Cardiovascular News - Issue 64 - February 2022 by BIBA Publishing

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Meta-analysis “moves the conversation forward” on left main revascularisation A meta-analysis comparing percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) to coronary artery bypass graft (CABG) surgery in patients with left main coronary artery disease has concluded there is no statistically significant difference between the two approaches in terms of mortality at five years.

owever, the analysis, which was led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham & Women’s Hospital in Boston, USA, did find that there were differences between the two strategies in terms of lower rates of spontaneous myocardial infarction (MI) and repeat revascularisation with CABG, as compared with a lower incidence of early stroke with PCI. Differences in the risk of procedural MI depended on the definition used, researchers found. TIMI Study Group chairman Marc Sabatine (Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) presented findings of the analysis at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November, virtual), which were simultaneously published in The Lancet. “Differences in trial composite endpoints and findings have led to persistent uncertainty among clinicians and practice guideline committees regarding the optimal revascularisation strategy,” Sabatine told AHA attendees. In order to address some of this controversy, Sabatine and colleagues from the TIMI Study Group set about analysing data from the four biggest randomised trials to examine revascularisation strategies in patients with left main coronary artery disease to date—SYNTAX, PRECOMBAT, NOBLE and EXCEL—comprising nearly 4,400 patients in total. Independent investigators, including noninterventional cardiologists, an interventional cardiologist, a cardiac surgeon and a statistician, as well as principal investigators of the four trials, all participated in the analysis. The primary endpoint was all-cause mortality through five years, with secondary endpoints including cardiovascular death, spontaneous MI, procedural MI, stroke and repeat coronary revascularisation. Investigators

also performed landmark, supplemental analyses using 10year data from the SYNTAX and PRECOMBAT trials, as well as a Bayesian analysis to quantify the probability and magnitude of any difference in mortality. Sabatine detailed that, overall, there was no statistically significant difference in mortality between the two treatment strategies despite an early diversion of the curves—in favour of PCI—that then crossed. The five-year rates of mortality stood at 11.2% for PCI, compared to 10.2% for CABG, Sabatine reported. In an attempt to further quantify the potential differences, a Bayesian analysis showed that there was an 86% probability that mortality was greater with PCI versus CABG, but only a 49% probability that the excess was 1% or more over five years, Sabatine detailed. “In other words, the difference was more likely than not less than 0.2% per year,” he told the AHA audience. Detailing the combined data from the trials to have followed patients out to 10 years, Sabatine noted that the rates of mortality also appeared to be similar, standing at 21.6% in the PCI arm and 22.1% in the CABG arm. In terms of secondary outcomes, Sabatine explained that patients treated with PCI had more than twice the risk of having a spontaneous MI (6.2% vs. 2.6%), with an absolute risk difference over five years of 3.5%. Likewise, he noted that patients treated with PCI had nearly twice the rate of repeat revascularisation (18.3% vs. 10.7%), with an absolute risk difference of 7.6%. Regarding procedural MI, Sabatine explained that each of the four trials had a prespecified primary definition, which, when using these definitions, showed that there were around one third fewer procedural MIs with PCI. “This was consistently seen in all four trials,” Sabatine commented.

11.2% 10.2% PCI

CABG

Mortality at five years

Marc Sabatine

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Acute page 00kidney injury in the cath lab page 22

Fresh revascularisation guidelines issued

New guidelines have been issued for the management of coronary artery revascularisation addressing key issues including the duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) and the involvement of a multidisciplinary heart team in treatment selection. THE GUIDELINE—ISSUED IN December jointly by the American College of Cardiology (ACC), American Heart Association (AHA) and the Society for Cardiovascular Angiography & Interventions (SCAI)—updates and consolidates previous guidelines from 2011 covering coronary artery bypass graft (CABG) surgery and from 2011 and 2015 covering percutaneous coronary intervention (PCI). “Coronary artery disease remains a leading cause of morbidity and mortality globally, and coronary revascularisation is an important therapeutic option when managing patients with this disease,” said Jennifer S Lawton, guideline writing committee chair and professor of surgery (Johns Hopkins Medicine, Baltimore, USA). “Treatment recommendations in the guideline outline an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularisation, with the intent to improve quality of care and align with patients’ interests.” The guideline updates recommendations for intervention, surgery or medical therapy in certain populations, including appropriate use of surgical revascularisation or percutaneous revascularisation for different disease states. Important updates in the document include new recommendations relating to patients with stable ischaemic heart disease (SIHD) and three-vessel coronary artery disease, as well as an enhanced recommendation for radial access in PCI. According to ACC, AHA and SCAI, evidence has shown that surgery is a reasonable recommendation to improve survival among patients with SIHD, normal left ventricular ejection fraction and three-vessel coronary artery disease, though it may not provide “as strong a benefit over medication therapy as previously thought”. When PCI is the most appropriate treatment, the guideline incudes recommendations for Continued on page 3

Continued on page 2

February 2022 | Issue 64

Top Stories

Meta-analysis “moves the conversation forward” on left main revascularisation

this analysis so they can come together and make a recommendation,” Sabatine added, referring to the ongoing review by the European Society of Cardiology (ESC) and the European Association for Cardiothoracic Surgery (EACTS) of available evidence for the treatment of patients with left main Continued from page 1 coronary artery stenosis. Discussing some of the controversy Two trials—SYNTAX and EXCEL— surrounding the debate around were reanalysed using the universal revascularisation strategies in left main definition of MI (UDMI), which in turn coronary artery disease, Sabatine said he suggested that there was no significant hoped that the findings of the analysis difference between CABG and PCI. would help to “move the conversation PCI “If anything, the pattern was reversed,” forward”. Sabatine commented. “Both interventional cardiologists and With regard to stroke, he noted that cardiac surgeons all have the same goal there was no statistically significant of doing the right thing for the patient difference between the two arms through in front of them and are appropriately five years (PCI=2.7% vs. CABG=3.1%), passionate about the approach that they but he did note that, as apparent from can offer,” he commented. “I think that the shapes of the cumulative incidence the advantage here is that, as the saying curves, the relationship differs early goes, people are entitled to their own CABG versus late. “In the first year there was opinions, but not to their own facts. This a lower rate of stroke with PCI, with should create some common ground. almost a two thirds reduction of risk, Rather than people just looking at one and an absolute risk difference of 1%. study or taking issue with a composite Convincingly, this pattern was seen in all endpoint, this allows one to really unpack four trials,” Sabatine commented. all of the issues by a neutral third party. “Of course for any given patient our “This was a collaboration between findings need to be put into the context of factors independent investigators and the principal that must be taken into account when deciding on a investigators for the trials, and for each trial there were revascularisation strategy,” Sabatine said, summarising interventionalists and surgeons. For the independent the findings. “The complex nuances of these data investigators, it is a mix of non-interventional emphasise the importance of a heart team approach to cardiologists, an interventional cardiologist, a cardiac assist patients in reaching a treatment decision that is surgeon, [and] a statistician, so that is the right best for them.” balanced mix. Now everyone has the same set of Speaking to Cardiovascular News, Sabatine said facts in front of them, and so I think that should help that the continuing controversy surrounding left main the conversation move forward, because everyone is revascularisation had provided the rationale for the starting on the same page.” study. “There has remained intense debate in the field, you need only look at Twitter, to how to approach this,” he said. “So to try to bring clarity to the field there was a call for having an independent group of experienced researchers gather the data and put them all together, and with all the data together hopefully provide a more complete picture that practitioners could use to guide the discussions they have with their patients about which revascularisation approach might be better for that particular patient.” Sabatine said he hoped that the review of data by the TIMI Study Group would provide some reassuring data for interventional cardiologists, cardiac surgeons and patients alike when considering treatment strategies. “Guideline committees have been waiting for

News in brief

The latest stories from the world of Cardiology

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n CARDIOGENIC SHOCK: Srihari Naidu details new guidance on the diagnosis and presentation of cardiogenic shock, aiming to simplify and standardise the management of these patients from the emergency room to the cath lab.

22.1%

For more on this story go to page 6.

Mortality at 10 years

Both interventional cardiologists and cardiac surgeons have the same goal of doing the right thing for the patient in front of them and are appropriately passionate about the approach that they can offer.”

n NEW DATA ON DRUG-COATED BALLOONS: Early data presented at the Transcatheter Cardiovascular Bruno Therapeutics annual Scheller meeting (TCT 2021; 4 – 6 November, Orlando, USA and virtual) suggest there may be a future for the use of sirolimuscoated balloons, offering an alternative to paclitaxel.

For more on this story go to page 15. n ABBOTT ON AI: Abbott’s chief medical officer Nick West offers insights from the company’s Beyond Intervention research programme and expands on how the company is using artificial intelligence (AI) to meet unmet needs in the cath lab.

For more on this story go to page 27.

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Issue 64 | February 2022

Fresh revascularisation guidelines issued Continued from page 1

radial access versus femoral when a clinician experienced in radial access is available. Of note, femoral access remains the default for patients unable to receive radial artery catheterisation because of anatomic limitations or because available clinicians are not experienced to perform radial access PCI. Other recommendations include the feasibility of a shorter one-to-threemonth duration of DAPT after PCI in select patients to reduce the risk of bleeding, compared with previous recommendations of six- or 12-months DAPT. “The heart team has become an important paradigm in clinical practice, emphasising the importance of team consensus on the optimal approach to revascularisation,” said Jacqueline E Tamis-Holland, guideline writing committee vice-chair and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, USA.

Cardiac surgery societies outline concerns Despite strongly endorsing a

Coronary Revascularisation multidisciplinary approach involving cardiac surgeons for decisionmaking relating to coronary artery revascularisation, the guidelines from the ACC, AHA and SCAI have not been uniformly welcomed within the cardiac surgery community, with the American Association for Thoracic Surgery (AATS) and The Society of Thoracic Surgeons (STS) opting not to endorse the new publication, despite being represented in the writing committee for the guideline. In a paper published in The Annals of Thoracic Surgery, Joseph Sabik (University Hospitals Cleveland Medical Center, Cleveland, USA) and colleagues detail the reasoning for the decision, outlining three main areas of concern within the guidelines. These include the downgrading of CABG in the treatment of three vessel coronary artery disease (CAD), a “lack of recognition” of the longterm benefits of CABG versus PCI in decreasing repeat reintervention and post-procedural myocardial infarction, and the award of a class of recommendation (COR) I to the radial artery as a CABG conduit. “Our main objection to these guidelines is the decrease in the COR from I (Strong) to IIb (Weak) for CABG to improve survival compared to medical therapy in patients with three-vessel CAD and normal left ventricular function,” Sabik and colleagues detail in their paper. “This two-level decrease in COR,

Key messages from ACC/AHA/ SCAI guideline for coronary artery revascularisation: n Overall, treatment decisions regarding coronary revascularisation in patients with coronary artery disease (CAD) should be based on clinical indications, regardless of sex, race, or ethnicity. n A multidisciplinary heart team approach is recommended in patients being considered for coronary revascularisation for whom the optimal treatment strategy is unclear. n For patients with significant left main disease, surgical revascularisation is indicated to improve survival relative to that likely to be achieved with medical therapy. n Percutaneous revascularisation is a reasonable option to improve survival, compared with medical therapy, in selected patients with low-to-medium anatomic complexity of CAD and left main disease. n The use of a radial artery as a surgical revascularisation conduit is preferred versus the use of a saphenous vein conduit to bypass the second most important target vessel with significant stenosis

after the left anterior descending coronary artery. n In patients undergoing percutaneous coronary intervention (PCI) who have acute coronary syndromes or stable ischemic heart disease, radial artery access is recommended to reduce bleeding and vascular complications compared with a femoral approach. Patients with acute coronary syndromes also benefit from a reduction in mortality rate with this approach. n A short duration of dual antiplatelet therapy (DAPT) after percutaneous revascularisation in patients with SIHD is reasonable to reduce the risk of bleeding events. n Staged PCI of a significantly stenosed non-culprit artery in patients presenting with an ST-segment elevation myocardial infarction (STEMI) is recommended in select patients to improve outcomes. n Revascularisation decisions in patients with diabetes and multivessel CAD are optimised by the use of a heart team approach.

as well as the decrease in COR from class I to class IIa for CABG to improve survival in patients with three-vessel CAD and mild to moderate left ventricular dysfunction, is not supported by available evidence and if adopted would bring a disservice to patients with multi-vessel CAD.” The paper’s authors noted that the ISCHEMIA trial was cited by the guidelines committee to support these downgrades, however they suggest that there are several reasons why ISCHEMIA should not be used to decrease the recommendation of

implies they have equivalent long-term benefit, which neglects to recognise the long-term benefits in addition to survival of CABG,” Sabik et al write. Furthermore, the authors write that the radial artery COR of I, rather than COR IIa with appropriate qualifiers strongly suggests that it should be used in essentially all CABG procedures. “This strong suggestion is not justified by present studies,” they claim. In their closing statement, Sabik et al write: “Given the inherent value to patients and practitioners of evidencebased guideline documents, the AATS

Treatment recommendations in the guideline outline an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularisation, with the intent to improve quality of care and align with patients’ interests.” CABG, including that the trial was not designed to determine whether CABG improved survival among patients undergoing an invasive revascularisation strategy. In addition, the paper’s authors note that patients enrolled in ISCHEMIA were not representative of patients with multivessel CAD a heart team would recommend CABG as the preferred revascularisation strategy. Less than half of the patients had stenosis of the proximal left anterior descending (LAD), and the cardiovascular mortality was low with or without intervention (~6% at five years), they add.

PCI versus CABG

On their objection to the guidelines grouping PCI and CABG as equivalent revascularisation strategies in decreasing ischaemic events, the paper suggests that multiple recent randomised studies have demonstrated the superiority of CABG over PCI in decreasing repeat reintervention and post-procedural myocardial infarction. “Grouping CABG and PCI together

Jennifer Lawton

and STS felt compelled to withdraw support for the recently published 2021 AHA/ACC/SCAI Coronary Revascularisation Guidelines. This decision is based upon the significantly different interpretation of the data related to the three areas of concern outlined in this editorial.”

Collaboration

Greater input from surgical specialists in drafting the guidelines would go some way to addressing these issues in future, the AATS and STS response suggests, noting that one representative from each body was included in the writing committee for the guidelines. The societies add: “The AATS and STS believe that there should be equal representation of surgeons and cardiologists on the writing committee, and that the surgical representatives should be chosen by the surgical societies. The AATS and STS also respect the right of the surgeons on the writing committee to remain as authors on these guidelines, despite the surgical societies not endorsing the guidelines.”

Joesph Sabik

February 2022 | Issue 64

Advertorial

THIS ADVERTORIAL IS SPONSORED BY SHOCKWAVE MEDICAL

Fresh data paint a positive picture for IVL in both eccentric and nodular coronary calcium The latest data from the Disrupt CAD clinical study programme, assessing the use of Shockwave intravascular lithotripsy (IVL) in the coronary arteries, provide compelling evidence that the technology is capable of modifying coronary calcium regardless of morphology—including eccentric and nodular calcium—prior to stent implantation. This is according to Javier Escaned (Hospital Universitario Clínico San Carlos, Madrid, Spain) and James Spratt (St George’s University Hospital NHS Trust, London, UK), who tell Cardiovascular News about the challenges of treating both eccentric and nodular calcium and discuss how new findings offer a reassuring picture of the use of IVL in these cases.

he treatment of eccentric and nodular calcium is seen as being particularly challenging in coronary vessels. The presence of eccentric calcium, whereby plaque volume is more concentrated on one side of the vessel, may cause uneven or incomplete stent expansion, ultimately increasing the likelihood of stent failure. This is particularly evident in the case of calcific nodules, blocks of calcified plaque that typically protrude into the lumen, which in addition to causing suboptimal stent expansion may cause gross malapposition of stent struts against the vessel wall. Current treatment approaches include balloonbased techniques, rotational atherectomy or orbital atherectomy, while IVL is an emerging treatment technique which uses sonic pressure energy, known as shockwaves, that pass through soft arterial tissue and preferentially disrupt calcified plaque by creating a series of microfractures. “IVL selectively targets calcium, with shockwaves that target the interface between calcium and non-calcific tissues,” says Spratt. Though IVL’s functionality in concentric lesions is well recognised, new data shed light on its use in treating both eccentric and nodular calcification. “We know that calcification has different patterns in the coronary arteries, and previous studies have shown that the degree of calcification plays a very important role in stent expansion, which at the end of the day, is one of the ways that calcification impacts on suboptimal stenting,” comments Escaned. “There was concern that perhaps the mechanical effect of IVL relied a lot on delivering energy inside a tubular calcific segment, and in an eccentric calcification, the elastic, calcific-free part of the vessel will in a way buffer the effect of the soundburst, of the energy delivered to the calcific components of the stenosis.”

