen, Germany and chairman of the ESH working group on interventional treatment of hypertension. “Renal denervation represents an evidence-based option to treat hypertension, in addition to lifestyle changes and blood pressure lowering drugs. Renal denervation expands therapeutic options to address the first objective of hypertension treatment, to effectively reduce elevated blood pressure and achieve blood pressure targets,” said Konstantinos Tsioufis, professor of Cardiology at the University of Athens, Athens, Greece, immediate past president of ESH. “Heightened cardiovascular risk such as evident organ damage or established disease like coronary artery disease or heart

Renal denervation: The most advanced and efficacious interventional approach to treat hypertension Following the release of the European Society of Hypertension’s (ESH’s) updated position paper on renal denervation, Konstantinos Tsioufis, professor of Cardiology at the University of Athens, Athens, Greece and immediate past president of ESH, discusses the use of renal denervation in the treatment of hypertension, considers the latest evidence in favour of the approach, and outlines the questions still to be answered.

What are the advantages of using renal denervation to treat hypertension?

In all recent sham-controlled trials there were clinically favourable effects of renal denervation for treatment of uncontrolled hypertension. The great advantage is that the intervention has shown meaningful office and ambulatory blood pressure decrease across multiple phenotypes of patients with mild to moderate, as well as more severe, hypertension in the presence and absence of medication. This constant reduction in blood pressure over 24 hours—the “always on” impact—of renal denervation differentiates the intervention-induced changes in blood pressure from those by drugs due to the diverse pharmokinetic profiles and dosing regiments along with patient non-adherence.

How does renal denervation compare to other treatment approaches that are available? According to latest second generation randomised controlled trials and the Global SYMPLICITY Registry (GSR), average blood pressure reduction

induced by renal denervation compared to sham ablation is 8-10mmHg in office systolic blood pressure reading and 5-7mmHg in ambulatory systolic blood pressure readings. Other interventional approaches to modulate sympathetic tone by baroreceptor activation is still under investigation.

What do trial data tell us about this approach and its outcomes in the longterm? The antihypertensive effect of renal denervation is durable and, taking into consideration the average drop of 10mmHg in office blood pressure, the effect can be translated to significant improved cardiovascular prognosis (approximately 20% reduction in cardiovascular events and 26% in stroke). It is also an early and late-term safe procedure with minimal complications based on data from registries and recent sham randomised controlled trials. The observed blood pressure reduction is maintained long term with data available up to three years after the procedure. Konstantinos Tsioufis

failure might be pointing towards treatment priority with renal denervation in hypertension. Additionally, patients who are unable or unwilling to take medication might be another renal denervation group, especially in the first stages of the hypertensive disease.” Arterial hypertension constitutes the most prevalent and important risk factor for cardiovascular morbidity and mortality globally despite the availability of pharmacological treatments. In addition, approximately half of individuals with hypertension do not meet guideline-directed blood pressure goals. “Many patients with uncontrolled hypertension struggle to adhere to lifelong drug therapy for a variety of reasons and may look to other options that complement traditional treatments,” said Reinhold Kreutz, professor of Clinical Pharmacology and Hypertension at the Charité Universitaetsmedizin, Berlin, Germany, and president of ESH. “We believe this advance could help clinicians work with patients to better manage their high blood pressure.”

Are there any unanswered questions to be investigated?

Currently there is an urgent need to define predictors of blood pressure response post renal denervation and there are efforts focusing on diverse parameters both clinical and laboratory. There are data showing that in untreated patients with higher baseline heart rate and plasma renin aldosterone levels renal denervation are associated with better blood pressure reduction. Moreover, the average and standard deviation of night-time ambulatory blood pressure has been identified as a potential robust predictor, which requires further research. Another question is the long-term durability of blood pressure lowering and safety beyond three years as well as safety and efficacy in patients with comorbidities such as renal failure. Further studies are also needed exploring the renal denervation-induced clinical impact in patients with heart failure (HF), atrial fibrillation (AF) and increased overall cardiovascular risk. The cost-effectiveness of the procedure for healthcare systems is an additional point that will also need to be addressed.

Are there any drawbacks to this approach?

Given the established efficacy and safety the only drawback for renal denervation is physicians’ inertia to consider and refer hypertensives for this approach. Additionally, there is a lack of information on the clinical impact of neuromodulation from the standpoint of hypertensive patients that limits the implication of the technology to everyday practice.

How should physicians evaluate which patients are suitable for renal denervation treatment for hypertension?

According to the latest evidence, the criteria for considering hypertensive patients for renal denervation is persistent uncontrolled hypertension despite guideline-based therapy including ameliorated lifestyle measures and efforts to increase adherence. Heightened cardiovascular risk or established disease might be pointing towards treatment priority with renal denervation in hypertension. Additionally, patients who are unable or unwilling to take medication might be another renal denervation group, especially in the first stages of the hypertensive disease. The shared decision-making process is important for renal denervation and according to patients’ preferences this interventional approach could be selected for diverse phenotypes of hypertension.

Do you see renal denervation as having a significant role to play in the future treatment of hypertension?

Renal denervation constitutes today the most advanced and efficacious devicebased interventional approach to treat hypertension, expanding therapeutic options as an alternative and not as a competitive strategy. This would be of important clinical value since approximately half of individuals with hypertension do not meet guidelinedirected blood pressure goals. Based on the available evidence, renal denervation is definitely included in the individualised treatment strategy of the future for better hypertension control and reduction of overall cardiovascular disease burden.

