Cardiovascular News 61‒May 2021 (EU)

May 2021 | Issue 61

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Featured in this issue:

Robotics in the cath lab The future of PCI?

Emotional Harassment Overall

What the statistics say:

Joseph Bavaria: Aortic valve trends

29%

43%

26%

Sexual Harassment Overall

Discrimination Overall

4%

12%

page 26

30%

1%

56%

21%

Hostile environment: Cardiologists report high prevalence of discrimination and harassment in the workplace Discrimination and harassment are a common experience among those working in cardiology, according to the findings from a global survey carried out by the American College of Cardiology (ACC), which have been published in the Journal of the American College of Cardiology (JACC). Responses suggest that as many as 44% of cardiologists report experiencing a hostile work environment (HWE) including being subject to emotional or sexual harassment, or discrimination.

A

uthors concluded that a renewed focus on organisational structure, processes, and practices to mitigate these problems in cardiology across the globe is critical to ensuring workforce wellbeing and optimal patient care.

The report is the culmination of a 50-item online survey conducted by the ACC in September to October 2019, reaching 5,931 cardiologists in Africa, Asia, the Caribbean, Europe, the Middle East, Oceana, and North, Central, and South America. Questions covered demographic information, practice environment, academic rank, discrimination, and harassment, with a particular focus placed on the professional and personal challenges of cardiologists.

Author Garima Sharma (Johns Hopkins School of Medicine, Baltimore, USA) noted that the incidences of HWE were more commonly reported among female (68%), Black (53%) and North American (54%) respondents.

Gender was the most frequent cause of discrimination (44%), the study found, followed by age (37%), race (24%), religion (15%), and sexual orientation (5%).

Of the participants 77% were men (n=4,584), and 23% (n=1,347) were women. Survey participants predominantly identified as white (54%), followed by Asian (17%), Hispanic (17%), and Black (3%); and 73% were ≤54 years of age. Most were married (75%); 12% were single, 7% were living with a partner, 3% were divorced, and 1% were separated.

Cardiologists from the European Union represented the largest group of respondents (32%), followed by respondents from South America (18%), the Middle East, Eastern Europe and Asia (all 9%), Africa (8%), North America (7%), Central America (6%), and Oceana (2%).

According to Sharma, the survey results indicate that

These data come at a crucial time when harassment and the culture of discrimination in medicine are being openly challenged. These findings support the need to improve the culture within medicine greatly and raise a call to action to address harassment and discrimination.”

Continued on page 3

Profile Cindy Grines page 18

CRT 2021: BIOSTEMI shows superiority of Orsiro stent to Xience for target lesion failure at two years Two-year follow-up data from the BIOSTEMI trial, presented during a late-breaking trial session at the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April, virtual) demonstrated the superiority of the ultrathin-strut, sirolimus-eluting Orsiro stent (Biotronik) over the everolimus-eluting Xience (Abbott) stent for target lesion failure (TLF) in patients with ST-segment myocardial infarction (STEMI).

BIOSTEMI IS AN INVESTIGATORinitiated, multicentre, superiority trial using a Bayesian design to compare the two stents in 1,300 patients with acute myocardial infarction.

The study used historical data from 407 acute myocardial infarction patients enrolled in the BIOSCIENCE trial—which compared the two stents in patients with chronic stable coronary artery disease or acute coronary syndromes— to assess the endpoints at two years.

“Recent refinements of drug-eluting stents involved the reduction of the strut thickness of the metallic stent platform, and the use of biodegradable polymers as a carrier for the antiproliferative substance,” Thomas Pilgrim, (Inselspital Bern, University Hospital, Bern, Switzerland), the trial’s lead investigator told the CRT 21 audience. “Improvements in stent design may mitigate arterial injury, facilitate endothelialisation, and reduce neointimal hyperplasia,” he added.

Detailing the study design, Pilgrim explained that STEMI patients undergoing primary percutaneous coronary intervention (PCI) at 10 Swiss centres were randomised 1:1 to receive either the Orsiro or the Xience stent.

The primary endpoint was TLF, a composite of cardiac death, target vessel myocardial infarction, or clinically-indicated target lesion revascularisation at one year.

One-year data from the study had previously been presented at the 2019 European Society of Cardiology Congress (ESC 2019; 31 August–4 September, Paris, France), and published in The Lancet and showed a lower rate of TLF with the Orsiro stent than with Xience.

Continued on page 2

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May 2021 | Issue 61

Top stories

CRT 2021: BIOSTEMI shows superiority of Orsiro stent to Xience for target lesion failure at two years

News in brief

The latest stories from the world of Cardiology

Continued from page 1

Presenting the two-year results of the study at components to it. It is not only strut thickness, CRT 21, which were published simultaneously it is also strut geometry, radial strength; the in JACC: Cardiovascular Interventions, Pilgrim polymer has a certain thickness, distribution, explained that superiority demonstrated by the drug elution, kinetics. There are many, many Orsiro stent for the clinical primary endpoint factors and it is probably more the effect of all of TLF at 12 months was further confirmed of these that may make a difference.” at 24 months with an incidence of 5.1%. In Offering a view on the importance of the comparison, the Xience stent showed a TLF findings to Cardiovascular News, Pilgrim said: incidence of 8.1% at 24 months (rate ratio, “The BIOSTEMI trial adds to the evidence that Thomas Pilgrim 0.58; 95% Bayesian credible interval, 0.4‒0.84; biodegradable polymer sirolimus-eluting stents posterior probability of superiority, 99.8%). are very safe and effective in the treatment of coronary The difference remained significant after the exclusion artery disease, and it also lends support to the notion that of historical data from the BIOSCIENCE trial with only even small differences in stent design may translate into the BIOSTEMI patients being analysed (rate ratio, 0.62; important differences with regard to clinical outcomes.

95% Bayesian credible interval, 0.40‒0.96; posterior Obviously based on the data that we have, biodegradable probability of superiority, 98.5%). The observed difference polymer, sirolimus-eluting stents may be the new between the two stents was driven by low rates of benchmark drug-eluting stent.” clinically-indicated target lesion revascularisation in patients treated with Orsiro, Pilgrim said. No significant differences were observed between the two treatment arms for safety endpoints.

In a panel discussion following the presentation, panellist Sripal Bangalore (New York University Grossman School of Medicine, New York, USA) was asked his view of the clinical significance of the findings.

He commented that while many stent trials in recent years had yielded non-inferior outcomes, “…we are now seeing some superiority, whatever the increment is, we are seeing the field being moved in the right direction.”

Bangalore then asked Pilgrim to speculate on the possible reason behind this superiority, questioning whether this could be driven by the use of a biodegradable as opposed to a durable polymer, or the thickness of the strut—Orsiro has a thickness of 60μm compared to 81μm for Xience.

However, Pilgrim dismissed either in isolation as a direct cause of the difference. He said: “If you look at the data, the effect of the Orsiro stent is very consistent in the first year and after the first year. We ask ourselves it is the strut thickness, or the polymer? Most of the polymer is still there because it degrades only after 12 months, but more likely after 24 months, so I do not think can be brought down to the polymer.”

On the question of strut thickness, Pilgrim said that a sub-analysis of the BIOSTEMI trial had led him to conclude that this is likely to have made a difference.

He commented: “…we are very tempted to reduce the polymer and strut thickness, but there are many more

It is not only strut thickness, it is also strut geometry, radial strength; the polymer has a certain thickness, distribution, drug elution, kinetics. There are many, many factors and it is probably more the effect of all of these that may make a difference.”

n SCAI 2021: Analysis presented during a late-breaking research session at the Society for Cardiovascular Angiography & Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual) has Saurav suggested that the patient Chatterjee population studied in the ISCHAEMIA trial may not be representative of patients entering cath labs in the USA today. The results shine a light into what is happening in modern cath labs, the authors say.

For more on this story go to page 4. n CARDIOVASCULAR SURGERY: In his presidential address at the Society of Thoracic Surgeons annual meeting (STS 2021, 29–31 January, virtual) Joseph Dearani (Mayo Clinic, Rochester, Joseph USA) warned that Dearani the risk of burnout among cardiothoracic surgeons, exacerbated by the COVID-19 pandemic, remains a stark concern. Dearani also sought to highlight racial and socioeconomic disparities brought to the forefront during the pandemic.

For more on this story go to page 9. n CRT 2021 : Catch up on the late-breaking trials from the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April), including data presented by Ankur Kalra (Cleveland Clinic, Cleveland, USA), suggesting direct oral anticoagulants (DOAC) use among patients receiving bioprosthetic heart valves is prevalent.

For more on this story go to page 27.

Ankur Kalra

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August 2021

Issue 61 | May 2021

Hostile environment

Hostile environment: Cardiologists report high prevalence of discrimination and harassment in the workplace Continued from page 1

there is a high level of professional dissatisfaction among the 44% who had experienced harassment or discrimination. Of those who reported HWEs, 30% felt dissatisfied with their financial compensation, 23% reported being treated unfairly, and 16% felt undervalued. Furthermore, 64% said it had some effect and 21% said it had a significant effect on the work environment.

A HWE also adversely affected professional activities with colleagues, where 62% of those experiencing HWEs reported some impact and 13% reported a significant impact. HWEs also adversely affected patient care, where 46% who experienced a HWE reported some impact on their activities with patients, and 6% reported a significant impact.

“HWE defined here as emotional harassment, discrimination, or sexual harassment, is experienced by nearly one-half of cardiologists globally, including across all regions, races or ethnicities, and both sexes and all gender identifications,” Sharma writes.

“Specific groups are at higher risk, including being a woman and being at an early career stage, whereas working in a physician-owned practice, being

times higher among women than men. Although women experienced more gender-based discrimination, men experienced more age-based discrimination, Sharma reports.

“Our study also uniquely investigated the perpetrators of discrimination, and this also differed by gender of the married, or being white conferred targeted group,” Sharma goes on to protection. Interestingly, there is add. “Women were especially targeted significant intersectionality among the by colleagues and patients, whereas three subgroups, where experiencing men were most commonly targeted by one type of HWE greatly increased administrators. This difference may have the odds of experiencing either of the important implications for the impact others. HWE has a pronounced and on the target. This also means that pervasive adverse effect on professional solutions should target not just peers but satisfaction and professional activities, also ancillary staff, administrators, and a finding suggesting that HWE is both patients.” a professional issue and a patient care Incidences of sexual harassment were issue. Our findings have important more commonly reported by women implications for organisations than men, the results indicate, and individuals seeking to also showing that 42% of optimise clinical wellbeing.” respondents had experienced Looking at each subset of more than one type of sexual the hostile work environment harassment. The study in detail, Sharma details authors say this consistent that emotional harassment with reports that targets of was experienced by nearly sexual harassment often face one-third of cardiologists. repeated harassment rather This can take the form of than one single incident.

Garima Sharma microaggressions, which are “These data come at a characterised as microassaults, crucial time when harassment microinsults, microinvalidations, or more and the culture of discrimination in overt “macroagressions”, representing medicine are being openly challenged,” institutional and structural biases.

Sharma writes. “These findings support The survey results indicate that at the need to improve the culture within least one form of discrimination was medicine greatly and raise a call experienced by 30% of cardiologists, to action to address harassment an outcome that was found to be three and discrimination.”

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In an editorial comment accompanying the study in JACC, Javed Butler (University of Mississippi Medical Center, Jackson, USA) and Ileana Piña (Central Michigan University, Midlands, USA), write that the importance of the research “cannot be underestimated”, although caution against drawing conclusions about whether the findings apply uniquely to the practice of cardiology, or would be generalisable across many medical specialties. “It needs to be understood that cardiology has been traditionally a white maledominated specialty and thus some of these observations may have this underlying feature. Further data are needed to understand and compare the workplace culture in medicine as a whole, and to learn from each other,” they write.

Butler and Piña go on to state: “When people feel threatened, undervalued, or discriminated against, it can affect productivity at work. It is unlikely, however, that the impact of such dynamics stops in the workplace and may affect individuals’ personal life and relationships with a potential to escalate into bigger problems with more dire consequences.

“Thus, there are both ethical and practical considerations why these results should be taken seriously. Lack of awareness by leadership coupled with a sense of not belonging may force the recipient of the hostility to leave the workplace. This loss of talent and dedication should be concerning to all.”

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May 2021 | Issue 61

Conference coverage

ISCHEMIA trial population not reflected in real-world patients Patients studied in the ISCHEMIA trial, the largest trial to date to compare revascularisation with a conservative strategy in patients with stable ischaemic heart disease (SIHD), may be unrepresentative of ischaemic heart disease patients entering US cath labs, research presented in a late-breaking trial session at the Society for Cardiovascular Angiography & Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual) has concluded.

I

SCHEMIA has been described as one of the most important trials in interventional cardiology in recent years. Supported by the US National Heart, Lung, and Blood Institute, the trial looked at the merits of an invasive or a conservative treatment strategy in stable patients with at least moderate ischaemia on a stress test.

Results of the trial were presented at the 2019 American Heart Association scientific sessions (AHA 2019; 16–18 November, Philadelphia, USA) by Judith S Hochman (New York University School of Medicine, New York, USA), and concluded that there is no additional benefit to revascularisation in these patients at a median of three years after the procedure.

However, a cross-sectional analysis of the National Cardiovascular Data Registry (NCDR) CathPCI registry, findings of which were presented at SCAI 2021 by Saurav Chatterjee (Northshore and Long Island Jewish Hospitals of the Northwell Health System, New York, USA), has found that only a minority of SIHD patients referred for coronary intervention in contemporary practice clearly resemble those enrolled in the ISCHEMIA trial.

ISCHEMIA patient population

“The ISCHEMIA trial is one of the most important studies in interventional cardiology over the last decade. While the findings are very valuable in informing our decision making in many patients, the population enrolled does not appear representative of the broad range of patients that modern US coronary interventionists encounter,” said study senior author Jay Giri (Penn Medicine, Philadelphia, USA).

Patients excluded from ISCHEMIA included those with acute coronary syndrome (ACS), cardiac arrest, cardiogenic shock, ejection fraction <35%, significant left main disease, cardiomyopathy, cardiac transplant, those non-adherent to medication, at high bleeding risk and those having anatomy unsuitable for revascularisation, Chatterjee told SCAI attendees during his virtual presentation.

“That made us hypothesise that potentially, this would lead to a significant proportion of patients who are routinely considered for revascularisation in current US practice,” he said.

“Additionally, there are patients, who

Jay Giri

Saurav Chatterjee

the ISCHEMIA trial, adding that there was evidence of significant variability in patient selection among SIHD PCI centres.

“Our study reveals that most patients who have intervention are not reflected in the ISCHEMIA trial,” said Chatterjee.

“These results help shine a light into what is truly happening in cath labs across the country, and the kinds of patients who are being referred for intervention.”

ischaemia on functional testing, lack of high-risk anatomic or clinical features— and those who did not, were identified.

Bottom line Among US patients undergoing PCI Following his presentation, Chatterjee for SIHD between October 2017–June was asked by session moderator David 2019, 32.3% met ISCHEMIA trial Cox (Brookwood Baptist Health, enrolment criteria.

Birmingham, USA) to summarise the for various reasons were enrolled over a Among SIHD patients that did not “bottom line” from the group’s research. decade for the ISCHEMIA trial, which meet criteria, 18.5% had SIHD with Chatterjee responded: “One of the may not be representative of the most high-risk features (35.2% left main things that we would like to highlight is current form of practice in the USA.” disease, 43.7% left ventricular systolic that while ISCHEMIA guides a certain dysfunction, 16.8% end-stage renal component of our clinical decisionVariability disease), 17.3% had SIHD with negative making, it does not represent all patients The study team also assessed variability or low-risk functional testing, and 31.9% who undergo PCI in the USA. among different centres in the proportion either had no stress testing or did “There is a large proportion of of ISCHEMIA-like versus patients who not have ischaemic burden patients who do not meet did not represent ISCHEMIA in the reported. these criteria, and future population of patients who underwent Compared with the research needs to identify percutaneous coronary intervention (PCI) other SIHD cohorts, the the appropriate patient for SIHD. ISCHEMIA-like cohort cohort who will derive the of patients met Analysis was conducted on data had the lowest in-hospital most benefit, especially ISCHEMIA trial collected from the CathPCI registry mortality rate (0.1%), and among patients with enrolment criteria between October 2017‒June 2019, which comparable in-hospital SIHD with a need for included 388,212 patients from more than bleeding (0.6%), and revascularisation.”

1,600 hospitals. Participants included acute kidney injury requiring patients undergoing PCI for SIHD in haemodialysis (0.04%).

Stone: "Apply insights routine clinical practice. This SIHD The findings led and wisdom" population represented 42.9% of all Chatterjee, Giri and Commenting on the performed PCI over the examined time colleagues to draw relevance of the findings, period, the analysis showed, with the the conclusion that Gregg Stone (Icahn School SIHD patients had majority of US PCI performed in patients a large proportion of of Medicine, Mount high-risk features with ACS, cardiac arrest, or cardiogenic contemporary patients Sinai, New York, USA), a shock. undergoing PCI for SIHD member of the ISCHEMIA Patients who met ISCHEMIA trial in the USA would not have research group, responded inclusion criteria—moderate-to-severe met criteria for inclusion in that “no single trial applies to all patients” and urged physicians to apply insights from other studies, as well as ISCHEMIA, to make the best choices for patients.

“First, the fact that nearly one-third of the patients with stable ischaemic heart disease undergoing PCI in the USA would have met enrolment criteria for the ISCHEMIA trial is notable,” Stone told Cardiovascular News. “The care of these patients may be directly affected by the study results. Regarding the stable patients that did not have at least moderate ischaemia, it is unlikely that these patients would fare even better with revascularisation than those enrolled in the study, and thus ISCHEMIA has relevance to this group as well.

“The ISCHEMIA-CKD [chronic kidney disease] results also have direct relevance to the high-risk patients excluded with end-stage renal disease.

Nonetheless, no single trial applies to all patients, and ISCHEMIA is no different.

It clearly does not apply to those with acute coronary syndromes, left main disease, substantial angina that is not medically controlled, and those with left ventricular dysfunction or heart failure.

For these patients, clinicians need to apply the insights from other studies and In-hospital outcomes for ISCHEMIA-like and non-ISCHEMIA-like patients presented their wisdom to make the best treatment

by Chatterjee at SCAI 2021 choices for each individual.”

32.3% 18.5%

The ISCHEMIA trial is one of the most important studies in interventional cardiology over the last decade. While the findings are very valuable in informing our decisionmaking in many patients, the population enrolled does not appear representative of the broad range of patients that modern US coronary interventionists encounter.”

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May 2021 | Issue 61

Conference coverage

Three-year COMPARE ABSORB results show similar TLF rate between Absorb scaffold and Xience stent Three-year results from the COMPAREABSORB trial, presented during a late-breaking trial session at the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April), indicate that the Absorb (Abbott) bioresorbable scaffold resulted in a similar rate of target lesion failure (TLF) to the Xience (Abbott) metallic stent in patients at high risk of restenosis.

THE TRIAL COMPARED THE now-discontinued Absorb bioresorbable vascular scaffold (BVS) to the Xience metallic drug-eluting stent (DES) for the prevention of restenosis following percutaneous coronary intervention (PCI).

Absorb is a temporary scaffold design to treat coronary artery disease by restoring blood flow to the heart and then dissolving into the body. The device is made of polylactide, a naturally dissolvable material that

is used in medical implants such as dissolving commented. sutures. Abbott withdrew the device from the Additionally, one-year landmark analysis market in 2017, citing low commercial sales for showed similar rates of TLF, target vessel the decision. myocardial infarction and device thrombosis Presenting the results of the investigatorfor both devices beyond one year. “Whether the initiated study of the device, Peter Smits absence of increased risk of very-late scaffold (Maasstad Hospital, Rotterdam, The thrombosis and target vessel myocardial Netherlands), commented that previous BVS infarction was prevented by a dedicated trials have shown an increase in myocardial implantation technique or prolonged DAPT infarction and device thrombosis rates up to [dual antiplatelet therapy] remains to be Target lesion failure determined,” Smits commented. three-year follow-up.

8.9% - Absorb scaffold The COMPARE ABSORB study team Summing up the findings of the trial, Smits hypothesised that the use of the Absorb 7.4% - Xience stent said that in a more-comer population at BVS in a high-risk population for restenosis high risk for restenosis, TLF rates were not may demonstrate better long-term outcomes compared significantly different between the two devices after to a metallic DES after full resorption. Unlike other three years. randomised studies of BVS, COMPARE ABSORB also Follow-up of seven to 10 years will show whether the mandated a dedicated optimal implantation technique BVS has long-term advantages over the metallic Xience from the start, Smits detailed. stent, Smits concluded.

Previous randomised trials with BVS showed an increase in myocardial infarction and device thrombosis rates up to three-year follow-up, Smits said, commenting that this was highly likely due to the intraluminal dismantling of the device during its resorption process.

Inclusion criteria for COMPARE ABSORB included patients with high-risk characteristics for restenosis, including known diabetes or multivessel disease, or complex de novo target lesion. A total of 1,670 patients were enrolled at 45 sites across Europe, who were randomised 1:1 to receive either the Absorb or Xience device.

Three-year rates of TLF stood at 8.9% in the Absorb arm, and 7.4% for those who received Xience, Smits explained. In terms of device thrombosis rates, these stood at 2.4% for Absorb and 1.1% for Xience. “These differences occur mainly in the early phase,” he

Polymer-free amphilimus-eluting stent non-inferior to zotarolimuseluting stent in PCI patients

Three-year clinical outcomes from the Recre8 trial, a multicentre study comparing the safety and efficacy of the polymer-free Cre8 (Alvimedica) amphilimus-eluting stent to the Resolute Integrity (Medtronic) permanent-polymer zotarolimus-eluting stent, found that the Cre8 stent was non-inferior to Resolute Integrity at longterm follow-up.

T

he findings were presented by Michiel Voskuil (University Medical Centre Utrecht, Utrecht, The Netherlands), during a late-breaking trial session at the Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April, online).

Voskuil said that rates of target lesion failure observed in patients receiving either of the two stents were similar, commenting that there was no major difference between the permanent polymer and polymer-free stent designs.

The investigator-initiated all-comers PCI trial, which was carried out in three Northern European centres, included patients with ischaemic heart disease who required PCI involving implantation of a drug-eluting stent. There were no exclusion criteria based upon clinical presentation or lesion characteristics.

The goal of the study was to establish non-inferiority of the polymer-free stent compared to the polymer stent with an endpoint of target lesion failure, which was a composite of cardiac death, target vessel myocardial infarction and target

lesion revascularisation.