OCT analysis

Two studies presented at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual) are among those to offer the clearest picture yet of the effectiveness of Shockwave IVL in both eccentric and nodular calcium. For the first analysis, researchers used optical coherence tomography (OCT) to analyse pooled data from 262 patients treated as part of the DISRUPT CAD I, II, III and IV studies with either eccentric or concentric calcium. Vessels were grouped depending on the arc of calcium seen. “The first thing to say is that it provides you with a level of detail that you do not get from an angiogram,” says Spratt, commenting on the use of OCT in the

degrees (6.2mm2 and 105%), respectively. Among the key aspects of the study is the relationship between the number of fractures seen in the calcium, relative to the type of calcium present, and the impact this may have on MSA and SE. Both Escaned and Spratt note that a greater number of fractures were seen in lesions with a greater degree of calcification. “Of course, you have a much wider region to find cracks, if you have 360 degrees than if you have 90 degrees, for example,” comments Escaned. In other words, according to Spratt, “the more calcium, the more fractures”. However, interestingly, Spratt notes that there did not seem to be a relationship between the number of fractures and stent expansion. “When you did not see the fracture, it did not seem to affect how well the stent expanded, which was a little bit of a surprise,” he comments. This is a point echoed by Escaned, who adds: “What is important is that if you divided into those that you see fractures and those that you do not see fractures, with all these different groups of calcification, there were no differences between groups and no differences

James Spratt

Javier Escaned

We know that calcification has different patterns in the coronary arteries, and previous studies have shown that the degree of calcification plays a very important role in stent expansion.”

For the first time we have objective evidence based on imaging and a solid dataset, that IVL is effective irrespective of the degree of calcification, in terms of the distribution of calcium that we see in the vessels.”

study, which represents the largest analysis of acute OCT outcomes of any calcium modification treatment. This provides a huge level of detail, he says. Turning to the data, he says that the findings should offer reassurance, due to the high number of patients included. “There are 262 cases, which is a lot of OCT studies, and that gives you more confidence in the finding,” Spratt adds. The analysis confirmed that coronary IVL achieved an excellent minimum stent area (MSA) and stent expansion (SE) consistently in lesions with both eccentric and concentric calcium. MSA and SE at the maximum site of calcification were similar across the four calcium arc quartiles analysed: ≤180 degrees (6.1mm2 and 104%), 181‒270 degrees (6mm2 and 101%), 271‒359 degrees (6.1mm2 and 98%) and 360

between the presence or absence of fractures in terms of MSA, or in terms of SE.”

Important lessons

Another learning point from the study, highlighted both by Escaned and Spratt is the mismatch between the location of the vessel with the most calcium and the narrowest point of the vessel. “What was found within the study was that the area that was narrowest was not the area with the highest calcium,” says Spratt. “That shows you a behavioural effect that where we see severe narrowing we often concentrate all of our treatment at these severe

Issue 64 | February 2022

Advertorial

IVL in eccentric calcification: Case report courtesy of Javier Escaned and Angela McInerney

Baseline

Post stenting

Ca2+ arc 85° 0. 70 mm thickness

Fracture

Post IVL OCT Eccentric calcific plaque in proximal LAD (baseline angiogram). After four cycles of energy delivered with a 4mm IVL system, OCT revealed plaque fractures (arrow) in the underlying eccentric plaque calcification. Left panel shows the final angiogram and OCT after stent implantation.

narrowings and ignore bystander areas,” he adds. Escaned suggests this is a finding that bodes well for IVL as a treatment modality. “The good thing about this technique is because it is delivering energy to a wider segment than the tightest point of the stenosis, you are already preparing the lesion to perform the proper stent implantation, that is the message here,” he says. In terms of the robustness of the data, the fact that there were no major differences in the procedural aspects across the subgroups of lesions should provide reassurance, according to Escaned. “It is a very solid dataset, because it was obtained in the context of prospective trials so that means that it is rigorous patient selection, acquisition and follow-up,” he comments. “When you looked at procedural time, contrast volume, predilation, the number of pulses that were delivered, there were no differences.” An important aspect to consider, according to Escaned, is stent expansion in the four different

groups depicting different degrees of eccentricity or concentricity of calcium after IVL. “In these four studies, there were no significant differences in minimal stent area, which suggests that for one reason or the other, from a practical perspective IVL was equally effective in all of these subgroups of lesions”, he comments. Summing up the totality of the data, Escaned adds: “This is the study that provides, for the first time, evidence suggesting that IVL is, from a practical perspective, equally effective in eccentric and concentric plaque.”

Calcific nodules

In a separate analysis of calcific nodules, coronary IVL was found to have a notable acute effect on calcific nodules, which were identified in 22% of cases, either by flattening or fracturing the nodule, resulting in consistent MSA (6.3mm2 vs. 6mm2) and SE (101% vs. 103%) in lesions with calcified nodules (n=54) or those without (n=194), respectively. The analysis also found that calcific nodules were more commonly associated with concentric calcium and greater overall calcium burden. “The main feedback in terms of the data was that with eccentric and nodular calcium you can still get good stent results,” says Spratt. “Lithotripsy, prior

Post stenting OCT to the recent data from TCT, was really an unknown. It was really unclear whether it would work, and the initial data are encouraging in that they show that it seems to treat nodular calcium pretty well.” Escaned describes nodular calcification as “the most extreme” subgroup of eccentric lesions. “Interestingly, the same thing was observed,” he says. “There was a very good result in this group of patients.” Reflecting on the overall message from each of the studies, Escaned and Spratt say that the new data add positively to the overall understanding of the outcomes of IVL in a range of morphologies. “I think that the overall message is that for the first time we have objective evidence based on imaging and a solid dataset, that IVL is effective irrespective of the degree of calcification, in terms of the distribution of calcium that we see in the vessels,” says Escaned. For Spratt, the simplicity and safety of IVL are further benefits. “IVL is a very easy technology to learn,” he comments. “There is no learning curve to it, [and] it is very safe. There is no signal for harm—acute or long-term harm. Those are two great foundational pieces to build an evidence base on and that means that you can try IVL therapy where you are not sure if it will work or not work. That will lead to its expansion into areas where we have been more concerned about a morbidity price to pay.”

February 2022 | Issue 64

Cardiogenic Shock

SCAI pushes revised standardised language to improve cardiogenic shock care New guidance on the diagnosis and presentation of cardiogenic shock aims to simplify and standardise the management of these patients from the emergency room to the cath lab. SPEARHEADED BY THE SOCIETY FOR Cardiovascular Angiography and Interventions (SCAI) the new expert consensus statement centres on a five-stage classification system intended to provide clinicians and researchers with a “unified and standardised vocabulary” for cardiogenic shock, applicable across a range of settings. Additionally, the system aims to facilitate recognition of risk for adverse outcomes, potential for benefit from various interventions with the goal of reducing mortality. SCAI Shock Stages builds upon a classification system first developed in 2019, designed for use by emergency room physicians and emergency medical services, critical care physicians, heart failure physicians, interventional cardiologists and surgeons. According to SCAI, though the system has been widely adopted for its simple framework and ability to discern gradations of severity of cardiogenic shock, recent validation studies conducted since 2019 have uncovered areas in need of refinement. A two-year update to the document was unveiled at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando, USA and virtual) by Srihari S Naidu (Westchester Medical Center, Valhalla, USA) who chaired the writing group tasked with developing the framework. Cross-disciplinary buy-in has been an important aspect of the document’s development, and SCAI has sought to work collaboratively with the American College of Cardiology (ACC), American College of Emergency Physicians (ACEP), the American Heart Association (AHA), the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), Cardiac Safety Research Consortium (CSRC), Society of Critical Care Medicine (SCCM) and The Society of Thoracic Surgeons (STS). “This topic spans a lot of different colleagues all taking care of these patients, so I am very proud of that fact,” Naidu tells Cardiovascular News, referring to the

diverse profile of organisations and experts involved in the drafting of the document’s latest version. “Having those organisations and critical care medicine endorse it will allow us to look at shock in all the different venues it occurs; be it at home, coming into the hospital, in the hospital, in the cath lab, in the critical care unit, or as they approach the surgeons.”

Unified language

“From soup to nuts we have one language that allows us to speak to anybody on the shock team. Each hospital will be quite different in terms of who is on that team and what location the patient is at. That has been a real benefit of the definition initially, enabling us all to speak the same language, but now we would

From soup to nuts we have one language that allows us to speak to anybody on the shock team.” like to improve that same language and broaden the number of people who are speaking it.” Naidu explains that the impetus for the project was to align the language, and therefore understanding, around the classification and treatment of cardiogenic shock. “The first questions were: ‘Are we talking about the same patients? How do we standardise so that we can generalise the findings of a trial to a patient population that we can more clearly envision?’” The resulting output is a system that describes the stages of cardiogenic shock from A to E. Stage A is those “at risk” for cardiogenic shock, stage B is “beginning” shock, stage C is “classic” cardiogenic

EXTREMIS A patient with refractory shock or actual/impending circulatory collapse.

DETERIORATING A patient who has clinical evidence of shock that worsens or fails to improve despite escalation of therapy.

CLASSIC A patient who has clinical evidence of hypoerfusion that intially requires pharmacologic or mechanical support. Hypotension is usually present.

BEGINNING A patient who has clinical evidence of hemodynamic instability (including hypotension, tachycardia or abnormal systemic hemodynamics) without hypoerfusion.

AT RISK A hemodynamically stable patient who is NOT experiencing signs or symptoms of CS, but is at risk for its development (i.e. large AMI or decompensated HF). ©2021 Society for Cardiovascular Angiography and Interventions

E D C B A

(A) Modifier: CA with concern for anoxic brain injury

shock, stage D is “deteriorating”, and E is “extremis”. Naidu explains that this system aids the simple categorisation of patients, as well as helping to track the progression and regression of shock within these cases, thereby informing whether to escalate treatment. Visually, the grades are displayed in an easy-tounderstand pyramid. “By doing that it facilitates the shock team to assess the patient, understand what direction the patient is going in and quickly have different minds tell us how we are going to impact this to defervesce. I think that the real benefit is that you get the diagnosis quickly, the table allows us to say ‘these are the things that would show you that you are getting into D or E, so you have to look for these proactively’.” While Naidu says he is encouraged by the take up of SCAI Shock so far, validation studies have informed the revisions and fine tuning that have gone into the second iteration of the document. Among the important points to have emerged from the studies is the correlation of SCAI Shock Stage with mortality across all clinical subgroups, including cardiogenic with and without acute coronary syndrome, cardiac intensive care unit (CICU) patients, and those presenting with out-of-hospital cardiac arrest (OHCA). Commenting on this finding, Naidu says: “As you moved up the stage it was very clear that mortality increased. It did not matter if it was a cardiogenic shock patient, or a general CICU patient, which is a variety of non-ischaemic and ischaemic cardiomyopathy or advanced heart failure disease substrates, and it did not matter if the patient had an out-of-hospital cardiac arrest or not. In all of these patient populations, as you went up the pyramid, the mortality was statistically significantly increased.” Among the updates to the document the SCAI Shock pyramid and associated figure now reflect gradations of severity within each stage, highlighting the variability based on risk modifiers within each stage, and pathways by which patients progress or recover. A streamlined table incorporating variables that are most typically seen, and a revised cardiac arrest modifier definition, is also provided and incorporates lessons from validation studies and clinician experience. Lactate level and thresholds have also been highlighted to detect hypoperfusion but may be dissociated from haemodynamics in cases such as chronic heart failure. In addition, patients may demonstrate other manifestations of end-organ hypoperfusion with a normal lactate level and there are also important causes of an elevated lactate level other than shock. SCAI proposes to develop a hub and spoke model for transfer of higher-risk patients including those with deteriorating SCAI Shock Stage. “We know that not all hospitals have the same resources, in terms of personnel,” Naidu said, explaining that the ultimate aim is for cardiogenic shock patients to be directed at the first instance to the hospital where they can receive the most appropriate treatment. “That will be a huge benefit to society because it is less resource utilisation if you have the right patients for the right hospital using appropriate resources for the appropriate patients, which ultimately will be cost saving and hopefully also life-saving by avoiding unnecessary transfer delays.” In terms of next steps, Srihari S Naidu Naidu said he expects that analysis of the impact that this latest iteration of the document will shape future direction. “Future directions will have to be—is this truly applicable in all settings?” he said.

Issue 64 | February 2022

Conference Coverage

“Tantalising” data open the door for further study of mechanical aspiration thrombectomy with PCI

is and so you may indiscriminately perform angioplasty in areas that do not necessarily need to be intervened upon,” he adds. Patients were eligible for the trial if they had a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade of 4 or 5, “a very high thrombus burden”, according to Mathews, and post-wire crossing. Patients were Results of the CHEETAH clinical study highlight the potential treated within 12 hours of symptom role of mechanical aspiration thrombectomy in conjunction with onset. Primary endpoints of the trial percutaneous coronary intervention (PCI) in native coronary included a composite of major adverse arteries in patients with high thrombus burden according to the clinical events (MACE) including study’s principal investigator, Jay Mathews (Manatee Memorial cardiovascular death, recurrent Hospital, Bradenton, USA). Mathews spoke to Cardiovascular myocardial infarction (MI), cardiogenic News following the presentation of the study’s findings at the shock and new or class IV heart Transcatheter Cardiovascular Therapeutics annual meeting (TCT failure. Secondary endpoints included 2021; 4–6 November, Orlando, USA and virtual). final TIMI flow and thrombus grade, myocardial blush grade rials including TASTE and continuous mechanical (MBG), distal embolisation TOTAL have previously aspiration prior to PCI using rate, and device-related investigated the utility of the Indigo CAT RX catheter adverse events and stroke routine thrombus aspiration in patients system (Penumbra). “CAT within 30 days. undergoing PCI. “They found that RX is a novel technology Headline findings presented routine manual aspiration really did not in comparison to prior by Mathews at TCT include show any benefit, and of more concern aspiration catheters that an overall freedom from did show an increased rate of stroke,” have largely been held MACE of 96.5%, as well as Mathews explains. back by the limitations Jay Mathews a significant reduction in In 2018, the TOTAL authors studied of manual aspiration, TIMI thrombus grade, with a subset of patients with high thrombus which is that the suction force drops 99.5% of patients having achieved TIMI burden from the trial. They found an off significantly over time,” Mathews thrombus grade 0 after CAT RX and increased rate of stroke in the high explains, adding that CAT RX combines PCI. Investigators also reported that the thrombus burden patient subset, but with a large bore catheter and allows for procedure improved TIMI flow grade a reduction of distal embolisation. continuous powered aspiration. “The with 97.5% of patients having TIMI This was the rationale for the reason why this is effective is it is able flow grade 3 after CAT RX and PCI, CHEETAH clinical study, Mathews to maintain a continuous aspiration force while TIMI 2‒3 increased significantly tells Cardiovascular News. “Essentially throughout the entire duration of the from 16.6% at baseline to 85% after everybody has shied away from procedure, as it is a powered system,” CAT RX alone. Additionally, the study thrombectomy, which we believe is he adds. “This is a significant advantage found an enhanced MBG, with 99.8% appropriate, but the concept still exists over these syringes that have been used of patients having achieved MBG 3 that selective bailout thrombectomy in the past.” after CAT RX and PCI—described by in high thrombus burden patients When performing PCI in patients Mathews as the most impressive take may potentially be beneficial if the with high thrombus burden without away from the study. Finally, no devicetechnology was better, so that is what aspiration, the key concerns are the related serious adverse events occurred. CHEETAH was trying to show,” he emergence of distal embolisation and Asked for his view on the says. potential damage to areas of the vessel implications of the findings, Mathews The prospective, single-arm study that do not have a lesion, Mathews expresses cautious optimism—noting enrolled 400 patients with high explains. “When you have thrombus you that a larger study is needed to inform thrombus burden who were treated with cannot really see where the true lesion any future change in practice.

Machine learning predicts 10-year risk of death in patients with suspected or known coronary artery disease The likelihood of patients with suspected or known coronary artery disease dying within 10 years, can be more accurately predicted using a novel artificial intelligence (AI) score, compared to established scores used by health professionals worldwide. This is according to the authors of research presented at EuroEcho 2021 (9–11 December, virtual). UNLIKE TRADITIONAL METHODS WHICH are based on clinical data, the new score includes imaging information on the heart, measured by stress cardiovascular magnetic resonance (CMR). The study author, Theo Pezel of the Johns Hopkins Hospital, Baltimore, USA, explained. “This is the first study to

show that machine learning with clinical parameters plus stress CMR can very accurately predict the risk of death,” he said. The study by Pezel et al included 31,752 patients referred for stress CMR during the time period of 2008–2018 to a centre in Paris, France, and data were collected on 23 clinical and 11 CMR parameters. These patients were referred due to chest pain, shortness of breath on exertion, or high risk of cardiovascular disease but were asymptomatic. In this study, a high-risk patient was defined as having at least two risk factors such as hypertension, diabetes, dyslipidemia, and current smoking habits. The average patient age was 64 years, and 66% of the cohort was male. Patients were followed up for a median of six years for all-cause death. During the follow-up period, researchers reported that 2,679 (8.4%) patients died. Machine learning was conducted in two steps. First, it was used to select which of the clinical and CMR parameters could predict death and which could not, and secondly, machine learning was used to build an algorithm based on the important parameters identified in step one, allocating different emphasis to each to create the best prediction. Patients were

“We used the word tantalising, because finally we have a device that works really effectively within the high thrombus burden space. Of course, changing practice cannot really be done without more data, but the present findings really point towards reopening this door and really looking at utilising this type of device in this population,” Mathews comments. “Certainly, it is going to invite more study and I think there are a lot of people who are very much interested in this now because, really, there has been no advance in the thrombectomy space for years, partly because everybody thought that the story was closed after the TOTAL trial.” In particular, Mathews believes the enhanced MBG witnessed among patients undergoing mechanical

We used the word tantalising, because finally we have a device that works really effectively within the high thrombus burden space.” thrombectomy is a key finding from the study, and says this should be an important area for future research. “I think CHEETAH now suggests that maybe this story is not over and that there could be a huge potential as MBG, as a surrogate marker, does seem to be associated with better outcomes in these patients in general. So, I think that we certainly will want to continue to study this and hopefully change practice in the future.”

given a score of 0 (low risk) to 10 (high risk) for the likelihood of death within 10 years from this algorithm. A prediction of which patients would survive through the machine learning presented 76% accuracy. Using the same data, the researchers calculated the 10-year risk of all-cause death using established scores (systematic coronary risk evaluation [SCORE], QRISK3, and Framingham Risk Score [FRS]) and a previously derived score incorporating clinical and CMR data (clinical-stress CMR [C-CMR-10])— none of which used machine learning. The machine learning score had a significantly higher area under the curve for the prediction of 10-year allcause mortality compared with the other scores: SCORE=0.66, QRISK3=0.64, FRS=0.63, and C-CMR-10=0.68. To conclude, Pezel drew attention to the benefits and future advantages of CMR. “Stress CMR is a safe technique that does not use radiation. Our findings suggest that combining this imaging information with clinical data in an algorithm produced by AI might be a useful tool to help prevent cardiovascular disease and sudden cardiac death in patients with cardiovascular symptoms or risk factors.”