October 2021 Issue 01 www.renalinterventions.net

In this issue:

Twelve-month Wrapsody results at CIRSE 2021 page 4

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:

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

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

Specialised source of news and education in the field of renal disease management Breaking news, in-depth analysis, and leading opinion from key industry figures Steered by globally-renowned physicians to monitor the latest innovations and controversies alike in the kidney care field Industry updates and real-time event coverage via social media, videos and more on print and digital platforms Visit www.renalinterventions.net and click ‘Subscriptions’ for complimentary print subscription* and e-newsletter subscription** *Available for US and EU readers only **Available worldwide

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Issue 63 | November 2021

Structural Heart Interventions Edoxaban non-inferior to vitamin k antagonists for adverse clinical events after TAVI, but bleeding rates higher

Edoxaban (Daiichi-Sankyo) was non-inferior to vitamin k antagonists (VKAs) for adverse clinical events in patients with atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI), results of the ENVISAGE-TAVI AF study, presented at the European Society of Cardiology’s 2021 congress (ESC 2021, 27–30 August, virtual), have shown.

owever, the results presented by the trial’s principal investigator George Dangas (Icahn School of Medicine at Mount Sinai, New York, USA) and published simultaneously in the New England Journal of Medicine, showed that the incidences of major bleeding were higher among patients receiving edoxaban compared with VKAs. ENVISAGE-TAVI AF compared the safety and efficacy of the direct oral anticoagulant edoxaban with VKAs (warfarin and its analogues) in AF patients with an indication for oral anticoagulation after successful TAVI. The trial enrolled 1,426 patients with AF from 173 medical centres in 14 countries on three continents. Participants were randomly assigned to either the locally available VKA (with or without antiplatelet therapy) or 60mg daily oral edoxaban (with or without antiplatelet therapy) from between 12 hours and five days after successful completion of TAVI. “Atrial fibrillation after transcatheter aortic valve replacement is common, especially among older patients, but there has been little research on the optimal treatment strategies, and this has resulted in heterogeneous use of anticoagulants in clinical practice,” said Dangas. “TAVI patients are typically very elderly and possess numerous comorbidities; therefore they are at high risk for all sorts of adverse events, both ischaemic and bleeding. It is important to further understand what treatment is most effective to prevent devastating complications.” The study’s primary efficacy endpoint was a composite of adverse clinical events, including all-cause death, myocardial infarction (MI) ischaemic stroke, systemic thromboembolism, valve thrombosis, and major bleeding, according to the International Society on Thrombosis and Haemostasis (ISTH) definition. The primary safety endpoint was the incidence of major bleeding according to the ISTH definition. Study participants were on average aged 82 years, Dangas detailed in his presentation at ESC 2021, and 47.5% of the study cohort were women. Among these patients, comorbidities were relatively common, with 83– 87% having congestive heart failure, 39–42% coronary artery disease, and 17% previous stroke or transient ischaemic event (TIE). Relaying the study’s results, Dangas reported that after an average follow-up of 18 months, edoxaban was found to be non-inferior to VKAs for the primary composite endpoint of adverse clinical events, with a rate of 17.5% George Dangas per year in the trial’s

edoxaban arm and 16.5% per year in the VKA group (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.85–1.81; p=0.01 for non-inferiority). Importantly, in terms of safety, Dangas revealed that the edoxaban group had a higher risk of major bleeding compared to the VKA group, which was mainly attributed to the occurrence of gastrointestinal bleeding. The rate of major bleeding was 9.7% per year in the edoxaban group, compared to 7% per year in the VKA group (HR 1.40; 95% CI 1.03–1.91). Secondary analyses showed that patients in the edoxaban group who required a downward close adjustment and those not prescribed oral antiplatelet therapy had a similar rate of major bleeding compared to the VKA group. Commenting on the results, Dangas said: “Overall, this trial showed the non-inferiority of edoxaban compared to warfarin (or similar analogues) with respect to the

We need to be attentive to the higher bleeding risks with edoxaban.” composite efficacy endpoint of adverse clinical events. On the other hand, we need to be attentive to the higher bleeding risks with edoxaban. Based on secondary analyses, it seems that lowering the edoxaban dosage when indicated and avoiding patients on mandatory antiplatelet therapy is reasonable safety advice from a clinical point of view. We will be conducting a detailed analysis on specific types of bleeding in the near future.” He adds: “ENVISAGE-TAVI AF suggests that treatment with edoxaban can be valuable in the management of this high-risk population of patients with atrial fibrillation after TAVI.” A further finding detailed by Dangas is that patients who received a lower dose of edoxaban (30mg instead of 60mg) due to poor kidney function or low body weight appeared to have similar rates of adverse thromboembolic and bleeding events to those on warfarin. He added that the next step would be to establish in randomised trials the optimal anticoagulant dose according to different bleeding-ischaemic risk profiles. “It seems that lowering the edoxaban dosage when indicated and avoiding patients with mandatory antiplatelet therapy because of their elevated bleeding risk is reasonable safety advice from the clinical point of view,” Dangas said.

Updated valvular heart disease guidelines highlight heart team decision-making

An updated version of the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) Guidelines for the management of valvular heart disease have been published in the European Heart Journal. THE GUIDELINES WERE LAST REFRESHED in 2017, and the new updates reflect latest evidence with the aim of assisting interventional cardiologists and cardiothoracic surgeons in proposing the best management strategies for an individual patient with aortic, mitral or tricuspid valve disease. According to the latest version of the guidance, current evidence reinforces the critical role of the heart team, which should integrate “clinical, anatomical, and procedural characteristics beyond conventional scores, and informed patients’ treatment choice”. “Valvular heart disease is too often undetected, and the guidelines stress the importance of clinical examination as the first step in diagnosis,” said Alec Vahanian of the University of Paris (Paris, France) who chaired the ESC taskforce that was jointly responsible for producing the guidelines. “Noninvasive evaluation using echocardiography first, and other cardiac imaging techniques when needed, is essential to assess severity and catheterisation should only be used when imaging is inconclusive.” According to the new guidelines, interventions (percutaneous or surgery) are indicated in symptomatic patients if there is an expected benefit. Decision-making in asymptomatic patients must weigh the risk of intervention against the expected natural history of valvular heart disease. If rapid symptom progression is predicted, intervention may be justified if the procedural risk is low. In elderly patients, decisions should consider the estimated impact on life expectancy and quality of life. “Patients’ expectations and values are an important part of the decision-making process,” said EACTS task force chairperson Friedhelm Beyersdorf of the University of Freiburg (Freiburg, Germany). “Patients and their families should be thoroughly informed and assisted in their choices. Symptom relief on its own may justify intervention if it is a priority for the patient. However, treatment is considered futile when it is not expected to prolong life or relieve symptoms.” Regarding surgery, increased experience and procedural safety have led to expanded indications toward earlier surgery in asymptomatic patients with aortic stenosis, aortic regurgitation or mitral regurgitation. The guidelines emphasise the need for comprehensive evaluation and earlier surgery in tricuspid regurgitation to avoid heart damage. Regarding percutaneous techniques, good results in high-risk or inoperable patients with aortic stenosis and mitral regurgitation have led to increased indications, provided futility is avoided. The guidelines state that the encouraging preliminary experience with transcatheter tricuspid valve interventions suggests a potential role for inoperable patients, but this needs to be confirmed by further evaluation.