Voskuil explained that the Cre8 stent works through the slow release of an amphilimus formulation via “abluminal reservoirs” from the thin strut cobaltchromium stent.

The trial randomised 1,502 patients on a 1:1 basis to either of the stent platforms. Patients were stratified for their troponin status at baseline, to assess whether they had troponin-positive or troponin-negative disease, and whether they had a history of diabetes, and were randomised for implantation to either the Resolute Integrity or Cre8 stent.

Troponin negative patients received one month of dual antiplatelet therapy (DAPT) post PCI, while the troponin positive patients received one year of DAPT according to guidelines, Voskuil explained.

Detailing the study population, Voskuil noted that 20.4% of patients presented with diabetes mellitus, 19.9% with previous myocardial infarction, 47.5% with acute coronary syndrome (ACS), 58.6% with complex lesion anatomy, and

8.9%

7.4%

Whether the absence of increased risk of verylate scaffold thrombosis and target vessel myocardial infarction was prevented by a dedicated implantation technique or prolonged DAPT remains to be determined.”

43.7% with multivessel disease.

Results after one year of follow-up, previously published in Circulation, showed the non-inferiority of the two platforms both on the composite endpoints, as well as cardiac death, target vessel myocardial infarction and target lesion revascularisation as separate endpoints, Voskuil commented.

The study team analysed patient subgroups, such as those presenting with diabetes, to establish whether there may be an extra benefit of the polymer-free stent design, but Voskuil noted that “none of the subgroups saw any statistical difference between both stent frames”.

Voskuil commented that they also assessed the “late catch-up phenomenon” following DAPT cessation. Target lesion revascularisation beyond this one-year follow-up post-DAPT cessation showed

We are looking for sub-groups of patients that might benefit from this particular stent design and one of the patients that we are particularly interested in is diabetic patients.”

similar rates between the polymer-free stent and the permanent polymer stent, 2.1% and 3.1% respectively, Voskuil noted.

He added that there were some limitations to the study, including that physicians were not blinded to the allocation of treatment, and no randomisation was performed for DAPT duration, which Voskuil commented “would have been interesting, but would have needed to increase the number of patients in follow-up dramatically”.

In his concluding remarks, Voskuil commented that the polymer-free amphilimus stent is clinically noninferior to the permanent-polymer zotarolimus-eluting stent at long-term follow-up, and that no late catch-up phenomenon could be shown in this patient cohort.

Discussion following Voskuil’s presentation centred on the noninferiority design of the study, with speakers considering whether new iterations in stent technology are likely to lead to improvements in outcomes in patients.

On this topic, Don Cutlip (Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, USA), said: “We often forget that non-inferiority designs are very helpful for approval pathways, but we really look for some secondary benefit, which is really part of the non-inferiority planning process and I think with all of these trials we are not seeing that, to the extent that it might be even less expensive would be a secondary benefit.”

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May 2021 | Issue 61

Robotics

Robotic PCI

Robotic PCI achieves high clinical and technical success “in a wide spectrum of lesions” Robotic-assisted percutaneous coronary intervention (PCI) using the secondgeneration CorPath GRX (Corindus) system achieved high rates of clinical and technical success, across a wide spectrum of lesions. These were the conclusions of the PRECISION GRX study, presented at the Society for Cardiovascular Angiography & Interventions virtual scientific sessions (SCAI 2021, 28 April–1 May, virtual) by Ehtisham Mahmud (The University of California, San Diego, USA).

MAHMUD COMMENTED THAT THE success of the system demonstrates the scope for robotic technologies to minimise risks faced by

interventional cardiologists over time including exposure to radiation and orthopaedic injuries related to the prolonged wearing of lead.

The latest generation system, he said, allows the control of the guide catheter, guidewire, stent or balloon delivery systems away from the tableside.

“During the procedure you are seated. You are not wearing your lead so you minimise the orthopaedic risk, and you are behind a cockpit, so not getting exposed to radiation,” Mahmud added.

PRECISION GRX was a prospective, international multicentre registry, assessing patients with obstructive coronary artery disease who were treated with the robotic system. The study analysed data from 980 patients. The majority had indications for acute coronary syndrome (ACS, 31.6%), stable angina

These data support robotic PCI being a viable option for addressing orthopaedicand radiation-associated risks for the practice of interventional cardiology.”

(29.1%) or had a positive stress test (25.7%), while a small number were indicated for heart failure or left ventricular dysfunction (11.6%) or ST-elevation myocardial infarction (STEMI, 2.7%).

The lesions treated were almost equally distributed across the left anterior descending coronary artery (LAD, 36.6%), left circumflex artery (LCx, 27%) and the right coronary artery (RCA, 32.8%), and there were a small proportion of left main or vein graft lesions (3.6%), Mahmud explained. Detailing the type of lesions treated, he explained that almost 70% were Type B2 (23.3%) or C (45.5%).

Mahmud noted that clinical success—defined as procedural completion with <30% residual stenosis and the absence of a major adverse cardiovascular event (MACE)—was achieved in 98.2% of lesions treated, with no statistically significant difference from type A (98.2%) to type C (97.9%) lesions. Technical success— clinical success along with the absence of manual assistance or conversion—was achieved in 89.8% of patients.

Concluding his presentation, Mahmud said: “The Corpath GRX system, with the addition of the guide catheter control, has been a new modification compared to previous devices and has minimised the need for manual assistance. These data support Robotic PCI being a viable option for addressing orthopaedicand radiation-associated risks for the practice of interventional cardiology.”

What role will remote robotic procedures play in the future of PCI? With the COVID-19 pandemic creating new barriers to the accessibility of healthcare, the successful completion of a pioneering robotic-assisted percutaneous coronary intervention (PCI) in December 2020 offers a glimpse of the role that long-distance procedures could play in future delivery of coronary angioplasty.

THE PROCEDURE, CARRIED out by Eric Durand at the Rouen Medical Training Center (Rouen, France) and Rémi Sabatier (Caen University Hospital, Caen, France)—spanning 75 miles—was the first of its kind in Europe completed with the R-One (Robocath) robotic platform, using an animal model. During the procedure, constant communication was maintained between Sabatier—who was operating the robot via a control console from Caen University Hospital—and Durand, who oversaw proceedings from the operating room at the Medical Training Center in Rouen. Cardiovascular News spoke to Sabatier to discuss the potential for remote robotics in cath labs in the future.

What potential do remote robotic PCI procedures offer, and how will this shape PCI in the future?

I was very excited to do this first case.

The excitement was surpassed by how easy it was to do, as it was very convenient. Of course I had Professor Durand in the medical training centre who managed the animal and the

introduction of devices into the robot, but I can do the procedure without any difficulty in quite a short time. It was surprising to me, to feel like I was near the animal. The distance was not really present, and this was new.

There are still a lot of questions around remote PCI in coronary angioplasty, but the technologic part is done now. It is both possible and convenient, and the question now is about how we organise the remote intervention. There are a lot of challenges, but none are insurmountable.

How does the procedure work in practice?

The pig was in the Medical Training Centre in Rouen. Professor Durand inserted a 6F sheath in the femoral artery and a guiding catheter (Amplatz Left 1) in the left coronary artery manually and connected it to the robot. He also inserted a guidewire in the robot. I was able to advance the guidewire in the circumflex artery using the joystick in Caen through the control console.

When the guidewire was positioned in the distal left circumflex artery, Professor Durand manually inserted

Remi Sabatier during the first remote robotic PCI in Europe

the stent on the wire in the robot. The remote control console of the robot allowed me to advance the stent in the circumflex from 75 miles away, and to implant it after manual inflation.

How easy is it for any interventional cardiologist to pick up the technology and use it?

I think the learning curve is easy to pick up. We run training workshops in Rouen, and we see that interventional cardiologists learn the positioning of the robot very quickly, and performing angioplasty, because it is very intuitive.

The joysticks do the same as you would do with your hand.The precision of the mechanism is also something that is very impressive.

How great is the need for remote technologies and how common might they be in the future?

There are still some gaps to fill, but the need is there. There are a lot of regions in the world, and especially developing countries, where patients are too far

from interventional centres and could not have angioplasty in case of acute myocardial infarction or thrombectomy in case of acute stroke.

We need more technical platforms to allow patients to be treated in noninterventional centres, we need to train nurses or doctors to place the introducer into the radial or femoral artery and then to engage the guiding catheter—but maybe in the future robots could do a part of this job.

What are the key questions that still need to be answered?

There is one that is always discussed and that is how do you manage robotic failure or angioplasty complications if nobody in the patient location can do the angioplasty.

Coronary angioplasty is quite a safe procedure, and hopefully the robot will not have a lot of failures, but we have to face this situation because it is important to overcome this barrier. It could be done by training doctors in specific procedures to manage complications, but there is still work to do in this field.

Issue Issue 6161 | May | May 2021 2021

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Cardiovascular surgery Risk of burnout “a growing concern” in cardiothoracic surgery The risk of burnout among cardiothoracic surgeons has been heightened by the COVID-19 pandemic, according to the outgoing president of the Society of Thoracic Surgeons (STS) Joseph Dearani (Mayo Clinic, Rochester, USA), who cited this as an increasing area of concern within the specialty during his address to the society’s 57th annual meeting (29–31 January, virtual).

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peaking during the second day of the threeday virtual event, Dearani described 2020 as a gruelling year for healthcare professionals, highlighting the physical and emotional toll of the pandemic.

“COVID-19 has affected every facet of our personal and professional lives. And, while we all hope to return to some sort of normalcy, it is certain that medicine and society will experience immutable adjustments as the new normal settles in,” he commented.

He noted that physicians across the USA have experienced record changes in working hours, noting that for some, workloads have increased, while others have faced cancellation of elective and even some urgent procedures. “This is a tricky business in cardiothoracic surgery, since nothing is really elective, but rather shades of urgency,” he said. “I did have personal experience with two patients who were delayed and died during the postponement, and it still troubles me to this day.”

Rapidly changing work practices are among the contributors to possible burnout among some cardiothoracic surgeons, which Dearani said had already been identified as a problem within the field, even before the pandemic.

“Prior to the pandemic, the STS released a workforce study, showing that overall career satisfaction for cardiothoracic surgeons was favourable, with 54% being ‘very’ or ‘extremely’ satisfied, and overall average number of work hours per week had decreased compared to prior surveys. Unfortunately, 56% of cardiothoracic surgeons also had symptoms of burnout and depression.

“Suffice it to say, COVID-19 has pushed many specialties to the edge, with increased awareness of this culture of overwork, stress and burnout, that has been a growing concern. The culmination of emotional exhaustion, depersonalisation with negative and callous responses to others, and diminished personal feelings of competence and accomplishment have affected many

Suffice it to say, COVID has pushed many specialties to the edge, with increased awareness of this culture of overwork, stress and burnout, and that has been a growing concern.”

of us to some degree. It certainly has affected me.”

The burnout risk is not exclusive to surgeons, Dearani noted, adding that research suggests cardiothoracic residents and nursing staff are also expressing similar sentiments. He said: “Just as physicians face burnout issues, so too have our nursing colleagues who have endured overwhelming challenges this past year. In my opinion, nurses have been the rock solid, drumming heartbeat of the healthcare system, treating COVID-19 patients with skill, compassion and dignity. The images of those responding to COVID-19 have been a reminder that dedicated physicians and healthcare providers come in all genders, races and ethnic groups, and no one is immune to the stress that comes with the calling of caring for the sick.”

Aside from the risk of burnout, Dearani’s address also touched on the racial and socioeconomic disparities brought starkly into focus by the pandemic.

“Morbidity and mortality outcomes for marginalised communities, particularly the African American and minority populations, have also been underscored by the pandemic,” he commented. “In addition to heightened awareness of access issues, concomitant comorbidities such as obesity or heart disease disproportionately affect racial and ethnic minorities and have played a central role in the severity of COVID-19 in marginalised populations.

“Many causes include racial, ethnic, and socioeconomic factors. But, referral bias and insurance barriers also contribute to an inequity of reduced access for medical evaluation that has been amplified further due to the virtual environment transition, where marginalised communities have suffered, due to the frequent lack of computer technology for telehealth consultation.”

Joseph Dearani

Women “less likely” to undergo CABG using guidelinerecommended approaches Women are significantly less likely than men to undergo coronary artery bypass grafting (CABG) using guidelinerecommended approaches, potentially resulting in worse outcomes after surgery, research presented at the 57th annual meeting of the Society of Thoracic Surgeons (STS 2021, 29–31 January, virtual) has concluded.

THE FINDINGS WERE PRESENTED BY Oliver Jawitz (Duke University, Durham, USA) who described the analysis of detailed demographic, clinical, and procedural data from more than 1.2 million patients, using data from the STS Adult Cardiac Surgery Database to identify adult patients who underwent first-time isolated CABG from 2011 to 2019. “This study highlights key differences between women and men in surgical techniques used for CABG and reveals opportunities to improve outcomes in women,” said Jawitz.

The correlation between sex and three different CABG surgical techniques that are recommended in official US and European guidelines was examined closely. According to Jawitz, all of these approaches— grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, complete revascularisation, and multiarterial grafting—have been associated with improved short and/or long-term outcomes. However, the results showed that women were 14‒22% less likely than men to undergo CABG procedures with these strategies.

“With these findings, we did in fact see less aggressive treatment strategies with women,” said Jawitz. “It is clear that sex disparities exist in all aspects of care for patients with coronary artery disease (CAD), including diagnosis, referral for treatment, and now, in surgical approaches to CABG. We must ensure that female patients undergoing CABG are receiving evidence-based, guideline-concordant techniques.”

Women are more likely to experience atypical, subtler symptoms of heart disease such as fatigue, abdominal pain, nausea, vomiting, indigestion, and back pain. Sometimes, women do not even feel the obvious chest pain and pressure that are characteristic of CAD. Women have their own risk factors, including relatively high testosterone levels prior to menopause, increased hypertension during menopause, and higher levels of stress and depression.

“Delayed diagnosis of CAD in women leads to late initiation of key behavioural and pharmacologic interventions for minimising heart disease risk, as well as delayed referral for invasive diagnostic and therapeutic procedures, including surgical revascularization with CABG,” said Jawitz.

“This often means that by the time female patients undergo these procedures, they have more severe disease than males, as well as a greater number of comorbidities, which leads to worse outcomes.”

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Issue 61 | May 2021

Cardiovascular surgery Mitral regurgitation patients treated with TEER will require mitral replacement surgery if treatment fails

Patients suffering from severe mitral regurgitation should be carefully screened and counselled before undergoing transcatheter edge-toedge mitral repair (TEER), as data show that as many as 95% of patients who needed surgery after failed TEER could not have their valves repaired and needed mitral valve replacement to resolve the issue.

THIS IS ACCORDING TO AN ANALYSIS of the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, presented at the American Association for Thoracic Surgery 101st Annual Meeting (AATS 2021, 30 April–2 May, virtual) and published in the Journal of the American College of Cardiology (JACC).

“The fact that TEER takes surgical repair off the table as an option for patients makes it essential that we have a very clear understanding of which patients will benefit. This finding has important implications for treatment choice in lower-risk patients with degenerative disease,” said Joanna Chikwe (chair of the Department of Cardiac Surgery in the Smidt Heart Institute at Cedars-Sinai, Los Angeles, USA) who presented the findings at AATS 2021. “These findings should inform patient consent for TEER, design of clinical trials, and clinical performance measures.”

The study evaluated national outcomes of mitral surgery after TEER, using a primary outcome of 30-day or in-hospital mortality.

Researchers identified 463 patients from the STS database having undergone mitral surgery after TEER. The patients were found to have a median age of 76 years (interquartile range [IQR] 67‒81 years), median left ventricular ejection fraction of 57% (IQR 48‒62%), and 177 (38.2%) patients had degenerative disease.

Major concomitant cardiac surgery was performed in 137 (29.4%) patients, Chikwe and colleagues reported.

In patients undergoing isolated mitral surgery, median STS predicted mortality was 6.5% (IQR 3.9‒10.5%), observed mortality was 10.2% (n=23/225) and the ratio of observed to expected mortality was 1:2 (95% confidence interval [CI] 0.8‒1.9).

Predictors of mortality

included urgent surgery (odds ratio [OR] 2.4, 95% CI, 1.3–4.6), non-degenerative/unknown aetiology (OR, 2.2; 95% CI, 1.1-4.5), creatinine >2.0mg/dl (OR 3.8, 95% CI 1.9-7.9) and age >80 (OR 2.1, 95% CI 1.1-4.4). In a volume outcomes analysis in an expanded cohort of 591 patients at 227 hospitals, operative mortality was 2.6% (n=2/76) in four centres that performed >10 cases versus 12.4% (n= 64/515) in centres performing fewer (p=0.01). The surgical repair rate after failed TEER was 4.8% (n=22), and 6.8% (n=12) in degenerative disease.

Writing in JACC, Chikwe and colleagues note that current consensus guidelines recommend TEER is performed for prohibitive and highrisk patients with severe symptomatic primary mitral regurgitation, and for a select subset of patients with chronic severe secondary mitral regurgitation, systolic dysfunction and persistent severe symptoms while on optimal goal directed medical therapy.

Close to 15,000 mitral TEER procedures have been performed in the USA since introduction into clinical practice in 2014, the study team notes. In order to inform future research into the procedure, Chikwe and colleagues accordingly analysed STS-ACSD data aiming to quantify the US mortality, complications and mitral repair rates after mitral surgery for failed TEER, including a subgroup analysis in patients with degenerative disease.

Discussing the findings of their analysis in JACC, Chikwe and colleagues note that repair of mitral valves late after TEER is technically challenging, as the devices are designed to provoke a proliferative response generating fibrotic tissue that secures the clip—rapidly causing substantial sclerosis, and thickening and distortion of the leaflets and subvalvular apparatus.

They add: “Surgical repair after failed transcatheter repair therefore requires advanced reconstructive techniques in addition to proficiency in degenerative mitral valve repair, and optimal results are most likely to be achieved by experienced mitral surgeons. The presence of functional mitral regurgitation or even a moderate degree of mitral stenosis in this setting is most effectively treated with replacement.”

The observation that surgical repair is not achieved after failed TEER in the vast majority of patients should inform the initial decision between transcatheter and surgical repair in patients with degenerative regurgitation who are suitable for both therapeutic approaches, Chikwe et al note. In over 80% of TEER patients adjudicated prohibitive risk for surgery, the rationale is attributed to frailty, “hostile Joanna mediastinum” or “unusual Chikwe circumstances”.

High-volume aortic centres needed offering “entire armamentarium” of approaches

The need for high-volume, expert aortic centres offering open, hybrid and endovascular solutions was underscored during the Thoracic Aortic Controversies session at the Charing Cross (CX) 2021 Digital Edition (19–22 April, online).

Taking place on the second day of the four-day global vascular education event, the Thoracic Aortic Controversies session featured high-level discussion from world leaders in the fields of both cardiothoracic and vascular surgery.

PATIENT INVOLVEMENT IN DECISION-MAKING was an important theme to emerge from discussion, as was agreement on reducing the place of hybrid procedures as physicians decide to offer either open or endo procedures more frequently. In addition, it was noted that staged procedures are becoming more common in challenging aortic anatomies, resulting in fewer complications.

Presenting an edited case of a fully percutaneous arch branch repair, Stéphan Haulon (Hôpital Marie Lannelongue, GHPSJ, Paris, France) highlighted the importance of selecting a procedure according to underlying pathology. In relation to the case presented, Haulon stressed the importance of choosing cases not at risk of emboli, detailing that he currently only performs this procedure on chronic dissection patients, who he stated are not at risk of stroke. In response to praise from the panel on the advanced nature of the procedure, the presenter was quick to emphasise the importance of a team approach in moving the field forward. “We all learn from each other”, he said.

Cardiothoracic surgeon Joseph Bavaria (University of Pennsylvania, Philadelphia, USA) gave a Podium 1st presentation detailing long-term data associated with a contemporary thoracic endovascular aortic repair (TEVAR) device—the Valiant Captivia TEVAR system (Medtronic).

Bavaria told attendees that the device has shown “consistent results across multiple thoracic pathologies”. He reported that all three of the large US Food and Drug Administration (FDA) investigational device exemption (IDE) clinical trials utilising the system had “excellent results”. He noted that all trials have recently published five-year outcomes data, which reveal “very stable” long-term results with “excellent” safety and efficacy profiles.

Echoing the view that pathology “must determine the mode of treatment”, Martin Czerny (University Hospital Freiburg, Freiburg, Germany) addressed the learning curve associated with new technologies. He summarised that the frozen elephant trunk technique has “excellent” results and that the outcomes of total endovascular aortic arch repair are “promising”. He was keen to stress that the creation of aortic centres with the “entire armamentarium” will aid in “doing the right thing in the right patient”, and that “by learning from your environment, the learning curve with new technologies can be kept to a minimum”.

A number of presentations addressed the benefits and drawbacks of open, hybrid and endovascular surgery.

Summarising a presentation on “pushing the limits” of redo open arch surgery, Joseph Coselli (Baylor College of Medicine, Houston, USA) argued that a multidisciplinary approach to a patient-tailored operation is “paramount”. In reasonable-risk patients, he added, the procedure should be extended to prevent recurrence, and stressed that all patients with redo surgery of the ascending aorta or arch require lifelong imaging surveillance.

May 2021 | Issue 61

12 Advertorial THIS ADVERTORIAL IS SPONSORED BY SINOMED

Targeted healing: A new stent concept that could contribute to shortened DAPT As newer-generation drug-eluting stent (DES) technologies continue to raise the bar for the treatment of coronary artery disease (CAD), offering improved rates of target lesion failure (TLF), low levels of stent thrombosis, and benefits in revascularisation compared to earlier-generation devices, the search for the next frontier in DES innovation becomes ever more challenging for device manufacturers.

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new entrant into this arena is the HT Supreme (Sinomed), a “healing targeted”, biodegradable polymer coated, sirolimus-eluting stent. While contemporary DES platforms have emphasised delayed healing through prolonged drug delivery, with the aim of suppressing the body’s response to the barotrauma injury of implanting a thrombogenic foreign body, HT Supreme is based upon the “wound-healing window” concept. This focuses on facilitating early healing and restoring natural endothelial function soon after stent implantation, and could benefit patients when used with a shorter duration of dual antiplatelet therapy (DAPT).