Issue 64 | February 2022

Cardiovascular surgery Research suggests many patients may be safely discharged without opioids after cardiac surgery Many patients undergoing cardiac surgery may be able to safely and effectively control postoperative pain without opioids after hospital discharge, according to research published in The Annals of Thoracic Surgery.

esearch by Catherine Wagner (University of The researchers also found that among the 909 Michigan, Ann Arbor, USA) and colleagues patients who did not take any opioids on the day examined data from 2019 for patients who before discharge, 415 (46%) still received an opioid underwent coronary artery bypass grafting (CABG), prescription at discharge. heart valve surgery, or a combination of both via “One should consider if these opioid prescriptions median sternotomy at 10 centres participating in the were truly necessary for patient pain relief,” said Michigan Society of Thoracic and Cardiovascular Wagner. “Our study shows that, particularly for Surgeons Quality Collaborative. (MSTCVS-QC). patients who did not take any opioids on the day “In some cases, patients assume that after before leaving the hospital, discharge without surgery, especially a big operation like cardiac opioids is safe. I think we need to ensure that surgery, that they will need to go home with only patients who truly need opioids get sent prescription pain medicine,” said Wagner. home with a prescription.” “This study shows that discharge without “For decades, surgeons have unwittingly opioid pain medicine after cardiac surgery is but substantially contributed to the opioid extremely well tolerated by some patients. In epidemic,” said Thomas E MacGillivray other words, we should not be reflexively (Houston Methodist, Houston, USA), Catherine Wagner prescribing pain medicine to people after commenting on the research. “No one surgery just in case they need it.” wants any patient to be discharged home after surgery The researchers found that 28% of patients without adequate pain relief. With the best intentions (547/1,924) did not receive an opioid prescription to help relieve pain and alleviate anxiety about pain, at the time of discharge. Patients who were older, discharge practices have frequently erred on the side spent more time in the hospital after surgery, or who of prescribing too many rather than too few narcotic underwent surgery and were discharged during the last pain pills. We have learned that many of the unused, unneeded narcotics end up in the community. This very important study will help surgeons identify patients who may comfortably be discharged home without narcotics.” Wagner explained that prior to the relatively recent awareness of the opioid epidemic, patients often would be prescribed 50 to 100 opioid pills after surgery for various reasons. Unrelated research has shown that leftover medication may be diverted into the community, contributing to the opioid epidemic. With increased attention on the excessive prescribing of opioids for pain treatment after surgery, national efforts such as prescribing guidelines and patient education programmes have begun to help “limit unnecessary three months of the study period (October–December) opioids in the community and decrease the risks of were more likely than other patients to leave the developing new persistent opioid use in patients,” hospital without an opioid prescription. she said. Conversely, the researchers found that patients with Moving forward, the researchers plan to focus on a history of depression, those who were treated with ensuring that only patients who truly need opioids opioids on the day prior to discharge, or patients whose are sent home with a prescription, while also race was non-black and non-white were more likely to eliminating “just in case” prescriptions that leave receive an opioid prescription at discharge. unnecessary opioids in communities and put patients Additionally, the researchers report that discharge and their family members at risk from opioid without an opioid prescription appears to have diversion. been well tolerated, as fewer than 2% of patients “It is important to balance excellent subsequently required a prescription after their pain control while limiting unnecessary discharge and before their 30-day follow-up opioids,” said Wagner. “We are still appointment. learning how to best find this balance “This study’s findings should provide patients for our patients and recommend that with reassurance that postoperative pain can be patients always work closely with managed with non-opioid pain medications at home,” their physicians/provider teams to said Wagner. decide what is best for them.”

This study shows that discharge without opioid pain medicine after cardiac surgery is extremely well tolerated by some patients.”

Joanna Chikwe appointed as editor-in-chief of The Annals of Thoracic Surgery

The Society of Thoracic Surgeons (STS) has appointed Joanna Chikwe (chair of the Department of Cardiac Surgery in the Smidt Heart Institute at Cedars-Sinai, Los Angeles, USA) as the new editor-in-chief of The Annals of Thoracic Surgery and its soon-to-be-launched open access journal, Annals Short Reports. “THIS IS AN EXHILARATING TIME TO RUN A journal of this calibre, because of the exciting science and technology transforming our specialty and the untapped potential of digital content,” said Chikwe. “STS is the most widely recognised organisation in cardiothoracic surgery, so the potential global impact is huge.” Chikwe previously served as associate editor and deputy editor for The Annals, and as a section editor for specialty journals such as the European Heart Journal and Journal of the American College of Cardiology (JACC). In addition, she has published more than 200 peer–reviewed contributions and three surgery textbooks, as well as led six expert consensus writing groups. Chikwe is the principal investigator of the National Institutes of Health-sponsored trial with the Cardiothoracic Surgical Trials Network of surgical versus transcatheter degenerative mitral valve repair. A recognised leader in the fields of robotic mitral valve repair and coronary revascularisation, Chikwe is the founding chair of the Department of Cardiac Surgery in the Smidt Heart Institute at Cedars-Sinai. She also serves as the Irina and George Schaeffer Distinguished Chair in Cardiac Surgery and professor of cardiac surgery. Chikwe completed her medical degree at the University of Oxford (Oxford, UK), cardiothoracic surgery residency at the Royal Brompton and Harefield Hospitals (London, UK) and cardiac surgery fellowship at Mount Sinai Hospital (New York, USA). She remained on the Mount Sinai faculty for more than a decade before being recruited to lead the Department of Cardiac Surgery at Cedars-Sinai. “Dr Chikwe is an accomplished cardiac surgeon with an impressive record of academic scholarship, effective leadership, and clinical achievement,” said STS president Sean C Grondin. “With her significant editorial experience, she has proposed exciting strategies to make The Annals the most impactful and engaging journal in cardiothoracic surgery. We are thrilled to welcome her to the leadership team and are looking forward to continuing our work together in providing a high-quality journal for our specialty.” Chikwe’s appointment follows the departure of G Alexander Patterson who has served as editorin-chief since 2015. Joanna Chikwe

February 2022 | Issue 64

Cardiovascular surgery CX 2022 returns to in-person format facing challenges and opportunities in the aortic field Anticipation is building for the Charing Cross International Symposium 2022 (CX 2022). This will be the first ever hybrid symposium and organisers look forward to welcoming around 2,000 participants in person and up to 6,000 virtually from around 100 countries.

his year the global cardiovascular community challenges the evidence as part of the CX three-year cycle of raising cardiovascular and endovascular controversies to challenge the available evidence in order to reach consensus after discussion with an expert audience. The year's comprehensive aortic programme will bring together world-leading experts from the cardiovascular, vascular and endovascular worlds including Joseph Bavaria, Gustavo Oderich, Joseph Coselli and Roberto Chiesa. Running from 26–28 April, the three-day symposium returns to an in-person format for 2022 in a new transition year location, the Hilton London Metropole in the heart of central London, and features livestream

and on-demand viewing options for a global audience. The symposium continues its three-year cycle of raising vascular and endovascular controversies to challenge the available evidence and be able to reach a consensus after discussion with an expert audience. The programme will include Aortic Challenges and CX Aortic Techniques and Technologies sessions with live and edited live cases. Challenges to practice, in all vascular domains, including peripheral arterial, venous, acute stroke and vascular access will also be explored in live, edited live and workshop demonstrations. Experts in every field will consider a range of options and weigh up the important issues head-tohead in CX debates.

CX returns to an inperson format for 2022

Research finds poor level of surveillance following aortic dissection repair

Patients who survive an aortic dissection often fail to receive comprehensive post-surgical follow-up care leaving them vulnerable to a lifetime of sustained risk. This is according to research published in the Journal of the American College of Cardiology (JACC), authored by Jennifer Chung (Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada). THE RESARCH LOOKED AT surveillance imaging following acute type A aortic dissection.“What we found in our study was that almost no one was receiving guideline-recommended imaging surveillance (GRIS) after

dissection,” says Chung. “These patients are at ongoing risk for aortic complications, reintervention and death. It is important to know that these risks do not subside over time.” Chung’s study examined 888 patients

The aortic programme aims to highlight novel approaches to the most pressing abdominal, thoracic and juxtarenal aortic, as well as radiation, challenges and focus on advancements in the aortic field. According to Stéphan Haulon (Hôpital Marie Lannelongue, GHPSJ, Paris, France), arch repair is among the important areas for discussion in the aortic space. “The next challenge in the aortic world is the repair of the arch,” Haulon, a member of the CX 2022 aortic executive board, comments, reflecting on the important talking points ahead of the April event. “We now have a couple of devices with three branch options—total endovascular repair of the arch, a percutaneous approach, or to have a less or minimally invasive approach. “The future will probably be type A dissections. We still do not know if there is a role for endovascular, but it seems that there is a lot of research and development going on and probably, in the near future, we will be able to do Endo-Bentall repairs and acute type A dissections will probably be a subgroup of patients that will benefit from this new technology.” Tara Mastracci (Barts Health NHS Trust, London, UK) reflects on the importance of developing more accurate fusion technologies and non-ionising radiation guidance. Techniques and technologies aimed at reducing radiation dosage and exposure are set to feature throughout the CX 2022 programme. “Technically, intraoperatively, getting more accurate fusion technology is something that I am super excited about, and I am excited to learn more about aortic deformation,” says Mastracci. “I cannot wait to see how the technologies emerge for non-ionising radiation guidance and other ways that we can use vessel guidance in the operating room that does not expose us to radiation.” New techniques to prevent stroke in thoracic endovascular aortic repair (TEVAR) are among the important areas highlighted by Tilo Kölbel (University Heart Center Hamburg, Hamburg, Germany), who also sits on the CX 2022 aortic executive board. “The most pressing aortic challenges that I look forward to learning more about at CX 2022 and seeing the discussion about new techniques is stroke in TEVAR,” says Kölbel. “There are some new techniques that make stroke less likely to occur during TEVAR including carbon dioxide flushing. I know that there are new data prepared to be shown at CX 2022 and I look forward to seeing those.”

who survived urgent aortic dissection repair between 1 April 2005 and 31 March 2018. If one survived the surgery, the mortality rate was 4% after one year, 14% at five years, and 29% at 10 years. The study also showed that the rate of surveillance imaging d ropped to 21% just two years post-surgery, and at eight years, it was less than 2%. Guidelines recommend surveillance at one, six and 12 months, and then annually, following dissection repair. Overall, only 14% of patients underwent surveillance at these timepoints. Other factors contributing to the lack of consistent follow-up care include distance between the patient’s residence and the referral centre where they received surgery, and misconceptions

surrounding the durability of the repair. Addressing this lack in comprehensive post-surgical followup is why Chung has established the Thoracic Aortic Surgery Clinic within the Peter Munk Centre of Excellence in Aortic Disease. “Our clinic is multidisciplinary—it includes a range of aortic experts, including cardiac surgeons, vascular surgeons, and interventional radiologists,” explains Chung. “We follow patients with aortic dissections and aortic aneurysm who may need ongoing imaging surveillance and possibly even surgery down the road. By providing clear and accessible follow-up, we hope to prevent future aortic catastrophe.”

Issue 64 | February 2022

Asymptomatic aortic stenosis patients benefit from early valve replacement surgery Asymptomatic patients with severe aortic stenosis (AS) may benefit from early aortic valve replacement surgery due to a reduced risk of death, heart attack, stroke and heart failure, according to late-breaking research presented at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November; virtual). THIS WAS THE CONCLUSION OF the AVATAR—Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis— trial, presented by Marko Banovic, professor of cardiology at University Clinical Center of Serbia and the University of Belgrade Medical School, Belgrade, Serbia. The decision to operate on an asymptomatic patient with severe AS and normal left ventricular (LV) function remains a matter of debate, Banovic said in his presentation, commenting that this remains a significant unmet need. Observational studies have challenged watchful waiting in such patients by noting increased mortality and morbidity, he noted, adding that recent randomised trial data suggest a benefit of early valve surgery in patients with critical aortic stenosis and high prevalence of bicuspid valves. “Managing an asymptomatic patient with severe aortic stenosis can make for a much more difficult decision since valve replacement is not needed to improve the person’s quality of life, and the risk of sudden cardiac death is perceived to be low—around 1% per year, though still higher than in the general population,” said Banovic. “Another factor to consider, though, is that sustained pressure overload of the left heart chamber in severe aortic stenosis during a watchful waiting period is associated with structural and functional cardiac impairment. Without treatment, these impairments may

progress and become irreversible by the time valve replacement surgery is done, and there may be potentially more serious complications including heart attack, stroke and death.” The study was designed to evaluate the safety and effectiveness of performing aortic valve replacement surgery earlier for adults who are asymptomatic and have normal left ventricle function. The study was conducted at nine centres across seven European countries and included a total of 157 adults, 57% men, with an average age of 67 years. All study participants were confirmed to have no symptoms associated with severe aortic stenosis via standardised exercise testing, and they did not have any significant health conditions such as severe lung disease, chronic kidney disease or an overall high surgical risk. The patients were randomly assigned to have early surgery (78 patients) or to receive conservative, non-surgical treatment of watchful waiting (79 patients), in accordance with current treatment guidelines. Analysis of both study groups found that 72 participants in the early surgery group received an aortic valve replacement. After an average followup of 32 months, they had lower rates of combined death, heart attack, stroke or unplanned hospitalization for heart failure compared to the watchful waiting group. Only 13 patients in the early surgery group experienced one or more of cardiac issues (death, heart attack, stroke or unplanned hospitalisation for heart failure), compared to 26 people in the non-surgical treatment group. One person in the early surgery group died within 30-days after the operation. Banovic noted the 1.4% intra-operative mortality rate in this group aligned with the anticipated mortality for elective isolated surgical aortic valve replacement. In conclusion, Banovic told AHA attendees that the AVATAR trial demonstrates the preliminary efficacy and safety of early surgical valve replacement in improving the clinicallyrelevant composite endpoint of all cause death, acute MI, stroke and unplanned heart failure hospitalisation. The findings advocate for early surgery once aortic stenosis becomes significant regardless of symptoms, Banovic said. “We believe our results provide new evidence to aid clinicians when they are considering treatment options for those patients who have undergone systematic exercise testing to assess truly asymptomatic aortic stenosis with mainly progressive disease and normal left ventricular function,” he added.

1.4%

intra-operative mortality rate after early valve replacement surgery

VEST device may lead to increased saphenous vein graft longevity after CABG

Use of a novel, venous external support device (VEST, Vascular Graft Solutions) may lead to increased longevity and durability of saphenous vein grafting during coronary artery bypass graft (CABG) surgery, according to investigators in the VEST trial, results of which were present by John Puskas (Icahn School of Medicine at Mount Sinai, New York, USA) at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November; virtual).

he VEST trial, which was conducted by the National Heart, Lung and Blood Institute Cardiothoracic Surgical Trials Network in collaboration with the Mount Sinai health network, investigated the safety efficacy of VEST, a small device comprising a braid of 42 cobaltchromium wires that is placed over a pencil-sized vein graft. The external support is designed to prevent veins from stretching under higher pressure, leading to better survival of vein grafts and improved patient outcomes. The initial phase of the research, which is the first US Food and Drug Administration (FDA)-approved trial to test the efficacy of this device, will prompt further long-term studies that may lead to FDA approval. Proliferative intimal hyperplasia of saphenous vein grafts (SVGs) after CABG predisposes to the later development of graft atherosclerosis and occlusion, resulting in adverse clinical outcomes, Puskas told AHA attendees. External support of SVGs, therefore, has the potential to prevent SVG dilation, Puskas noted in his presentation “Vein grafts have a limited durability—about half of them will be closed 10 years after coronary bypass surgery. We need to find a solution to improve outcomes of surgery and prevent patients from having complications and repeated procedures,” said Puskas, the principal investigator.

We need to find a solution to improve outcomes of surgery and prevent patients from having complications and repeated procedures.”

John Puskas

To study VEST’s efficacy, researchers conducted a randomised patient trial in 17 cardiovascular surgery centres in Canada and the USA between January 2018 and February 2019. They enrolled 224 patients scheduled to undergo CABG with two or more saphenous vein grafts. Patients were their own controls: for each patient, one vein graft was supported with VEST and the other vein graft or grafts had no external support. Investigators used the thickness of the inner cell layer lining the vein graft as the trial’s primary endpoint. To assess this, researchers placed a catheter inside the vein graft and conducted an intravascular ultrasound (IVUS) 12 months after surgery. In all, 203 of the 224 patients returned for the one-year follow-up angiogram and IVUS. However, 90 of them did not have not have IVUS completed for both vein grafts, due to narrowed grafts or other technical reasons including catheter issues; for these patients, researchers replaced missing information with substituted values from estimates based on data already collected from other patients in the trial. Data from these 203 patients showed that VEST did not significantly reduce intimal hyperplasia in vein grafts, compared to non-VEST vein grafts. But when researchers did the same type of analysis on the subset of 113 patients who did complete ultrasounds, the VEST grafts had significantly lower amounts of hyperplasia compared to non-VEST grafts. “These findings are encouraging despite the fact that the p-value of the primary analysis did not quite reach statistical significance,” Puskas commented.