22 Structural Heart Interventions

November 2021 | Issue 63

Registry data show comparable outcomes for bicuspid and tricuspid TAVI in low risk patients

<3%) were included in the analysis. Among the propensity matched patients (mean age, 69 years; 69.8% men; mean [SD] STS-predicted risk of mortality, 1.7% [0.6%] for bicuspid and 1.7% [0.7%] for tricuspid), Makkar and colleagues found that there was no significant difference between the bicuspid and tricuspid groups’ rates of death at 30 days (0.9% vs 0.8%; hazard Patients at low surgical risk who had undergone transcatheter aortic ratio [HR], 1.18 [95% CI, 0.68‒2.03]; valve implantation (TAVI) for bicuspid aortic stenosis had no significant p=0.55) and at one year (4.6% vs 6.6%; difference in mortality or stroke at 30 days or one year compared to HR, 0.75 [95% CI, 0.55‒1.02]; p=0.06) those who had undergone TAVI for tricuspid aortic stenosis. or stroke at 30 days (1.4% vs 1.2%; HR, 1.14 [95% CI, 0.73‒1.78]; p=0.55) and at his was the finding of a registrystatus (New York Heart Association one year (2% vs 2.1%; HR 1.03 [95% CI, based cohort study comparing [NYHA] heart failure class), and health 0.69‒1.53]; p=0.89). outcomes of TAVI using the status (the Kansas City Cardiomyopathy The study team found that there Sapien 3 and Sapien 3 Ultra (Edwards Questionnaire overall summary score were no significant differences between Lifesciences) balloon-expandable valve, [KCCQ-OS]; score range, 0-100 [higher the bicuspid and tricuspid groups published online in the Journal of the scores indicate less symptom burden and in procedural complications, valve American Medical Association (JAMA), better quality of life]). haemodynamics (aortic valve gradient: aimed at addressing the “limited” data on A total of 3,168 propensity-matched 13.2mmHg vs. 13.5mmHg; absolute outcomes for bicuspid aortic stenosis. pairs of patients, at low surgical risk, risk difference [RD], 0.3mmHg [95% “In carefully selected, low-risk undergoing TAVI for bicuspid CI, −0.9 to 0.3 mm Hg]), patients, this minimally invasive TAVI versus tricuspid aortic and moderate or severe procedure may be beneficial,” said Raj stenosis who underwent paravalvular leak (3.4% vs Makkar, vice president of Cardiovascular TAVI at 684 US centres 2.1%; absolute RD, 1.3% Innovation and Intervention at Cedarswere included in the study. [95% CI, −0.6% to 3.2%]). Sinai (Los Angeles, USA), the study’s Participants were enrolled Discussing the findings lead author. “We are in the midst of in the Society of Thoracic in JAMA, Makkar et al a transcatheter heart valve revolution Surgeons (STS)/American note that this is the first and expect this particular procedure to College of Cardiology (ACC) report from the STS/ACC Raj Makkar become more and more commonplace Transcatheter Valve Therapies registry on outcomes in low with each passing year.” (TVT) registry from June 2015 to risk TAVI patients with bicuspid aortic The study’s primary outcomes were the October 2020. Among 159,661 patients stenosis. “There are currently no ongoing rates of death and stroke at 30 days and 1 (7,058 bicuspid, 152,603 tricuspid), randomised trials of TAVI versus surgery year. The secondary outcomes included 37,660 patients (3,243 bicuspid and for the treatment of bicuspid aortic procedural and in-hospital outcomes, 34,417 tricuspid) who were at low stenosis,” they note. “Given the paucity echocardiographic outcomes, functional surgical risk (defined as STS risk score of data, patients with bicuspid aortic

Randomised trials needed to evaluate safety and efficacy of mitral valve replacement Randomised trials are needed to evaluate the safety and effectiveness of transcatheter mitral valve replacement (TMVR) against current standard of care therapies such as transcatheter edgeto-edge repair (TEER). This is according to lead author Jason Rogers (University of California Davis Medical Center in Sacramento, USA) and colleagues, writing in an opinion paper published in JACC: Cardiovascular Interventions. This consensus document summarises the recommendations of key opinion leaders from interventional cardiology, cardiac surgery, and heart failure specialties. TMVR IS A RAPIDLY EVOLVING THERAPY for the treatment of symptomatic mitral regurgitation (MR) and mitral stenosis (MS), Rogers et al note, adding that numerous TMVR devices are currently under investigation. A major potential benefit of the technique, the authors suggest, is the predictable, complete elimination of MR, which is less certain with TEER. This benefit needs to be evaluated against its risks, Rogers and colleagues suggest, including the relative procedural invasiveness, need for anticoagulation, and long-term structural

stenosis, especially those at low surgical risk, are often considered more suitable for surgery.” Makkar and colleagues suggest that bicuspid TAVI outcomes are comparable with published surgical series on bicuspid aortic stenosis and reported 30-day mortality ranging from 0.4% to 2.5% in younger patients. They add that prior reports from the same registry in patients at higher surgical risk have reported higher rates of stroke, paravalvular regurgitation, and permanent pacemaker implantation after TAVI in patients with bicuspid aortic stenosis. In the present study of patients at low surgical risk and severe aortic stenosis, the rates of stroke, paravalvular regurgitation, and permanent pacemaker implantation were not significantly different between patients with bicuspid vs tricuspid aortic stenosis. Possible explanations for this, they note, include better patient selection due to availability of surgical alternative in patients at low surgical risk, evolution of device technology (fourth-generation balloonexpandable transcatheter heart valves associated with decreased paravalvular regurgitation), and procedural technique (higher valve implantation associated with decreased pacemaker rates). “Our hope is for this data to translate into better advocacy and decision-making among healthcare providers and patients diagnosed with bicuspid aortic stenosis,” said Makkar. “By carefully selecting lowrisk surgical patients with bicuspid aortic stenosis, we can add years to life and life to years.”