“The concept was to develop a drug-eluting stent with a known drug [sirolimus] that could be eluted with a pharmacokinetic profile that would maximise its ability to supress neointimal hypoplasia, while promoting early endothelialisation,” explains Martin B Leon, (Columbia University, New York, USA), who is the chairman of the Executive Committee for the PIONEER III study—the largest randomised trial to date to evaluate the use of the HT Supreme device.

Leon explains that the HT Supreme stent releases at least 80% of its drug within the first month of implantation, a process that takes place simultaneously alongside degradation of the biodegradable polymer coating. This leaves behind an electrografted thromboresistant base layer that is designed to promote rapid endothelial coverage and accelerate a positive healing response, as well as protecting the underlying metal stent from corrosion and heavy metal ion release. “That positive healing response is the greatest protection against platelet deposition, thrombus formation [and] blood clots forming on the device, which can cause late safety concerns,” says Leon.

“You could look at it as a super bare metal stent, because it has got a smooth permanent layer on it,” comments Andreas Baumbach (Queen Mary University of London, London, UK), who also participated as European co-principal investigator in the PIONEER III study.

According to Baumbach, after completion of drug delivery and once the biodegradable polymer has fully degraded, what remains is a stent that “really encourages healing”. He comments: “In order to have HT Supreme is a “healing targeted” stent

Patrick Serruys

Andreas Baumbach

Martin B Leon

good long-term results, you need to have a vessel that is able to restore function.”

Patrick Serruys (National University of Ireland, Galway, Ireland), who chaired the CE mark trial PIONEER I, agrees that the promotion of endothelial function is one of the important facets of this technology and comments that it offers the potential for clinical benefit in CAD patients in the long term.

In order to have good long-term results, you need to have a vessel that is able to restore function.”

“A good endothelium is less permeable for a lot of molecules, including LDL cholesterol,” he says. “We believe that because the endothelium is there early, and is of good quality, there will potentially be less thrombogenic and atherosclerotic problems in the long term, but that is something that has to be proved.”

Promoting endothelial function

To date, study of the HT Supreme stent has focused on the non-inferiority of the device in terms of safety and efficacy to two best-in-class, durable polymer everolimus-eluting stents, for the treatment of CAD— Xience (Abbott) and Promus (Boston Scientific).

PIONEER III was carried out in 74 participating

centres in North America, Europe and Japan, enrolling 1,629 patients (randomised 2:1) with a primary composite endpoint of TLF at one year. The first 12-month results from the study, presented at the American Heart Association 2020 scientific sessions (AHA 2020, 13–17 November, virtual), showed that the HT Supreme met the non-inferiority TLF endpoint at 5.4% compared to 5.1% from the durable polymer DES (p=0.002). A grouped analysis of secondary endpoints also showed a numerically-better result for HT Supreme in cardiac death or target-vessel myocardial infarction (TVMI) with 3.5% in the HT Supreme arm compared to 4.6% in the control arm (p=0.27).

Lower late stent thrombosis data (HT Supreme 0.1% compared to DP DES 0.4%, p=0.22) also suggested exceptional safety for the HT DES. Commenting on these results, Leon says: “Certainly the results indicate that the major endpoints, TLF and clinically-driven target lesion revascularisation were low and equivalent to the comparator stents—which is encouraging.”

Furthermore, he adds that there were no major differences in stent thrombosis, but a trend towards benefit from the standpoint of a composite safety endpoint, comprising TVMI, stent thrombosis, and cardiovascular death.

However, Leon also points out that while PIONEER III shows “trends going in the right direction”, longerterm follow-up will give a clearer picture of whether the wound-healing concept brings about real clinical benefit. “If this device is going to truly live up to its technology reputation, then it should reveal itself not in the first year, but in the several years thereafter in terms of safety—specifically in late stent thrombosis and target-vessel myocardial infarction,” he comments.

Ongoing study

Further data on the performance of the device is anticipated, with Baumbach to present a subgroup analysis of the performance in complex lesion anatomy from the PIONEER III study at EuroPCR (18–20 May, virtual), as well as further ongoing landmark analyses in the pipeline up to five years. Alongside these studies, the PIONEER IV trial is also underway—a prospective, single-blind, 1:1 randomised controlled multicentre study in an all-comer population prescribed only one month of DAPT —comparing outcomes between angiography-derived physiology guidance and standard guidance, with unrestricted use of HT Supreme. The trial has a patient-oriented composite endpoint of all-cause death, stroke, myocardial infarction, and revascularisation, which will be assessed at one year, while patients will be followed for up to three years.

Baumbach says PIONEER IV is an “exciting trial” that will answer questions around the use of HT Supreme, as well as having wider implications for the practice of percutaneous coronary intervention (PCI), including comparing quantitative flow ratio (QFR) and fractional flow reserve (FFR) measurements. The study of a one-month course of DAPT will be an important aspect of the trial, offering insights into the scope to reduce bleeding events, particularly in patients considered at high risk of bleeding, who may not have been considered for stents in the past.

For Serruys, chairman of the study, these are important aspects of the PIONEER IV trial, which will offer greater insight into the applications of the HT Supreme, and answer questions for the future of cath lab practice. Treatment of “physiologically significant” lesions is an aspect of interventional cardiology that is at the heart of the study. Serruys adds: “There has been an excess of stenting—and the more metal you put in the coronary artery the worse it can become.” This is where the trial’s use of QFR will play a central role— which Serruys says will “justify” the treatment offered to patients taking part in the trial.

May 2021 | Issue 61

14 Coronary interventions

Rate of target vessel failure “significantly lower” after IVUS-guided PCI

78.5% of patients presented with acute coronary syndromes (ACS). Multivessel disease was found in 54.9% of patients.

Larger stents were implanted in the IVUS guidance group, with more frequent post-dilation using larger noncompliant balloons at higher pressures.

The primary endpoint for the study Drug-eluting stent implantation guided by intravascular ultrasound was the risk for target vessel failure at (IVUS) is associated with significantly lower rates of target vessel three years, while the study’s safety failure at three-year follow-up compared to procedures performed endpoint was definite or probable stent using angiographic guidance. thrombosis.

The study team reports that target his is according to the latest data Patients were enrolled from vessel failure occurred in 47 patients from the multicentre, randomised August 2014 to May 2017 (6.6%) in the IVUS-guided ULTIMATE trial, published in and randomly assigned group and in 76 patients JACC: Cardiovascular Interventions. to undergo (10.7%) in the One-year findings of the trial were IVUS-guided or angiography-guided Target vessel failure first reported at the 2018 Transcatheter angiography-guided group (p=0.01), occurred in of Cardiovascular Therapeutics (TCT) stent implantation driven mainly by meeting (21–25 September, San Diego, in a 1:1 ratio the decrease in IVUS-guided patients USA), pointing to a significantly lower immediately clinically-driven vs. of rate of clinically-driven target vessel after coronary target vessel angiography failure in all-comers patients after 12 angiography. revascularisation months.

All patients (4.5% vs. 6.9%; guided patients In the present study, author Xiaowere prescribed a p=0.05).

Fei Gao (Department of Cardiology, loading dose of aspirin Dual antiplatelet Nanjing First Hospital, Nanjing (300mg) and a P2Y12 therapy (DAPT) was Medical University, Nanjing, China) inhibitor (clopidogrel 600mg prescribed to 274 patients and colleagues report on 1,448 or ticagrelor 180mg) if not receiving (37.8%) in the angiographic guidance patients undergoing drug-eluting stent antiplatelet therapy before the procedure. group and 263 patients (36.3%) in the implantation who were randomly After the procedure, all patients IVUS guidance group (p=0.55), while assigned to either IVUS guidance or were treated with 100mg/day aspirin angiographic follow-up was completed in angiographic guidance in the ULTIMATE indefinitely and 75mg/day clopidogrel (or 488 patients (67.4%) in the angiography trial, and followed out to three years. ticagrelor 90mg twice a day) for at least group and 507 patients (70%) in the Patients were eligible to participate one year, the study team reports.

IVUS group at three years after the index in this trial if they had silent ischaemia, The patient groups were well matched, procedure (p=0.28). stable or unstable angina, or myocardial Gao and colleagues note, with a mean Gao and colleagues write: infarction (MI) with more than 24 age of 65.2 years in the IVUS-guided “Prespecified subgroup analysis hours between onset of chest pain and group, and 65.9 years in the angiographic revealed a consistently lower threeadmission and de novo coronary lesions guidance group (p=0.19). Diabetes was year rate of TVF [target vessel failure] requiring drug-eluting stent implantation. present in 30.6% of enrolled patients, and in the IVUS guidance group across

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6.6%

10.7%

Older STEMI patients more reluctant to undergo PCI in study from China Patients aged over 65 years were more likely than their younger counterparts to turn down percutaneous coronary intervention (PCI) for the treatment of ST segment-elevation myocardial infarction (STEMI), research published in the Chinese Medical Journal has found.

RESEARCHERS FROM SHANDONG University, Jinan, China investigated the phenomenon of STEMI patients refusing PCI after previous studies had suggested that many choose not to undergo the procedure. Women in particular, have a reduced likelihood of undergoing guideline-based management and acute reperfusion therapy, they said.

Lead researcher of the team, Yu-Guo Chen, said: “Understanding the factors that influence patients’ decisions to reject medical advice may facilitate efforts to improve treatment compliance, quality of care, and prognoses.” Chen and team conducted analyses of treatment data to identify the predictors of PCI refusal for patients with STEMI. For their analysis, the researchers used data that had been prospectively collected through a cohort study involving patients with STEMI who presented to any of six Chinese emergency departments between August 2015 and September 2017. After excluding patients who never had the opportunity to decide whether to

undergo PCI, as well as patients transferred to other hospitals and those discharged against the treating clinicians’ advice, the researchers had a dataset of 957 patients, including 260 women and 697 men. On this dataset, they used multivariable logistic regression analyses to identify the predictors of PCI refusal.

Understanding the factors that influence patients’ decisions to reject medical advice may facilitate efforts to improve treatment compliance, quality of care, and prognoses.”

numerous subgroups, with a tendency for patients with ACS, chronic kidney disease, multivessel disease, type B2/C lesions, or bifurcation lesions to possibly benefit from IVUS guidance. Post hoc analysis suggested that IVUS guidance provided greater benefit in complex PCI [percutaneous coronary intervention], although no interaction existed. Lesionlevel analysis showed that the three-year rate of clinically-driven TLR [target lesion revascularisation] or definite stent thrombosis in the IVUS guidance group was significantly lower than that in the angiographic guidance group.”

The rate of definite or probable stent thrombosis was recorded as 0.1% in the IVUS-guided group and 1.1% in the angiography-guided group (p=0.02).

Notably, the IVUS-defined optimal procedure was associated with a significant reduction in three-year target vessel failure relative to that with the suboptimal procedure, they add.

it is time to overcome the barriers, including cost, availability, expertise, and procedure prolongation, to promote IVUS use in daily clinical practice.”

In total, 98 of the patients in the dataset (10.2%) chose not to undergo PCI. One factor that influenced their decisions was age, with patients older than 65 years being more likely than their younger counterparts to refuse PCI. Some predictors of PCI refusal were having a history of myocardial infarction, experiencing cardiac shock while in the emergency department, a more than 12-hour delay in reaching the hospital after STEMI onset, and having a faster heart rate.

Some other factors included being married, receiving treatment at a tertiary hospital, and having a higher body mass index value.

Comparisons between male and female patients showed that female patients were older, less likely to be married, had lower body mass index values on average, and were less likely to receive treatment at tertiary hospitals. Given that these factors were all predictors of PCI refusal in the regression model, these differences may help to explain why women with STEMI are more likely to refuse PCI than their male counterparts, the researchers suggest.

In conclusion, the researchers at Shandong University identified a host of factors that may help to predict whether a patient with STEMI will give or withhold consent to PCI. Asked about the long-term medical and societal importance of these findings, Chen notes that knowledge of these predictors may aid healthcare providers in efforts to persuade more patients with STEMI to consent to PCI. He predicts that increasing the number of patients who undergo PCI “will lead to reductions in mortality and improvements in long-term clinical outcomes”.

Issue 61 | May 2021

Antiplatelet therapy 15

Prolonged DAPT “should remain the standard of care” in ACS patients Analysis of the Fuwai PCI Registry, using selection criteria from the TWILIGHT trial, has concluded that long-term dual antiplatelet therapy (DAPT) remains an optimal treatment option for acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI).

This is contrary to the findings of other recent evidence pointing towards the withdrawal of aspirin early after the start of antiplatelet therapy, according to the authors.

THE STUDY, PRESENTED DURING A LATEbreaking trial session at the Society for Cardiovascular Angiography & Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual) by Hao-Yu Wang (Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China), concluded that long-term DAPT reduces ischaemic events without increasing bleeding or other complications compared to short-term DAPT treatments.

Patients with ACS are given a dual course of antiplatelet therapy—comprising aspirin and an oral P2Y12 inhibitor, including ticagrelor or clopidogrel— to reduce their risk of ischaemic events after PCI. According to Hao-Yu Wang and colleagues, “recent emphasis” on reduced duration or intensity of antiplatelet therapy following PCI, irrespective of

Ticagrelor monotherapy associated with a lower bleeding risk than standard DAPT after PCI Dropping aspirin shortly after percutaneous coronary intervention (PCI) is associated with lower bleeding and mortality risks, without a concomitant increase in cardiovascular ischaemic recurrences compared with standard dual antiplatelet therapy (DAPT) continuation, a meta-analysis published in JACC: Cardiovascular Interventions has concluded.

T

he analysis was authored by Marco Valgimigli (Cardiocentro Ticino Institue, Ente Ospedaliero Cantonale, Lugano and Department of Cardiology, Bern University Hospital, Bern, Switzerland) et al, and sought to compare the use of ticagrelor monotherapy to DAPT—the current standard of care post-PCI. Patients undergoing a dual course of

indication, may fail to account for the substantial risk of findings, which demonstrated the potential benefit of subsequent non-target lesion events in ACS patients. ticagrelor monotherapy, after three-months of DAPT, The study team sought to investigate the benefits of in halving clinically relevant bleeding events without extended-term (>12-month) DAPT as compared with a negative impact on composite ischaemic events, short-term DAPT in high-risk ACS patients undergoing compared with ticagrelor plus aspirin in patients with PCI. To do this they analysed patients from the Fuwai NSTE-ACS. PCI registry, defined by at least one clinical and one “Our study extended theses earlier results to a angiographic feature based on the selection criteria used high-risk ACS cohort (including STEMI patients) by in the TWILIGHT trial. providing the benefits of long-term DAPT with respect Findings from TWILIGHT were presented at the to ischaemic events are preserved via clopidogrel. Due Transcatheter Cardiovascular Therapeutics scientific to current evidence, early single antiplatelet therapy with symposium in 2019 (TCT 2019; 25–29 September, a potent P2Y12 inhibitor after a short period of DAPT San Francisco, USA), concluding that ticagrelor may be reasonable among ACS patients, potentially monotherapy after three months of DAPT reduces leaving a standard 12 month or longer DAPT (with bleeding events without increasing the risk of death, possible de-escalation if not done before, or association myocardial infarction (MI), or stroke in high-risk of low dose rivaroxaban plus aspirin) to high-risk patients who have undergone successful PCI. A ACS patients with extensive coronary disease and subsequent sub-analysis of the trial—TWILIGHTcomplex target-lesion anatomy, and therefore at high ACS—including 5,739 patients with non-ST elevation risk for ischemic recurrences in the presence of low acute coronary syndromes (NSTE-ACS) concluded that risk of bleedings. Further prospective trials specifically ticagrelor monotherapy reduced the risk of clinically targeting patients with ACS are required to clarify this relevant bleeding compared to DAPT over 12 months. issue,” the study’s authors told Cardiovascular During their study, Hao-Yu Wang and colleagues News. analysed data from 4,875 high-risk “TWILIGHT-like” “Our findings suggested that prolonged patients with ACS who were event-free at 12 months DAPT in ACS patients who present with after PCI. The primary outcome was the composite of a particularly higher risk for thrombotic all-cause death, MI, or stroke at 30 months.. complications without excessive risk,” Results showed that slightly more than two thirds said Hao-Yu Wang. “Not only did we see of ACS patients remained on DAPT beyond long-term DAPT was associated with a 12 months after PCI, while extended DAPT lower risk of a major cardiovascular compared with shorter DAPT reduced the event without an increase in bleeding composite outcome of all-cause death, MI or events, but it could be considered stroke by 63%. The effect of long-term DAPT on an effective strategy to balance the primary across the proportion of ACS patients with risk for bleeding and ischaemia in one‒three, four‒five, or six‒nine risk factors was high-risk patients with ACS. Our consistent. results reinforce prolonged DAPT in Discussing the findings, Hao-Yu Wang patients with acute coronary syndrome commented that the current study appeared without excessive risk of bleeding Hao-Yu Wang “somewhat discordant” with the TWILIGHT-ACS should remain the standard of care.”

antiplatelet therapy are given aspirin and an oral P2Y12 inhibitor after PCI to reduce the risk of ischaemic events, but its prolonged use can create a Marco Valgimigli heightened risk of major bleeding, mortality and morbidity.

Valgimigli and colleagues note that an emerging bleeding reduction strategy has been to discontinue aspirin and maintain patients on P2Y12 inhibitor monotherapy. However, they note that data are still limited on this strategy, and the interpretation of available evidence is challenged by variations in patient selection, choice of P2Y12 inhibitor, duration of the initial DAPT regimen, timing of randomisation, and endpoint ascertainment. To address this, the study team carried out a systematic review and individual patient data (IPD) analysis of randomised trials to compare the safety and efficacy of ticagrelor monotherapy with standard DAPT. Two randomised trials met the inclusion criteria—GLASSY (a substudy of the GLOBAL LEADERS trial) and TWILIGHT—including a total of 14,628 patients undergoing PCI. Primary outcomes included the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at

one year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.

Analysing the findings of the two randomised trials, Valgimigli et al report that BARC type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively), while the composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT. Ticagrelor was associated with lower risk for all-cause and cardiovascular mortality.

Rates of myocardial infarction (2.01%

was associated with a lower risk for major bleeding without any measurable increase in ischaemic events compared with standard DAPT. The study’s authors also observed that there was a significant reduction in all-cause mortality among those patients randomised to ticagrelor monotherapy, driven mostly by a reduction of cardiovascular death, but they point out that this “requires a cautious interpretation” in view of the similar rates of myocardial infarction, stent thrombosis and stroke.

In conclusion, the authors write: “Compared with conventional DAPT,

Compared with conventional DAPT, ticagrelor monotherapy was associated with a lower risk for major bleeding without evidence of a trade-off in terms of an increase in ischaemic risk among patients who underwent drugeluting stent implantation.” vs. 2.05%), stent thrombosis (0.29% vs.

0.38%), and stroke (0.47% vs. 0.36%) were similar.

Discussing the findings of their analysis, Valgimigli et al write that the study provides “strong evidence” that ticagrelor monotherapy, after a short course of one- or three-month DAPT,

ticagrelor monotherapy was associated with a lower risk for major bleeding without evidence of a trade-off in terms of an increase in ischaemic risk among patients who underwent drug-eluting stent implantation. The observed benefit in terms of mortality needs further investigation.”

May 2021 | Issue 61

16 Advertorial THIS ADVERTORIAL IS SPONSORED BY OSPREY MEDICAL

Preventing kidney damage in the cath lab There is a growing recognition of the risk of contrast-associated acute kidney injury (AKI) to patients undergoing coronary interventions in the cath lab, as well as the strategies that can be employed to limit the damage in those at the most risk. That is according to Carlo Briguori, chief of the Laboratory of Interventional Cardiology at Mediterranea Cardiocentro in Naples, Italy, who spoke to Cardiovascular News about the need for vigilance over preventing AKI, effective treatment of acute coronary syndrome (ACS) patients at high risk for kidney damage, and his experience with the DyeVert Contrast Reduction System (Osprey Medical), which is designed to help limit patients’ exposure to contrast media—a major cause of kidney damage during invasive coronary procedures.

“I

n the past, interventional cardiologists did not have such a good awareness of this risk, and were much more concentrated on treating the coronary [artery], or the heart,” says Briguori, discussing the understanding of the risks faced by patients with chronic kidney disease (CKD). “Today, I think that the majority of interventionalists have a good knowledge of the risk to the kidneys and the poor outcomes, so they are performing preventative strategies.”

For the majority of patients who visit the cath lab, the risk of AKI is low. However, there is a subset of patients, particularly those with CKD, who are at the greatest risk of harm. Briguori comments: “In general, if you think about all of the people undergoing coronary interventions, including coronary angiography or angioplasty, globally the risk of AKI may be considered low, between 1‒5%. But, if you look specifically at a subgroup of patients with baseline CKD, which nowadays is roughly 30% of the population, the risk is increased, and may be up to 10‒13%.”1 AKI is associated with increased hospital length of stay, increased 30-day readmissions, and poor clinical and economic outcomes for patients2, meaning that identification of those at the most risk, prior to the formation of any treatment plan, is fundamental to preventing the potential adverse effects of kidney damage. Briguori explains that there are a number of predictors that can point towards an elevated risk of AKI during a coronary procedure, which include age, the presence of diabetes, CKD, anaemia, and haemodynamic instability.

One of the major contributors to kidney damage during a coronary intervention is over-exposure to contrast media used to improve contrast resolution during angiographic imaging. This can lead to contrastassociated AKI, which is an independent predictor of major adverse renal and cardiovascular events.

The rate of AKI is commonly defined as a serum creatinine (sCR) increase ≥0.3 mg/dl within 72 hours of exposure to contrast media, and can be stratified

Dyevert Contrast Reduction System

according to criteria set out by the Acute Kidney Injury Network3, which offers a staged assessment of kidney damage based upon the severity of sCR increase following a procedure. For the most severe cases, the worst outcome can be dialysis, explains Briguori.

“Dialysis is of course a very bad complication for the patients, but also for the physician performing the coronary procedure, so we do not want to have any patients going on dialysis, even the patients at high risk,” he comments.