February 2022 | Issue 64

Cardiovascular surgery RAPID CABG trial finds in favour of bypass surgery sooner after ticagrelor cessation Coronary artery bypass graft sugery (CABG) between two and three days after ticagrelor cessation was found to be non-inferior in incurring severe or massive perioperative bleeding compared to waiting between five and seven days prior to the procedure, per current guidelines.

his is according to findings of the RAPID CABG study, presented during a late-breaking science session at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November; virtual) by Derek So (University of Ottawa Heart Institute and a professor at the University of Ottawa, Ottawa, Canada). The findings could influence future guidelines and prompt a reduced waiting time prior to CABG surgery, the study’s authors claim. According to So, 10% of patients with acute coronary syndromes require CABG, among whom perioperative bleeding is a major concern. In the PLATO trial, which assessed the antiplatelet medication ticagrelor versus clopidogrel in patients with acute coronary syndromes, patients undergoing CABG one day or less after ticagrelor were found to have high mortality. Current guidelines recommend that people taking ticagrelor requiring CABG should stop taking the medication between five and seven days before the surgery to reduce their risk of massive bleeding. A potential concern, however, is the risk of a recurrent heart attack or angina pains during the window of time during which they are not not taking the medicine. To evaluate if a shorter waiting time for surgery after stopping ticagrelor is safe, the RAPID CABG study assessed bleeding after bypass surgery in people at two centres in Canada. The study investigators randomly assigned 143 people who previously had suffered heart attacks, had received ticagrelor and required bypass surgery into two groups—one for earlier surgery after stopping ticagrelor and the other for surgery after the standard wait time. A total of 72 people (average age of 64 years, 80.6% male) were in the early bypass surgery group and had surgery two to three days after stopping ticagrelor, and 71 people (average age of 65.5 years, 83.1% male) were in the delayed surgery group, following current standard of care of stopping ticagrelor five to seven days before surgery. The people in both groups had similar baseline characteristics, including age and percentages of coexisting health conditions. Study researchers gauged the number of people who had severe or massive perioperative bleeding during the early postsurgical period, as defined Derek So

by the universal definition of perioperative bleeding (UDPB). Severe or massive bleeding defined by UDPB includes massive blood transfusions of >5 units of red cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000mL in the first 12 hours and reoperation for bleeding. The investigators also compared length of stay in the hospital and rates of episodes of angina, recurrent heart attack, stroke and death among the two groups.

Results

The investigators found that bypass surgery in the early surgery group (after two to three days of stopping ticagrelor) showed no increased risk of early post-surgical bleeding, and rates of bleeding were similar between the two groups. The rate of severe or massive perioperative bleeding (using the universal definition of perioperative bleeding) was 4.6% in the early surgery group and 5.2% in the delayed group. For clinical reasons, some people in the delayed surgery group had to have CABG surgery sooner than the planned date; 9% experienced recurrent angina (chest pains), recurrent heart attack and ventricular arrhythmias (abnormal rhythms which may be due to the blockages) that prompted earlier surgery. In contrast, no one in the early surgery group had to have surgery earlier than two days after they stopped taking ticagrelor. The average length of hospital stay was reduced by three days among the participants in the early surgery group compared to the delayed group. “We discovered no significant increase in bleeding when people had bypass surgery after two to three days of discontinuing ticagrelor,” said So. These findings may be surprising based on the assumption that the presence of a strong blood thinner should predispose people to severe bleeding, he commented. “Research such as this, with people randomly allocated to early versus delayed surgery, is integral to assure cardiologists and surgeons that early surgery is safe, especially since it conflicts with the present guidelines for people who are taking ticagrelor,” So added. “Furthermore, although our study was not large enough to evaluate whether early surgery protects people from suffering early recurrent heart attacks or angina, it opens this hypothesis and may prompt future research in the area.”

AI-based algorithm could predict outcomes after cardiac surgery A novel artificial intelligence (AI) algorithm that identifies a cardiac dysfunction from a single-lead electrocardiogram (ECG) can also predict long-term patient survival after cardiac surgery, according to new research from Mayo Clinic (Rochester, USA).

THE STUDY, PUBLISHED IN MAYO CLINIC Proceedings, finds that an algorithm that previously has shown it can detect patients with reduced left ventricular ejection fraction (LVEF) may also predict long-term mortality after cardiac surgery, making it a potentially valuable tool for assessing risk as patients and their health care providers consider surgery. “Our study finds there is a clear correlation between long-term mortality and a positive AI ECG screen for reduced ejection fraction among patients without apparent severe cardiomyopathy,” said Mohamad Alkhouli, a Mayo Clinic cardiologist and the study’s senior author. “This correlation was consistent among patients undergoing valve, coronary bypass, or valve and coronary bypass surgery.” The retrospective study involved reviews of 20,627 patients at Mayo Clinic in Rochester from 1993 to 2019. The patients underwent coronary artery bypass grafting (CABG), valve surgery or both, and they had a left ventricular ejection fraction of more than 35%. Of these patients, 17,125 had a normal AI ECG screen and 3,502 had an abnormal screen. Patients with an abnormal screen tended to be older with more comorbidities.

This may aid in risk stratification of patients referred for surgery and facilitate shared decision-making.” The algorithm was applied to the most recent ECG the patients had within 30 days before surgery. Baseline characteristics, as well as in-hospital, 30-day and longterm mortality data, were extracted from the Mayo Clinic cardiac surgery database. Probability of survival at five years was 86.2% for patients with a normal screen versus 71.4% for those with an abnormal screen. The 10-year probability of survival was 68.2% and 45.1%, respectively, for the two groups. “Our study documented the algorithm’s prognostic value in predicting long-term, all-cause mortality after cardiac surgery,” said Alkhouli. “The analysis showed that an abnormal AI screen was associated with a 30% increase in long-term mortality after valve or coronary bypass surgery. For clinicians, this may aid in risk stratification of patients referred for surgery and facilitate shared decision-making.” The study is believed to be the first large-scale research to explore the usefulness of AI algorithms with a single ECG to better predict cardiac surgery outcomes. Because the algorithm uses a routine and relatively inexpensive test, it could be applied widely after validation. Additional studies are underway to determine whether the information provided by the algorithms can improve diagnosis, decision-making and clinical outcomes.

Issue 64 | February 2022

Conference Coverage 15

“Promising” early data shared on alternatives to paclitaxel drug-coated balloons at TCT 2021 Early data presented at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando, USA and virtual) suggest there may be a future for the use of sirolimus-coated balloons, offering an alternative to paclitaxel for the treatment of both in-stent restenosis and de novo lesions. LATE-BREAKING STUDIES delivered by Wan Asman Wan Ahmad (University Malaya Medical Center, Kuala Lumpur, Malaysia) and Bruno Scheller (University of Saarland, Saarland, Germany) have provided initial insights into the use of the sirolimus-coated SeQuent (B Braun) balloon compared with a paclitaxelcoated balloon (PCB). A further presentation by Kai Xu (General Hospital of Northern Theater Command, Shenyang, China) delivered during the same session has detailed findings from BIO-RISE CHINA trial, assessing the safety and efficacy of a Biolimus A9 (BA9)-coated balloon compared to plain balloon angioplasty (POBA). “Paclitaxel-coated balloons are the standard of care for the treatment of coronary in-stent restenosis outside of the USA,” Scheller said in the introduction to his presentation, which summarised the findings of two trials, FIM Malaysian and a German-Swiss randomised study comparing the SeQuent sirolimus-coated balloon (SCB, 4μg/mm²) with the SeQuent Please Neo PCB (3μg/mm²). The studies had a primary endpoint of angiographic late lumen loss—the angiographic minimum lumen diameter immediately after percutaneous transluminal angioplasty minus the minimum lumen diameter at angiographic follow-up—at six months with a non-inferiority margin of 0.35mm to test the difference in SCB and PCB. “The use of limus on a balloon is far more complicated than the use on a stent because with a stent platform you can guarantee the controlled release of the drug in the tissue to allow for long therapeutic levels of the drug,” Scheller told TCT attendees. “In the case of the balloon application, you only have this one-time drug transfer, and you have to allow for an amount of the drug to be transferred,” he went on to explain. “In addition, you have to allow for a longer persistence of the drug to guarantee therapeutic effect. This is easier with paclitaxel because you have irreversible binding of the drug to the microtubes in the cell, whereas limus and its analogues have reversible binding.” Both the Malaysian and GermanSwiss studies were conducted in parallel, Scheller explained, using an identical study protocol. In total, 101

patients were randomised, 50 in the SCB group and 51 in the PCB group. Patients underwent clinical follow-up at 30 days, six months and 12 months. Detailing the clinical characteristics of the two groups, Scheller noted that there was very little difference between the two groups, and that a majority of patients had multivessel disease. Looking at the primary endpoint, Scheller noted that distribution of late lumen loss was similar in the two groups, 0.30mm in the SCB group and 0.30mm in the PCB group for in-lesion late lumen loss, and 0.26mm in the SCB group and 0.25mm in the PCB group for in-segment late lumen loss. These findings led Scheller to conclude that that a novel sirolimuscoated balloon with a highly crystalline

paclitaxel-coated balloons remain the standard,” Scheller summarised. Prior to Scheller, Kai Xu presented insights from BIO-RISE CHINA, a multicentre randomised superiority trial in 10 centres in China. The firstin-human study assessed the safety and efficacy of a Biolimus A9 (BA9, Biosensors) DCB in patients with small vessel coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients were eligible if they had small vessel native coronary artery disease, defined as reference vessel diameter 2–2.75mm. The study had a primary endpoint of in-segment late lumen loss at nine months assessed by an independent core-lab blinded to treatment assignment. Secondary endpoints included device and procedural success, binary restenosis, target lesion failure (TLF) at 30 days and at six, nine and 12 months. Patient orientated clinical outcome (POCO) was defined as a composite of all-cause death, myocardial infarction and any revascularisation at the same timepoints.

BIO-RISE CHINA

Xu told TCT attendees that in total, 212 patients were randomised between treatment with the BA9-coated balloon and POBA. The study met its primary endpoint by demonstrating a statistically significant reduction of late lumen loss with the BA9-coated balloon compared to POBA at nine months (0.16±0.29mm vs. 0.30±0.35mm ∆ 0.14mm; 95% CI

I think we have to declare that the results we have seen today are very promising, but we only have this short followup time, and we cannot give any answer on a potential late catch-up…” coating with 4µg/mm2 balloon surface was non inferior to a best-in-class PCB with respect to angiographic late lumen loss at six months. “Since coating of balloons with limus agents is relatively complex, I think the findings are not applicable to other SCBs,” he said. “The question we can discuss is whether there are potentially differential indications potentially for SCBs versus PCBs also with respect to late lumen enlargement for de novo lesions. Of course, we need longer follow-up with larger trials powered for clinical endpoints to further investigate sirolimus-coated balloons, so for now

discussion between panellists about the future for the use of DCBs in the coronary arteries. Session chair Juan Granada (president and chief executive officer of the Cardiovascular Research Foundation [CRF]) said that the studies marked the first time there had been data available for three sirolimus-coated balloons “showing some consistency”. However, he asked Scheller to comment on whether the shorter delivery time for sirolimus than paclitaxel is likely to be problematic. “Sirolimus is more difficult to handle than paclitaxel, and one of the things that I am concerned about is the durability of the event. With paclitaxel you can really find it in the artery for a long time, but sirolimus goes away quickly once it is dissolved. Is a potential late catch up, something that stays in your head as a concern?” Granada said to Scheller. Scheller responded: “That is one of the unanswered questions and that is my concern too. Therefore, I think we have to declare that the results we have seen today are very promising, but we only have this short follow-up time, and we cannot give any answer on a potential late catch-up, for example, with sirolimus and its reversible binding.” Another of the panellists, Wayne Batchelor (Inova Heart and Vascular Institute, Falls Church, USA), questioned the use of late lumen loss as a primary endpoint in the trials, commenting that, for patients, “it is target vessel revascularisation and in-

Bruno Scheller

-0.23 to -0.05; p=0.001). “This first-in-human randomised controlled trial has confirmed the safety and efficacy of a biolimus-coated balloon in patients with small vessel coronary artery disease compared to plain old balloon angioplasty,” Xu remarked in his closing statements. He noted that late lumen enlargement was more common with the biolimus-coated balloon, with a trend towards improved outcomes at one year. “Future studies are warranted to compare the biolimuscoated balloon to drug-eluting stents and/or other DCBs,” he remarked. The presentations prompted a

stent restenosis that lead to symptoms and that is where there might be a little bit of a disconnect”. To this point, Scheller responded: “I fully agree with what you are saying. The point is that, at the moment, we are in the very early stage of learning about sirolimus-coated balloons, and at this early stage it is important mechanistically. Do we have the biological effect that we expect from the preclinical trials? Can we translate and find this effect in humans? This is what was addressed by these three trials. This is not an answer about what the clinical impact will be.”

February 2022 | Issue 64

16 Interview

Profile

Susheel Kodali

Born in India and raised in Pittsburgh, USA, Susheel Kodali now practices in New York, where he is the director of the Structural Heart & Valve Center at NewYork-Presbyterian, and the Avenassians associate professor in medicine at Columbia University Irving Medical Center. Specialising in structural heart disease, Kodali has been a key figure in the PARTNER trial, the world’s first prospective, randomised trial for transcatheter aortic valve implantation (TAVI), as well as being at the forefront of research into transcatheter tricuspid valve intervention. In this interview, Kodali discusses his early career, influences and latest research.

My parents and a couple of other family members were physicians, and what you get exposed to drives a lot of your interests. I went to Stanford University and started as a computer science major. This might have been a better career path because in my class there were a lot of founders of large tech companies! I enjoy things that involve logical paths from step A to step B, and I saw computer sciences as involving action and reaction. This goes into why I went into interventional cardiology—for the technical aspects of it as well as the pace of innovation. During medical school I went through a lot of different paths. Initially, I was interested in neuroscience and neurology, but I eventually settled on pursuing either critical care or cardiology. A lot of my interest was driven by the technical aspects of the two fields. Both of them deal with acutely ill patients where an intervention is performed and immediately a clinical change is seen. In the end, the reason I went down the interventional cardiology route was the rapid pace of innovation.

Who have been the major influences throughout your career?

Clearly, one person stands out—Marty Leon. I always tell fellows, sometimes it is just a case of being in the right place at the right time and when opportunities present themselves you take advantage. I did all of my training in California. I did my medicine, cardiology training at University of California, San Francisco (UCSF) and I decided to get a different experience for my interventional cardiology fellowship, and came to New York. My wife and I had planned to be in New York for a year and then go back to California. I was the only fellow here and so I got to work very closely with Jeff Moses and Marty Leon. Marty then asked if I was interested in staying on for another year because the REVIVAL trial, which was the first early feasibility study of transcatheter valve replacement, was starting at Columbia. Marty has been the single most important mentor in helping my career move forward. He is a visionary, but he also provides other people opportunities. It is an incredible strength of his. He recognises when people are deserving of opportunities and he will mentor them. I can definitely say I am where I am now due to his support. I consider myself lucky to have had the opportunity to work with him.

During your career in interventional cardiology, has there been any one development that you think has shaped the field more than any other? I do not think anything else compares to TAVI. It is such a disruptive, revolutionary technology that has changed the way we practice medicine and has opened up treatment options to patients that were not getting treated. It is something that clearly improves survival,

improves quality of life, and it is a complete mind shift in how we address this disease. It has changed guidelines, repeatedly, and they still cannot keep up because of all of the data that that is coming forward. I had the fortune to be in the TAVI space early and it has really evolved and iterated over the next 15 years to a much more predictable, reliable procedure. That did not come easy, it came because people looked at it rigorously. The majority of publications from the PARTNER trial onward are about the impact of complications on outcomes, looking at stroke and its impact, looking at vascular complications, looking at bleeding, and looking at paravalvular leak (PVL). Those are what drove innovation in the field—devices got smaller and there were solutions for PVL. There needs to be further innovation.

Is there anything that has had potential to change practice, but has not done so?

At this point I expected to have more options for treating mitral valve disease, and though it is not a failure of devices, I do think it speaks to the complexity and the variability of the disease process. On the TAVI side I think there are still opportunities for innovation. We can look and see what the weaknesses are, whether

TAVI is a disruptive, revolutionary technology that has changed the way we practice medicine and has opened up treatment options to patients that were not getting treated.” it is bicuspid valves, whether it is small annuli, and how to continue to iterate. Continuing to find ways to reduce complications is important.

What are your current research interests?

Clinically, we are still very involved in TAVI and trials with new generation devices. What has been driving most of my time and energy has been looking at transcatheter options for treating tricuspid regurgitation. We have been involved in this space for more than five years and continue to work with the different technologies. I think the space is incredibly exciting. Part of the challnege in tricuspid valve disease is in terms of guidelines. We do not know, unlike with aortic and mitral valves, when we should treat these patients. A lot of the initial learnings are going to be when and who we should treat, but at the same time understanding how these novel devices work.

alisonlang.com

What influenced you to pursue a career in medicine, and why did you choose to specialise in interventional cardiology in particular?