valve deterioration. mortality and progressive heart failure symptomatology, “The design of clinical trials for novel TMVR devices the primary endpoint for TMVR trials should include must take into account the complexity and heterogenous endpoints that are related to heart failure (i.e. mortality nature of mitral valve pathologies and available and/or heart failure hospitalisations).” treatment options,” Rogers and colleagues write, Quality of life may be considered as a component adding that although there can be benefits associated of a composite primary endpoint depending upon the with complete MR elimination from valve replacement trial’s intent, but should not be used in isolation, Rogers versus valve repair, “the risks of valve replacement must and colleagues write. Furthermore, trials with TEER be weighed against other available therapies”. as a control group could be designed to demonstrate For transcatheter technologies targeted to patients either superiority or non-inferiority depending upon the with primary MR, they write, randomised trials must device features, and results from such trials could be be considered against surgical mitral valve repair for used to define anatomies for which TMVR may be more surgical candidates or TEER for patients who are at high suitable than TEER and vice versa. risk for surgical mortality. For transcatheter technologies Secondary endpoints should include those pertaining targeted to patients with severe secondary MR, to safety, for example a composite of major adverse randomised clinical trials may be considered against events, stroke, bleeding, myocardial infarction, device guideline-directed medical therapy, TEER, or surgery effectiveness (MR severity), measures of success depending on patient anatomy or surgical candidacy. (technical success, device success, patient success), Single-arm trials for patients with an unmet clinical left ventricular (LV) dimensions (LV end-diastolic and need—for example those with severe mitral annular end-systolic volumes), quality of life (Kansas City calcification or with primary MR who are not candidates Cardiomyopathy Questionnaire score), and functional for surgery or TEER— may be considered but are most capacity (six-minute walk distance, New York Heart meaningful if performed within an overall construct Association [NYHA] functional class). that includes a randomised trial to best interpret the The paper’s authors acknowledge that there are safety and effectiveness of novel first-in-class challenges to the execution of a randomised controlled transcatheter devices against the standard trial with current-generation TMVR technologies. of care, Rogers et al write. They note that the clinical community may be Considering appropriate endpoints for reluctant to randomise patients because of competing any such trials, the paper’s authors write: commercially approved therapies (TEER), the current “Depending upon the trial’s objectives, requirement for transapical access, and the anatomic primary, secondary, and descriptive restrictions limiting TMVR candidacy including left endpoints may be chosen from the ventricular outflow tract obstruction and mitral annular options provided within the Mitral sizing. In addition, TEER technology continues Valve Academic Research to advance and there is improving operator Consortium documents. experience with TEER, “both of which have As patients with untreated been shown to lead to greater effectiveness MR are at high risk for Jason Rogers and better safety”.

Structural Heart Interventions 23

Issue 63 | November 2021

Ultrasound guidance “should be routine” for transfemoral TAVI access

Ultrasound-guided transfemoral transcatheter aortic valve implantation (TAVI) is associated with a significant reduction in the risk of access site vascular and bleeding complications, compared to a fluoroscopy-guided strategy, a systematic review and meta-analysis comparing the two approaches has concluded. THE RESULTS OF THE ANALYSIS SUPPORT the routine adoption of ultrasound to guide primary access in TAVI as a tool that can modify the risk of vascular and bleeding complications, the study’s authors suggest. Led by senior author Adrian Banning (Oxford Heart Centre, Oxford University Hospitals, Oxford, UK) and colleagues, the review published in Circulation: Cardiovascular Interventions compared access site vascular and bleeding complications according to the Valve Academic Research Consortium-2 classification following the use of either ultrasound- or conventional fluoroscopy-guided transfemoral TAVI access. Ultrasound-guided transfemoral access has been proposed as an alternative strategy to reduce access site complications, Banning et al write, noting that it offers realtime, cross-sectional visualisation of the puncture site anatomy, reducing accidental vascular injury and enhancing the efficacy of vascular closure devices. However, despite being recommended by some interventional society guidelines, there are currently no conclusive data confirming whether an ultrasoundguided strategy confers superior outcomes to a fluoroscopic-guided technique. The review sought to assess the evidence for access site vascular and bleeding complication rates comparing the use of either modality to guide transfemoral access. The authors selected studies that compared ultrasound and fluoroscopy-guided transfemoral access, with two groups of participants pertaining to each intervention from the Medline, Embase, Web of Science, and the Cochrane Library. A priori defined primary outcomes were extracted including: major, minor, and major and minor (total) access site vascular complications, lifethreatening/major, minor, and life-threatening, major, and minor (total) access site bleeding complications. Authors included eight observational studies in their review, involving a total of 3,875 participants. The studies had a mean participant age of 82.8 years, Society of Thoracic Surgeons (STS) score of 5.81, and peripheral vascular disease was present in 23.5%. The study team reports that an ultrasound-guided approach was significantly associated with a reduced risk of total (Mantel-Haenszel odds ratio [MH-OR], 0.50 [95% CI, 0.35–0.73]), major (MH-OR, 0.51 [95% CI, 0.35–0.74]), and minor (MH-OR, 0.59 [95% CI,

0.38–0.91]) access site vascular complications. Ultrasound guidance was also significantly associated with total access site bleeding complications (MH-OR, 0.59 [95% CI, 0.39–0.90]). The association remained significant in sensitivity analyses of maximally adjusted minor and total vascular access site complications (MHOR, 0.51 [95% CI, 0.29–0.90]; MH-OR, 0.44 [95% CI, 0.20–0.99], respectively). The study team write that although the study synthesises data from low-moderate quality studies, sensitivity analysis including including maximally adjusted results shows that ultrasound guidance is associated with a significant 56% reduction in access site vascular complications. “In the absence of randomised studies, the current study represents an important synthesis of available evidence and should

We propose a randomised trial comparing ultrasound to fluoroscopyguided percutaneous transfemoral access in TAVI to provide high-level evidence.” inform clinical practice,” they write. Banning and colleagues add that the findings of their analysis is consistent with another meta-analysis considering the role of ultrasound guidance for coronary angiography, which also found that the use imaging modality was associated with a reduction in bleeding events. “The adoption of ultrasound by centres in our meta-analysis was associated with almost halving of vascular and bleeding complications,” they write. Furthermore, the authors note, the association remained significant for both major and minor access site vascular complications. “However, the association of ultrasound guidance with bleeding complications reduction was no longer statistically significant

FDA monitoring sex differences in outcomes with LAAO devices The US Food and Drug Administration (FDA) has informed healthcare providers of recent information about the potential for differences in procedural outcomes between women and men undergoing implant of a left atrial appendage occlusion (LAAO) device.