Strategies to limit kidney damage

Strategies to limit kidney damage in these high-risk patients, historically have focused on management of hydration through saline infusion—which can be tailored to the patient based upon characteristics such as left ventricular end diastolic pressure4, or urine flow rate.5 However, according to Briguori, this approach is more challenging in an acute setting, where there may not be time to appropriately tailor the required level of hydration to the needs of the patient. He says: “If I have

We have found an important reduction in AKI, in the subgroup with DyeVert, which means that we have an important impact on kidney damage prevention.” a patient coming into the cath lab for acute myocardial infarction (MI), I cannot wait one hour to hydrate—I need to go into the cath lab immediately. If the patient is anaemic, diabetic, or has CKD, it is important, but I cannot wait to do optimal hydration because there is an acute MI.” A second important strategy is to limit the patient’s exposure to contrast media. This is where the DyeVert system comes into play. The system is designed to reduce contrast media delivered to the patient while maintaining image quality during a procedure, as well as shot-by-shot monitoring of the contrast media volume that is administered to the patient. DyeVert is a single-use, sterile device connected by a manual injection syringe, allowing modulation of contrast media during injections. A portion of the injected contrast media is diverted through a secondary fluid pathway controlled by a pressure-compensating diversion valve during an injection, allowing a decrease in over-injection of contrast media and less aortic reflux.

Briguori has been at the forefront of investigating the effectiveness of DyeVert, leading the first major pivotal study of the device, findings of which were published in the journal Catheterization and Cardiovascular

Interventions in 20205. The singlecentre study assessed whether use of the DyeVert system reduced the AKI rate in ST-elevation myocardial infarction (STEMI) and high-risk Non-ST-elevation myocardial infarction (NSTEMI) patients Carlo Brigouri undergoing invasive coronary procedures in the Interventional Cardiology Unit at Mediterranea Cardiocentro, Napoli, Italy between 2017 and 2019. A total of 180 patients were analysed in two groups, 90 patients undergoing a coronary intervention assisted by the DyeVert system were compared to a control group of 90 patients in whom contrast media was regulated using a manual injection syringe.

Briguori and colleagues found that contrast media volume was higher in the control group than in the DyeVert group (130ml vs. 99ml; p<0.001), with AKI occurring in seven patients (8%) in the DyeVert group and in 17 patients (19%) in the control arm (odds ratio, 0.37; p=0.047). Overall, the study found that contrast media volume was reduced by 38% among those for whom DyeVert was employed, compared to patients in whom contrast media was deployed manually. A further finding was a 25% reduction in hospital length of stay in the DyeVert group compared to those whose procedures did not involve the device.

“What this translates to is a clinical advantage,” says Briguori, commenting on the findings. “We have found an important reduction in AKI, in the subgroup with DyeVert, which means that we have an important impact on kidney damage prevention.”

He adds: “The device has been demonstrated to reduce contrast volume in the procedure up to 40%.7 That means if we inject 100ml, actually we then save 40ml, and the real contrast volume injection to the patient is 60ml, which is really important in high-risk patients. Limiting contrast media volume by 40% will translate into an important reduction of the AKI events in the Cath Lab.” Further study of the system is taking place in the REnal Insufficiency Following Contrast MEDIA Administration TriaL IV (REMEDIAL IV) randomised trial, in which Briguori is the principal investigator, taking place across six Italian centres. Around half of the trial's 400 patients have been recruited, randomised 1:1 to undergo the DyeVert assisted procedure, or contrast by normal manifold—with enrolment expected to be concluded in 2021.

Briguori comments that the trial will provide important insights into the potential for the widespread use of the DyeVert system in cath labs, and its particular importance for the patients at risk of AKI. Carlo Brigouri is chief of the Laboratory of Interventional Cardiology at the Clinica Mediterranea, Naples, Italy and co-director of clinical research at the Laboratory of Interventional Cardiology, Vita e Salute San Raffaele University Medical School, Milan, Italy.

References 1. Tsai, et al. Contemporary Incidence, Predictors, and Outcomes of Acute Kidney Injury in patients undergoing PCI. JACC Cardiovasc Interv. 2014; 7(1): 1–9.

2. Prasad A, et al. Contemporary trend of acute kidney injury incidence and incremental costs among US patients undergoing percutaneous coronary procedures. Catheter Cardiovasc Interv. 2020 Nov;96 (6) :1184–1197.

3. Palevsky et al, KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury, Am J Kidney Dis 2013; 51 (5): 649–672.

4. Brar, et al. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. The Lancet. 2014;383: 1814–1823 5. Briguori C, et al. Left Ventricular End-Diastolic Pressure Versus Urine Flow Rate-Guided Hydration in Preventing Contrast-Associated Acute Kidney Injury. JACC Cardiovasc Interv . 2020 Sep 14;13(17):2065–2074 6. Briguori C, et al. Impact of a contrast media volume control device on acute kidney injury rate in patients with acute coronary syndrome [published online ahead of print, 2020 Jul 18]. Catheter Cardiovasc Interv.

2020;10.1002/ccd.29136. doi:10.1002/ccd.29136.

7. Desch S, et al. Impact of a Novel Contrast Reduction System on Contrast Savings in Coronary Angiography – The DyeVert Randomized Controlled Trial. Inter Jour of Cardiology 257 (2018) 50–53.

Issue 61 | May 2021

Journal update 17

Five-year results of REDUCE study point in favour of PFO closure for ischaemic stroke Five-year results of the Gore REDUCE clinical study point in favour of the use of patent foramen ovale (PFO) closure compared to antiplatelet therapy alone to reduce the incidence of ischaemic stroke in PFO patients. Findings of the study were published as a research letter in the New England Journal of Medicine (NEJM) in March.

PFOS OCCUR AFTER BIRTH when the foramen ovale—an opening between the heart’s upper two chambers in an unborn baby—fails to close and allows blood to flow between the two atria. PFO occurs in about one in four people, and while most people do not need to be treated for PFO, in some patients, stroke can occur if a blood clot travels through the opening and to the brain. Around one quarter of first-time strokes are cryptogenic, or due to an unknown cause, and up to half of patients who have a cryptogenic stroke are found to have PFO. The REDUCE study evaluated whether PFO closure with a Gore Device—the Cardioform or Helex septal occluder— plus antiplatelet therapy reduces the risk of stroke, compared to antiplatelet therapy alone. The controlled, openlabel study included 664 randomised patients at 63 investigational sites in seven countries. A total of 441 patients were treated with a Gore Device for PFO closure plus antiplatelet therapy and 223 patients were treated with antiplatelet therapy alone. In an intention-to-treat analysis, the rate of stroke recurrence was compared between the two groups.

Study author Scott E Kasner (University of Pennsylvania,

Philadelphia, USA) and colleagues report that during the initial follow-up period of 3.2 years, 18 patients had recurrent strokes (six [1.4%] in the PFO closure group and 12 [5.4%] in the antiplateletonly group). After the end of the initial follow-up period, two strokes occurred (both in the PFO closure group) during the extended follow-up period.

Thus, they write, during a median duration of follow-up of five years (interquartile range, 4.8 to 5.2), a total of 20 patients had recurrent ischaemic strokes—eight patients (1.8%) in the PFO closure group (0.39 strokes per 100 patient-years) and 12 patients (5.4%) in the antiplatelet-only group (1.26 strokes per 100 patient-years) (hazard ratio, 0.31; 95% confidence interval, 0.13 to 0.76).

Furthermore, Kasner et al report that the incidence of serious adverse events was similar in the two trial groups, as was the incidence of death, major bleeding, and deep-vein thrombosis or pulmonary embolism. They add that there were no fractures, thromboses, or embolisations of the device, nor were there cardiac erosions, during the extended follow-up period.

But, atrial fibrillation or flutter occurred in a higher percentage of patients in the PFO closure group than

in the antiplateletonly group (6.8% Cardioform septal [30 patients] vs. 0.4% occluder [1 patient]); 12 patients (2.7%) in the PFO closure group had prolonged atrial fibrillation or flutter lasting 30 days or more, one National Principal Investigator for the of whom had recurrent stroke while REDUCE study. receiving anticoagulation. The authors In a press release highlighting the write that predictors of atrial fibrillation results, Gore said that 25 patients or flutter related to PFO closure and would need to be treated with a Gore subsequent stroke risk require further septal occlude device to prevent one investigation, and report that a patientrecurrent stroke event over five years, level meta-analysis relating to these “demonstrating compelling real-world predictors is under way. therapeutic value for patients treated with In conclusion, Kasner and colleagues a GORE Cardioform septal occluder”. write: “With the two additional strokes “These outcomes for long-term in the PFO closure group that occurred safety and recurrent stroke reduction between the last report and this one, speak volumes to the durability, the absolute difference in risk between performance and effectiveness of the the trial groups at five years was 3.6 GORE Cardioform septal occluder,” said percentage points in favour of PFO John Laschinger, Gore’s cardiac chief closure, and the number needed to treat medical advisor. “The unique benefit of to prevent one stroke in five years was our conformable design, tailored to fit approximately 25 patients.” unique PFO anatomies, is underscored “We are excited to publish the by the fact that GORE Cardioform septal REDUCE study extended follow-up. occluder has a 99% effective closure rate These are important data as they confirm at 24 months.” the procedure is safe with only one new The GORE Cardioform septal episode of atrial fibrillation and no issues occluder received US Food and Drug related to frame fractures, thrombus, Administration (FDA) premarket embolisation or erosion. Overall, the approval for the percutaneous benefit of PFO closure persisted during closure of PFO in 2018, and it is also late follow-up by lowering the risk of approved in the European Union (EU) recurrent stroke with minimal risk for for percutaneous closure of PFO. adverse events,” said John F Rhodes, Furthermore, it is approved in the USA Medical University of South Carolina, and EU for closure of a type of atrial Charleston, USA and US Cardiology septal defect.

SCAI updates consensus guidelines on cath lab standards The Society for Cardiovascular Angiography and Interventions (SCAI) has released an expert consensus statement providing cardiologists, cath lab directors, and hospital leadership guidance for contemporary cath lab standards.

T

he document, “SCAI Expert Consensus Update on Best Practices in the Cardiac Catheterization Laboratory” was presented at the SCAI 2021 scientific sessions (28 April–1 May, virtual) with simultaneous publication in the journal Catheterization & Cardiovascular Interventions. The statement has been endorsed by the American College of Cardiology (ACC), American Heart Association (AHA), and the Heart Rhythm Society (HRS).

“First released in 2012, then updated in 2016 and now 2021, the document highlights a patient- centric approach to procedures in the cardiac catheterisation laboratory, incorporating all the latest advances and standards,” said Srihari S Naidu, New York Medical College, New York, USA, chair of the writing

SCAI has updated its cath lab standards

committee. “Dividing the logistics into the preprocedure, intra-procedure, and post-procedure periods, and including staffing, quality metrics, industry relations and governance, the document should hopefully further serve as a contemporary look at the optimal running of these busy areas. We have also included areas where operators overlap, such as interventional cardiologists and electrophysiologists (EPs), for a more collegial, collaborative spirit towards these complex patients and provided guidance on procedures performed in various settings including outpatient labs.”

The new 2021 recommendations include: Emphasis on practical recommendations to optimise quality & outcomes through best practices, registries, risk calculators, and vascular access (radial first, vascular ultrasound) Updated discussion of ambulatory surgery centres and settings without on-site surgery

Expanded section on cath lab governance, including dyad leadership, respective roles, “culture-setting”, industry relationships, and patient experience optimisation Emphasis on the heart team for various patient subsets, and new recommendations for collaboration with EP Updated pre-procedure checklist and pre-percutaneous coronary intervention (PCI) time out Updated infection control guidance, including use of PPE and hand anti-septic solutions Emphasis on same-day discharge for select patients.

“This comprehensive statement, prepared by experts across a range of disciplines, builds on prior consensus statements and provides updates focused on current patient-centered and evidence-based approaches to care,” stated Daniel Kolansky, University of Pennsylvania, Philadelphia, USA, vice-chair of the writing committee and SCAI 2021 programme chair.

“The document covers topics ranging from preprocedure assessment to intra-procedural best practices and safe discharge and follow-up needs of the patient.

The document highlights regulatory and accreditation requirements for cath labs, a heart team approach to complex care, and discussion of what constitutes an optimal cath lab team. It also addresses collaboration between disciplines such as interventional cardiology and cardiac electrophysiology. This document will serve as a guide for lab directors, hospitals, and health systems in establishing current best practices for catheterisation labs.”

May 2021 | Issue 61

18 Interview

Profile

Cindy Grines Cindy Grines is an interventional cardiologist and chief scientific officer of Northside Hospital Cardiovascular Institute, Atlanta, USA. She has recently completed a term as the president of the Society for Cardiovascular Angiography & Interventions (SCAI). During her varied career, she has been involved in clinical trials that have revolutionised the care of ST-elevation myocardial infarction (STEMI) patients worldwide, and is a pioneer of primary percutaneous coronary intervention (PCI) for heart attacks.

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

I did not decide to become a doctor until I was near the end of my college career. There were not any physicians in my family, but I had taken a lot of pre-med classes, as that is just what I found interesting. I ended up getting good grades, so it was the other students who talked me into going into medicine—the thought had never crossed my mind! I did cardiology rotations when I was an intern and it was very interesting and I thought you could save a lot of lives. Also, it was never a stagnant field, there were acute breakthroughs constantly. I thought I would be a non-invasive cardiologist based on where I did my general fellowship, but when I went to University of Michigan to do my cardiology fellowship, they were just really into acute myocardial infarction (AMI), thrombolysis and rescue angioplasty at that time and I fell in love with the interventional component and acute care cardiology.

Who have been your career mentors?

When I was a resident at Ohio State University there were a couple of general cardiologists who helped to shape my career—Charlie Wooley and Haris Boudoulas.

Then, when I did my cardiology fellowship, I had several mentors. Bill O’Neill, an interventionalist, and Eric Topol, were probably the two that were the most influential in my career.

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

I was lucky to be involved in researching the use of primary PCI for STEMI patients. We did the original multicentre trials proving that it was better than thrombolytic therapy, and ultimately were able to change the way those patients are managed worldwide. There are very few coronary interventional procedures that save lives, but primary angioplasty for heart attacks is a huge lifesaver, so I am really thrilled to have been part of that.

The second thing is the use of stents to stabilise vessels so they do not have a high risk of abrupt closure due to dissections. The third thing was the use of TAVI [transcatheter aortic valve implantation]—percutaneous valve replacements—that is a big lifesaver as well.

What has been the biggest disappointment—something you hoped would change practice, but did not?

There have been a lot of renditions of different types of stents—the thinner strut stents are good because they are more flexible and deliverable, and there is less restenosis. But, we have tested all these types of stents, like the bioresorbable scaffolds, the bioresorbable polymers, all those have really not panned out to be advantageous, and that has been a real disappointment.

The other thing that is disappointing is the fact that if you look at complex multivessel disease, we are still not as good as bypass surgery in the most complex cases and that has been particularly frustrating to me.

What are your current research interests?

We are still trying to look at the nuances with regard to STEMI care, and trying to get networks available for the National Cardiogenic Shock Initiative. We are working on revising the SCAI shock classification, as well as looking at a lot of different issues with regard to ischaemic heart disease in women, which I think is a very important area. Also, complex coronaries in general and the use of percutaneous support devices.

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

Trying to distinguish which patients absolutely need to have surgery versus angioplasty is one big unanswered question. Secondly, the acute outcomes with angioplasty are always superior to bypass surgery—but it is in the late outcomes where bypass surgery seems to be the big winner. The question is: why is that? What can we do to prevent that—can we do better screening to identify the patients who have restenosis or the presence of vulnerable plaques in areas that have not been treated?

Can we apply various medications for that, or can we better analyse those plaques to identify which ones might be prone to plaque rupture?

There are very few coronary interventional procedures that save lives, but primary angioplasty for heart attacks is a huge lifesaver.”

What has been the main accomplishment during your time as president of the Society for Cardiovascular Angiography and Interventions (SCAI)?

This has been the only year where the president has never had a single face-to-face meeting and everything was virtual! We really beefed up all of our online presence—we had a new website developed, hosted a number of different webinars providing education, and we did all of our Scientific Sessions meetings virtually.

This has allowed us to expand greatly overseas, with a lot more presence in China and India in particular, but also several other countries.

We have also completely revamped our strategic plan, and we are trying to turn SCAI into a more flexible organisation, to be able to react more quickly.

With regard to the pandemic, we have produced white papers and recommendations, and have started a couple of registries, including the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) registry just published recently.

Being only the third woman ever in the history of SCAI to be president, I made it my goal to try to expand diversity, equity, and inclusion and so we developed a brand new committee in that regard. We also completed a white paper looking at disparities in the diagnosis, management, and treatment and outcomes among any type of interventional disease. This covered coronary artery disease, peripheral disease, structural heart disease, and congenital defects. We pulled together lots of different people, all interventional cardiologists from different disciplines to identify disparities and care gaps, and make recommendations about what we should do.

How has the COVID-19 pandemic impacted the field of interventional cardiology?

The main impact has been the withholding of care.

We noticed very early on, after the recommendations for people to stay at home, that there was a 40% drop

Issue 61 | May 2021

Interview 19

in patients coming to the hospital with heart attacks.

Subsequently, there was a huge increase in out-ofhospital-cardiac arrests, and deaths occurring at home.

Obviously, patients needed to be told to not go out and socialise but the message was not there for them to continue to seek medical care if they had symptoms, and I think that is a travesty to not have thought about that in advance. In SCAI, we conducted a survey of consumers to find out what their concerns were, and we developed a campaign called ‘Seconds Still Count’.

I am not sure that it is 100% back to normal yet, but it has been wildly successful at trying to get them back to hospital.

What advice would you give to someone looking to start a career in medicine?

I think that we definitely need more bright minds in cardiology. A lot of medical students seem to be more into the lifestyle, and they are going into professions that are perceived to be easier. Unfortunately, those may not be as interesting as cardiology. You have to look at the big picture: what is your career going to look like in 30 years? Secondly, what is the level of satisfaction? In cardiology, it is great because you know you are making a huge difference in these patients, you are saving lives on a daily basis. Not only that, on a daily basis there is something new and exciting that is happening, so there is no way that you are ever going to get bored in cardiology.

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

I think the biggest detriment is the time required to get to that end goal. If I want to be an interventional cardiologist, I have to do four years of college, I have to do four years of medical school, I have to do three years of internal medicine, three years of general cardiology, then one to two years of interventional cardiology.

That is a big problem, and many people do not want to wait that long. I think that if we could get cardiology out from underneath internal medicine and have our own specialty that would totally shorten the timeframe required to become a cardiologist, I guarantee there would be a lot more people willing to go into it. The second thing is that medical school does not require cardiology as a rotation—do not ask me why because it is the number one cause of death worldwide!

alisonlang.com

What are your hobbies and interests outside of medicine?

I am a big explorer. I like to go to different countries and I love the national parks here in the USA. I visit friends, lots of whom are scattered around the country, and also I like to read a lot. Interestingly enough, everybody thinks ‘oh you’re an intellectual!’—but I like to read like mystery stories or historical fiction.

Fact file Appointments (selected past and present)

Chief Scientific Officer, Northside Hospital Cardiovascular Institute, Atlanta, USA Professor and Chair Cardiology, Zucker School of Medicine at Hofstra/Northwell, New York, USA Professor of Medicine, Wayne State University, Detroit, USA Director, Interventional Cardiology Fellowship Program, William Beaumont Hospital, Royal Oak, USA

Affiliations

Society for Cardiovascular Angiography and Interventions American College of Cardiology American Heart Association European Society of Cardiology

Education

Cardiology Fellowship, University of Michigan Hospital, Ann Arbor, USA Research Fellowship, Internship & Residency, MD Cum Laude, Ohio State University, Columbus, USA

Honours and Awards (selected) Master Interventionalist of SCAI American College of Cardiology Distinguished Mentor Award Devotion to Mentoring Women in the Interventional Cardiology and Improving Outcomes of Patients with Cardiovascular Disease, SCAI Luminary in Interventional Cardiology, SCAI American Medical Women’s Association Scholastic Achievement Award

May 2021 | Issue 61

20 Advertorial THIS ADVERTORIAL IS SPONSORED BY SHOCKWAVE MEDICAL

Intravascular lithotripsy: Not an eccentric option for eccentric calcium Severe coronary artery calcification presents a major obstacle for percutaneous coronary intervention (PCI), increasing the likelihood of complications such as impaired stent expansion and limited lesion crossing. Eccentric calcified lesions, whereby plaque volume is more concentrated on one side of the vessel, provides a further layer of complication.

The challenge of treating eccentric coronary calcification is well known, and established technologies such as balloon angioplasty, cutting or scoring balloons, and atherectomy suffer limitations when faced with the presence of eccentric plaque.

C

oronary intravascular lithotripsy (IVL, Shockwave Medical) offers an alternative method for the treatment of eccentric calcium. IVL uses sonic pressure waves, known as shockwaves, that pass through soft arterial tissue and preferentially disrupt calcified plaque by creating a series of microfractures. Carlo Di Mario (Careggi University Hospital, Florence, Italy) and Holger Nef (Giessen University Hospital, Giessen, Germany) have experience of the use of IVL in eccentric coronary lesions, and believe that the technology has the potential to bring about consistent improvements in procedural and clinical outcomes when deployed in this challenging subset of lesions. The pair spoke to Cardiovascular News about the challenges of treating eccentric lesions, and offer their experience of having used IVL in these complex cases.

“A common belief is that when the calcium arc is less than 180 degrees you can achieve a normal expansion stretching the opposite wall—but, this is only partially true,” says Di Mario, outlining why interventional cardiologists should pay particular attention to the challenge posed by eccentric calcification. Nef adds that due to the eccentricity of calcified lesions, high pressure balloon dilatation often results in disruption or dissection of healthy intima or fibrous plaques rather than modification of calcified segments within the artery.

“When you have a very thick eccentric calcium plate, fracturing the calcium with balloons on their own is very difficult,” says Di Mario. “If you do not break the calcium the shape of the final lumen after stenting will be oval or kidney-shaped and struts will have unavoidable major malapposition—two abnormalities that are only partially correctable with in-stent final postdilatation, no matter how large the balloon and high the pressure.”

Using IVL in eccentric coronary calcification

Di Mario explains that in most cases only predilatation is used, adjusting the pressure of the balloon expansion if the operator is skilled enough to monitor expansion in a view perpendicular to the calcified eccentric lesion.

Cutting or scoring balloons may be considered, Di Mario adds, but comments that they are potentially dangerous if the opposite, non-calcified wall has limited or no plaque.

Rotational or orbital atherectomy is often reserved for lesions that are uncrossable or undilatable, Di Mario explains, commenting that the principle of differential cutting means the non-calcified wall is spared during activation, “except in tortuous anatomies with sharp bends and prominent wire bias”. He comments that the main limitation of this approach, however, is a relative inefficiency to ablate calcium unless the initial minimal lumen of the lesion is very small or the wire bias is favourable to push the burr in contact with calcium.