What do you feel are the important questions that future TAVI trials need to address?

We need better understanding of one device versus another device, and to address the lifetime management question. We are treating younger patients now, so if you do TAVI in someone at 65 and the average survival is another 20 plus years, are they going to be able to get through their life without surgery? Durability issues are critical to understand, as is the ability to do valve-in-valve. These are important questions that we need to answer. Another important question is with bicuspid valves. We have some data, but it is limited to the patients that were felt to be anatomically suitable. I do not know that we will need dedicated TAVI devices for bicuspid, my personal feeling is we need leaflet modification technologies to allow the current devices to work in because the real problem is valve expansion.

Issue 64 | February 2022

Interview 17

What do you think is likely to be the biggest talking point in interventional cardiology in the year to come?

It is not my area of expertise, but if you look at percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) with the fractional flow reserve (FFR) trial published last year, that has generated a lot of discussion. There are arguments that you could look at the data and the population enrolled to say it completely changes practice, or to say this is a starting point and we need to learn more. I think that debate is never going away and the conversations have ramped up in this past year.

As a founder of the Fraternity of Advanced Cardiovascular Techniques and Solutions (FACTS), what is your proudest achievement?

It is heavily driven by my colleague in India, Sreenivas Kumar. I have an Indian background, having been born there, and it was important to me to be engaged. I am fascinated by the level of enthusiasm and how people are excited to talk about trials and to learn and grow. As a result of the partnership between FACTS and the Cardiovascular Research Foundation (CRF) we are able to bring a lot of educational programmes to India with people like Marty Leon and Eberhard Grube. Interventional cardiology is not just a western specialty—it is a broader community. It is really exciting to be a part of that.

Looking back over your career, are there any cases in particular that stand out to you?

There are a lot of them! There was a patient just a month ago who came into the cath lab, and he arrested due to a thrombus in the left main. From thinking he was not going to survive, he managed to go home and leave the hospital. There are a lot of times that you see cases like that which are remarkable. More so than that, I would say many of the patients that I have met are remarkable themselves. Because the transcatheter valve space has an elderly population, there are a lot of people from the World War Two generation. I have done procedures on patients that were Holocaust survivors, or were injured in the Battle of the Bulge. Hearing these remarkable stories and getting a chance to meet these people is one of the most rewarding aspects of the job.

Outside of medicine, what are your hobbies, interests and passions?

I have three boys, they keep my wife and I occupied! Although I do not play a lot of sport, I enjoy watching sport with my kids. American football is my main passion, and I am a big Pittsburgh Steelers fan. Between August and February it is my main interest. I also love to travel, that keeps me going.

Fact file Appointments

Columbia University Irving Presbyterian Medical Center, Avanessians Associate Professor of Cardiology NYPresbyterian/Lawrence Hospital, Medical Staff Attending Fraternity of Advanced Cardiovascular Techniques and Solutions (FACTS), co-founder and vice president

Education & training

Stanford University UCLA School of Medicine Interventional Cardiology Fellowship, Columbia Presbyterian Medical Center Cardiovascular Disease Fellowship, University of California

Memberships

Society of Cardiovascular Angiography and Intervention (SCAI) American College of Cardiology (ACC)

Clinical trials

PARTNER CLASP TR early feasibility study TRILUMINATE study TRISCEND study

February 2022 | Issue 64

18 Renal Denervation

Six-month RADIANCE-HTN TRIO results “open a window” for renal denervation

to the totality of evidence around renal denervation. Responding to a question as to whether, given the relative differences in the reduction in blood pressure in both arms, patients would be more willing to undergo an invasive intervention for hypertension, Kandzari noted that reducing medication burden is of “increasing importance” to patients. He added: “The opportunity to reduce the medication Six-month outcomes from the randomised RADIANCE-HTN TRIO trial, comparing burden in discrete choice experiment studies is one of endovascular ultrasound renal denervation to a sham procedure for treatment-resistant the key drivers of patient motivation for an alternative hypertension, demonstrate the additional effects of pharmacologic intervention with therapy or approach like renal denervation. maintenance of a blood pressure-lowering effect of renal denervation at six months, “Indeed, patients do not typically want to undergo according to investigators. an interventional procedure, but if there is durability with it and if there is a meaningful reduction he six-month results were presented during a medications at six months following in blood pressure, which, interestingly by late-breaking trial session at the Transcatheter the addition of the SSAHT was 0.7±1 patients’ criteria does not have to be that Cardiovascular Therapeutics annual meeting for renal denervation and 1.1±1.1 for large of a reduction in blood pressure to be (TCT 2021; 4–6 November, Orlando USA and virtual) sham (p=0.045). The use of aldosterone meaningful, and the opportunity to reduce by Ajay Kirtane (Columbia University Irving Medical antagonists at two months was 3% for renal medicines, then it is clinically important Center/NewYork-Presbyterian Hospital, New York, denervation and 11% for sham (p=0.16). to them.” USA). These build upon the presentation of the At six months, the number increased in Kandzari also referred to new data to trial’s two-month findings at the American College of both groups but to a lesser extent in the be presented at TCT 2021, that has sought Cardiology’s 70th Annual Scientific Session (ACC.21, renal denervation group (40% for renal Ajay Kirtane to quantify US patient preferences for 15–17 May, virtual) and also published in The Lancet. denervation compared to 60.9% for sham, considerations of interventional procedures Patients with hypertension require a multi-faceted p=0.017). in the treatment of high blood pressure, including approach for blood pressure control, Kirtane explained, The addition of the stepped care antihypertensive treatment mode, effectiveness and risks. detailing that in RADIANCE-HTN TRIO, patients with regimen to the initially randomised therapy further Roxana Mehran (Icahn School of Medicine at daytime ambulatory systolic blood pressure (dASBP) decreased blood pressures in both arms; the overall Mount Sinai, New York, USA) questioned if the results 135/85mgHg despite a fixed dose combination pill change from baseline in dASBP was -11.8±14.2mmHg demonstrate the “durability” of renal denervation, but consisting of a calcium channel blocker, angiotensin in the renal denervation group versus -12.3±14.2mmHg described the study as an “exciting next step”. “To me receptor blocker, and thiazide diuretic, were for sham (p=0.65). Home blood pressure was lower in it is opening a window,” she remarked. “Previously the randomised to renal denervation using the Paradise patients initially randomised to renal denervation when doors might have been closed for renal denervation, renal denervation ultrasound system (ReCor Medical, adjusted for baseline blood pressure and number of but I think the window is opening and it may be a n=69) or a sham procedure (n=67). medications (-4.28mmHg, p=0.027). Safety outcomes large one!” The trial’s two-month results found that, in were similar for both groups. conjunction with the three-drug fixed-dose combination “Blood pressure reductions after renal denervation pill, renal denervation reduced dASBP by an additional were achieved with a smaller increase in additional 8mmHg, a 4.5mmHg greater reduction compared medications prescribed and less use of aldosterone with a sham procedure (–8mmHg versus –3mmHg; antagonists compared with a sham procedure,” said median between-group difference–4.5mmHg; adjusted Kirtane. “These results demonstrate the additional p=0.022). effects of pharmacologic intervention with maintenance During months two through five, the addition of a of a blood pressure-lowering effect of endovascular standardised stepped-care antihypertensive treatment ultrasound renal denervation at six months.” (SSAHT) was recommended sequentially with the During a press conference in which Kirtane addition of spironolactone 25mg/d, bisoprolol 10mg/d, presented the latest findings of the study, describing full dose of a centrally acting α2 receptor agonist, and them as “exploratory”, he relayed that the addition an α1 receptor blocker if monthly measured home of a pharmacologic intervention led to further blood blood pressure was ≥135/85mmHg, with the goal pressure reductions after renal denervation with a of achieving blood pressure control in both groups. smaller increase in additional medications prescribed Adherence to prescribed medications was similar in and less use of diuretics. both groups (71% for renal denervation versus 78% for In ensuing discussion during the press conference, sham, p=0.41). David Kandzari (Piedmont Heart Institute, Atlanta, The increase in the number of antihypertensive USA) described the findings as “welcome” as they add

These results demonstrate the additional effects of pharmacologic intervention with maintenance of a blood pressure-lowering effect of endovascular ultrasound renal denervation at six months.”

Randomised trials show “consistent” reduction in blood pressure through renal denervation Randomised placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure, the findings of a systematic review and meta-analysis suggest. FINDINGS OF THE PAPER, authored by Yousif Ahmad (Yale School of Medicine, Yale University, New Haven) and colleagues, were published in JACC: Cardiovascular Interventions and presented during an oral abstract session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual). Ahmad and colleagues note that renal

denervation has undergone several blinded placebo-controlled trials, covering patients with drug-resistant hypertension to those not yet taking antihypertensive medication. The authors performed an updated analysis of randomised controlled trials and specifically compared the effect of renal denervation in patients taking medications and those not taking medications.

The study’s primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure, and analysis was stratified by whether there was background antihypertensive medication use. Ahmad and colleagues report that there were seven eligible trials, totalling 1,368 patients. Outlining the results, the study team notes that renal denervation significantly reduced ambulatory systolic (mean difference −3.61mmHg; 95% confidence interval [CI]: -4.89 to -2.33mmHg; p<0.0001), ambulatory diastolic (-1.85mmHg; 95% CI: -2.78 to -0.92mmHg; p<0.0001), office systolic (-5.86mmHg; 95% CI: -7.77 to -3.94mmHg; p<0.0001), and office diastolic (-3.63 mm Hg; 95% CI: -4.77 to -2.50; P < 0.0001) blood pressure. There was no evidence that the

use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (p-interaction=NS for each comparison). Ahmad and colleagues conclude that the randomised placebo-controlled trials show “consistently” that renal denervation provides significant reduction in ambulatory and office blood pressure. “Although the magnitude of benefit, about 4/2mmHg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents,” the study’s authors note. “Whether the effect changes with time is currently unknown.”

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Issue 64 | February 2022

Advertorial 21

THIS ADVERTORIAL IS SPONSORED BY MEDTRONIC

Evolut PRO+ provides options in the toughest TAVI cases Evolut PRO+ is the latest generation of self-expanding transcatheter aortic valve implantation (TAVI) system in Medtronic’s CoreValve and Evolut family of devices. In this interview, David Hildick-Smith (professor of interventional cardiology and consultant cardiologist, University Hosptials Sussex, Brighton, UK) discusses key features of the Evolut PRO+ device, how its low delivery profile can be advantageous in cases with challenging access, and how data from studies including Evolut Low Risk and SURTAVI reinforce the haemodynamic performance of the device.

ith TAVI procedures being offered to a wider population of patients, including those with moderate or low surgical risk, more challenging vascular access, and bicuspid anatomies, having the right valve technology available that is adaptable to a broad range of anatomical variations is increasingly important. The Evolut PRO+ system is available in four valve sizes including 23, 26 and 29mm diameters, which are able to access vessels down to 5mm, and a 34mm device that offers an access solution in vessels down to 6mm, making it the widest annulus range of any self-expanding TAVI system currently on the market. “The potential advantage is that you can introduce the Evolut into systems where otherwise you might have to consider a transcaval or a transaxiliary approach,” Hildick-Smith tells Cardiovascular News. “There are patients with quite significantly diseased femoral and iliac systems who will benefit from TAVI in whom you are worried about putting in a 16 French or bigger sheath,” he explains, adding that to be able to deliver a slightly smaller sheath size may be the difference between being able to advance the valve through the iliac vasculature or not. “Every small decrement in valve diameter for the delivery system is to be greatly welcomed, even though each individual change only allows you to treat an extra 1 or 2% of patients,” HildickSmith comments. He estimates that patients with smaller vessels requiring alternative vascular access, including potentially transcaval or transaxiliary approaches, represent between 5–8% of TAVI cases. “The advantage of the Evolut here is the calibre and the sheathlessness of the system,” he says. “Commonly, when we are looking at quite poor vascular access, we will say ‘maybe this is an Evolut case’. That means that it does have that niche of being able to handle relatively hostile femoral and iliac anatomy.” The Evolut system is designed with an outer porcine pericardial tissue wrap that adds surface area contact and tissue interaction between the valve and the native aortic annulus, which Hildick-Smith sees as an important feature. “The pericardial wrap is a help as far as sealing is concerned. The Evolut is very good because it has a good radial opening force, good radial strength, and so even after you have implanted it, it keeps expanding into little crevices, nooks and crannies, and will diminish any aortic

regurgitation that you are left with at the end of the procedure, usually from very mild to zero.” The increased surface contact with the valve’s native anatomy created by the pericardial wrap assists in the Evolut platform’s David good performance in reducing Hildick-Smith paravalvular leak (PVL). Discussing his experience of the performance of Evolut PRO+ in this regard, HildickSmith comments that while previous generations of the CoreValve and Evolut platforms held up well in this area, Evolut PRO+ maintains this strength. “We have been very pleased with the outcomes,” he says.

Ever since we first put in the CoreValve in 2007 I have been of the view that it has the best haemodynamic profile. This is because of the combination of the porcine leaflets, which are very thin, present no resistance to outflow, and the supra-annular positioning of the valve leaflets.” “We have used the system in some fairly hostile aortic anatomy with very good results, so I think at this stage we are very encouraged. We are finding it a slightly more dependable system than before, with slightly less chance of any significant movement on final release, and we have been very happy with it.” Haemodynamics are another important area in which Evolut PRO+ appears to perform favourably. This is enforced by results from the Evolut Low Risk trial, presented at EuroPCR 2021 (18–20 May, virtual), assessing the performance of the CoreValve,

Evolut R and Evolut PRO valves in over 700 low surgical risk patients with severe aortic stenosis versus surgical valve replacement. Two-year results demonstrated a statistically significantly lower mean aortic valve gradient (9mmHg vs. 11.7mmHg) and a larger effective orifice area than surgery (2.2cm2 vs. 2cm2). “Ever since we first put in the CoreValve in 2007 I have been of the view that it has the best haemodynamic profile,” comments Hildick-Smith. “This is because of the combination of the porcine leaflets, which are very thin, present no resistance to outflow, and the supra-annular positioning of the valve leaflets.” Evolut Low Risk trial results were followed by five-year outcomes from the SURTAVI trial, presented at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando USA and virtual), adding further to the evidence of haemodynamic benefits of the CoreValve and Evolut platforms. In the study, the TAVI arm demonstrated durable valve longevity, as evidenced by better mean aortic valve gradients (8.6mmHg vs. 11.2mm Hg; p<0.001) at five years. Considering these results, Hildick-Smith says the findings were largely unsurprising. “In terms of the low risk studies, I think in many respects there was no surprise. What you get for the Evolut is in my view worth getting, which is that you have the greater radial strength, greater continued opening force, and most crucially, you are rarely left with any significant aortic regurgitation.” Another important study assessing the performance of the Evolut PRO and PRO+ platforms has been the OPTIMIZE PRO clinical study, a postmarket, prospective multicentre study, covering 46 sites in the USA and Canada, and up to 15 sites in Europe. Interim data from the trial, presented at the Society for Cardiovascular Angiography and Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual), offer key insights in particular on the use of Evolut PRO+ in conjunction with the cusp overlap technique. This is intended to help implanters assess and achieve the target implant depth in an effort to reduce interaction with the conduction system. “We do this routinely for all supra-valvular implants,” explains Hildick-Smith, “ideally we want no aortic regurgitation and do not want the patient to have any changing QRS complex. Usually in the cusp overlap view, you are able to do that.” Discussing the findings from OPTIMIZE PRO, he details: “The results were very good, they had just under 10% pacing which in a low risk group is perfectly acceptable. All the pacing rates are coming down slightly as people modify their implant techniques.” As the first and so far only in Europe transcatheter valve with indication for the treatment of patients with bicuspid aortic valves who are at intermediate or higher risk of surgical mortality, a congenital heart defect affecting 1–2% of the general population, Evolut PRO+ offers an important treatment for patients in who had previously had limited options. “In a bicuspid case, the one thing that you are at more risk of generally is adverse outcomes such as annular rupture, which is usually catastrophic, whilst at the same time trying to get the best result in terms of aortic regurgitation, PVL and gradient across the valve. The Evolut allows you to do all that, and to do it safely, because it is a self-expanding valve, moulding itself to the anatomy, rather than imposing itself on the anatomy,” comments Hildick-Smith. “I do not think there is much doubt at the moment as to the number one valve for bicuspid anatomy in Europe.”

February 2022 | Issue 64

22 Conference Coverage

Understanding the risk of acute kidney injury in the cath lab Roxana Mehran Comment & Analysis Huge strides have been made in preventing contrast-associated acute kidney injury among patients undergoing percutaneous coronary intervention (PCI) and other interventional procedures in recent decades, Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA) tells Cardiovascular News, but many patients still remain at high risk of suffering kidney damage when they undergo a procedure in the cath lab. In this interview, Mehran explains the rationale behind the Mehran-2 CA-AKI Risk Score an updated tool to help interventional cardiologists assess the burden of risk their patients face before undergoing a procedure.

How big of a problem is contrast induced injury?