he FDA is evaluating an analysis published in the Journal of the American Medical Association (JAMA) Cardiology of real-world data in the National Cardiovascular Data Registry (NCDR) LAAO Registry from patients undergoing LAAO procedures with the Watchman (Boston Scientific) left atrial appendage closure device from 2016 to 2019 indicates that procedural outcomes such as major adverse events and lengthened hospital stay may be

more common in women compared to men. The causes for these differences are yet to be determined. The article by Douglas Darden (University of California, San Diego, La Jolla, USA) et al presented an analysis of 49,357 patients from the LAAO registry (41.3% women and 58.7% men) treated with the Watchman device between 2016 to 2019. The authors found a statistically significant higher rate of adverse procedural events in women compared

Adrian Banning

when total access site bleeding complications were separated into life-threatening and major, and minor access site complications,” Banning et al detail. This may be partly attributed to between study heterogeneity and the insufficient power of the metaanalysis due to the low number of

bleeding events. “The lower number of events when compared with vascular complications is expected since access site bleeding is usually due to an access site vascular injury and is within rates described in contemporary literature,” the study team writes. Banning et al write that their review supports the routine adoption of ultrasound to guide primary access in TAVI as a tool that can modify the risk of vascular and bleeding complications. This is particularly important in the TAVI setting as patients are elderly ad comorbid and at higher risk of sustaining access site related bleeding complications than young patients that undergo femoral access for coronary angiography or percutaneous coronary intervention (PCI) indications. “Reducing access site complications should lead to reductions in the associated morbidity and mortality, and streamline discharge pathways reducing postoperative length of stay,” the study team writes. “As TAVI expands to lower risk and younger patients with severe aortic stenosis, further reducing access site complications with simple, resource neutral modifications can improve the risk-benefit and cost-effectiveness profile of TAVI”. The authors write that the study has a number of limitations, primarily that it is an aggregate level metaanalysis based on low-moderate quality observational studies, and that the time frame of the study conduct was heterogenous, including patients recruited from 2012, which introduces temporal bias related to learning curves and advances in TAVI technology and patient care over time. Despite this, the study team concludes that their metaanalysis reports significant association of an ultrasoundguided access approach with reductions in total vascular bleeding and access site complications by 50% and ≈40%, respectively, and has important patient-oriented ramifications for all vascular procedures requiring largebore percutaneous access. They conclude: “We propose a randomised trial comparing ultrasound to fluoroscopy-guided percutaneous transfemoral access in TAVI to provide high-level evidence. In the interim considering the resource neutral nature of ultrasound guidance and the reducing familiarity of operators with fluoroscopyguided femoral access, ultrasound guidance should be considered to obtain percutaneous access in TAVI.”

to men including any adverse events (6.3% vs. 3.9%, p<0.001), any major adverse events (4.1% vs 2.0%, p<0.001), and hospital stay longer than one day (16% vs 11.6%, p<0.001). Among specific procedural adverse events, the rates of pericardial effusion requiring percutaneous drainage was 1.2% vs. 0.5% and major bleeding was 1.7% vs. 0.8% in women compared to men, respectively. Procedure-associated death was 0.3% in women and 0.1% in men. As well as the Watchman device, Abbott’s Amplatzer Amulet is also approved for use in the USA. The FDA has said that it will work with the manufacturers of approved LAAO devices to evaluate information from several sources, including premarket studies, mandated post-market studies, and real-world data to provide additional information on this issue. Currently, the

FDA has said that it believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use. Current recommendations from the regulator include to continue monitoring patients who have been treated with LAAO devices per the current standard of care, and to discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation (AF) as part of shared clinical decision-making. Additionally, the FDA has advised healthcare providers to report any adverse events or suspected adverse events experienced with the use of LAAO devices. Voluntary reports can be submitted through MedWatch, the FDA Safety Information and Adverse Event Reporting programme.

November 2021 | Issue 63

24 Market Watch

Medtech insights

Philips’ Bert van Meurs talks the future of imaging in the cath lab Bert van Meurs is the chief business leader for Image Guided Therapy within Royal Philips, the multinational medical technology company, which offers a portfolio of devices comprising interventional imaging systems, smart catheters, planning and navigation software. In this interview, van Meurs tells Cardiovascular News Philips’ strategy for addressing challenges in the cath lab and future areas for innovation, including Fiber Optic RealShape (FORS) technology.

mproving outcomes, lowering costs, and improving staff and patient experience are the “quadruple aims” sitting at the heart of Philips’ healthcare business strategy. According to van Meurs, these aims are in tune with many of the challenges faced within interventional cardiology today. As an example of this strategy in practice, he offers recent updates to the company’s flagship cath lab platform Azurion, which now incorporates imaging control, physiology, haemodynamic and informatics applications, among other functionalities. “Rather than focusing on that single modality to see how we can help to provide efficiency, we look horizontally at overall efficiency for these procedures,” Van Meurs tells Cardiovascular News. However, Van Meurs notes that while Azurion is ostensibly an X-raybased technology, in future, cath lab procedures are likely to move in a direction that will eliminate the need for the exposure to radiation. “That is where we potentially integrate imaging sources like ultrasound and new technologies like FORS that we have in vascular surgery, that enables a device to image itself without any X-ray,” he says. “That [FORS] is still a nascent technology, but it shows the vision over time if we address these challenges, we should not

focus purely on optimising one modality, but looking at the entire procedure.” FORS was first introduced into clinical practice in 2018, and has been used in more than 200 cases predominantly involving aortic and peripheral procedures. The technology enables real-time 3D visualisation of the full shape of devices inside the body without the need for fluoroscopy, using light rather than X-ray. Van Meurs acknowledges that the technology has great potential, including possibly in coronary procedures, though he admits that it remains in its infancy. “In the future, I believe we should eliminate radiation, maybe this will not happen in my generation, but I think my grandson’s generation will not believe that we used X-rays for these procedures!” Van Meurs comments. “I think that will happen, and if you have that vision then you need to invest in technologies that will take you there. FORS, we strongly believe, is that kind of technology.” At present, the use of FORS is being studied in vascular surgery, where it is seen as an exciting technology, but Van Meurs comments that clinical study and proof of evidence is needed before this can be adopted more widely. “That is where we are now,” he adds. “As a next step, we will look at other applications,

Product News Biotronik gains FDA approval for the Orsiro Mission drug-eluting stent