Nef adds that although cutting and scoring balloons are able to debulk lesions more intensely than noncompliant (NC) balloons, they suffer from the same limitation. “Even rotational or orbital atherectomy, the most effective techniques for modification of calcified plaques available prior to IVL, are limited due to guidewire bias, that may result in inhomogeneous ablation leaving significant areas of the calcified plaques unmodified, particularly in eccentric lesions,” he suggests.

This is where IVL becomes an option. Di Mario comments: “Theoretically, IVL does not suffer the limitations of rotational or orbital atherectomy.”

He notes that if a balloon large enough to match the reference diameter has been selected it should

When you have a very thick eccentric calcium plate, fracturing the calcium with balloons on their own is very difficult.”

Carlo Di Mario

be in contact with the calcified plate promoting the development of microfractures.

Whilst Di Mario describes the technology as “sophisticated”, creating rapidly expanding vapour bubbles within the balloon that result in acoustic shockwaves that hit the calcium with ~50atm of pressure, for the operator it is no different to the delivery of a conventional balloon, he comments.

Adds Nef: “IVL catheters are equipped with lithotripsy emitters that deliver localised pulsatile acoustic pressure waves circumferentially to modify vascular calcium. This provides the unique opportunity to modify the calcified plaque homogenously and reach calcification even in deeper vessel layers. Since the IVL works as a rapid exchange system—like a normal angioplasty balloon catheter—the ease of use is obvious.”

Safety and efficacy

The effectiveness and safety of IVL in eccentric calcified coronary lesions has been studied via a patientlevel pooled analysis from the DISRUPT CAD I and II studies, findings of which were recently published in

Shockwave C2 IVL catheter

Issue 61 | May 2021

Advertorial 21

study (Grade D–F) were 0% eccentric, and 1.7% concentric (p=0.54). Nef comments: “From a safety perspective, there were no perforations, abrupt closure, slow flow or no reflow events observed in either group, and there were low rates of flow-limiting dissections.”

Di Mario emphasises that safety is the main advantage of IVL—with no perforations or no-reflow post-IVL confirmed in both eccentric and concentric lesions during the study.

A further consideration in the treatment of eccentric

Make your own experience with IVL in eccentric lesions when you do not want to take chances.”

Holger Nef

Clinical Research in Cardiology. Authored by Nef and colleagues the study gathered data from 47 patients with eccentric lesions, which was defined as having one of its luminal edges in the outer quarter of the apparently normal vessel lumen. These patients were compared to 133 patients with concentric lesions. In the study, Nef and colleagues reported a similar level of clinical success with IVL in both the eccentric lesions and concentric lesions, defined as residual stenosis <50% after stenting with no in-hospital major adverse cardiac events (MACE), (93.6% vs. 93.2%, p=1).

The study reports similar final acute gain and percentage of residual stenosis in both eccentric and concentric cohorts. Final residual stenosis of 8.6±9.8% in the eccentric and 10±9% (p=0.56) in concentric stenosis, while the final minimum stent diameter was significantly greater in eccentric versus concentric lesions (3±0.5 vs. 2.7±0.5mm, p=0.004).

Rates of flow-limiting dissections reported in the

calcification is the use of imaging technology to optimise the IVL, which Di Mario suggests is an important aspect. “Without intravascular imaging the attribution of a calcific lesion to the eccentric group is purely speculative since only intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can precisely measure the arc of calcium, the length of calcium and, for OCT, also the thickness of the calcific sheet,” he comments.

More data on IVL in eccentric calcific coronary lesions

In a study published in Cardiovascular Revascularization Medicine, titled “Intravascular imaging to guide lithotripsy in concentric and eccentric calcific coronary lesions,” Di Mario and colleagues showed similar outcomes in more complex realworld patients who failed other calcium modification strategies before turning to imaging-guided IVL, compared to the patients treated with de novo lesions in

DISRUPT CAD I & II. The study involved 28 patients who were selected based upon severe calcium load confirmed with IVUS or OCT. Results showed that the final minimal stent area measured with OCT or IVUS was 7.06mm2 in the eccentric lesion group and 7.13mm2 in the concentric lesion group. The similarity of outcomes in eccentric and concentric lesions are consistent with the angiographic analysis from DISRUPT I and II where residual stenosis >30% was present in less than 3% with quantitative coronary angiography (QCA) in both eccentric and concentric lesions.

“In our centres we are constantly updating the results of this small initial single-centre series dividing the lesions based of the circumferential distribution of calcium assessed with OCT or IVUS,” explains Di Mario. “In this updated series of more than 100 calcified lesions, which is currently yet to be published, we found similar expansion post-stenting, measured with angiography and confirmed with intravascular imaging, in both eccentric and concentric calcified lesions post IVL,” he adds.

Offering a final piece of advice to his interventional cardiology colleagues as to whether they should seek to adopt IVL for eccentric coronary calcified lesions, Di Mario argues that there is “overwhelming” experience that IVL works in both eccentric and concentric lesions, but says it is for operators to draw their own conclusions based upon practical experience. “Make your own experience with IVL in eccentric lesions when you do not want to take chances,” he says. “For instance, start treating thick calcific plaques in large important vessels, especially opposite to the origin of large branches when you do not want to create large dissections and you need a predictable method to safely expand the calcium.”

This is echoed by Nef who says that due to inherent limitations with currently available devices in the treatment of eccentric lesions, “IVL provides a unique possibility also to address these specific kinds of lesions”.

IVL in eccentric and concentric coronary lesions

Representative angiography and optical coherence tomography images from DISRUPT CAD I & II cases involving an eccentric lesion (left) and concentric lesion (right). Fractured calcium is visible within the intimal and medial vessel layers for both lesions. In each example, increased lumen area is notable post-IVL treatment and post-stent.

Figures above show pre-IVL, post-IVL, and post-stent angiography and OCT imaging of eccentric and concentric lesions treated with IVL

Source: Blachutzik F, Honton B, Escaned J, et al. Safety and effectiveness of coronary intravascular lithotripsy in eccentric calcified coronary lesions: a patient-level pooled analysis from the Disrupt CAD I and CAD II Studies.

Clin Res Cardiol 110, 228–236 (2021).

May 2021 | Issue 61

22 COVID-19

Research lays bare the impact of the COVID-19 pandemic on cardiovascular care The success of vaccine roll-outs in Israel, the USA, UK and parts of Europe offer hope that the tide against the COVID-19 pandemic is beginning to turn. But, as societies slowly reopen after more than a year in and out of lockdown, the wide-reaching impact of the pandemic on health outcomes is only now beginning to be fully understood.

C

ardiovascular patients are among those feared to have been at the greatest risk during the pandemic—from both the direct consequences of COVID-19 and wider disruption to the delivery of care.

New research appears to confirm these fears.

“We are seeing an alarming trend of the deadly impact of this pandemic on high-risk minority heart attack patients,” Payam Dehghani (University of Saskatchewan, Regina, Canada) told attendees at the Society for Cardiovascular Angiography and Interventions virtual scientific sessions (SCAI 2021, 28 April–1 May, virtual), presenting findings from the North American COVID-19 (NACMI) Registry.

The NACMI registry is a joint undertaking between the American College of Cardiology (ACC) Interventional Council, Canadian Association of Interventional Cardiology, and SCAI, with an overall goal to understand demographic characteristics, management strategies and outcomes of COVID-19 patients with ST-Elevation Myocardial Infarction (STEMI).

“Leading clinicians and researchers have quickly and efficiently come together to understand the relationship between COVID-19 and heart attacks. This registry is an amazing feat of collaboration, speed and scale involving more than 60 sites, and three leading medical societies across the USA and Canada,” said Dehghani, a co-lead investigator in the project, reflecting on the speed at which the project came together.

During his SCAI presentation, Deghani told attendees that NACMI investigators collected data from more than 1,600 patients, including 331 STEMI patients with COVID-19, 645 STEMI patients with suspected COVID-19 and a control group of 662 age and sexmatched STEMI patients treated pre-COVID-19.

These groups were assessed against the primary outcome of a composite of in-hospital death, stroke, recurrent myocardial infarction or repeat unplanned revascularisation.

Results reveal that in this series of STEMI activations during the COVID-era, patients who tested positive for COVID-19 were less likely to receive diagnostic angiograms, while those with COVID-19-positive status had higher in-hospital mortality.

Further analysis of the registry shows that COVID19-positive patients were more likely to be of minority ethnicity, to have diabetes, and to undergo medical therapy as a first-line treatment rather than percutaneous coronary intervention. Results also indicated that STEMI patients have higher survival rates when receiving timely access to primary PCI. Among COVID-19 positive patients who received angiography, 69% received PCI and 20% had no culprit vessels identified on angiography (both p <0.01 relative to controls). The primary outcome, composite of all-cause death or MI or stroke occurred in 35% of COVID-19-positive patients, 14% of suspected COVID19-positive patients and 5% of control patients (p<0.001 relative to controls).

The authors of the investigational registry are planning to conduct additional research to further understand the impact on of COVID-19 on specific minority and diabetic patient populations. In addition, investigators plan to carry out follow-up at one year to verify the initial findings.

Presentation of acute myocardial infarction sees major drop during lockdown

During the early months of the pandemic, as healthcare centres became overwhelmed with COVID-19 cases, concerns began to surface that patients were avoiding essential care due to a fear of contracting the virus themselves. New data, also presented at SCAI 2021, seem to give this theory some weight and have prompted discussion about the optimal messaging for future public health crises.

Nina Talmor, (NYU Langone Health, New York, USA) and colleagues conducted a single-centre retrospective observational study comparing patients with myocardial infarciton (MI) who underwent urgent invasive coronary angiography at NYU Langone Health in April 2020, during the peak of the pandemic, versus those presenting in April 2019, prior to the pandemic.

The study’s results showed that only 13 patients with AMI underwent invasive angiography at the institution in April 2020, compared to 59 in 2019—a drop of 70%.

We are seeing an alarming trend of the deadly impact of this pandemic on high-risk minority heart attack patients.”

COVID-19 and cardiovascular care in numbers

33% In-hospital mortality rate of COVID positive patients

70% Drop in acute myocardial infarctions presenting during the pandemic

22% New heart failure patients with COVID who had no previous cardiovascular disease

Anuradha Lala

Nina Talmor

Payam Dehghani

No differences in demographics, comorbidities, or baseline medications between the two time periods were observed. There was a numerically greater proportion of STEMI presentations (39% vs 20%, p=0.30) and a longer median delay from symptom onset to hospital presentation (70.7 vs. 34.2 hours, p=0.06) in 2020 versus 2019, the study team found.

“We were surprised to observe a significant reduction in the number of patients referred for coronary management of MI; this suggests that many patients may have stayed at home despite their symptoms of a heart attack,” said Talmor, the study’s lead investigator.

“Our findings point to the need for improved public health messaging for future health crises, so that people do not remain at home out of fear, rather than seeking necessary and potentially lifesaving care. We hope our study will bring awareness to the need for timely cardiac care both in and out of a pandemic.”

Hospitalised COVID-19 patients at higher risk of developing heart failure

Further research, published in the Journal of the American College of Cardiology (JACC) has found that patients hospitalised with COVID-19 may be at risk of developing heart failure even if they do not have a previous history of heart disease or cardiovascular risk factors. Researchers say that while these instances are rare, physicians should be aware of this potential complication.

“This is one of the largest studies to date to specifically capture instances of new heart failure diagnosis among patients hospitalised with COVID-19.

While rare, the finding of new heart failure was more common among patients with pre-existing cardiovascular risk factors or disease. But there were select individuals who developed new heart failure without risk factors or disease. We need to learn more about how SARS-CoV-2 may directly affect the cardiovascular system and precipitate new heart failure—whether it is an indirect effect of critical illness or direct viral invasion,” said lead researcher Anu Lala, Director of Heart Failure Research at the Icahn School of Medicine at Mount Sinai, New York, USA. “Importantly, though symptoms of heart failure— namely shortness of breath—can mimic symptoms associated with COVID-19, being alerted to the findings of this study may prompt clinicians to monitor for signs of congestion more consistent with heart failure than COVID-19 alone.”

Researchers looked at electronic medical records of 6,439 admitted and confirmed COVID-19-positive adult patients between February 27 and June 26, 2020, at Mount Sinai Health System hospitals. The median age was 64. Investigators found 37 patients (0.6%) with no prior history of heart failure who developed new cases of heart failure during their hospitalisation for COVID-19.

Of those new heart failure patients, eight (22%) had no previous cardiovascular disease or risk factors, while 14 had a history of heart disease and 15 had no heart disease but at least one risk factor for it. The eight patients with no prior history were younger with an average age of 43, mostly male, and had lower body mass index and fewer comorbidities, such as respiratory or renal diseases. These patients also had more instances of cardiogenic shock. The patients who did have a history or risk factors for heart disease were, on average, 73 years old. All new heart failure patients were in the hospital for a similar amount of time, and survival rates were similar among both groups.

May 2021 | Issue 61

24 Advertorial THIS ADVERTORIAL IS SPONSORED BY PI-CARDIA

Leaflex: Changing the conversation about aortic stenosis?

As more transcatheter aortic valve implantation (TAVI) procedures are performed in lower-risk patients, there is an increasing focus on the long-term lifespan of the bioprosthetic valve—with a recognition that for a younger cohort of patients there may be a greater potential need for repeat procedures due to valve degeneration over time.

LEAFLEX (PI-CARDIA) IS A novel, non-implant device that could defer the need for TAVI in younger patients who may require multiple valve implants in their lifetime, or potentially even prevent the need altogether for TAVI in some patients. Further to this, Leaflex could act as a possible alternative to balloon valvuloplasty in patients who may be deemed too old or frail for TAVI, or to improve TAVI outcomes in heavily calcified and bicuspid aortic valves. Cardiovascular News speaks to Eberhard Grube (University Hospital, Bonn, Germany) about the potential for the device to “change the way we think about aortic stenosis” and the next steps for study of the procedure.

“You could say that this is a next-generation aortic valve repair device, or maybe you can say that it is an alternative aortic valve repair device,” Grube describes. Leaflex is a transfemoral transcatheter device that uses two mechanical structures for scoring aortic valve calcification. This consists of a proprietary Expander, which is positioned into the left ventricular outflow tract and lifts the aortic leaflets into contact with the frame, three scoring arms positioned in the aortic root. “Basically, it modifies the motion of the leaflets, by a controlled application of force—scoring the calcification within the leaflets without embolisation of the calcium particles,” Grube explains. This has the advantage of allowing the valve leaflets to move more easily, be more pliable, and open up the area of flow, he adds.

During the Leaflex procedure, a deflectable transfemoral delivery catheter is inserted via a 16Fr sheath, delivered and positioned into the aortic root using fluoroscopic guidance.

Mechanical expansion of the device scores calcification within the leaflets, and rotation of the arms allows scoring to be performed at different targeted sections of each aortic valve leaflet.

Scoring lines create separation between the calcium deposits on the two sides of the scoring line, in order to regain leaflets’ flexibility, allow their mobility, and improve valve haemodynamics.

“When this particular force is applied to the calcified leaflets, it scores from the aortic side, but the ventricular side of the leaflets remain basically intact, which is

Eberhard Grube

obviously very important because you would like to preserve the integrity of the leaflet so that the patient does not end up with aortic insufficiency,” says Grube.

First-in-human study of Leaflex was completed across six European centres and has demonstrated the functionality and safety of the device, as well as its potential to have a significant effect on aortic valve area among aortic stenosis patients. Grube comments that the initial results show that the device can improve flow access across the valve, increase the mobility of valve leaflets and increase the opening area of the aortic valve without damaging the leaflets. He notes: “So far the application in humans both during surgery and TAVI , the device has proved to be very safe, and very efficacious as far as gradients and aortic opening areas are concerned.”

Clinical study

Further clinical studies have commenced to evaluate the acute and long-term results following treatment with Leaflex as a standalone procedure. Grube believes that this will be important in establishing exactly which scenarios and in which patients the device is best suited. He sees the procedure as having a particular potential in younger patients—where although there has been an increase in the number of TAVI procedures performed in recent years, questions still remain over the long term—although a benefit could also be seen in older patients, or those for whom a TAVI procedure is not feasible. There is further potential, Grube comments, for the device to be deployed in regions where there is limited access to TAVI, or

where the lack of reimbursement for a TAVI procedure means it is out of reach for much of the population.

“There is an ongoing discussion, and a very important discussion, on the present TAVI platforms, [about] the lifetime management for aortic stenosis patient” says Grube. “Do we start with surgery or do we start with TAVI—given our present experience that bioprosthetic valves might degenerate within a ten year timeframe.”

This leads to questions about how best to treat a patient aged 65 years or younger, he comments, who potentially could require two implants over the remainder of their lifetime. This is where he sees the greatest opportunity for Leaflex. “If we apply the Leaflex in these patients we might defer the need for TAVI over the next few years and then start the discussion, which is a lot different in their outcomes than beginning at 65,” Grube says.

On the need for robust data, he adds: “It is very important that we

can demonstrate with this device, not only feasibility but particularly the sustainable results of scoring the calcium, improving the opening area and the flow through the aortic valve. I think this is interesting and I hope we have those results in the near future. Then we will see how the debate will change.”

Grube suggests that if further study of the device can demonstrate its efficacy, Leaflex will be of great interest to the interventional cardiology community as an option for the treatment of aortic stenosis. “The first thing that we have to look into as physicians is what we are doing for our patients,” he says. “That is something that definitely carries weight and I think that once the device is more broadly known, and we have more results, then we will think differently about how to approach aortic stenosis— I am convinced about that. Whether we call it a game changer remains to be seen, but it will definitely change the landscape of our platforms for treating this disease.”

There is an ongoing discussion, and a very important discussion, on the present TAVI platforms, [about] the lifetime management for aortic stenosis patient.”

Pi-Cardia Leaflex

Issue 61 | May 2021

25

Structural Heart Interventions Two-year PARTNER 3 outcomes show convergence between TAVI and surgery on stroke and death

Two-year outcomes of the PARTNER 3 clinical trial, in which low surgical risk aortic stenosis patients were randomised to receive either transcatheter aortic valve implantation (TAVI) or surgery, found that initial differences in death and stroke, which favour TAVI, were diminished after two years. Despite this, the primary endpoint of death, stroke, or rehospitalisation remains significantly lower for TAVI than surgery.

T

hese were among the conclusions of a study surgery; and that valve thrombosis was more frequent after published in the Journal of the American College TAVI versus surgery through two years—associated with of Cardiology (JACC), authored by Martin B Leon an increase in aortic valve gradients in 54% of TAVI cases.

(Columbia Irving Medical Center/New York Presbyterian, In an editorial comment accompanying the study in New York, USA) et al, which also found that patients JACC, Bernard Predergast, Simon Redwood and Tiffany who underwent TAVI had increased valve thrombosis Patterson (St Thomas’ Hospital, London UK) consider the at two years compared to those who underwent surgery. implications of the findings for heart teams. They write: PARTNER 3 enrolled nearly 1,000 patients undergoing “TAVI is the clear treatment of choice in most patients TAVI using the Sapien 3 (Edwards Lifesciences) balloonage >80 years where concerns regarding durability are expandable valve or surgery for severe aortic stenosis, usually not applicable. Conversely, SAVR [surgical aortic and one-year results demonstrated the superiority of TAVI valve replacement] remains the default in those age <70 for the primary endpoints of death, stroke, or years (and certainly <65 years) given the paucity rehospitalisation. of long-term TAVI durability data in younger The study’s primary endpoint was a composite patients. Both modes of intervention are effective of death from any cause, stroke, or cardiovascular in patients between these age thresholds, and the rehospitalisation at one year. Key secondary choice should be determined following a shared endpoints for the two-year follow-up were acute decision-making process incorporating the pros myocardial infarction (MI), new-onset atrial and cons of SAVR and TAVI guided by patientfibrillation, need for a new pacemaker, new left specific anatomic and clinical considerations, bundle branch block, coronary obstruction, aortic Martin Leon the potential need for repeat valve interventions valve reintervention, aortic valve endocarditis, over a lifetime journey (including their mode, and valve thrombosis. sequence, and associated risks), and the patient’s values Of the 950 patients in the as-treated population, 496 and preferences.” underwent TAVI and 454 surgery. Patients had a mean age Asked to comment on the findings, Leon told of 73 years, included more men (69.3%), had fewer severe Cardiovascular News: “I do not believe that the catch-up symptoms, and fewer co-existing conditions than patients in death/stroke events between one to two years suggests enrolled in previous TAVI trials. diminishing TAVI benefit or an expected trend and is more Outlining primary endpoint events at two years, the likely random chance, given the very low event rates for study team notes that the composite of death from any both therapies. cause, all stroke, or cardiovascular rehospitalisation “Remember, the absolute death/stroke rates still occurred in 57 patients (11.5%) after TAVI and 78 favour TAVI after two years and the primary composite patients (17.4%) after surgery (HR: 0.63; 95% CI: 0.45 endpoint still indicated TAVI benefit versus surgery. Both to 0.88; p=0.007). Between one and two years, TAVI therapies—surgery and TAVI—are excellent choices in was associated with more deaths than surgery (seven vs. low-risk patients and the basis for decision-making still three), more strokes (six vs. one), and a similar number of rests on an individual patient assessment accounting for rehospitalisations (10 vs. eight). The combined endpoint all factors, including age, specific comorbidities and other of death or disabling stroke at two years for TAVI was 3% clinical factors, and anatomical considerations favouring compared with 3.8% for surgery. one or the other treatment.”

In terms of secondary endpoints, Leon and colleagues note that there were small changes between one and two years for both TAVI and surgery in most secondary endpoints, including aortic valve re-intervention and endocarditis. However, the rates of valve thrombosis, which were numerically higher at one year after TAVI (1%) compared with those of surgery (0.2%; p=0.13), continued to diverge through two years (TAVI: 2.6%; surgery: 0.7%; p=0.02).

Among the patients with valve thrombosis at two years, seven of 13 (54%) patients who underwent TAVI and 0 of three patients who underwent surgery had an echocardiographic aortic valve mean gradient >20mmHg, with an increase from post-treatment of >10mmHg. Leon et al suggest that the two-year PARTNER 3 follow-up study raises several key findings, chiefly the reduction in the primary endpoint by 37% after TAVI compared with surgery.

Further key points highlighted by the study team include that death from all causes and strokes were more frequent with TAVI between one and two years, such that cumulative event rates through two years were similar to

Both therapies are excellent choices in low-risk patients and the basis for decision-making still rests on an individual patient assessment accounting for all factors, including age, specific comorbidities and other clinical factors, and anatomical considerations favouring one or the other treatment.”