In the USA alone 280 million radiological procedures utilising contrast media are being performed every year. A lot of good work has been done in the last two decades in improving our risk assessment, minimising the volume of contrast media in highest risk patients and also hydrating our patients before, during and after our procedures. But, acute kidney injury is still one of the most frequent complications of interventional procedures that require contrast media and has been previously associated with a significant increase in mortality, prolonged hospital stays and costs. So, the stage is set that we absolutely should be focusing on risk assessment, it is one of the most important things we could do to prevent this complication—to evaluate who is at risk and make sure that we are very careful with those patients.

What was the rationale for developing a new risk score to assess acute kidney injury?

Two decades ago we developed the Mehran risk score, it was externally validated by multiple settings, and I am so thrilled to see that many people now use this. I knew that it was time to refocus and look at this, because in the last two decades there have been remarkable advances in recognition and implementation of preventive measures, enhancing definitions for AKI, and improvement of the overall incidence. In the original Mehran Risk Score, if you had a high score, you had a 57% chance of incurring acute kidney injury. These estimations needed to be recalibrated, especially given that the rates had decreased over the last years. During these last years, the Acute Kidney Injury Network (AKIN) have also changed the definition acute kidney

Endoscopy study could have implications for post-PCI antiplatelet regimens Patients receiving antiplatelet therapy following percutaneous coronary intervention (PCI) developed gastrointestinal (GI) injury regardless of the antiplatelet regimen used. This is according to the findings of the OPTPEACE trial, which used a magneticallycontrolled capsule endoscopy system (MCE, Ankon Technologies) to assess GI injury in PCI patients. BUT, THE STUDY FOUND THAT THOUGH nearly all patients receiving antiplatelet therapy developed evidence of abnormal GI mucosal

injury with a staging definition that is quite useful. Therefore, it was absolutly important to evaluate the indicence of AKI using these new defnitions. This is why it was important for to do this work. It took us two years to get this together, I have been thinking about this recalibration and making sure that we had a good cohort, both a derivation and a validation cohort, and then externally evaluating this through very important unbiased and independent statistical analytical work.

Were there any important differences in the data between the original research and your latest iteration?

First of all, the best news is that the rate of acute kidney injury, using the AKIN definition, is below its previous rate— about 4% on average for all comers— that is pretty good. This is despite the fact that procedural complexities have gone up, that we see more older patients with more risk factors and acute presentations. With this new analysis, we have two models—one with just preprocedural variables and another that also gives us procedural variables. This enables the users to have some risk assessment

The best news is that the rate of acute kidney injury, using the AKIN definition, is below its previous rate.” before the procedure, and then with procedural factors contributing, clinicians can be more vigilant in following patients who have complex anatomy, or experience a bleed or no reflow, for example.

findings on capsule endoscopy, those receiving dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) had less GI injury than those receiving continued DAPT. Findings of the study were reported at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual) by Yaling Han (General Hospital of Northern Theater Command, Shenyang, China). GI bleeding is a frequent complication of antiplatelet therapy, but little is known regarding its relationship with different antiplatelet regimens. In OPT-PEACE, investigators utilised the Ankon capsule endoscopy system that does not require discontinuation of antiplatelet therapy. A total of 783 eligible patients at low risk for bleeding were enrolled. After a second capsule endoscopy, 505 event-free patients without GI ulceration or bleeding at baseline and six months were randomised to aspirin plus placebo (n=168), clopidogrel plus placebo (n=169) or aspirin plus clopidogrel (n=168) for an additional six months.

What are the fundamentals when dealing with patients who are at high risk for acute kidney injury? It depends on what those high risks are. For someone who comes into the cath lab having an acute myocardial infarction (MI) or needing an urgent procedure you must proceed as usual and without delay. But, in cases meeting the criteria for a risk of acute kidney injury, you may need to be more vigilant, keeping the patient in hospital if needed for IV hydration, and following kidney function with evaluation of creatinine and estimated glomerular filtration rate (e-GFR). Any time you have an older patient who is anaemic, diabetic, and also has history of kidney disease—be vigilant—these are high risk parameters for AKI. Be cognisant of the kind of work you are doing in the cath lab and when you are performing procedures, think about the whole patient, not just what you see on the screen.

What is your message for colleagues who have used the previous generation of the risk score, or have not used it at all?

We have tried really hard to come up with a very simple score. But, use your common sense, if you are not going to use the score! At least look at this paper, read and understand it and know that our risk score is there to make your assessment very simple. Think about the patient as a whole and all of the complications that could have a negative impact, even if you get a perfect result in the lab—you do not want to have a beautiful result and then have the patient die because you caused damage to their kidneys. There has been incredible progress in reducing incidence of AKI after PCI. In the past the rates of acute kidney injury were 15‒20%. We are down to single digits now, so it is pretty good, but the score still matters, as AKI is independently associated with mortality.

The primary endpoint was the incidence of gastric or small intestinal mucosal injury detected either by capsule endoscopy at six or 12 months or at any clinically-driven standard endoscopy. The study found that GI mucosal injury through one year was less with SAPT (94.3% vs. 99.2%, p=0.02). Ulcers were observed in 14.4% of patients on SAPT and 18.5% DAPT (p=0.30). Among 68 patients without any GI injury at randomisation (including no erosions), SAPT was associated with less GI injury (68.1% vs. 95.2%, p=0.01), including fewer new ulcers (8.5% vs. 38.1%, p=0.006), than DAPT. “The use of a novel magnetically-controlled capsule endoscopy system showed that nearly all low bleeding risk patients developed gastrointestinal injury during 12-month follow-up after PCI regardless of antiplatelet regimen,” said Yaling Han. “However, DAPT followed by SAPT resulted in less gastrointestinal mucosal injury and clinical bleeding. These findings are valuable for clinical decision-making on gastroprophylaxis and optimising antiplatelet therapy type and duration.”

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Issue 64 | February 2022

Structural Heart Interventions TAVI in low-risk patients is cost effective, PARTNER 3 finds

An economic analysis of data from the PARTNER 3 randomised trial, comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis and low surgical risk, found that despite higher up-front procedural costs, at two-year follow-up, quality-adjusted life expectancy was greater and total costs were lower with TAVI.

his was the headline finding delivered by David J hospital discharge and two years, follow-up costs were Cohen (director of clinical and outcomes research less for TAVI compared with SAVR (US$19,638 vs. at the Cardiovascular Research Foundation and US$22,258, a difference of US$2,620). director of Academic Affairs for St Francis Hospital The total combined two-year cost was lower for TAVI and Heart Center, New York, USA) during a lateversus SAVR (US$66,834 vs. US$68,864, a difference of breaking trial session at the Transcatheter Cardiovascular US$2,030), Cohen detailed. Two-year quality-adjusted Therapeutics annual meeting (TCT 2021; 4–6 November, life expectancy was greater with TAVI than SAVR (1.71 Orlando USA and virtual). Cohen told TCT attendees vs. 1.66 quality-adjusted life years, p=0.06)—driven that the findings show that at two years, TAVI was costby early benefits in both quality of life and survival. effective for low-risk patients. Although long-term outcomes are unknown at present, Previous studies have demonstrated that TAVI is cost assuming there are no long-term differences in survival or effective compared with medical therapy for patients cost, TAVI was projected to be an economically dominant with severe aortic stenosis and extreme surgical risk strategy (lower cost, better outcome) with a 95% and compared with SAVR for patients at intermediate probability of being cost-effective compared with SAVR. and high surgical risk. Based on the results from recent “Data from the PARTNER 3 trial show that for patients trials, including PARTNER 3, TAVI has been with severe aortic stenosis and low surgical risk, approved for low-risk patients in the USA. TAVI is cost-saving compared with SAVR at Currently, there is little evidence as to whether two-year follow-up and is projected to be highly TAVI is cost effective for low-risk patients. cost effective over a lifetime horizon—as long as Between March 2016 and October 2017, there are no major differences in late mortality 979 patients in the USA were enrolled in the between the two strategies,” said Cohen. “Given PARTNER 3 trial and randomised to either the importance of long-term outcomes in these TAVI using the Sapien 3 valve (Edwards projections, extended follow-up through at Lifesciences; n=492) or SAVR (n=487). Of David Cohen least 10 years will be critical to validate these, 485 underwent TAVI and 444 underwent these findings.” SAVR. During the index hospitalisation, TAVI resulted in In a press conference following the presentation of the significant reductions in procedure duration (53 vs. 198 data, Luca Testa (IRCCS Policlinico S. Donato, Milan, minutes) as well as ICU (0.7 vs. 2.6 days) and non-ICU Italy) was asked to comment on his view of the data. He length of stay (1.2 vs. 3.7 days, all p<0.001), Cohen remarked that the findings regarding cost effectiveness of detailed. Between discharge and six-month follow-up, the TAVI procedure in low-risk patients were reassuring, TAVI also resulted in fewer rehospitalisations and less but said that further data on the durability of the use of rehabilitation services—benefits that were largely procedure would be key. sustained through two years. “The picture is still incomplete, because in order Costs were assessed based on a combination of to have a final word we need to see the concept and resource utilisation and linked Medicare claims for all what is the application of the durability concept,” Testa other costs through two years. In the study population, said. “I am reassured because what we are doing looks index hospitalisation costs were US$47,196 for TAVI and cost effective from an economic perspective, but also US$46,606 for SAVR (a difference of US$591). Between reassuring in terms of long term follow-up.”

Five-year SURTAVI data show comparable performance for TAVI and SAVR on mortality, stroke FIVE-YEAR CLINICAL and echocardiographic outcome data from the SURTAVI trial comparing transcatheter aortic valve implantation (TAVI) using an early-generation device to surgical aortic valve replacement (SAVR) have shown no difference in allcause mortality or stroke between the two procedures in patients at

intermediate surgical risk. SURTAVI findings were presented by Nicolas van Mieghem (Erasmus University Medical Center, Rotterdam, The Netherlands) during a late-breaking trial session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando USA and virtual)

A total of 1,660 intermediaterisk patients underwent attempted implant using the CoreValve/Evolut platform (Medtronic, n=864) or a surgical valve (n=796) at 87 centres. The primary endpoint, consisting of the composite of death or disabling stroke at five years, were similar in both groups with 31.3% for TAVI and 30.8% for surgery (HR 1.02, 95% CI .085‒1.22, p=0.85). All-cause mortality had similar rates and disabling stroke was 4.1% for TAVI compared to 5.8% for surgery (HR 0.69, 95% CI 0.43‒1.10, p=0.12).

First clinical data backs use of Jenavalve TAVI system in patients with aortic regurgitation First clinical results of transcatheter aortic valve implantation (TAVI) using the Jenavalve system (Jenavalve) in patients with severe aortic regurgitation show that the device is safe and efficient in high-risk patients, significantly improves New York Heart Association (NYHA) classification.

MATTI ADAM (UNIVERSITY HEART Centre, Cologne, Germany) presented data on the use of the transfemoral TAVI device as a late-breaking study at PCR London Valves 2021 (21–23 November, London, UK and virtual). “We know that treatment options for severe aortic regurgitation in patients not suitable for cardiac surgery are limited,” Adam said in his presentation. “We also know that patients with severe aortic regurgitation and preserved left ventricular [LV] function benefit from aortic valve replacement [AVR], and they have a 29% higher mortality if we do not do AVR at 10 years.” This prompted the examination of the transfemoral Jenavalve device, which has previously been evaluated transapically as an earlier technical version. “What is special about the design is that the prosthesis carries three locators which allow the valve to clip onto the aortic leaflets and implant the prosthesis in an anatomically correct manner,” Adam detailed. Outcomes were reported in 10 patients, all of whom were high-risk with aortic regurgitation. All patients were highly symptomatic and were in NYHA class III/IV. Median annulus size was 26.4mm (23.9–29.4mm). Outlining the results, Adam explained that the study’s primary efficacy endpoint was technical success with a reduction of aortic regurgitation grade of at least one at discharge. JenaValve implant was attempted in all patients, with one valve-in-valve case requiring bailout treatment with a Sapien 3 (Edwards Lifesciences) prosthesis, and no moderate or severe aortic regurgitation reported. The efficacy endpoint was met in nine out of 10 patients. With regard to safety endpoints, patients were monitored for major adverse events including death, myocardial infarction, cardiothoracic surgery or stroke at 30 days. Adam reported that no cardiovascular mortality occurred, vascular access complications or acute myocardial infarction (MI) though two cerebrovascular events did occur, meaning the safety endpoint was met in eight out of 10 patients. All patients were alive at follow-up and seven out of the ten patients reported functional improvement to NYHA class I or II, Adam explained, commenting that this represented a significant improvement of clinical presentation of all patients. In conclusion, he commented: “This first, real-world data study suggests that transcatheter treatment of severe aortic regurgitation using the JenaValve system is safe and efficient in high risk compassionate use patients.”

24 Structural Heart Interventions

February 2022 | Issue 64

Six-month TRISCEND results “encouraging” for Evoque tricuspid valve

replacement, are truly remarkable and very promising for patients who suffer from tricuspid regurgitation.” “We are quite encouraged by these data, not only related to the therapy and procedural success rates demonstrated by the Evoque system, but also for the significant TR reduction and sustained improvements in quality-of-life Six-month results from the TRISCEND study of the Evoque measures experienced by patients,” (Edwards Lifesciences) transcatheter tricuspid valve replacement said Bernard J Zovighian, Edwards’ system were presented during a late-breaking trial session at the corporate vice president, transcatheter Transcatheter Cardiovascular Therapeutics annual meeting (TCT mitral and tricuspid therapies. “Our 2021, 4–6 November, Orlando USA and virtual). goal is to lead the transformation of RISCEND investigator Susheel including 89% of patients in NYHA treatment for this diverse and expansive Kodali (Columbia University class I or II, and a 27-point population of tricuspid Medical Center, New York, USA) increase in KCCQ score valve disease patients. told TCT attendees that the device over baseline High We are committed to demonstrated that favourable patient survival rate of 96%, building a strong outcomes, which were sustained at six and freedom from body of evidence months. heart failure to support Patients enrolled in the TRISCEND hospitalisation emerging study had symptomatic, moderate or of 94%. therapies like greater functional or degenerative “Severe the Evoque tricuspid regurgitation (TR), despite tricuspid system, which will optimal medical therapy. Following regurgitation is continue with our positive 30-day outcomes that were becoming increasingly randomised pivotal trial, presented at EuroPCR 2021 (18–20 recognised to have a Evoque TRISCEND II, currently May, virtual), the six-month results significant impact on underway.” (n=56) demonstrated significant TR quality of life and may be a predictor of The TRISCEND study is a reduction by core laboratory assessment. increased mortality. Unfortunately, most prospective, single-arm, multicentre Headline figures delivered by Kodali patients with TR are at high risk for study, designed to evaluate the safety include a significant reduction in TR conventional surgery and there currently and performance of the transfemoral severity, with 100% of patients with are no approved transcatheter options in Evoque tricuspid valve replacement none/trace or mild TR in 43 patients the USA,” said Kodali. “The six-month system in TR. Results were reported on with paired echocardiographic data results that we have seen, with patients 132 patients enrolled, with six-month available, significantly improved enrolled in the TRISCEND study who follow-up results on 56 patients. The functional and quality-of-life outcomes, received the Evoque tricuspid valve study continues to enrol and additional

Early data presented for Intrepid TMVR using transfemoral delivery system Early data for the self-expanding Intrepid (Medtronic) transcatheter mitral valve replacement (TMVR) system in patients with severe, symptomatic mitral valve regurgitation (MR) utilising the transfemoral access route, were presented during a late-breaking trial session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual). THE DATA FROM THE FIRST 15 PATIENTS enrolled in an Early Feasibility Study of the Intrepid transfemoral system show 100% survival and no stroke, a median procedure time of 46 minutes, and none/trace MR in all implanted patients at 30 days. The data were published simultaneously in the Journal of the American College of Cardiology (JACC): Cardiovascular Intervention. “These data indicate that the new Intrepid transfemoral delivery system is a promising option for the delivery of the Intrepid valve with all patients in the study showing almost complete elimination

of MR at 30 days,” said Firas Zahr, co-director of the Complex Heart Valve Program at Oregon Health and Science University, Portland, USA, and investigator in the study. “The addition of transfemoral access into the APOLLO trial will provide study Firas Zahr investigators with an access route that could present less risk to patients during the procedure.” Zahr told TCT attendees that the device achieved favourable procedural characteristics, familiar mitral valve manoeuvres, simplified positioning, anchoring and deployment and short procedure times, as well as improved 30-day major clinical outcomes versus transapical experience. However, he noted that there had been vascular complications and major bleeding events, likely driven by the large bore sheath, though commented that a lower profile version is in development. The Intrepid valve has been used to treat more than 350 patients as part of global clinical survival trials. Currently, the Medtronic APOLLO Trial is evaluating the Intrepid TMVR system in patients with severe MR with one cohort evaluating patients with primary a median or secondary MR who are procedure time of unsuitable for conventional mitral valve surgery or transcatheter edge-to-edge repair (TEER). A second cohort minutes is evaluating patients with severe

The sixmonth results that we have seen with patients enrolled in the TRISCEND study who received the Evoque tricuspid valve replacement are truly remarkable and very promising for patients who suffer from tricuspid regurgitation.”

symptomatic MR who are deemed ineligible for conventional mitral valve surgery with mitral annular calcification (MAC). To date, patients enrolled in the study have received the Intrepid TMVR system using the transapical access route where the valve is compressed inside a hollow catheter and inserted between the ribs into the heart. With IDE approval, APOLLO study investigators will now have the additional option to insert the valve via an incision in the groin into the femoral vein, which has historically been the preferred approach for most transcatheter procedures. The Intrepid TMVR system, which received Breakthrough Device Designation from US Food and Drug Administration (FDA)—for patients unsuitable for transcatheter edge-to-edge repair or mitral valve surgery— integrates self-expanding, dual-stent technology with a replacement tissue heart valve to facilitate a catheter-based implantation. “The development of the Intrepid transfemoral delivery system is an important milestone for the Intrepid TMVR program stroke and we are excited to introduce it into the APOLLO trial,” said Nina Goodheart, senior vice president and president of the Heart & Aortic none/trace MR in all Structural business, which is part of the implanted patients at Cardiovascular Portfolio at Medtronic. “We believe this advancement will expand our clinical trial offerings days to more patients.”

x15 patients

100% 0% 46

patient follow-up will take place at one year and annually up to five years. The trial endpoints are device and procedural success, a composite of major adverse events (MAEs) at 30 days and TR reduction. The Evoque valve replacement system is an investigational device and is not available for sale in any country.