Biotronik has announced that it has received US Food and Drug Administration (FDA) approval of its Orsiro Mission bioabsorbable polymer drug-eluting stent system (BP-DES). The company also announced the first US implant and full commercial launch of the new DES system, which offers advanced deliverability and an ultrathin strut design considered the thinnest available in the USA. “We welcome the availability of the Orsiro Mission DES in the USA as a novel percutaneous coronary

intervention device offering better outcomes,” said David Kandzari, chief of the Piedmont Heart Institute and Cardiovascular Service Line; director, Interventional Cardiology of the Piedmont Heart Institute; and chief scientific officer for Piedmont Healthcare in Atlanta, USA, whose facility is among the first to receive the device. “The outstanding deliverability and the extensive clinical data give strong evidence for continued Orsiro Mission adoption.” The Orsiro Mission DES features the same proprietary stent design and bioabsorbable coating with controlled drug release as the Orsiro

coronary could potentially be one, but it is not yet fully on the radar screen.” Gathering clinical evidence to back any new technology being brought to market is described as “fundamental” by Van Meurs, who says that Philips is committed to supporting clinical science to assess the scope of its technologies to improve practice. Among the trials that Philips is currently supporting is DEFINE GPS, a multicentre randomised study evaluating the use of instantaneous wave-free ratio (iFR) measurements in combination with Philips’ co-registration system—SyncVision—to enhance percutaneous coronary intervention (PCI) guidance and provide superior treatment outcomes. “You need to come with two-, three-, or up to five-year outcome data to support the claims that you make, that has become a fundamental part of how

In the future, I believe we should eliminate radiation, maybe this will not happen in my generation, but I think my grandson’s generation will not believe that we used X-rays for these procedures! I think that will happen, and if you have that vision then you need to invest in technologies that will take you there.” stent. Improvements to the new Orsiro Mission DES system include a reengineered delivery system and a new deep embedding process to further improve deliverability, including ‘bestin-class’ trackability and crossability, Biotronik said in a press release. “We will continue to bolster our interventional cardiology portfolio with innovations like the Orsiro Mission and state-of-the-art PK Papyrus covered stent system to support and improve patient care,” said David Hayes, chief medical officer, Biotronik. “This emphasises our commitment to excellence and reinforces our vision to ensure the highest quality.”

we do the innovation,” he comments. “It is essential, these days you cannot make any claim if you do not come with the medical evidence based upon clinical studies.” Discussing areas where he sees room for innovation in interventional cardiology, Van Meurs notes that the deployment of artificial intelligence in diagnosis is likely to be a significant future development. “There is so much data that is being acquired for a patient along the care pathway, and if you translate that data into valuable information that can help you decide what will be the best protocol for this patient based upon the data of thousands of patients that also had a mitral valve replacement, for example,” he comments. Robotics is another area in which he sees potential for further development, although he says this will merely be in support of, and not at the expense of the human operator. “If you use robotics as a technology for procedure automation, using imaging as the eyes of the robot, you can navigate more easily. That is where robots will play a role,” he notes, though commenting that, like FORS, these types of developments remain a way away from becoming common practice. Turning to the near future, Van Meurs previews Philips’s participation at the upcoming Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November; Orlando, USA) where he says there will be a focus on how its technologies can integrate to optimise PCI procedures and showcasing devices including the VeriSight Prointracardiac echocardiography catheter.

Bert van Meurs

imaging chain, comprehensive dose optimisation, cybersecurity features, and detector-sharing capabilities for radiography. In a press release, Siemens Healthineers said that the fully digital Luminos Impulse offers high-end features and superior imaging that have not been available at this economical price in the past. “Being able to offer such a compelling product in this price segment makes me really proud of what our team has achieved. We

Siemens launches Luminos Impulse fluoroscopy system Siemens Healthineers has launched the Luminos Impulse fluoroscopy system, including features such as a seamless

Luminos Impulse

Issue 63 | November 2021

Market Watch 25

European launch for ReCor Medical’s Paradise ultrasound renal denervation system

Product News work diligently to bring high-end features to our ‘smaller’ systems while also maintaining their excellent image quality and clinical versatility. Customers can use Luminos Impulse for fluoroscopy and radiography with virtually no limitations,“ says Ronald Fröhlich, head of marketing X-ray Products at Siemens Healthineers. Luminos Impulse is built for the needs of modern-day fluoroscopy and radiography, the company’s press release said. Fluoroscopy enables the continuous dynamic observation of moving processes in the human body using pulsed X-rays.

Portico

US approval for Abbott’s Portico with FlexNav TAVI system

Abbott has announced that the US Food and Drug Administration (FDA) has approved the company’s Portico with FlexNav transcatheter aortic valve implantation (TAVI) system to treat people with symptomatic, severe aortic stenosis who are at high or extreme risk for open-heart surgery. “For people in the USA suffering from aortic stenosis and unable to have surgery, the Portico with FlexNav system offers a safe and effective treatment option,” said Raj Makkar, associate director of Interventional Technologies at Cedars-Sinai’s Smidt Heart Institute, Los Angeles, USA who served as co-principal investigator for the study that led to FDA approval. Gregory Fontana, national director, Cardiothoracic Surgery at Hospital Corporation of America and American Research Institute, also served as coprincipal investigator of the Portico IDE study. Portico is a self-expanding TAVI valve with intra-annular (within the native valve) leaflets that help provide optimal blood flow (haemodynamics) when placed inside a patient’s natural valve. The structure of the replacement valve also preserves access to the critical coronary arteries for future coronary interventions, Abbott said in a press release. The Portico device is implanted using Abbott’s FlexNav delivery system, which features a slim design to accommodate different patient anatomies and small vessels, and optimises flexibility, ease of tracking and precision of valve placement. “With the approval of our TAVI therapy in the USA, physicians now

have access to an even more robust set of solutions to treat structural heart disease,” said Michael Dale, senior vice president of Abbott’s structural heart business. “This latest and important introduction of Portico with FlexNav represents another milestone in our work to advance our mission to restore health and improve quality of life so more people can get back to living fuller lives.”