One-year outcomes show promise for Harmony valve in congenital heart disease patients One-year outcomes from the pivotal trial examining the effectiveness of the Harmony transcatheter pulmonary valve (TPV, Medtronic) system for patients with congenital heart disease and severe pulmonary regurgitation (PR) were presented during a late-breaking trial session at the Society for Cardiovascular Angiography & Interventions 2021 scientific sessions (SCAI 2021, 28 April–1 May, virtual).

THE PROSPECTIVE, NON-RANDOMISED study was conducted at 10 sites in the USA, Canada, and Japan and included a total of 67 patients. The study's primary safety and effectiveness endpoints included freedom from procedure or device-related mortality at 30 days, and percentage of patients with acceptable haemodynamic function at six months and no Harmony valve intervention.

Investigators analysed two sizes of the Harmony valve, a 22-mm valve (TPV22) and a modified version of the original 25-mm valve (mTPV25). Clinical outcomes through one year included no mortality, endocarditis, major stent fractures, or need for surgical intervention. One patient underwent a valve-in-valve intervention for residual stenosis. Over 90% of patients reported having little to no pulmonary regurgitation during follow-up visits.

The Harmony TPV is designed to be a less invasive treatment option for patients with irregularity in their right ventricular outflow tract (RVOT) needing pulmonary valve placement to restore valve function. Prior to TPV technology, congenital heart disease patients were treated with invasive procedures such as open heart surgery or opted for surgical valve replacement later in life. The Harmony TPV is designed to be a non-invasive, non-surgical treatment option for these adolescent and adult congenital heart disease patients.

“This is a brand-new class of cardiac devices designated to help a very specific patient population where no less-invasive, percutaneous treatment options were available until now,” said Thomas Jones, director, Cardiac Catheterization Laboratories at Seattle Children’s Hospital, Seattle, USA. “Unlike any other TPV, this novel technology is designed to expand into the enlarged RVOT in these patients while simultaneously deploying a suitable bioprosthetic pulmonary valve. The Harmony TPV system has the potential to fundamentally alter the lifetime management of congenital heart disease patients from here on out.”

In March 2021, the Harmony TPV system was granted US Food and Drug Administration (FDA) approval for use in the USA. Additionally, investigators plan to follow-up through five years.

A post approval study will also be conducted with follow-up to 10-years.

26 Structural Heart Interventions

May 2021 | Issue 61

Understanding trends in surgical aortic valve replacement and TAVI Joseph Bavaria Comment & Analysis With recent data pointing to a shift towards more transcatheter aortic valve implantation (TAVI) procedures taking place across the USA, overtaking surgical aortic valve replacement (SAVR) for the first time in 2019, Cardiovascular News spoke to Joseph Bavaria, vice chief of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, USA, a former president of the Society of Thoracic Surgeons (STS) and recent chair of the STS/ACC TVT Registry, the US national TAVI database, to discuss the future of TAVI and SAVR.

What is your expectation for future trends in TAVI and SAVR?

TAVI is increasing dramatically. This tends to happen in fits depending on the data that come out in the prospective randomised trials regarding risk profiles.

For example, when the first data on TAVI in high-risk patients came out it [TAVI] went straight up and then plateaued, as the high-risk cases were absorbed. Then, the intermediate risk data came out, the slope of the curve went up, and started to flatten again. In low-risk patients it is in the acceleration phase right now.

My expectation is that the low-risk prospective randomised trial data will make its way through the community over the next 24 months, so the number of TAVI cases will go up, and then it will start to plateau, with a more organic level of growth—maybe 6% per year, instead of 30% growth per year.

What have we learned from the latest studies on TAVI in low-risk patients?

The data from the low-risk trials may indicate a “crossing” of the outcomes at two to three years. The two-year

procedures. Isolated AVR has come down about one-third over the past three or four years. AVR-CABG has also come down a little bit, around 10%. That is because people are getting TAVI with percutaneous coronary intervention (PCI)—two sequential endocardiac procedures. On the other hand, the AVR/Other category—which includes aortic valve replacement with an ascending aorta, aortic valve with an electrophysiological procedure, aortic valve replacement with a mitral valve, etc.—is either flat or actually slightly up. That is not going away. TAVI does not address these problems, it is not sophisticated enough to address complex cardiac structural issues, whereas surgery can correct three problems at the same time. Fourthly, Bentall, which is an aortic root procedure, are up about 12–18% per year for the last five years, according to the STS National Database.

Surgical AVR as a whole is coming down slightly, when you add up all four of those categories and you can even add a fifth—aortic valve repair—what you see is that TAVI outnumbered isolated AVR

PARTNER 3 data were slightly worrisome in the sense that surgery was steady, but the TAVI outcomes were getting worse. The curves were coming together, and if they stay like that they will end up crossing, which would mean that surgery will actually end up being better at three to five years. That data is going to be very powerful, regarding adoption of TAVI into low risk patients.

It is very interesting on that score, to understand that the new ACC/AHA guidelines for aortic valve disease, which came out in early December, were not 100% favourable for low-risk TAVI. The guidelines walk the fine line between too much and too little. They made a very specific point of recommending that if you are under 65 years of age TAVI is not indicated. The guidelines are still a little bit of a moving target.

When you have something that is complex, the heart team is really important because you have different perspectives and knowledge bases on all of the components of the best treatment plan.”

What can we expect to see in terms of trends in SAVR procedures?

back in 2016, but TAVI did total more than the entire universe of AVR until 2019.

Right now we have more TAVI in the USA than the whole AVR universe.

Aortic valve replacement surgery is not going away, but it is not really growing either, as a whole.

Surgical aortic valve procedures are segmented into isolated aortic valve replacement, aortic valve replacement with coronary bypass surgery (AVRCABG), AVR/Other, and Bentall

Wealth gap may play a role in a patient’s access to surgery or TAVI

Socioeconomic factors may play a deciding role in a patient’s referral for either transcatheter aortic valve implantation (TAVI) or surgical aortic aortic valve replacement (SAVR), with TAVI hospital programmes predominantly located in metropolitan areas serving wealthier patients.

This is according to data presented at the Society for

Cardiovascular Angiography and Interventions virtual scientific sessions (SCAI 2021, 28 April–1 May, virtual)

by Ashwin Nathan (Hospital of the University of Pennsylvania, Philadelphia, USA).

Nathan and colleagues carried out a cross-sectional analysis of US Medicare claims data from January 2012–December 2018. The study team used linear regression models to compare characteristics of patients treated at hospitals that did and did not establish TAVI programmes to determine the association between markers of socioeconomic status and TAVI rates.

The findings reveal inequitable access to TAVI for non-metropolitan or lower income areas across the country. Between 2012 and 2018, 554 hospitals developed new TAVI programmes including 543 (98%) in metropolitan areas, and 293 (52.9%) in metropolitan areas with pre-existing TAVI programmes.

What is your advice to heart teams about how to best navigate the choice of TAVI or SAVR?

When you have something that is complex, the heart team is really important because you have different perspectives and knowledge bases on all of the components of the best treatment plan. It is not really an either/or question, sometimes it is that a particular patient will have a multitude of issues, and maybe the team needs to go one way or the other.The heart teams have to know the data. The data change every day a little bit. TAVI is not a totally mature therapy yet and so the heart team is really important to navigate all of those questions, for example, if you have a bicuspid valve patient, they should probably go to surgery, because the results of surgery are excellent. But, if it is an 80+ year old, maybe you want to try TAVI, even though it is not quite as established as a treatment in a bicuspid valve patient. If the patient has coronary disease, the team will have to weigh whether they want to do an AVR-CABG, which may be more definitive than a TAVI with a PCI, and realise that a PCI after TAVI is more complicated.

What developments should we expect in TAVI in the coming years?

The problem for companies now is that new-generation technology has to be good because the bar is already high. I think we will still see more incremental improvements as time goes on—it might be more iterative, as opposed to dramatic.The two biggest disappointments regarding TAVI in the last six years or so, are that we have not improved our stroke rates or our pacemaker rates over that timeframe.

This is despite having better valves, and despite going into lower-risk patients.

This is a problem that has been clearly documented by the big data from the STS/ACC TVT Registry.These are the areas that any new technology has to address. We have improved at everything else over the past decade.

Transcatheter mitral and tricuspid procedures are coming along very strong, and a really satisfactory and effective transcatheter mitral valve replacement would be revolutionary.

Compared with hospitals that did not start TAVI programmes, hospitals that did treated patients with higher median household incomes (difference US$1,305, 95% confidence interval [CI] US$134 to US$12,477, p=0.03). Furthermore, TAVI rates per 100,000 Medicare beneficiaries were higher in areas with higher median income, despite adjusting for age and comorbidities.

“TAVI has the potential to be an innovative and effective treatment option for heart valve patients, but can only work to its full potential if all patients have access to it. Our study results show a gap, and as clinicians, we know that these inequities can unfortunately translate into differing outcomes,” said Nathan. “While this is just one example of health inequities, our hope is that these findings will activate a change in how we introduce high-tech solutions, so that all communities can access the care they need.”

Structural Heart Interventions 27

Issue 61 | May 2021

Registry data highlight growing use of DOACs among bioprosthetic heart valve patients Registry data charting the use of direct oral anticoagulants (DOACs) in patients receiving mechanical and bioprosthetic heart valves suggest that, despite being contraindicated and off-label, respectively, there is a prevailing use of DOACs among these patients.

THE FINDINGS, GAINED FROM analysis of the Society of Thoracic Surgeons (STS) National Database, were presented by Ankur Kalra (Associate Professor, & Director of Research for Regional Cardiovascular Medicine, Cleveland Clinic, Cleveland, USA) during a late-breaking trial session focused on valve and structural heart disease at the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April). They have also been Ankur Kalra published as a research letter online in JAMA Network Open.

Kalra’s data pointed to a significant increase in the trend of off-label DOAC use among patients with bioprosthetic heart valves—in both aortic and mitral replacement—from 2014–2017, while at the same time suggesting that DOAC-use among mechanical heart valve patients has been constant.

During his presentation, Kalra said that the study sought to establish the current state of the use of DOACs in patients with surgical prosthetic heart valves in the USA, with an objective to evaluate differences in preoperative and postoperative profiles among patients who received DOACs versus warfarin.

He commented that presently there is only one clinical trial to compare DOACs in mechanical valve patients—

Registry data finds BASILICA has a low coronary artery obstruction rate Data from an international registry of patients undergoing a procedure known as BASILICA, which is intended to prevent coronary obstruction during transcatheter aortic valve implantation (TAVI), show that the technique is safe, with low stroke and death rates, and feasible, with high procedure success and low coronary artery obstruction rate.

T

he findings were presented by Jaffar Khan (National Institutes of Health, Bethesda, USA) in a late-breaking trial session at the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April) and simultaneously published in JACC: Cardiovascular Interventions.

Coronary artery obstruction occurs in around 0.7% of TAVI cases, the study’s

RE-ALIGN, results of which were published in The New England Journal of Medicine in 2013. “[RE-ALIGN] actually reported harm with dabigatran in patients with mechanical valves,” Kalra explained, adding: “Not only was there an increase in thrombotic events, but also in bleeding events.”

US Food and Drug Administration (FDA) labelling for DOACs contraindicates their use in patients with mechanical valves, whilst their use in patients with bioprosthetic valves is offlabel, Kalra said.

To understand their current usage, Kalra and colleagues extracted data from version 2.81 of the STS database, tracking patients who underwent surgical aortic or mitral valve replacement, with either mechanical or bioprosthetic valves, between 2014‒2017.

Detailing usage at discharge, Kalra noted that around 1.1% of aortic mechanical valve patients received DOACs, compared with 1.04% of mitral mechanical valve patients, 4.66% of aortic bioprosthetic valve patients, and 5.89% in those with mitral bioprosthetic vavles. Analysis of trends in DOAC-use among these patients showed an increasing trend in prescriptions of these agents for bioprosthetic valves, whereas in mechanical valves it stayed at around the 1% mark.

authors suggest, and is associated with around 40–50% mortality. BASILICA— bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction— is a transcatheter electrosurgical procedure performed immediately before TAVI in which catheters and guidewires are used to first traverse, then lacerate, the aortic leaflet in front of the threatened coronary artery to preserve coronary perfusion.

The study’s authors note that, to date, safety and feasibility data on the technique in a large patient cohort is lacking, and they therefore sought to determine the safety of the procedure through the International BASILICA Registry, a retrospective, multicentre, real-world registry of patients at risk of coronary artery obstruction undergoing BASILICA and TAVI. A total of 214 patients from 25 centres in North America and Europe were included in the study between June 2017 and December 2020. Of these, 72.8% had bioprosthetic aortic valves and 78.5% underwent solo BASILICA. The authors note that leaflet traversal was successful in 94.9% and leaflet laceration in 94.4%. Partial or complete coronary artery obstruction was seen in 4.7%. Procedure success, defined as successful BASILICA traversal and laceration without mortality, coronary obstruction or emergency intervention,

Outlining some of the factors that led to the prescription of these agents, Kalra said that older patients were discharged on DOACs compared with warfarin among those with bioprosthetic valves, whilst the same was also true, and statistically significant, for the mechanical valve patients.

Turning to the preoperative characteristics for patients, he explained that hypertensive patients, patients with arrhythmias, and patients with vascular disease in the mechanical valve group were more likely to be discharged on a DOAC compared with warfarin. For the bioprosthetic valves, he noted that patients with more comorbidities were discharged on DOACs compared with warfarin.

Noting that the findings are somewhat limited by the lack of follow-up data to compare outcomes of DOACs versus warfarin in patients with prosthetic valves, he summarised that the study points to a prevailing offlabel use of DOACs in patients with prosthetic valves.

He concluded: “Until the completion of randomised clinical trials that provide sufficient evidence for DOAC use, physicians may wish to exercise caution with regard to DOAC prescription in patients with prosthetic valves.”

Until the completion of randomised clinical trials that provide sufficient evidence for DOAC use, physicians may wish to exercise caution with regard to DOAC prescription in patients with prosthetic valves.”

was achieved in 86.9%. Thirty-day mortality was 2.8% and stroke was 2.8%, with 0.5% disabling stroke.

Thirty-day death and disabling stroke were seen in 3.4% of patients. VARC-2 composite safety was achieved in 82.8%.

One-year survival was 83.9%. Outcomes were similar between solo and doppio BASILICA, native and bioprosthetic valves, and with the use of cerebral embolic protection.

The findings led the study team to conclude that BASILICA is safe, with low reported rates of stroke and Jaffar death, and is feasible in the real-world Khan setting, with a high procedure success rate and low rates of coronary artery obstruction.

Speaking during his presentation of the results at CRT, Khan said: “This is the largest registry of the BASILICA procedure and it demonstrates, in our view, that BASILICA is safe, with low rates of stroke and death; feasible in the real world with high rates of success and low rates of coronary artery obstruction.

The reassuring data should facilitate wider dissemination of the BASILICA procedure at high-volume centres.”

28 Structural Heart Interventions

May 2021 | Issue 61

Minimally invasive aortic valve surgery or TAVI: The need for randomised trials Ahmed Bendary Comment & Analysis Minimally invasive aortic valve replacement (miAVR) in select patients with severe aortic stenosis offers a number of possible advantages over alternative approaches, writes Ahmed Bendary (Benha University, Benha, Egypt), who notes that there has been renewed interest in the technique in recent years. He discusses the evidence for situations favouring miAVR over transcatheter aortic valve implantation (TAVI), and argues that head-to-head studies comparing the two approaches should be considered.

M

ost of the available literature focuses on the comparison of transcatheter aortic valve implantation (TAVI) and classic surgical aortic valve replacement (SAVR) in managing patients with severe aortic stenosis (AS).

In recent years there has been a renewed interest in minimally invasive aortic valve replacement (miAVR) in selected patients, being associated with decreased blood loss, shorter intensive

care unit stay durations, and lower acute kidney injury (AKI) and perioperative mortality rates.

Potential advantages of miAVR over TAVI include the ability to directly observe the valve during the operation, removal of annular calcifications, and lower incidence of paravalvular leakage (PVL). However, these may come at the cost of longer hospital stay durations and higher risk of AKI. Unfortunately, no randomised trials have attempted

to compare outcomes of TAVI versus miAVR, and observational studies have inherent biases.

In an attempt to reduce these potential biases, our group has recently published a meta-analysis in OpenHeart-BMJ,1 pooling data of matched observational studies comparing miAVR to TAVI outcomes. This was led by Ahmed Sayed (Ain Shams University, Cairo, Egypt), with Abdelrahman Abushouk (Beth Israel Deaconess Medical Center, Boston, USA) as a senior author.

We included 11 cohort studies spanning 2009‒2019 comparing TAVI with miAVR only, seven of which were either multivariate or propensity matched. The final study cohort consisted of 4,674 patients (mean age, 82 years) undergoing either TAVI (n=2,346) or miAVR (n=2,328) and followed for an average of 26.7 months.

Among five studies with available data, there were no differences observed between both procedures for 30-day mortality, but mid-term mortality (defined as follow-up of at least one year) was significantly higher for TAVI among data from four studies. TAVI showed more PVL in five studies, less AKI in four studies, and shorter hospital length of stay in six studies. Importantly, there were no differences observed for stroke and major bleeding.

We observed no difference in AF between TAVI and miAVR but found less postoperative AF when looking only at transfemoral route for TAVI, a group in which the use of newer-generation valves was frequent (RR 0.14; 95% CI

Analysis shows proportionality fails to account for divergent COAPT and Mitra-FR trials

0.04‒0.48).

One of the most notable findings from the study was the higher rate of midterm mortality for TAVI over miAVR. It makes full sense because this is consistent with longer-term follow-up data from randomised controlled trials comparing TAVI to classic SAVR in either intermediate- or even low-surgicalrisk patients, which showed that the large effect size favouring TAVI seen in the first year of follow-up wanes with time.

In other words, TAVI might be losing ground with years. However, caution should be exerted in interpreting these data, taking into consideration the observational nature of the included studies, and the potential for unmeasured confounders.

The present study is the first of its kind in the literature that pooled data comparing TAVI versus miAVR with a higher degree of certainty and statistical power. The results will of course help the heart team as a whole in deciding on the best option for each individual patient with AS. At this point, the evidence is not sufficient to recommend practice changes, and a randomised comparison is needed but is unlikely to happen—with industry funding for such a study likely to be challenging.

Ahmed Bendary is at Cardiology department, Benha faculty of medicine, Benha University, Benha, Egypt.

References 1. Sayed A, Almotawally S, Wilson K, et al. Minimally invasive surgery versus transcatheter aortic valve replacement: a systematic review and meta-analysis.

Open Heart. 2021 Jan 1;8(1):e001535.

were ≈30% smaller, indicative of disproportionate MR. To test the validity of this theory, Lindenfeld et al carried out a post hoc secondary analysis of the COAPT trial, evaluating a sub-group of 56 COAPT patients with characteristics consistent with those in Mitra-FR (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20‒50%, and New York Heart Association A secondary analysis of the COAPT trial, which sought to account for differences in the function class II-IV). These were compared with the findings of COAPT and the Mitra-FR trial in patients with secondary mitral regurgitation remaining 492 COAPT patients using the end point of (MR), has concluded that a divergence between the two studies over inclusion criteria all-cause mortality or heart failure hospitalisation at relating to “proportionate and disproportionate” MR did not predict outcomes within the 24 months, components of the primary end point, and COAPT trial. quality of life (QOL).

The analysis by Lindenfeld and colleagues found that COAPT WAS A RANDOMISED TRIAL The hypothesis that proportionate and in the sub-group of patients consistent with those in evaluating transcatheter mitral valve repair with the disproportionate MR could reconcile the results of the the Mitra-FR trial, there was no significant difference MitraClip (Abbott) in patients with heart failure and Mitra-FR and COAPT trials was first put forward in the composite rate of all-cause mortality or heart moderate-to-severe or severe secondary MR who

by Paul Grayburn (Baylor Heart and Vascular failure hospitalisation between those receiving remained symptomatic despite guideline directed Institute, Dallas, USA), Anna Sannino the MitraClip plus guideline-directed medical medical therapy.

(Federico II University of Naples, Naples, therapy versus medical therapy alone at 24 % Results of COAPT showed that at two years, using Italy) and Milton Packer (Baylor Heart months (27.8% vs. 33.1%, p=0.83) compared vs MitraClip to manage patients with secondary mitral and Vascular Institute, Dallas, USA) with a significant difference at 24 months regurgitation was associated with a significant reduction in an editorial published in JACC: (31.5% vs. 50.2%, p<0.001) in the remaining % in heart failure hospitalisation.

Cardiovascular Imaging in 2019, in which patients.

Controversially, however, this was at odds they set out a 'conceptual framework' to While this finding supports the hypothesis with findings of Mitra-FR, which also compared explain the diverging results. that disproportionate MR benefits from MitraClip percutaneous edge-to-edge repair using the MitraClip Grayburn et al suggested that the Mitrain terms of mortality and HF hospitalisation, device with medical therapy alone in patients with FR trial enrolled patients who had MR all subgroups randomised to receive Composite rate secondary mitral regurgitation, concluding that the use that was proportionate to the degree MitraClip versus those treated with of all-cause mortality of the device does not significantly reduce the composite of left ventricular (LV) dilatation, medical therapy alone had significantly rate of all-cause death and hospitalisation for heart and during long-term follow-up, greater improvement in QOL at 12 or heart failure failure compared with medical therapy. the LVEDV and clinical outcomes months, Lidenfeld and colleagues hospitalisation between Analysis by JoAnn Lindenfield (Vanderbilt Heart and of these patients did not differ from reported.

MitraClip versus Vascular Institute, Nashville, USA), published online medically-treated control subjects.

The results led Lindenfeld and medical therapy at in JAMA Cardiology, looked to test the “proportionateIn comparison, Grayburn and colleagues to conclude that the benefit disproportionate hypothesis”, which centres on the colleagues noted that patients of transcatheter mitral valve repair is 24 months ratio of effective regurgitant orifice area (EROA) to left enrolled in the COAPT trial had an not fully supported by the proportionateventricular end-diastolic volume (LVEDV).

EROA ≈30% higher but LV volumes that disproportionate hypothesis.