Structural Heart Interventions 25

Issue 64 | February 2022

Two-year GALILEO data show comparable outcomes for TAVI with selfexpanding or balloon-expandable valves Two-year findings of a post-hoc study from the GALILEO trial, investigating the clinical outcomes after successful transcatheter aortic valve implantation (TAVI) with a balloonexpandable or a self-expanding valve, suggest that there are comparable outcomes between the two devices. THIS WAS AMONG THE CONCLUSIONS was defined as placement of a single transcatheter presented by Taishi Okuno (University Hospital valve into the proper anatomical location achieving of Bern, Bern, Switzerland) during a late-breaking the intended performance without periprocedural presentation at PCR London Valves (21–23 November, complications. The primary endpoint of the trial London, UK and virtual). was major adverse cardiac and cerebrovascular After recent updates in both European and North events (MACCE), a composite of all-cause death or American guidelines, TAVI has become a first-line thromboembolic events including: stroke, myocardial treatment option for elderly symptomatic patients with infarction (MI), symptomatic valve thrombosis, severe aortic valve stenosis irrespective of surgical systemic embolism, deep-vein thrombosis or risk, Okuno noted in his presentation.To optimise a pulmonary embolism, Okuno detailed. TAVI procedure there are multiple device options, he Among 1,644 patients recruited in 136 centres added, with different technologies in bioprosthesis across 16 countries between December 2015 and designs and also different deployment systems. May 2018, 499 received a self-expanding valve and “As there are no definitive data to prioritise one 757 patients a balloon-expandable valve. Patients device over another, device selection between balloontreated with the self-expanding valve were less likely expandable and self-expanding transcatheter heart to be male, had higher surgical risk score and a lower valves is usually based on individual patient anatomy haemoglobin level, and were more likely to have a and local operator or heart team experience, focusing permanent pacemaker at baseline as compared to those primarily on the successful implantation of the device,” with a balloon-expandable valve, Okuno explained. Okuno said, adding that it remains unclear whether Most patients in both arms were treated with newerthere are differences in mid- to long-term clinical generation devices, he said, adding that mean valve outcomes between the devices once successfully size was larger, and the portion of valve-in-valve implanted with intended valve performance. procedures for degenerated prostheses was higher for Okuno and colleagues compared two-year the self-expanding TAVI procedure than the balloonclinical outcomes after successful implantation of expandable procedure. the CoreValve or Evolut (Medtronic) self“The self-expanding valve was associated with a expanding valves and Sapien 3 and Sapien larger effective orifice area, and a lower mean XT (Edwards Lifesciences) balloonaortic valve gradient, but had a higher rate of expandable valves, in the context of the paravalvular regurgitation as compared to a GALILEO trial. balloon-expandable valve,” he said. GALILEO was a randomised, openOkuno explained that there were no label, event-driven trial comparing significant differences in the primary endpoint low dose rivaroxaban-based versus of MACCE, and also its components including antiplatelet-based antithrombotic all-cause death and stroke, while there was also therapies in patients without an no significant difference in the occurrence of established indication for major or life-threatening bleeding between oral anticoagulation after the two groups at two years. successful TAVI. Patients with a higher risk Successful TAVI profile at baseline were more likely Taishi Okuno

Triclip shows “excellent performance” in real-world study An analysis of findings from the bRIGHT registry, detailing realworld results of tricuspid edge-to-edge repair (TEER) in 200 patients, indicate that the Triclip (Abbott) transcatheter device is safe and effective at reducing tricuspid regurgitation, with a majority of patients studied experiencing clinically meaningful improvements in functional status and quality of life at 30-day follow-up.

his was according to a presentation by Philipp Lurz (University Leipzig, Leipzig, Germany) delivered at PCR London Valves (21–23 November, London, UK and virtual) setting out the first insights into the use of the Triclip and Triclip G4 TEER systems outside of a clinical

trial setting. Triclip and Triclip G4 have both recently gained CE mark approval as transcatheter treatment options for severe tricuspid regurgitation. bRIGHT, a prospective, single-arm, multicentre registry study, involves symptomatic patients with severe tricuspid regurgitation despite medical

to have been selected for a self-expanding than a balloon-expandable transcatheter heart valve, he said, adding that after successful TAVI, a self-expanding transcatheter heart valve was associated with more favourable forward-flow haemodynamics but inferior outcomes in terms of paravalvular regurgitation compared with a balloon-expandable transcatheter heart valve. Mortality, thromboembolic and bleeding outcomes did not differ significantly up to two years between the valves after successful implantation, he added. Okuno noted that there were limitations of the study, including that it was a post-hoc analysis based on a clinical trial in which the selection of valve type was made by a treating heart team at each participating centre in a non-randomised fashion. In conclusion, Okuno said that the two-year follow-up data from the GALILEO trial indicate that successful TAVI, either with newer generation self-expanding or balloon-expandable valves according to physician discretion, results in comparable clinical outcomes. “The findings support current real-world practice where the TAVI devices are chosen based on individual patient anatomy to achieve the primary goal of successful implantation with optimal device and procedural outcome,” he said.

As there are no definitive data to prioritise one device over another, device selection between balloonexpandable and selfexpanding transcatheter heart valves is usually based on individual patient anatomy and local operator or heart team experience, focusing primarily on the successful implantation of the device.”

therapy, who are a high risk for tricuspid valve surgery. Investigators looked at a primary endpoint of acute procedural success, defined as survival to discharge with successful implantation of the Triclip device with resulting tricuspid regurgitation reduction of at least one grade. Detailing the findings of the registry during his presentation at PCR London Valves, Lurz, bRIGHT’s principal investigator, reported that 90% of patients had tricuspid regurgitation reduced by at least one grade at 30 days, with the majority (66%) reduced to moderate or less. Lurz commented that though these early results were promising, there

remains some room for improvement, particularly relating to patient selection and morphological criteria. “The Triclip system showed excellent performance in a real-world setting,” Lurz said. “The procedure was extremely safe with only 1% of patients experiencing major adverse events.” Furthermore, Lurz reported that the acute procedural success was achieved in a diverse population, and that most patients had experienced clinically meaningful improvements in functional status and quality of life at 30day follow-up. The bRIGHT investigators will continue to enrol patients to study the performance of the Triclip g4 device, Lurz noted in his concluding remarks.

66%

of patients had tricuspid regurgitation reduced to moderate or less

Issue 64 | February 2022

Market Watch 27

Medtech insights

Abbott’s Nick West points to future role of AI in the cath lab Abbott has released a second round of insights from its Beyond Intervention global research programme, digging into the experience of patients, physicians and healthcare providers in the diagnosis and treatment of cardiovascular disease. Speaking to Cardiovascular News Abbott’s chief medical officer and divisional vice president of medical affairs, Nick West, said that the research will shape the company’s direction of travel “to really drive meaningful improvements in patient care”.

he Beyond Intervention initiative gathered feedback from more than 1,800 patients with cardiovascular disease, physicians and healthcare leaders. The research highlights some potential areas for integration of technology into the healthcare pathway, including potential for greater use of artificial intelligence (AI) and digital health tools to aid diagnosis. Patient feedback also pointed to frustration in a lack of compatibility with electronic medical records, with the report noting that this may also create inefficiencies and barriers for early and accurate diagnosis of coronary artery disease (CAD) and peripheral arterial disease (PAD). “What we heard from year one is that the biggest barriers, and where tech had the greatest impact, was upstream of the cath lab,” West told Cardiovascular News. “Everyone—physicians and healthcare providers—told us loud and clear that the biggest use of data and tech is either when formulating a diagnosis, making the initial diagnosis and then when plotting a treatment path. “That is why in this year two survey, having started this conversation, we have now focused in on what happens on that first part of the journey.” Important findings from the research include, according to West, a disparity in the perception of the current patient experience held by healthcare

providers and patients, and difficulty have on quality of life. accessing care for underserved communities. “If we are moving now away from some West also discussed how digital tools could of these hard endpoints, and if you think have a greater role to play in the diagnosis about some of the choices that patients have of monitoring of symptoms and outcomes, for vascular disease treatment, you could commenting: “Patients are now monitoring have a minimally invasive or percutaneous themselves with smart devices, watches, approach, you could have a coronary or phones and various other trackers, and I lower limb angioplasty, you could have Nick West think there is a really clear need that those open surgery, or you could have medical need to be integrated into the health journey. therapy,” said West. “Patients want it, we need to see how we can help “In many situations the choice between those three provide that.” things may not end up in a prognostic difference, but This was reflected in the first phase of the Beyond certain things are important to certain patients, and Intervention research, West commented, noting what we need to see as clinicians is an acceptance that that this may point towards a greater involvement patients’ wishes need to be taken into account, rather of patients in understanding the treatment options than what we might view as the best choice.” available to them, and the likely impact these may Other fields including cardiac rhythm management have made greater strides at integrating digital tools to aid condition diagnosis and patient monitoring, West said, using the example of pacing devices and arrhythmia monitors with Bluetooth capability that can provide real-time data. Discussing some of the innovations that Abbott is bringing to the interventional cardiology space to address some of the needs highlighted in the Beyond Intervention report, West pointed to the launch of the company’s Ultreon optical coherence tomography (OCT) software, which uses AI to guide stent placement. “The whole point of that upgrade to the software, was to try and democratise OCT usage,” said West. “The problem with OCT is it is viewed as a research Abbott tool, it needs a lot of training, so how can we bring Austin that into the mainstream to enable more patients to benefit from imaging-guided PCI [percutaneous coronary intervention]?” AI algorithms within the software will detect the degree of calcification and the external elastic lamina (EEL) automatically, West explained, as well as supporting correct stent sizing. Further insights into OCT technology are expected in 2022 via the ILUMIEN IV study which has completed enrolment. “We hope and expect that that is going to show it is on a par with IVUS [intravascular ultrasound],” said West. Other uses of AI could include the creation of predictive algorithms, using existing datasets to predict target lesion failure, as well as exploring ways to tailor care for patients. Looking ahead, West says that the next step of the Beyond Intervention programme will look “downstream”, focusing on what happens after an intervention.

Patients are now monitoring themselves with smart devices, watches, phones and various other trackers, and I think there is a really clear need that those need to be integrated into the health journey.”

Product News Sapien 3 with Alterra prestent gains FDA approval

Edwards Lifesciences has received approval from the US Food and Drug Administration (FDA) for the use of the Edwards Sapien 3 transcatheter valve with the Alterra adaptive prestent— Sapien 3 with Alterra—for patients with severe pulmonary regurgitation. The Edwards Sapien 3 transcatheter pulmonary valve (TPV) system combines the proven Sapien 3 transcatheter heart valve and the Alterra adaptive prestent to expand transcatheter therapy options for congenital heart valve disease patients,

Edwards said in a press release. The Alterra prestent compensates for variations in size and morphology of the right ventricular outflow tract to provide a stable landing zone for the Sapien 3 valve. While pulmonic heart valve replacements represent a small fraction of the heart valve replacements done each year, it is generally required to replace valves in adolescent and adult patients suffering from Tetralogy of Fallot or other congenital heart valve defects. The Edwards Sapien 3 TPV system with Alterra adaptive prestent is indicated for use in the management of paediatric and adult patients with

severe pulmonary regurgitation as measured by echocardiography, who have a native or surgically repaired right ventricular outflow tract and are clinically indicated for surgical pulmonary valve replacement.

Robocath announces completion of first robotic coronary angioplasty with R-One in China

Robocath has announced the successful completion of what it has described as the first coronary angioplasty in China assisted by the R-One robotic platform. The procedure took place at the 301 Hospital in Beijing on 24 November, performed by Yundai Chen (Department of Cardiology, Chinese PLA General Hospital, Beijing, China). This robotic-assisted procedure is the first intervention within a clinical study carried out by CathBot; a joint venture between Robocath and MedBot (the

Robocath

robot-focused subsidiary of MicroPort Scientific Corporation). This clinical study will include over 100 patients, across four centres with a goal to obtain marketing authorisation for the R-One robotic platform in China, via the National Medical Products Administration (NMPA). Chen said: “Robocath’s robotic platform enables a coronary angioplasty to be carried out safely, whilst being totally protected from radiation, and under more comfortable

February 2022 | Issue 64

28 Market Watch

Product News conditions. It is intuitive and the system is incredibly precise; it is possible to position stents to the exact millimetre. I am flattered to have been the first person to use this technology in China and to help push forward the progress of robotics in our country.” He Chao, president of MedBot, said: “This first clinical trial of a robotic percutaneous coronary intervention (PCI) with R-One is an important milestone in the surgical robotics field for our company. There is no similar product available in our country. With the clinical development and subsequent launch of R-One, it will fill

Evolut PRO TAVI system

the field gap in robotic PCI in China and will benefit both doctors and patients.” Lucien Goffart, Robocath’s CEO, added: “In the interventional cardiology field, the Chinese market currently has the highest growth rate in the world. More than a million procedures per year are performed in the country and the number of catheterisation labs has doubled since 2010—now reaching 2,000. This procedure comes only one year after the joint venture set up; it marks a key step in its development. This puts us in a strong position to be awarded marketing authorisation from the NMPA in the near future.”

Evolut PRO TAVI valve gains approval in China

Medtronic has announced that the National Medical Products Administration (NMPA) has approved the CoreValve Evolut PRO transcatheter aortic valve implantation (TAVI) system for the treatment of severe aortic stenosis (AS) for symptomatic patients in China who are at high or extreme risk for open-heart surgery. As the first Medtronic selfexpanding TAVI system approved in China, the Evolut PRO system approval is based on clinical data from more than 32,000 patients, which showed high survival, low rates of stroke, minimal paravalvular leak (PVL), and excellent haemodynamics. Full commercial launch is anticipated early this year.

The Evolut PRO TAVI system is the next generation of Medtronic’s supraannular CoreValve Evolut R system. The recapturable and repositionable Evolut PRO valve features a selfexpanding nitinol frame with an outer wrap that adds surface area contact between the valve and the native aortic annulus to further advance valve sealing performance. The approval is based on data from high- and extreme-risk patients across Medtronic-sponsored studies and realworld registries with the CoreValve Evolut TAVI platform. Implanted in more than 400,000 patients in 160 countries worldwide, the CoreValve Evolut TAVR platform has shown consistently low, single-digit gradients and large effective orifice areas that promote valve performance, Medtronic said in a press release. “We are excited to introduce the Medtronic supra-annular, selfexpanding and recapturable TAVI platform to physicians and their patients in China as we look to expand access to our technology in new geographies,” said Nina Goodheart, president of the Structural Heart & Aortic business, which is part of the Cardiovascular Portfolio at Medtronic.

FDA clears CavaClear IVC filter removal laser sheath

Royal Philips has announced US Food and Drug Administration (FDA) de novo clearance for the Philips inferior vena cava (IVC) filter removal laser sheath—CavaClear—to remove an IVC filter when previous methods of removal have failed. Philips CavaClear IVC filter removal laser sheath is the first and only FDAcleared solution for advanced IVC filter removal, the company said in a press release. In 2021, the FDA granted the device Breakthrough Device Designation. Laser has been clinically proven to provide a success rate over 99%, with low complication rates, the press release adds. IVC filters are used to treat patients with venous thromboembolism, in which blood clots form in the deep veins of the leg and groin, and can travel through the circulatory system. They are placed in the inferior vena cava to capture blood clots from moving to the lungs. Prior to CavaClear, limited options for removal existed if the filter became difficult to remove, according to Philips. Advanced retrieval tools and techniques are required if the IVC filter becomes embedded in the vasculature. Physicians previously had very few tools to remove the filter when complications occurred and until now there were no FDA-approved devices for this type of advanced removal. “Today is a historic day. With the approval of CavaClear, physicians

CavaClear

now have a device specifically geared to remove chronically embedded IVC filters,” said Kush Desai, associate professor of Radiology, Surgery, and Medicine, and director of deep venous interventions at Northwestern University Feinberg School of Medicine (Chicago, USA).

Initial implants of Thubrikar TAVI system to commence

Thubrikar Aortic Valve has received approval from a Competent Authority in Poland to conduct initial patient implants with its Optimum transcatheter aortic valve implantation (TAVI) system. The company will sponsor this CE mark-enabling pilot study on patients with severe aortic stenosis and begin to implant the first five patients in early 2022. According to a press release from Thubrikar, Optimum TAVI is the shortest profile valve among selfexpanding transcatheter aortic valves, and its short profile facilitates coronary access. The company has designed a second-generation delivery catheter— the Precision 2 Catheter. Mano Thubrikar, the inventor of the Optimum transcatheter aortic valve and the company’s founder and president, stated: “We are thankful to our engineers and medical advisors for this progress. Durability remains the key issue in TAVI—younger patients still require open-heart surgery because no approved transcatheter aortic valves have demonstrated the durability of surgical valves. We designed the Optimum transcatheter aortic valve after the natural aortic valve because we discovered that it has the optimal geometry for efficient performance and durability. We also ensured that Optimum transcatheter aortic valve’s leaflets do not contain suture holes. As a result, Optimum transcatheter aortic valve has unparalleled durability and will greatly benefit patients.”