Latest-generation Evolut TAVI system from Medtronic gets FDA approval

Medtronic has announced US Food and Drug Administration (FDA) approval of its newest-generation, self-expanding transcatheter aortic valve implantation (TAVI) system, the Evolut FX. The Evolut FX system incorporates the supra-annular valve design that has shown haemodynamic performance superior to surgical aortic valve replacement (SAVR) across largescale, randomised clinical trials, Medtronic said in a press release. The fourth-generation Evolut technology is equipped with gold markers built into the frame to provide implanters with direct visualisation of depth and valve leaflet location during implant. In addition, the Evolut FX system incorporates a redesigned catheter tip for a smoother insertion profile, a more flexible delivery system that allows for 360-degree freedom of motion, with a stable, predictable deployment. Like its predecessor (Evolut PRO+), the newest system includes four valve sizes for the largest indicated patient treatment range and the lowest delivery profile currently on the market. Severe aortic stenosis occurs when the aortic valve leaflets become stiff and thickened and have difficulty opening and closing, making the heart work harder to pump blood to the rest of the body. Severe aortic stenosis often reduces a patient’s quality of life and limits their daily activities. If left untreated, patients with symptomatic severe aortic stenosis can die from heart failure in as little as two years. The Evolut TAVI platform (including

Evolut

the Evolut R, Evolut PRO, Evolut PRO+, and Evolut FX) is indicated for symptomatic severe aortic stenosis patients across all risk categories (extreme, high, intermediate and low) in the USA. Limited commercial release is planned for the autumn with a full launch anticipated in early 2022.

ReCor Medical has announced that its Paradise ultrasound renal denervation system is now available for the treatment of uncontrolled hypertension in Germany. The first hospitals performing the procedure commercially are Heart Center Leipzig, Leipzig and Saarland University Hospital, Homburg/Saar. “Despite the availability of antihypertensive medications, many patients fail to control their hypertension, a dangerous condition that can lead to heart attack and death. Clinical data from the ACHIEVE, RADIOSOUND, RADIANCE-HTN SOLO and TRIO trials show that ultrasound renal denervation with the Paradise system can lower blood pressure and is a new treatment option for physicians to help their selected patients,” said Felix Mahfoud of Saarland University Hospital and chairman of the Arterial Hypertension Working Group of the German Society of Cardiology (DGK), investigator for the RADIANCE-HTN SOLO and TRIO trials. “We are pleased to be one of the first hospitals in Europe to offer renal denervation with ultrasound.” In Leipzig, the first procedure was performed at the Heart Center Leipzig at the University Clinic for Cardiology. There, Philipp Lurz and Karl Fengler led the RADIOSOUND trial, and both have participated in the RADIANCE-HTN SOLO and TRIO studies in patients with uncontrolled hypertension. Paradise ultrasound renal denervation is a device-based, minimally invasive procedure for the treatment of high blood pressure. During the procedure, which usually takes less than an hour, the Paradise catheter is placed in the renal artery. Typically, three doses of ultrasound energy lasting a few seconds are applied to each of the main arteries leading to the kidneys. The ultrasound emissions denervate the renal nerves and cause a reduction in sympathetic nervous system activity, which can result in lower blood pressure. In September 2021, the European Society of Hypertension (ESH) published a position paper stating that renal denervation “is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity.” ESH noted that five independent shamcontrolled randomised trials—including RADIANCE-HTN SOLO and TRIO— provide “conclusive evidence” that renal denervation can lower ambulatory and office blood pressure both in patients with and without concomitant antihypertensive medication.

NeoChord announces completion of first-in-human case with NeXus TMVR technology NeoChord has announced successful completion of the first-in-human

procedure with the NeoChord NeXuS transcatheter mitral chordal repair (TMVR) technology. The first-inhuman procedure was performed at the University Hospital of Bordeaux, Bordeaux, France in collaboration with the Universitätsmedizin Mainz, Mainz, Germany. The patient treated has been discharged from the hospital and is back to a normal lifestyle. “We are thrilled to announce this achievement,” said David Chung, president and chief executive officer of NeoChord. “On behalf of our entire organisation, I want to thank the collective team of physicians for bringing this first-in-human procedure to success. Coupled with our successful, clinical experience with the transapical device, this transcatheter milestone further establishes NeoChord as the leader for beating heart, off-pump mitral chordal repair, providing another tool for the heart teams to offer patients a surgically-proven technique with an interventional approach.” “We are pleased with the positive result of this first-in-human procedure of the NeoChord NeXuS transcatheter mitral chordal repair device. The ability to replace a ruptured native chord by precisely placing suture in the mitral leaflet and securing with an anchor contributed to a very safe procedure,” said Thomas Modine, University Hospital of Bordeaux and Ralph Stephan von Bardeleben, Universitätsmedizin Mainz, who both co-led the procedure. “We integrated four decades of heart surgical experience into a venous transseptal intervention.” “Chordal replacement was completed in textbook fashion,” said Azeem Latib from New York, USA who has been closely involved in the development of the NeoChord NeXuS transcatheter mitral chordal repair device and procedure. “Minimally invasive transcatheter chordal repair offers the promise of driving surgicallike results by maintaining the physiologic construction of the mitral valve, translating to better long-term outcomes.” Mitral regurgitation (MR) is a common heart valve disease, affecting millions worldwide. If left untreated, MR may lead to chronic heart failure. The investigational NeoChord NeXuS transcatheter mitral chordal repair device is designed to restore function in patients with severe symptomatic primary MR, a disease where blood leaks backwards within the heart, due to ruptured native chords and the mitral valve’s inability to close properly. The NeoChord NeXuS transcatheter mitral chordal repair device is unique from other mitral valve repair technologies in maintaining a natural physiologic functionality of the mitral valve. It is deployed through the vein using a transfemoral delivery catheter, navigated transeptally to the diseased native mitral valve. Due to minimal hardware used and the proven leaflet connection, NeoChord NeXuS preserves options for patients who may need reintervention in the future.

November 2021 | Issue 63

26 Market Watch

Clinical News ABILITY Diabetes Global enrols thousandth patient

Concept Medical has announced the enrolment of the thousandth patient in ABILITY Diabetes Global (Randomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents versus Everolimus-Eluting Stents in Coronary Artery Disease Patients with Diabetes Mellitus Global), which it has described as the world’s largest randomised controlled trial (RCT) for coronary artery disease (CAD) patients with diabetes as a comorbidity. The RCT measures the safety and efficacy of the Abluminus DES+ which is designed with patented Envisolution technology and has proven to be effective in managing the proliferative CAD lesions seen in diabetes mellitus (DM). In the trial, Abluminus is compared against the Xience EES family (Abbott Cardiovascular). Patient enrolment began on 11 June 2020 in Italy through principal investigator Antonio Colombo (Raffaele Scientific Institute, Milan, Italy) and the pace of enrolment since then has been steady and consistent, Concept Medical said in a press release. The trial is targeting more than 3,000 diabetic patients across 100 centres, spanning more than 25 countries. Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA), chair of the trial’s steering committee, commented: “I am encouraged by the progress we are making on this largest trial in PCI [percutaneous coronary intervention] and diabetes and incredibly enthusiastic about the future of what we can offer to these complex patients with progress in innovation in PCI.”