27.8 33.1

Structural Heart Interventions 29

Issue 61 | May 2021

Meta-analysis points to “inverse” relationship between TAVI centre volume and outcomes The authors of a systematic review and meta-analysis looking at the effect of institutional transcatheter aortic valve implantation (TAVI) volume on mortality, have concluded that more focus is needed on “strong referral networks and consolidation” rather than expansion of existing TAVI centres. The review suggested that existing research points to an “inverse” relationship between annual TAVI centre procedure volume and all-cause mortality among patients.

CONDUCTED BY DEVIKA KIR (University of Miami/Jackson Memorial Hospital, Miami, USA, previously Yale School of Medicine, New Haven, USA), Nihar Desai (Yale School of Medicine, New Haven, USA) and colleagues, the analysis sought to examine the existence of any association between institutional TAVI centre volume and all-cause mortality. Findings of the analysis were published online in Catheterization and Cardiovascular Interventions.

The study team wrote that since the inception and adoption of TAVI in 2011, there has been an “exponential” increase in the number of centres performing the procedure across the world. They add that multiple studies have questioned if there is a relationship between the number of TAVI procedures performed within an instution and the outcomes among patients undergoing the procedure. Through their analysis Kir and colleagues sought to establish whether this link could be established.

In order to probe this connection, the study team performed a systematic literature search for relevant articles using a combination of free text terms in the title or abstract related to volume, TAVR [TAVI], and patient outcomes. Two reviewers screened all of the titles and abstracts for their eligibility for the analysis based upon a set of pre-specified criteria.

All-cause mortality data were pooled from eligible

One-year outcomes after TAVI in lowrisk bicuspid aortic stenosis patients meet expectations Clinical outcomes up to one year after transcatheter aortic valve implantation (TAVI) in lowrisk patients with symptomatic, severe bicuspid aortic stenosis are consistent with those witnessed during early analysis, which supported the safety of TAVI in this patient group.

T

he findings were presented by Toby Rogers (MedStar Heart & Vascular Institute, Washington, USA) during a late-breaking trial session at the 2021 Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April) on behalf of the LRT (Low-risk TAVI)

studies and centres were categorised as being either low (30–50 cases), intermediate, or high-volume (75–130 cases) centres based upon the number of TAVI procedures that they were performing per year.

The search yielded a list of 11,153 citations. In total, 120 full-text studies were reviewed, and of these, seven met the inclusion and exclusion criteria. In total these studies yielded 193,498 TAVI procedures among them.

Categorising the TAVI procedures into groups based upon their centre’s annual volume, the study team calculated that around 25,062 of the procedures were performed at low-volume centres, 77,093 were performed at intermediate-volume centres and a total of 91,343 were performed at high volume centres.

With the expansion of TAVI to lowsurgical risk patients, we need to focus on optimisation of patient outcomes, while ensuring adequate access.”

study team.

The LRT trial is the first US Food and Drug Administration (FDA)-approved investigational device exemption (IDE) to study low-risk bicuspid patients with aortic stenosis (AS) undergoing TAVI. Interim, 30-day findings from the LRT trial were presented at CRT 2020 by Ron Waksman (Georgetown University and MedStar Heart & Vascular Institute, Washington DC, USA).

Presenting the one-year findings Rogers said that the clinical outcomes and TAVI valve haemodynamics “remained excellent” at one-year, and repeated the initial finding that subclinical leaflet thrombosis rate was similar to patients with tricuspid aortic stenosis.

The results also showed that bicuspid patients are younger than patients with tricuspid aortic sentosis.

LRT is a prospective, multicentre registry, with a primary outcome of all-cause mortality at 30 days (VARC-II defined). Secondary outcomes include safety and efficacy (New York Heart Association, NYHA), clinical outcomes (VARC II), valve haemodynamics by echocardiography, and subclinical leaflet thrombosis evaluation by computed tomography (CT) at 30 days. Patients were enrolled between 2016–2020.

The objective of the bicuspid cohort

Devika Kir

Nihar Desai

Furthermore, the study team's analysis showed that there was a relative reduction in mortality rates of 37%, for high volume centres versus low volume centres; a 23% relative reduction in mortality for high volume centres versus intermediate volume centres; and 19% for intermediate volume centres versus low volume centres.

In their concluding remarks, Kir and colleagues write that the existing research “clearly shows an inverse relationship between annual TAVI procedural volume and all-cause mortality”.

This relationship they state, suggests that there is a “need to focus on development of strong referral networks and consolidation rather than expansion of existing TAVI centres to improve patient outcomes, while ensuring adequate access-to-care”.

Futrthermore, the study team suggest that as TAVI expands into a lower risk patient population, a greater focus is needed on optimising the outcomes of the procedure, rather than expansion of existing TAVI centres..

Commenting on the findings to Cardiovascular News, Kir said: “This volume-outcome relationship has persisted despite evolution of the techniques and operator experience, and hence, we need to focus on development of strong referral networks and consolidation rather than expansion of existing TAVI centres.

“With the expansion of TAVI to low-surgical risk patients, we need to focus on optimisation of patient outcomes, while ensuring adequate access.”

within LRT was to assess the feasibility of TAVI with commercially-available valves in low-risk patients with symptomatic severe aortic stenosis, Rogers said.

Researchers enrolled a total of 72 patients, all of whom were confirmed as low-risk for surgery, with an STS Score <3, and who were eligible for transfemoral TAVI. The patient cohort had a mean age of 68.1 ±7.7 years, were majority women (54.2%), and 15 (20.8%) had NYHA classification III or IV. These were we compared to a contemporary cohort of patients undergoing surgical aortic valve replacement (SAVR) from the same institutions, although one-year outcomes were not available for these patients.

Rogers reported that at one-year follow-up, death occurred in one patient out of the 67 for whom complete data were available, while non-disabling

TAVI valve haemodynamics remained excellent for one year.”

stroke was seen in two patients.

The permanent pacemaker rate at one year was 13.6%, which Rogers commented is “almost double that of the tricuspid cohort, which was 7.3%. That is clearly something we have to think about when we are considering TAVI versus surgery in a younger patient.”

Improvements in NYHA class were borne out to one-year as expected, Rogers said, while valve haemodynamics were also consistent with previous TAVI studies.

Toby Rogers

May 2021 | Issue 61

30 Market watch

Product News FDA grants pre-market approval for use of Shockwave IVL for severely calcified coronary artery disease

Xience

Xience stent gains CE mark for short duration DAPT

Abbott has announced that its Xience stent has received CE mark in Europe for shorter duration of dual anti-platelet therapy (DAPT)—including for 28 days—for patients with high bleeding risk (HBR).

The approval follows recent results from two studies that demonstrated both one-month or three-month DAPT followed by aspirin monotherapy is safe in HBR patients and is intended to improve patient outcomes and provide physicians more options to treat their patients.

Patients who receive stents are typically on DAPT regimens (aspirin and antiplatelet drugs known as P2Y12 inhibitors to prevent blood clots) for six to 12 months to support vessel healing and prevent clotting from blocking the stented vessel. However, HBR patients can experience side effects such as bleeding during prolonged courses of DAPT. Abbott’s XIENCE 28 and XIENCE 901 studies show that DAPT can be safely discontinued early with no increased risk in patient adverse events, further confirming the industry-leading safety profile of the Xience stent.

“The results of the studies examining the Xience stent in high bleeding risk patients with shorter durations of dual anti-platelet therapy were highly consistent—with no increase in cardiac events and significant reduction in severe bleeding. To see such consistency is important for physicians seeking the best possible outcome for our patients,” says Marco Valgimigli, deputy chief of CardioCentro Ticino, Lugano, Switzerland.

The XIENCE 28 and XIENCE 90 clinical trials enrolled more than 3,600 participants from Europe, the Americas and Asia. The studies monitored two DAPT durations—one-month and threemonths—in HBR patients. The results are consistent and conclusive: patients who receive the Xience stent with shorter DAPT durations do not have an increase in cardiac events and showed a reduction in severe bleeding, proving short DAPT strategies with the Xience stent are safe in HBR patients.

Shockwave Medical has announced that its intravascular lithotripsy (IVL) technology has received pre-market approval for the treatment of severely calcified coronary artery disease from the US Food and Drug Administration (FDA).

The technology, which was granted Breakthrough Device designation by the FDA, is a novel application of lithotripsy, an approach that has been used to break up kidney stones. With this approval, IVL is now commercially available in the USA to treat problematic calcium in the coronary arteries, which can reduce blood flow in the heart.

As coronary artery disease progresses, plaque in the arterial wall often evolves into calcium deposits, which narrow the artery and restrict blood flow. These bone-like structures make the artery rigid and more difficult to reopen with conventional treatments including balloons and atherectomy.

Intravascular lithotripsy uses sonic pressure waves, also known as shockwaves, that pass through soft arterial tissue and preferentially disrupt calcified plaque by creating a series of micro-fractures. After the calcium has been cracked, the artery can be expanded at low pressure and a stent safely implanted to improve blood flow, with minimal trauma to normal arterial tissue. The coronary technology has been widely adopted internationally and is now available in 50 countries, with more than 25,000 patients successfully treated since the initial commercial availability in early 2018.

“Coronary calcification is a major challenge for physicians because it limits the success of coronary angioplasty procedures and our current tools for addressing calcium have limitations,” said Dean Kereiakes, president of The Christ Hospital Heart and Vascular Institute and professor of Clinical Medicine, The Ohio State University, Columbus, USA, and the co-principal investigator of the pivotal Disrupt CAD III US study. “This approval represents a major advance in both the safety and simplicity of some of our most challenging procedures – and potentially promises to become a new standard of care.”

The approval comes following the publication of the US pivotal study

Shockwave Lithotripsy

recently in the Journal of the American College of Cardiology (JACC), which confirmed that coronary IVL met both the primary safety and effectiveness endpoints with a low rate of major adverse events and a high rate of procedural success.

Medtronic receives FDA approval for Harmony transcatheter pulmonary valve

Medtronic has received US Food and Drug Administration (FDA) approval for its Harmony transcatheter pulmonary valve (TPV), the first minimally invasive therapy created to treat patients with a specific type of congenital heart defect of the right ventricle (RV).

The Harmony TPV, which is placed inside a patient’s native anatomy during a catheter-based procedure, was designated as a Breakthrough Therapy under FDA’s Breakthrough Device Designation (BDD) programme, an approval pathway intended to help patients receive more timely access to certain life-saving technologies.

“The typical congenital heart disease patient will face a multitude of openheart surgeries over their lifetime, to continually address issues with their pulmonary valve. Furthermore, congenital heart disease patients require lifelong monitoring, preventive care and specialised treatment all the way from childhood to adulthood,” said Matthew J Gillespie, attending interventional cardiologist, co-director of the Pediatric Valve Center and director of the Cardiac Catheterization Laboratory at Children’s Hospital of Philadelphia, Philadelphia, USA, and principal investigator in the Harmony TPV Clinical Study.

“The availability of the Harmony TPV will allow a broader range of congenital heart disease patients access to transcatheter technology,” said Nina Goodheart, president of the Structural Heart & Aortic business, which is part of the Cardiovascular Portfolio at Medtronic. “Harmony TPV’s novel attributes make it the only non-surgical solution designed to adapt to a wide variety of anatomies for this specific patient population living with congenital heart disease.”

FDA clearance for AcQCross family of transseptal crossing devices Acutus Medical has announced US Food and Drug Administration (FDA) clearance of the AcQCross family of universal transseptal crossing devices.

The transseptal puncture system is specifically engineered to pair with Acutus’ own suite of sheaths and with sheaths sold by other manufacturers.

In a press release, the company said that there are over 300,000 electrophysiology (EP) and structural heart procedures per year involving the use of transeptal crossing devices in the USA. The company will initiate its full US commercial launch of AcQCross in the coming weeks.

Crossing the septum to gain access to the left atrium of the heart is a critical

Harmony TPV

and required step in any atrial fibrillation or left sided tachycardia ablation procedure, as well as in many left sided structural heart procedures (such as left atrial appendage closure device implants or percutaneous mitral valve repair). Achieving the proper crossing angle and location of septal crossing can significantly impact the efficiency of the entire procedure.

The expanded family of AcQCross catheters include versions that are length-, diameter- and tip-matched and designed to lock into the hub of sheaths now used in the majority of left heart procedures, including those provided

by Acutus and by other vendors. This compatibility allows physicians to utilise AcQCross with their sheath of choice during virtually any left heart procedure, the company added in its press release.

MedAlliance gains FDA breakthrough designation for sirolimus DEB treatment of de novo coronary lesions MedAlliance has been awarded breakthrough status for Selution SLR, its sustained limus release drug-eluting balloon (DEB) catheter, in the treatment of atherosclerotic lesions in native coronary arteries. This is the fourth breakthrough designation awarded to MedAlliance for its sirolimus DEB, following coronary in-stent restenosis, peripheral below-the-knee and AVFistula indications.

According to the US Food and Drug Administration (FDA), the Selution SLR 014 DEB breakthrough designation is for improving luminal diameter in patients with atherosclerotic lesions in native coronaries.

“MedAlliance is honoured to have our sirolimus DEB selected for the FDA’s Breakthrough Device Program for a fourth time. This may provide US patients faster access to our novel 90-day sustained sirolimus release technology, with the potential to provide safer and more effective treatment,” says Jeffrey B Jump, chairman and CEO of MedAlliance. “This designation, combined with the previous coronary ISR Breakthrough Designation, will give US cardiologists exciting new tools to fight coronary disease.”

The FDA Breakthrough Device Program is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective

Issue 61 | May 2021

Market watch 31

treatment or diagnosis for lifethreatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide MedAlliance with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.

with structural heart disease,” says Mike Dale, senior vice president of Abbott’s structural heart business. “Our novel TriClip therapy offers the best possible outcomes for people suffering from a debilitating condition and gives doctors even more options for customising repair of this complex anatomy.”

Next generation TriClip gains CE mark approval

Emblok embolic protection system used for the first time in Europe

Abbott has received CE mark for its next-generation TriClip transcatheter tricuspid valve repair system, the firstof-its-kind minimally invasive tricuspid heart valve repair device available in Europe to treat tricuspid regurgitation (TR).

The clip-based therapy, known as TriClip G4, is a non-surgical heart valve

Triclip

repair option specifically designed for the treatment of TR, or a leaky tricuspid valve, that allows physicians to tailor repair of the valve to each patient’s unique anatomy.

“Since its initial CE mark in April 2020, TriClip has emerged as a much-needed treatment option, offering physicians the opportunity to dramatically improve the quality of life for people in Europe with severe, symptomatic tricuspid regurgitation who are not responding to medical therapy and are often so ill they cannot undergo surgery,” said Philipp Lurz, professor and deputy head of cardiology, Heart Center Leipzig, University of Leipzig, Leipzig, Germany. “This newest generation device further improves cardiologists’ ability to safely and effectively repair the tricuspid valve, which historically has been extremely challenging to treat.”

Recent data for TriClip from the TRILUMINATE CE mark study showed sustained symptomatic improvement, reduction in the severity of TR, and improvement in functional status, demonstrating the benefits of the therapy and ultimately proving TriClip as a safe and durable treatment option for highrisk patients with symptomatic moderate or greater TR. TriClip is delivered to the heart via a catheter inserted through the femoral vein in the leg and works by clipping together a portion of the leaflets of the tricuspid valve to reduce the backflow of blood.

“Tricuspid regurgitation is considered the most undertreated valve issue and our newest generation device to address it is the result of our unwavering commitment to restore health and improve the quality of life for patients

Innovative Cardiovascular Solutions (ICS) has announced the success of its first European clinical cases using the next generation of the Emblok embolic protection system in patients undergoing transcatheter aortic valve implantation (TAVI). The procedures were performed

by Federico De Marco at IRCCS Policlinico San Donato, Milan, Italy.

TAVI procedures have experienced rapid growth over the past several years as the indication has broadened to include lower risk patients, and as more institutions have adopted procedures.

Despite recent innovations including the reduction of TAVI device profiles, and enhanced procedural techniques, the risk of clinical complications associated with embolic debris liberated into the vascular circulation remains.

The Emblok embolic protection system is designed to provide circumferential aortic coverage to capture and remove embolic debris released during TAVI procedures, preventing debris from reaching cerebral and peripheral vascular circulation.

“The Emblok system performed exceptionally well. We experienced smooth insertion and precise filter positioning in patients with challenging anatomy. We were able to successfully pass interventional devices, including the TAVI system beyond the filter without any device interaction enabling complete embolic protection during the duration of the TAVI procedure,” says De Marco. “We are extremely enthusiastic with the initial results of the Emblok system.”

“Although last year created many global challenges, we are encouraged with our continued progress and the clinical experience with our next generation of Emblok,” says R Kevin Plemmons, co-founder and CEO of Innovative Cardiovascular Solution.

“We anticipate that 2021 will be an exceptional year for ICS as we launch our US IDE clinical study and continue to demonstrate the performance of the Emblok embolic protection system, highlighting the clinical advantage of complete embolic protection.”

Cardiovascular Systems announces first uses of Wirion embolic protection system

Cardiovascular Systems has announced that the first patients in the USA have been treated with the Wirion embolic protection system. Wirion is a distal embolic protection filter used to capture thrombus and debris that can be associated with all types of peripheral

vascular intervention procedures, including atherectomy.

Lawrence Garcia, St Elizabeth’s Medical Center, Boston, USA and Nicolas Shammas, Unity Point HealthTrinity Bettendorf, Davenport, USA participated in the WISE LE study where Wirion demonstrated a major adverse event (MAE) rate of 1.9%, which is lower than previously reported rates for other lower extremity embolic protection filters. Importantly, no clinically significant distal embolisation was observed when Wirion was used.

Garcia comments: “Wirion represents a critical advancement for distal embolic protection devices. With Wirion, I can use my preferred 0.014” guidewire to cross the lesion and then place the filter anywhere on the wire. As a result, I am able to provide extensive support, individualized to each patient and intervention.”

Shammas adds: “Delivery and retrieval of Wirion are easy with a minimal learning curve. Debris capture is very efficient, making Wirion exceptionally suited for use with any atherectomy device.”

Scott R Ward, CSI chairman, president and chief executive officer, says: “We are excited to announce the commercialisation of Wirion.

This product will be an important part of our comprehensive portfolio of differentiated products designed to save limbs and improve outcomes for patients undergoing complex peripheral interventions.”

First European patient treated with Diamondback 360 coronary orbital atherectomy system

Cardiovascular Systems has announced that the first patient in Europe has been treated with its Diamondback 360 coronary orbital atherectomy system (OAS).

Nicolas Van Mieghem, director of interventional cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands, who successfully treated the first European patient, says: “Patients with calcific coronary artery disease have poor clinical results. Diamondback 360 coronary OAS streamlines treatment with a unique mechanism to successfully modify severe calcium and optimise stent performance. I am confident European physicians will like this fascinating technology to help treat their patients with calcific coronary artery disease.”

Orbital atherectomy has demonstrated clinical advantages compared to historical rotational atherectomy data, including lower rates of target lesion revascularisation and persistent slow flow/no reflow. CSI’s ORBIT II and COAST clinical studies demonstrated that OAS is safe and effective in treating patients with de novo severely calcified coronary lesions.

Two real-world studies with approximately 1000 patients have reinforced Diamondback’s safety, high procedural success and long term

clinical success.

ControlRad Select imaging system gains FDA market clearance

ControlRad has announced US Food and Drug Administration (FDA) 510(k) clearance to market ControlRad Select, a technology that utilises proprietary semi-transparent filters, a user-interface tablet, and image processing algorithms to reduce radiation exposure during fluoroscopically guided procedures.

The technology is retrofitted onto customers’ existing Siemens Artis zee interventional imaging systems. In preparation for the commercialisation efforts, ControlRad has entered into an exclusive agreement with Boston Scientific to sell the ControlRad Select technology.

“With the FDA clearance and the reach of the global medical device sales team, every cath [catheterisation], EP [electrophysiology], and IR [interventional radiology] lab in the country that has a Siemens Artis zee will now have the opportunity to reduce their radiation dose by 85%1 without compromising image quality,” stated Guillaume Bailliard, CEO of ControlRad. “The health risks to the medical staff due to lifetime radiation exposure in cath labs have been well documented, including increased incidence of cataracts, atherosclerosis and even left-brain tumours,” stated Simon Dixon, chief of cardiology at Beaumont Hospital, Royal Oak, USA. “We recently completed a clinical trial designed to evaluate how this novel technology might reduce radiation exposure in the cath lab. I have long been passionate about finding innovative ways to improve safety for my colleagues in the lab while they are performing lifesaving procedures for our patients.”

iVascular announces availability of Angiolite DES for longer lesions

iVascular has announced that its Angiolite drug-eluting stent (DES) is available 44mm and 49mm lengths, for the treatment of long lesions. The longer stent sizes received the CE mark approval for the treatment of diffuse lesions.Angiolite is a sirolimuseluting coronary stent, indicated for patients with symptomatic ischaemic heart disease due to de novo stenotic and restenotic lesions and patients with occlusive disease due to acute myocardial infarction.

The device is composed of alternating links to achieve a homogeneous arterial coverage with high rates of endothelialisation due to its fluorinated polymer and TransferWise, proprietary iVascular nanotechnology.

In a press release, iVascular said that the new lengths will facilitate the treatment of long lesions in the coronary arteries. This can help to reduce cost and increase procedural efficiency, avoiding complications such as stents overlapping, and less intervention time versus the use of more than one DES.

May 2021 | Issue 61

32 Market watch

Clinical News

Impella

First patient enrolled in PROTECT IV randomised controlled trial of Impella

Abiomed has announced that the first patient has been enrolled in PROTECT IV, a large, prospective, multicentre randomised controlled trial (RCT) that is designed to provide the level of clinical evidence needed to achieve a Class I guideline recommendation for Impella in high-risk percutaneous coronary intervention (HRPCI).

The first patient was enrolled at Ascension St John Hospital in Detroit

by Ted Schreiber, chief of cardiology at Ascension St John Macomb-Oakland Hospital and Amir Kaki, interventional cardiologist and director of mechanical circulatory support at Ascension St John Hospital.

The two-arm trial will compare the benefits of HRPCI with Impella versus HRPCI without Impella support.

The primary endpoint of the study is the composite of all-cause death, stroke, myocardial infarction (MI), or hospitalisation for cardiovascular (CV) causes at a minimum of one year. The trial has an adaptive design. It aims to enrol 1,252 consecutive qualified patients at more than 100 hospital sites across the USA and Europe.

The PROTECT IV RCT will leverage advancements in technology and best practices learned since the completion of the PROTECT II RCT and the FDA pre-market approval (PMA) for Impella 2.5 for HRPCI. Data from PROTECT II found, when compared to intra-aortic balloon pump (IABP), Impella 2.5 led to a 29% reduction in MACCE, defined as composite of death, stroke, myocardial infarction, and repeat procedures, at 90 days.