HeartFlow submits premarket application for coronary plaque assessment

HeartFlow has announced it has submitted a 510(k) premarket application to the US Food and Drug Administration (FDA) to add advanced anatomic assessment and plaque evaluation to the HeartFlow FFRct Analysis. The PreRead anatomic assessment will help identify the presence and location of narrowings or stenoses in

the coronary arteries based on coronary computed tomography (CT) scans. The HeartFlow Plaque technology will provide plaque volume and characterise the type of plaque present. By adding the anatomic assessment and plaque evaluation to the physiological information currently provided by the HeartFlow Analysis, physicians will gain a more comprehensive understanding of a patient’s coronary disease burden and support efficient risk stratification of patients who may be at high risk of death from a heart attack, the company said in a press release. PreRead is designed to provide a rich anatomic assessment of each coronary CT that, when considered by physicians in conjunction with other patient clinical information, helps physicians to quickly identify where coronary disease is present and understand the severity of the narrowing. The PreRead assessment highlights areas of modelled stenosis greater than 30% for vessels 1.8mm or larger in diameter. This information will be provided as a 2D image of the coronary arteries, with areas of concern colour-coded by severity. In addition, CT images of each of the three main arteries are provided so physicians can more easily confirm the PreRead colour-coded narrowings. The PreRead assessment is intended to support clinical workflow efficiency, diagnostic accuracy, and CT reader consistency as measured by repeatability and reproducibility. In an internal study, the PreRead assessment was 35% more repeatable and 47% more reproducible in classifying percent stenosis than expert CT readers’ (Level 3) classification of the same cases. In addition, the HeartFlow Plaque feature is based on a fully automated deep learning (a form of AI) algorithm for characterising and quantifying plaque. In an internal study, the HeartFlow Plaque technology was found to be more reliable than expert CT readers in identifying different types of plaque and quantifying total plaque volume.

Svelte Medical Systems receives US FDA approval for Slender IDS and Direct RX

Svelte Medical Systems has received US Food and Drug Administration (FDA) approval to commercialise the Slender IDS fixed-wire and Direct RX rapid-exchange drug-eluting stent (DES) systems for the treatment of coronary artery disease in the USA. Slender IDS and Direct RX, incorporating the same specialised stent, bioresorbable drug coating, and balloon technologies, achieved 1.5% clinically-driven target lesion revascularisation (TLR) at one year in the OPTIMIZE investigational device exemption (IDE) clinical study. “Slender IDS and Direct RX are extremely low profile, highly deliverable DES systems that

Issue 64 | February 2022

Market Watch 29

Product News provide excellent early and long-term clinical outcomes in complex patient populations. Slender IDS uses a unique DES delivery platform while both systems incorporate a novel drug carrier and other technologies, which I believe will add value in the treatment of patients in the US,” said Dean Kereiakes, president of The Christ Hospital Heart & Vascular Institute in Cincinnati, USA, clinical professor of Medicine, The Ohio State University and co-principal investigator of the OPTIMIZE study. In a press release, Svelte describes the Slender IDS as an ‘all-in-one’ integrated delivery system featuring Asahi guidewire technology, and Direct RX as a workhorse rapid-exchange delivery system. Both are low-profile DES systems designed to enhance transradial intervention (TRI) and indicated by the FDA for use with direct stenting, the company adds. “Materially lower system and crossing profiles facilitate TRI, which, when combined with a direct stenting approach in appropriate clinical indications, streamline procedures, limit complications and enhance the patient experience,” added Sunil Rao, professor of Medicine at Duke University in Durham, USA and coprincipal investigator of the OPTIMIZE study. “TRI has been long regarded as the standard of care overseas. With its increased adoption and use in the majority of cases recently in the USA, approval of these products is very timely. I am excited to integrate them into my practice.”

Opsens files 510(k) submission to US FDA for TAVI guidewire

Opsens has filed a 510(k) submission with the US Food and Drug Administration (FDA) for regulatory clearance of its new guidewire, SavvyWire for transcatheter aortic valve implantation (TAVI). Osens has also filed for approval with Health Canada. “The FDA submission is a key milestone for Opsens, in introducing our innovative product to the cardiovascular market. The SavvyWire has been designed and developed to improve the workflow in transcatheter aortic valve replacement,“ commented Louis Laflamme, president and chief executive officer of Opsens. “The introduction of a novel and advanced guidewire that has the ability to both deliver a valvular prosthesis while allowing continuous haemodynamic pressure measurement during the procedure is considered to be a significant benefit to the medical community, especially given the rapid growth in TAVI procedures. We look forward to the agency’s review of our application and will continue to prepare

our organisation for an anticipated approval in late summer or fall of 2022.” The SavvyWire, a pre-shaped, structural guidewire with integrated pressure monitoring, aims at improving procedural efficiency and clinical outcomes by allowing multiple steps over the same device without exchange, Opsens said in a press release. The device has been designed to support the minimalist TAVI approach that has been growing among structural heart physicians, the company adds.

Soundbite Medical gains fifth US patent for its plaque modification technology

Soundbite Medical Solutions has announced that the US Patent and Trademark Office has issued a patent to a device for delivering high amplitude broadband mechanical pulses to treat a lesion present in a blood vessel. The device includes a catheter body, an inflatable balloon, and at least one mechanical waveguide connected to a source of high amplitude broadband mechanical pulses for propagating the pulses to the lesion. The patent protects novel Soundbite Active Balloon devices, intended for plaque modification of calcified arteries. This is the fifth US patent to be issued around the Soundbite technology, further solidifying and broadening the scope of protection for the company’s technology platform. The patent allows Soundbite to compete in the plaque modification space with a broader array of active devices addressing a larger market and clinical challenge. “Building our patent portfolio to address complex calcium is a testament to our highly talented engineering team. The pursuit of excellence in serving our patients with clinical solutions begins with medical devices that are unique, differentiated, and of the highest quality. Protecting that work while innovating to meet the growing challenges inherent in calcific occlusive disease will establish Soundbite as a leader in its field,” said Lori Chmura, president and CEO of Soundbite.

Gore’s Cardioform Septal Occluder reaches 10-year milestone

WL Gore & Associates has announced that its Cardioform Septal Occluder has achieved 10 years of clinical use, treating patients through clinical studies and commercially in approved indications globally. The device offers an option to treat patients with atrial septal defects (ASD) and patent foramen ovale (PFO). The device is backed by the Gore REDUCE clinical study, a study in which 664 patients were enrolled to evaluate whether PFO closure with

the Cardioform Septal Occluder or the Helex Septal Occluder plus antiplatelet therapy significantly reduces the risk of stroke compared to antiplatelet therapy alone. The REDUCE study is the only US Investigational Device Exemption (IDE) study that achieved its primary endpoint and over five years showed a significant reduction in recurrent ischaemic stroke across all PFO anatomies compared to medical therapy alone. “The impact and longevity of the Gore Cardioform Septal Occluder illustrate Gore’s ongoing commitment to helping patients,” said Jens Erik Nielsen-Kudsk, cardiology department clinical professor at Aarhus University Hospital in Aarhus, Denmark, investigator for the Gore REDUCE clinical study and consultant for Gore. “Gore engineers worked closely with healthcare professionals to understand what patients need and created a device that conforms to the individual anatomy.” “This major milestone shows that the

Cardioform septal occluder

Gore Cardioform Septal Occluder is meeting a recognised unmet need. We continue to see healthcare providers around the globe trusting and choosing this device for their patients,” said Jake Goble, innovation leader, Medical Products Division at Gore. The Gore Cardioform Septal Occluder is a permanently implanted device approved in the USA and European Union for the percutaneous, transcatheter closure of ostium secundum atrial septal defects up to 17mm. The device received US Food and Drug Administration (FDA) premarket approval for the percutaneous closure of PFO in 2018. It is also approved in the European Union for percutaneous closure of PFO.

Philips integrates cloudbased AI and 3D mapping into its mobile C-arm system series

Royal Philips has announced physicians will now have access to advanced new 3D image guidance capabilities through its image-guided therapy mobile C-arm system—Zenition. The system will deliver enhanced clinical accuracy and efficiency, according to Philips, and aims to improve outcomes for patients undergoing endovascular treatment. The company has signed a strategic partnership agreement with Cydar, a UK-based provider of cloud-based procedure maps software to plan and guide surgery in real time. As patient numbers rise and

procedures become more complex and time-consuming, patient-specific real-time procedure planning and guidance, optimisation of equipment utilisation, and usability, have become ever more important. To help overcome these challenges, Philips details that its image-guided therapy mobile C-arm system—Zenition—brings together innovations in image capture and processing, ease-of-use, and versatility, many of which were pioneered on Philips’ image-guided therapy platform Azurion. Like Azurion, the Zenition mobile C-arm system allows hospitals to maximise operating room performance, enhance their clinical capabilities, and provide staff with a seamless user experience, the company claims. The integration of Cydar EV Maps software into the Zenition platform now adds extended procedure planning and real-time 3D guidance. Philips states that Cydar EV Maps assists in the planning, real-time guidance, and postprocedure review of the endovascular surgery. It brings cloud-based artificial intelligence (AI) and computer vision to mobile surgery, enabling reductions in radiation exposure, fluoroscopy time and procedure time together with improved ease of use. It enables surgeons to create a detailed, patient-specific 3D map of the target vasculature to help plan surgery, the company adds, and then uses these maps to augment intraoperative live image guidance, updating the maps in real time to account for deformations during surgery, such as guidewires and instruments deforming the patient’s blood vessels. Philips notes that Cydar EV also facilitates post-procedure outcome analysis. The combined result of this integration of procedure planning, guidance and review is that surgeons can work more accurately and efficiently—enabling an approximate 50% reduction in radiation exposure, a significant reduction in fluoroscopy time and a reduction of procedure times by more than 20%.

Philips' Zenturion platform

“With Philips’ integrated portfolio, using validated AI and cloud technologies, we can facilitate collaborative care to optimise surgical pathways,” said Karim Boussebaa, general manager Image Guided Therapy Systems at Philips. “Philips has a strong global network of mobile surgery systems and recognises that Cydar’s EV Maps solution can play a key role in further improving our integrated offering for endovascular procedures.”

February 2022 | Issue 64

30 Market Watch

Clinical News

vFFR contour step

First patients enrolled in FAST III study of vFFRguided PCI

The first patients have been enrolled in the FAST III trial at the Erasmus University Medical Center in Rotterdam, The Netherlands. This marks the beginning of a multicentre, randomised controlled, open-label study in which the outcome of therapy for coronary artery disease is being investigated after fractional flow reserve (FFR) has been determined using different methods. The principal investigator in the FAST III study is Joost Daemen, cardiologist in the Thoraxcenter at the Erasmus University Medical Center (Rotterdam, The Netherlands). The FAST III study compares the impact of percutaneous coronary intervention (PCI) guided by CAAS vFFR (cardiovascular angiographic analysis systems for vessel fractional flow reserve), a software from Pie Medical Imaging, with the outcome of PCI guided by the conventional, invasive, pressure wire-based method. FAST III is subtitled “Fractional Flow Reserve or 3D-Quantitative-CoronaryAngiography Based Vessel-FFR Guided Revascularization”. CAAS vFFR is an innovative technology that enables a less invasive physiological evaluation of coronary lesions, Siemens Healthineers said in a press release. Pressure drop and the vFFR value are determined on the basis of two angiographic images, which eliminates the need for an invasive pressure wire and hyperemic agent. A total of 2,228 patients in up to 35 hospitals in seven European countries will be enrolled in the study; randomised in a one-to-one process to either vFFR- or FFR-guided approach. The leading clinical centres involved

Calendar of events

include, but are not limited to, Erasmus University Medical Center (The Netherlands), John Radcliffe Hospital Oxford (UK), Mater Private Hospital Dublin (Ireland), University Hospital of Verona (Italy), University Hospital Valladolid (Spain), Charité Berlin (Germany), and University Hospital Lille (France). The European Cardiovascular Research Institute (ECRI) in Rotterdam, The Netherlands, is the sponsor of the investigator-initiated FAST III trial. FAST III is funded by Pie Medical Imaging and Siemens Healthineers, who joined forces to strengthen the body of evidence for the use of angio-derived FFR in the pursuit of a faster and less stressful diagnosis along with the potential for a lower cost of care.

Cardiovascular Systems announces enrolment in first-in-human study of everolimus-coated coronary DCB

Cardiovascular Systems has announced the start of enrolment in a first inhuman trial of the coronary everolimus drug-coated balloon (DCB) being developed by Chansu Vascular Technologies. The first patient was successfully treated by Irakli Gogorishvili, head of the Interventional Cardiology Department, Israeli-Georgian Medical Research Clinic Helsicore, Tbilisi, Georgia. The coronary DCB was used to treat in-stent restenosis (ISR) located in the left anterior descending artery. DCBs are a widely accepted percutaneous interventional treatment option for femoro-popliteal lesions in patients with peripheral artery disease and are increasingly recognised for their potential in complex coronary artery disease, ISR, small vessels, and bifurcation lesions. Everolimus, the active drug in Chansu Vascular Technologies’ DCB formulation, acts as a cytostatic agent to reduce tissue hyperplasia and associated restenosis, and has a long history of safety and efficacy in coronary drug-eluting stent applications. Under the terms of the agreements

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

10–12 March Houston Aortic Symposium Houston, USA

26–28 April Charing Cross (CX) Symposium 2022 London, UK

houstonaorticsymposium.com

Two-year results of mitral valve repair using ChordArt device published

CoreMedic has announced the publication of two-year followup results from the first in-human CHAGALL trial of its ChordArt mitral valve repair device in the treatment of mitral valve regurgitation (MR). Chordal replacement with ChordArt is reported to be safe, effective, and durable at two years follow-up. The CHAGALL data were presented earlier this year at the American Association for Thoracic Surgery 101st annual meeting (AATS 2021, 30 April–2 May, virtual) by Thierry Carrel (University Hospital Zürich, Zürich, Switzerland), corresponding author of the study. The ChordArt device is being developed as a first-line treatment option for mitral valve regurgitation (MR). MR is the most common heart valve disease and a growing medical burden, particularly in ageing societies, and affects more than 25 million patients worldwide. The device is designed to enable safe and effective repair of the mitral valve by replacing damaged mitral valve chords with a physiological approach respecting the natural anatomy. Due to its minimal footprint, the implant keeps the door open for possible future therapy needs, CoreMedic said in a press release. The article “Mitral valve repair with a device for artificial chordal implantation at two years” was published on 29 October by the Journal of Thoracic and Cardiovascular Surgery.

First patient enrolled in COSIRA-II trial of Neovasc Reducer

Neovasc has announced the enrolment of the first patient in the COSIRA-II

clinical trial. COSIRA-II (Coronary sinus reducer for the treatment of refractory angina) is a pivotal trial that will study the Neovasc Reducer, designed to reduce angina symptoms in patients with refractory angina. The results of this study will complement existing international safety and effectiveness data and support a premarket approval application (PMA) to the US Food and Drug Administration (FDA) for approval of the Reducer device in the USA. The first patient was enrolled at St Francis Hospital & Heart Center, Roslyn, United States of America (USA), under the care of Ziad Ali, and principal investigator Evan Shlofmitz. Neovasc reports that the patient has a history of chronic refractory angina and previously endured multiple cardiac catheterisation procedures at various hospitals to treat his recurrent symptoms. None of these previous procedures had been successful in alleviating his chest pain. COSIRA-II is designed to evaluate the safety and effectiveness of the Reducer in treating patients suffering from refractory angina. The randomised, double-blinded, placebocontrolled trial will enrol approximately 380 patients in the USA and Canada at as many as 50 investigational sites. The primary endpoint of the trial is

Neovasc Reducer

the change in exercise tolerance testing time measured at six months via a treadmill test. “Enrolment of the first patient in COSIRA-II is a major step forward for patients in the USA suffering from chronic chest pain,” stated COSIRA-II Executive Steering Committee member Allen Jeremias, St Francis Hospital & Heart Center, Roslyn, USA. “For the first time, patients that experience the debilitating effects of refractory angina have access to an FDA-designated ‘Breakthrough Medical Device’ in a placebo-controlled trial. The COSIRA-II Trial offers hope for patients that previously had a poor prognosis and faced a future of unrelenting chest pain.”

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

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

signed with Chansu Vascular Technologies, Cardiovascular Systems is providing milestone-based financing to Chansu Vascular Technologies for the development of coronary and peripheral DCBs. Under an acquisition option agreement, upon Chansu Vascular Technologies’ completion of key technical and clinical milestones in the development programme, Cardiovascular Systems will have exclusive rights and obligations to acquire Chansu Vascular Technologies, subject to the satisfaction of closing conditions set forth in the agreement.

accscientificsession.acc.org

cxsymposium.com/cx2022

17–20 May EuroPCR 2022 Paris, France

8–11 June TVT2022 Chicago, USA

19–22 May SCAI 2022 Scientific Sessions Atlanta, USA

27–30 August ESC Congress 2022 Barcelona, Spain

pcronline.com/courses/europcr

scai.org/scai2022

crf.org

escardio.org

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