Enrolment completed in study of Tria aortic valve

Foldax has announced completion of enrolment in the US early feasibility study of the Tria surgical aortic heart valve. According to Foldax, the Tria valve reimagines the heart valve by combining the company’s proprietary biopolymer—LifePolymer—with an innovative valve design intended to

resist calcification, withstand stresses and strains without failure, and restore patient quality of life without lifelong use of anticoagulants. “We were thrilled to participate in the first human study of the novel Tria biopolymer heart valve, which offers the potential to improve upon the durability of commonly used tissue valves today,” said Geoff Answini, chief, Division of Cardiovascular Surgery at The Christ Hospital, Cincinnati, USA, and an investigator in the study. “Several of our patients have reached one-year followup with good outcomes and we look forward to seeing how a polymer heart valve performs for them over time.” “This first clinical trial of our novel Tria heart valve technology is a landmark in the heart valve replacement market as the first biopolymer valve ever to be studied in man. We have also recently commenced an early feasibility study of our surgical mitral valve and are fast-tracking development of our transcatheter aortic heart valve (TAVI),” said Frank Maguire, chief executive officer of Foldax.

Neovasc to begin COSIRA-II trial of Reducer for refractory angina

Neovasc has announced that it has received US Food and Drug Administration (FDA) approval for the investigational device exemption (IDE) for the COSIRA-II IDE clinical trial. The study is designed to answer key questions arising from the October 2020 Circulatory Systems Devices Panel Meeting regarding the Neovasc Reducer. The approval of the supplement is consistent with Neovasc’s internal target, and the company remains on track to enrol the first patient in the trial late this year. COSIRA-II is a randomised, shamcontrolled trial investigating the safety and effectiveness of the Reducer for patients suffering from refractory angina. The primary endpoint of the trial is change in exercise tolerance testing time via a modified Bruce protocol between baseline and six-month follow-up.

The study is planned to enrol 380 patients at up to 50 sites in the USA and will also include limited sites outside of the USA. The trial will include patients with Canadian Cardiovascular Society Class III-IV refractory angina on maximally tolerated medical therapy without further options for revascularisation via coronary intervention or bypass grafting. Principal investigators of the trial are Gregg Stone (Mount Sinai Health System, New York, USA) and Tim Henry (Christ Hospital, Cincinnati, USA). FDA approval of the IDE Supplement is another important milestone for Neovasc, commented Lisa Becker, vice president of regulatory affairs, Global Angina Therapies, at Neovasc.

aortic implantation (TAVI) guidewire. The SavvyWire is the first guidewire intended to both deliver the aortic valve prosthesis while allowing continuous haemodynamic pressure measurement during the procedure. Louis Laflamme, president and CEO of OpSens, said: “Health Canada’s approval of the first in-man study is an important milestone for the Company and an important step towards filing for 510k clearance with the US Food and Drug Administration (FDA). We remain on track to submit for regulatory approval in the USA in early 2022.” Health Canada’s approval allows OpSens to commence the 20-patient study shortly at two structural cardiology institutions that contributed to the development of the device.

Peijia Medical announces first implant in the clinical trial of its TaurusNXT TAVI system Neovasc Reducer

“We are grateful for the collaborative work with FDA and we are pleased that our study initiation remains on track”, she continued. “Refractory angina is a debilitating condition, and we are excited to offer patients in the USA and Canada a clinical trial with a treatment option that may alleviate their suffering.” The Reducer is CE-marked in the European Union and under investigation in the USA for the treatment of refractory angina, a painful and debilitating condition that occurs when the coronary arteries deliver an inadequate supply of blood to the heart muscle, despite treatment with standard revascularisation or cardiac drug therapies. While the Reducer is not approved for commercial use in the USA, the FDA granted Breakthrough Device designation to the Reducer in October 2018.

OpSens receives Health Canada approval to begin clinical study of TAVI guidewire

OpSens has announced that it has received Health Canada approval to commence the first in-man study with its SavvyWire, transcatheter

Peijia Medical has announced the initiation of its multicentre clinical trial for TaurusNXT, the third-generation transcatheter aortic valve implantation (TAVI) system, following the first successful patient implant in Zhongshan Hospital of Fudan University, Shanghai, China. Led by Ge Junbo, the procedure was completed successfully with support from the medical team comprising Zhou Daxin, Pan Wenzhi, Zhang Xiaochun, Chen Shasha. TaurusNXT is Peijia’s latest generation TAVI system with nonglutaraldehyde cross linked dry-tissue and pre-mounted prosthetic aortic valve (PAV). TaurusNXT incorporates the company’s non-glutaraldehyde treated anti-calcification technology, which is designed to result in the elimination or significant reduction of tissue calcification by removing residual aldehyde in the pericardium. The clinical trial is a multicentre, prospective, single-arm objective performance criteria (OPC) study to evaluate the safety and efficacy of the TaurusNXT TAVI system for treating calcific severe aortic stenosis for National Medical Productions Administration (NMPA) registration. The study is led by Ge Junbo from Zhongshan Hospital and involves participation from more than 15 centres across China.

Calendar of events Please be advised that the events listed opposite, because of COVID-19, are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

2021

4–6 November Transcatheter Cardiovascular Therapeutics (TCT) 2021 Orlando, USA crf.org/tct2021

21–23 November PCR London Valves 2021 London, UK pcronline.com/Courses/PCR-London-Valves

2022

26 February–1 March Cardiovascular Research Technologies (CRT) 22 Washington, DC, USA crtmeeting.org

13–15 November AHA Scientific Sessions 2021 Boston, USA

29–31 January Society of Thoracic Surgeons (STS) Annual Meeting Miami Beach, USA

2–4 April American College of Cardiology Scientific Sessins 2022 (ACC.22) Washington, DC, USA

professional.heart.org/en/meetings/scientific-

sts.org/sts-58th-annual-meeting

accscientificsession.acc.org

sessions

Issue 63 | November 2021

Section Name 27

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

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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 n = 1,491/1,506

p < 0.001

37 mm 225

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