PROTECT IV also builds on PROTECT III, a contemporary, prospective, single-arm FDA postapproval study of Impella 2.5 and Impella CP for HRPCI. Interim results presented at TCT 2020 found a statistically significant improvement in 90-day MACCE rates versus PROTECT II (15.0% vs. 21.9%, p=.035) with lower in-hospital bleeding complications (1.8% vs. 12.5%, p<0.001) despite substantially sicker and more complex patients. Impella-supported PCI has

shown higher rates of optimal and complete revascularisation, which leads to improved long-term survival and quality of life.

“This trial aims to generate the highest level of scientific clinical evidence to definitively demonstrate that Impella-supported PCI improves outcomes for high-risk patients, and we are excited to enrol the first patient in the trial,” says Schreiber. “Dr Kaki and I are proud of the entire team at Ascension St John Hospital for being at the forefront of cardiovascular research in this landmark RCT.” The trial’s principal investigators are Gregg Stone, professor of medicine, professor of population health sciences and policy and director of academic affairs for the Mount Sinai Heart Health System, and co-director of medical research and education at The Cardiovascular Research Foundation and Stephan Windecker, director and chief physician in the department of cardiology at the Swiss Cardiovascular Center in Bern, Switzerland.

“PROTECT IV is a landmark trial with the potential to revolutionise the interventional treatment of patients with complex coronary artery disease and left ventricular dysfunction,” says Stone. “This academically-led study is designed to provide the highest level of robust evidence to guide management and improve global clinical outcomes for these high-risk patients.”

“This study is important for the field of interventional cardiology in that it will demonstrate whether forward flow unloading will protect the heart during a high-risk PCI, allowing for more complete revascularisation and improved long-term outcomes,” comments Windecker.

Elixir Medical commences INFINITY-SWEDEHEART randomised study of DynamX bioadaptor

Elixir Medical has announced commencement of the INFINITYSWEDEHEART randomised controlled trial (RCT) of the DynamX coronary bioadaptor system, which is described by the company as the first metallic coronary artery implant that adapts to vessel physiology.

The INFINITY-SWEDEHEART RCT is a prospective, multicentre, single-blind, randomised study enrolling 2,400 patients at approximately 20 sites in Sweden treated with the DynamX bioadaptor in a 1:1 randomisation to

DynamX

Resolute Onyx (Medtronic) drug-eluting stent (DES). The study will utilise the SWEDEHEART registry database to support patient follow-up.

The primary endpoint of the study is a device-oriented clinical endpoint (DOCE) of non-inferiority of target lesion failure (TLF), a composite endpoint that includes cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation, at one year.

Powered secondary endpoints include superiority in the overall population and pre-specified sub-groups, including small vessel, long lesions, left anterior descending artery (LAD), chronic angina and diabetes.

David Erlinge, Lund University, Lund, Sweden, is the principal investigator of the INFINITYSWEDEHEART RCT, and Stefan James, Uppsala University Hospital, Uppsala, Sweden, chairs the Executive Steering Committee for the trial.

The DynamX bioadaptor is a metal implant with a drug-eluting bioresorbable polymer coating that supports the coronary artery during healing, with radial strength similar to a DES. Over six months, the polymer coating dissolves, uncaging the bioadaptor and freeing the artery to move with the natural expansion and contraction of the artery, unlike DES. This has been shown to (a) maintain the ability for positive adaptive remodelling, (b) restore vessel function, and (c) allow for the vessel’s return toward baseline angulation.

The bioadaptor is designed to address the major adverse cardiac event (MACE) rate that occurs with drugeluting stents each year without plateau.

The rigid design of a DES constrains, or “cages,” natural artery movement, restricting its natural ability to accommodate disease progression. This has been associated with MACE. Studies have shown adverse event rates associated with DES of 20% at five years and 40‒50% at 10 years.

Published papers have demonstrated that a DES prevents positive adaptive remodeling, inhibits vessel compliance and dilation in response to the body’s changing blood flow needs, and causes vessel straightening, which has been associated with increased MACE. “Drug-eluting stents have been very useful in opening blocked arteries, but the rigid stent structure cages the artery, impacting its ability to respond to disease progression and maintain blood flow lumen, as it would otherwise do naturally,” says Erlinge. “We are enthusiastic about studying the novel DynamX device, which is the first metallic device treating coronary artery disease that has been shown to restore pulsatility and positive adaptive remodelling of coronary arteries. The benefits of restored vessel function may provide greater benefit in patients with complex disease. The INFINITYSWEDEHEART study includes these complex patients with both Chronic Coronary Syndrome and Acute Coronary Syndrome.”

CytoSorbents granted US FDA approval for STAR-T trial

CytoSorbents has announced that the US Food and Drug Administration (FDA) has granted conditional approval of its investigational device exemption (IDE) application for the US Safe and Timely Antithrombotic Removal—Ticagrelor (STAR-T) randomised, controlled trial.

Based on this conditional approval, study initiation activities, including clinical trial agreement negotiations and institutional review board (IRB) submissions, can now commence, putting the study ahead of the company’s internal schedule.

The company has already identified and pre-screened a number of US clinical centres that have indicated strong interest to participate in the STAR-T trial. The company believes conditions for full IDE approval can be appropriately addressed within the 45day timeframe outlined by the FDA, and once accepted, the company expects to provide additional detail on the trial.

David Cox, vice president of Global Regulatory of CytoSorbents states: “We are pleased that the FDA has approved our randomised, controlled clinical trial for the removal of ticagrelor during cardiothoracic surgery to reduce perioperative bleeding complications.

We will promptly address FDA’s conditions of approval and finalise the IDE protocol to best support a US marketing submission of our FDA Breakthrough Device technology for this application.”

Vincent Capponi, president and chief operating officer of CytoSorbents adds: “We are very excited to have received the go ahead from the FDA to begin the STAR-T trial, that if successful, is expected to support our first US FDA marketing submission. In the future, we plan to leverage the alignment with FDA and the STAR-T study infrastructure, including the academic leadership, operational framework, and participating clinical trial sites to seek label expansions in antithrombotic removal beyond ticagrelor.“ In April 2020, the FDA granted CytoSorbents Breakthrough Device Designation to remove ticagrelor during cardiothoracic surgery, recognising this major unmet medical need. Each year, ticagrelor is prescribed to millions of cardiovascular patients worldwide to reduce the risk of recurrent hearts attack, stroke or cardiovascular death.

Randomised trial data supports use of the PleuraFlow system

ClearFlow has announced clinical trial results published in the Journal of Cardiothoracic Surgery evaluating the use of the PleuraFlow active clearance technology (ACT) system.

The findings are reported by cardiac surgeons at the Montréal Heart Institute, Montréal, Canada, in the article, “Active clearance vs conventional management of chest tubes after cardiac surgery: a randomized controlled study.”

The randomised prospective trial

Issue 61 | May 2021 evaluated the use of the PleuraFlow ACT system in the effective reduction of retained blood complications in heart surgery patients and showed improved outcomes by minimising chest tube clogging and reducing the need for take back for bleeding after heart surgery.

PleuraFlow is a medical device used at the bedside in the ICU that enables clinicians to proactively maintain chest tube patency following cardiac surgery without breaking the sterile field. A patent chest tube enables evacuation of blood and fluid from the operative site after closure of the surgical wound and reduces retained blood, which is accepted by physicians as contributing to many common retained blood complications after surgery, including post-operative atrial fibrillation (POAF), pleural effusions and pericardial effusions.

This was a pragmatic, singleblinded, parallel randomised control trial held from November 2015 to June 2017, including a 30-day post index surgery follow-up. The setting was two academic centres affiliated with the Université de Montréal School of Medicine; the Montréal Heart Institute and the Hôpital du Sacré-Coeur de Montréal.

A total of 520 adult patients undergoing cardiac surgery were randomised to receive either PleuraFlow (n=257) or standard drainage (n=263).

PleuraFlow was associated with a 72% reduction in re-exploration for bleeding (5.7% vs. 1.6%, p = .01) and an 89% reduction in complete chest tube occlusion (2% vs. 19%, p=0.01). There was also an 18% reduction in POAF between the PleuraFlow and control group (31% vs. 38%, p=0.08).

“Chest tubes are used in all cases after heart surgery to collect and externally drain any shed blood in the early hours after heart surgery,” says Edward M Boyle, founder and chairman of ClearFlow. “However, they can occlude with clots, leading to retained blood that can impair recovery by leading to complications. When this happens in the early hours, the patient may require a return to the operating room emergently and the chest re-opened to wash out the clotted blood around the heart. We developed this technology to better enhance patients’ recovery potential after surgery by reducing ‘take back for bleeding’ and associated complications.”

“The results of this trial, combined with earlier published peer reviewed trials, further emphasise the importance of prevention of chest tube clogging and retained blood following cardiac surgery,” says Louis Perrault, study participant and cardiac surgeon at the Montreal Heart Institute. “Conventional chest tubes are prone to clogging, and that can lead to the need to take the patient back for bleeding complications in the early hours after surgery. Our findings in this trial, combined with other groups’ studies, further strengthen the rationale to add active clearance to chest tubes in patients recovering from heart surgery.”

“A randomised clinical trial is the

Market watch 33 gold-standard of evidence proving that a technology is effective at providing patient benefits,” says Paul Molloy, President and CEO of ClearFlow. “The data in this randomised clinical trial has once again shown that more effectively clearing chest tubes following cardiac surgery with PleuraFlow, thwarts retained blood and materially reduces the risk of complications after heart surgery. This randomised controlled trial further supports and endorses our earlier clinical trial data, and strongly establishes active chest tube clearance as a critical element for any program striving to enhance recovery after cardiac surgery. The study also bolsters the evidence-driven expert consensus Class I, Level B-NR ERAS Cardiac Society recommendation that chest drain patency must be preserved for every case after cardiac surgery.”

First patient enrolled in SUCCESS PTA post-market study of Selution drugeluting balloon

MedAlliance has announced enrolment of the first patient in SUCCESS PTA, its large post-market study with the drug-eluting balloon Selution SLR for the treatment of patients with peripheral arterial disease (PAD). Selution SLR is a novel sirolimus-eluting balloon that provides a controlled sustained release of drug, similar to that of a drug-eluting stent (DES).

The objective of the study is to collect real-world safety, efficacy, health economics and patient reported qualityof-life data in over 700 patients with PAD treated with Selution SLR. It is a single arm all-comers study including all lower limb indications and will cover at least 50 sites in Europe, Asia, and South America. Patients will be followed-up at 30 days; six months; then every year out to five years.

The primary endpoint of the study is clinically-driven target lesion revascularisation (CD-TLR) at 12 months. Secondary endpoints include device success and procedure success, major adverse limb events (MALE), and target limb revascularisation (TLR).

“Given the impressive performance of this novel device in earlier studies, we are very excited to see how Selution SLR will perform in a larger group of patients in a real world setting”, commented the study’s principal investigator Michael Lichtenberg (Arnsberg, Germany).

“SUCCESS PTA is part of the SUCCESS post-market study family, designed to show patient benefits in real world use of our technology”, added chairman and CEO Jeffrey B Jump. “This is the largest study we have ever undertaken with Selution SLR, involving the most diverse group of patients. We are confident that the results will confirm the safety, efficacy and cost-effectiveness of our sirolimuseluting balloon.”

In February 2020, MedAlliance received CE mark approval for Selution SLR in the treatment of PAD. This award was supported by results from the

Selution SLR Balloon

first-in-human study.

Data from the SUCCESS PTA study will be part of the clinical evidence supporting CE mark renewal in 2023/2024 under the new European Medical Device Directive (MDR).

Selution SLR has also received US Food and Drug Administration (FDA) Breakthrough Device Designation Status for peripheral below-the-knee lesions, as well as for the treatment of AV-Fistula.

SELUTION SLR’s technology involves unique MicroReservoirs made from biodegradable polymer intermixed with the anti-restenotic drug sirolimus.

These MicroReservoirs provide controlled and sustained release of the drug. Extended release of sirolimus from stents has been proven highly efficacious in both coronary and peripheral vasculatures. MedAlliance’s proprietary CAT (Cell Adherent Technology) enables the MicroReservoirs to be coated onto balloons and adhere to the vessel lumen when delivered via an angioplasty balloon.

First procedure performed in SMART head-to-head TAVI study

The first procedure has been completed in the SMART (Small Annuli Randomized to Evolut or Sapien) postmarket trial, a randomised, head-to-head study comparing two transcatheter aortic valve implantation (TAVI) systems in patients with severe symptomatic aortic stenosis (AS).

The trial compares valve safety and performance of the self-expanding Evolut PRO and PRO+TAVR systems (Medtronic) with the balloonexpandable SAPIEN 3 and SAPIEN 3 Ultra Transcatheter Heart Valves (Edwards Lifesciences).

The study will enroll 700 patients at more than 90 international sites, and is being led Howard C Herrmann, the John Winthrop Bryfogle Professor of Cardiovascular Diseases at the Perelman School of Medicine at the University of Pennsylvania and Health System Director for Interventional Cardiology, Philadelphia, USA. Herrmann and Pavan Atluri, an associate professor of Surgery, recently completed treatment of the first patient in the study.

The study evaluates valve performance in patients with small annuli, a small aortic valve, which represents about 30% of the global TAVI market. Due to its focus on small annulus patients, the SMART Trial will enrol predominantly women, which will provide important clinical insight into a currently underrepresented patient population in the TAVI literature.

“Penn Medicine has been in on the ground floor of many of the early

and landmark trials in TAVR research since performing one of the first investigational procedures in 2007, and, since then, we have completed thousands of these procedures,” Herrmann says. “Subsequently, multiple devices have been FDA-approved, and the procedure has grown to become the predominant one for all patients with aortic stenosis. The outcome of this study will help cardiac teams to make more tailored decisions about which kind of valve to use on which patients.”

The SMART Trial includes prespecified endpoints of haemodynamic superiority and clinical non-inferiority with the Evolut platform compared to Sapien for mortality, stroke, or rehospitalisation at 12 months.

B Braun and Infraredx collaborate on IDE clinical trial for the SeQuent Please ReX

B Braun Interventional Systems has announced a collaboration with Infraredx to accelerate the US Food and Drug Administration (FDA) Investigational Device Exemption (IDE) clinical trial for the SeQuent Please ReX drug-coated PTCA balloon catheter, which received FDA Breakthrough Device Designation in late 2019. This announcement furthers the long-term global cooperation between the B Braun group of companies and Japan-based Nipro Corporation to advance coronary artery disease management.

The companies are positioned to leverage shared resources to accelerate the US clinical trial of the SeQuent Please ReX to study the treatment of coronary in-stent restenosis (ISR), defined as the re-narrowing of a coronary artery following stent implantation, they comment in a press release.

“B Braun and Nipro have worked together over the last decade to arm vascular specialists in Europe and Asia with alternative therapies for coronary interventions,” said Nozomu Fujita, president & CEO of Infraredx, a Nipro Company. “Our decision to also align the resources of our US entities will accelerate how quickly U.S. Interventionalists will be able to access the SeQuent Please ReX technology for US clinical trials.”

“Over the last decade, together with Nipro, we have been able to develop the market for coronary drug-coated balloons by delivering high-quality clinical evidence and optimal physician and patient access,” said Philip Steen, director of Medical, Scientific & Regulatory Affairs, B Braun Melsungen AG Vascular Systems. “Aligning with Infraredx to work toward bringing the SeQuent Please Technology to the US marketplace through the US IDE process is a logical next step to address an important unmet clinical need.”

Steen, an interventional cardiologist by training, had used the SeQuent Please portfolio to treat patients in Germany prior to joining B Braun Melsungen AG Vascular Systems as a senior leader and strategic clinical advisor to the organisation.

May 2021 | Issue 61

34 Market watch

Industry News Shockwave Medical to bring IVL to the Chinese market

Shockwave Medical has announced that the company has signed an agreement to form a joint venture with Genesis MedTech Group to introduce its intravascular lithotripsy (IVL) technology to the Chinese market.

Together, Shockwave and Genesis strive to bring coronary and peripheral IVL products to patients in mainland China, the companies say in a press release.

“Shockwave is a pioneer in their field and our partnership will be of long-term strategic significance not only for Genesis MedTech, but also for the medical community in China,” says Warren Wang, chairman and chief executive officer of Genesis MedTech International. “We share Shockwave’s passion for developing technologies to serve unmet medical needs and are confident that together we can help many patients in China who suffer from calcified arterial disease.”

“This joint venture represents another step in the continuation of our strategy to ensure that patients globally have access to IVL and to do so with a strong, local presence. We are pleased to have a partner with such a solid, established track record in developing and commercialising innovative technologies in China,” says Doug Godshall, president and chief executive officer of Shockwave Medical. “We look forward to joining forces with Warren and his team as we work together to bring IVL to the large and growing Chinese interventional market.”

According to the agreement, the new joint venture will be named Genesis Shockwave Private Limited and enables the commercialisation of both imported Shockwave-branded IVL products as well as IVL products that are locally developed, manufactured, and branded by Genesis Shockwave Private Limited. The creation of the joint venture is subject to the satisfaction of certain closing conditions, including the approval of relevant government authorities in China.

Shockwave IVL received pre-market approval for the treatment of severely calcified coronary artery disease from the US Food and Drug Administration (FDA) in February 2021.

ACC.21 switches to a virtualonly meeting The American College of Cardiology (ACC) has announced that its 70th annual scientific session, will be held as an all virtual meeting. The meeting had been due to be held as a hybrid event, across 15–17 May, with in-person sessions taking place in Atlanta, USA, as well as a digital offering for attendees unable to travel.

However, in a statement this week, ACC announced that it has now taken the decision to move the meeting to an all-virtual format due to the continued presence of COVID-19 and an increase in travel restrictions imposed by healthcare institutions.

Its statement read: “As planning for the hybrid ACC.21 kicked into high gear last year, the College was hopeful that delaying the meeting until the Spring would allow an opportunity for ACC and its membership to safely reconnect in Atlanta, Georgia, for the 70th Annual Scientific Session and Expo. Unfortunately, with the continued presence of COVID-19 and a sudden, sharp increase in ongoing travel restrictions imposed by healthcare institutions, academic medical centres and exhibitor companies, the decision has had to be made to transition the meeting from a hybrid model to entirely virtual.

“While we are saddened that we will need to wait another year before seeing everyone in person, the virtual component of ACC.21 will continue as planned, building on the success of last year’s meeting with an enhanced worldclass programme delivered through our

innovative digital platform built for learning, collaboration, and networking.

Included will be a robust virtual Expo offering both exhibits and education in our Learning Destinations and, last but not least, more opportunities to engage and interact with attendees from around the world.”

As a result of the move, 2021 will be the second consecutive year that the ACC has hosted its annual scientific session as an online meeting, following ACC.20/WCC, which was held jointly with the World Congress of Cardiology in March 2020.

Terumo reaches agreement to acquire predictive analytics specialist Health Outcomes Sciences

Terumo Corporation has signed a definitive agreement to acquire all assets of Health Outcomes Sciences, a specialist in predictive analytics and clinical decision support for healthcare organisations.

“The acquisition of Health Outcomes Sciences and the ePRISM platform expands Terumo’s presence in the digital healthcare arena and represents a compelling growth opportunity for our company. It further allows Terumo to deliver innovative digital solutions, providing healthcare systems with critical data needed to lower the cost of healthcare delivery while substantially improving patient outcomes,” says Toshi Osada, president of Terumo Corporation’s Cardiac and Vascular Company. ePRISM delivers a patient’s unique risks to physicians prior to treatment, based upon a calculation that includes their unique disease severity, comorbidities and demographics. The use of validated predictive models in routine care has the capacity to improve the consistency, outcomes, and costeffectiveness of care across various cardiac procedures and care pathways, Terumo said in a press release.

“When combined with Terumo’s 100-year history and commitment to transforming global healthcare, our ePRISM technology will enable healthcare providers to deliver uniquely focused patient care; improving patient satisfaction, decreasing variability, optimising outcomes, and minimising

costs. This acquisition provides Terumo with a digital solutions platform that can be scaled globally across multiple healthcare segments,” says John Spertus, founder of Health Outcomes Sciences.

The acquisition was slated to close in February 2021. Following the close, the ePRISM platform is to be integrated into Terumo Business Edge, a business unit of Terumo Medical Corporation.

HeartFlow and MedAxiom announce to improve access to coronary CTA

HeartFlow and MedAxiom, an American College of Cardiology (ACC) company have announced a collaboration to improve cardiovascular care for patients with coronary artery disease (CAD) by increasing awareness about the coronary computed tomography angiography (CTA) and the HeartFlow FFRct Analysis diagnostic pathway.

“MedAxiom is at the forefront of transforming cardiovascular medicine and we recognise there is a true need to change the way patients with CAD are diagnosed while improving clinical, operational and financial outcomes for cardiovascular service providers,” said Gerald Blackwell, president and chief executive officer, MedAxiom.

“By bringing together our clinical practice expertise with HeartFlow’s innovative approach to provide precision diagnostics based on coronary CTAs, we have the opportunity to transform the way care is delivered.”

The collaboration will focus on tackling the core barriers preventing cardiovascular service providers from adopting a coronary CTA–HeartFlow pathway. The collaboration will include data, education and tools around best practices for providers and service lines, optimising financial performance, clinical utilisation, organisational efficiencies and payor value.

“As CAD diagnosis increasingly moves to a coronary CTA-led pathway, HeartFlow’s mission is to harness the power of coronary CTA and provide a comprehensive, integrated solution to help physicians deliver precise, personalised diagnoses and optimise treatment for their patients,” said John H Stevens, president and chief executive officer, HeartFlow.

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

15–17 May ACC Scientific Sessions Virtual

9–12 June TVT 2021 Chicago, USA

27 August–1 September ESC Congress 2021 Virtual

accscientificsession.acc.org

tctmd.com/node/34295

escardio.org/Congresses-&-

4–6 November Transcatheter Cardiovascular Therapeutics (TCT) 2021 Orlando, USA

18–20 May EuroPCR Virtual

17–19 June International Society for Minimally Invasive Cardiothoracic Surgery 2021 Virtual

Events/ESC-Congress

crf.org/tct2021

pcronline.com/Courses/EuroPCR

meetings,ismic.org

14–16 October EACTS 35th Annual Meeting Barcelona, Spain eacts.org/annual-meeting/