Cardiovascular News - Issue 57 (June 2020) US edition

June 2020 | Issue 57

COVID-19 linked to a near 40% drop in STEMI cases in US cath labs

Santiago Garcia (Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, USA) and colleagues report in the Journal of American College of Cardiology that there was a 38% drop in cath lab ST-segment elevation myocardial infarction (STEMI) activations in the USA after the COVID-19 pandemic started to substantially affect US social life and medical operations (1 March 2020). The authors suggest that this could be because patients are avoiding seeking medical attention for fear of contracting the virus in hospital.

G

arcia et al write that the US Centers for Disease Control and Prevention (CDC), to preserve resources such as hospital beds, recommended, at the start of the pandemic, deferring elective procedures— for example, percutaneous coronary intervention (PCI) for patients with stable coronary artery disease. However, they add that both the Society for Cardiac Angiography and Interventions (SCAI) and the American College of Cardiology (ACC) advise that primary PCI should still be performed in STEMI patients regardless of whether or not elective procedures are being performed.

According to the authors, anecdotal evidence suggests that the number of primary PCI procedures in the USA and across the globe have declined since the outbreak began. “To determine if a decrease in primary PCI is occurring in the USA in the COVID-19 era, we analysed and quantified STEMI activation for nine high-volume cardiac catheterisation laboratories from 1 January 2019 to 31 March 2020,” they write.

Using a mixed model, Garcia et al compared STEMI activations that occurred between 1 January 2019 and 29 February 2020 with those that occurred between 1 March 2020 and 31 March 2020. 1 March was chosen as the start of the “after COVID” period because that was when, the authors note, US social life and medical operations started to be significantly affected. In particular, New York City (the epicentre of the virus in the USA) reported its first case on 1 March and the US government recommended social distancing on 15 March.

The mixed model showed an estimated 38% reduction in cardiac catheterisation laboratory STEMI activations in March 2020, compared with the previous 14 months.

The authors comment: “All sites combined reported >180 STEMI activations in the before COVID-19 period. In contrast, all sites combined reported only 138 activations.” They say that the 38% reduction is similar to a 40% reduction that has been seen in Spain.

Santiago Garcia

Deepak Bhatt

Garcia et al observe that, during the pandemic, activations might have been expected to go up “given the potential heightened environmental and psychological stressors”. Cases of STEMI induced by viral illness and STEMI mimickers such as COVID-19 myopericarditis may also have theoretically caused activations to increase. “Potential aetiologies for the decrease in STEMI primary PCI activations include avoidance of medical care due to social distancing or concerns of contracting COVID-19 in hospital, STEMI misdiagnosis, and increased use of pharmacological reperfusion due to COVID-19,” the authors speculate.

It is particularly crucial to understand if patient-based anxiety is decreasing presentation of STEMI patients to the US hospital system.”

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Transcatheter mitral valve implantation

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Survey provides insights into how to tackle COVID-19 elective backlog A BIBA MedTech Insights survey indicates that 50% of centres performing structural heart procedures believe that they will need to increase the number of operating days per week to manage the elective cases that have been put on hold because of COVID-19. However, 22% believe that no extra measures will be required and the backlog will be cleared in time.

THE GLOBAL OUTBREAK of COVID-19, and its impact on healthcare resources, prompted many centres to postpone, or at least reduce, the elective procedures that they were performing. However, there are concerns that delayed procedures will lead to poorer prognosis in the long term for patients whose conditions may worsen because of lack of intervention. Additionally, postponement may cause a large backlog that will need to be addressed once elective procedures start to be reintroduced.

To better understand the impact of COVID-19 on elective procedures, BIBA MedTech Insights polled centres across the USA and Europe, asking interventional cardiologists and cardiac surgeons about the structural heart procedures that they were currently performing. Out of 220 centres, 49% said that they were only performing procedures for the most critical patients and 26% said that they were not performing any procedures at all. However, Continued on page 4

Continued on page 2

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June 2020 | Issue 57

COVID-19 in the cath lab

COVID-19 linked to a near 40% drop in STEMI cases in US cath labs Continued from page 1

Garcia and colleagues conclude that their preliminary paper by saying that they continue to “follow this early signal and investigate its causes”. “It is particularly crucial to understand if patient-based anxiety is decreasing presentation of STEMI patients to the US hospital system,” the authors state.

Garcia told Cardiovascular News: “We need to understand what are the forces driving this unexpected fall in the number of cardiac catheterisation laboratory activations for the most serious heart attacks.

Importantly, this decline in cath lab activation coincides with reports of an increased number of cardiac arrests at home. We cannot be certain the two are linked, but it is possible that many patients with heart attacks are deciding to stay home due to concerns about contracting COVID-19 in the hospital or because they

scared to come to hospitals because of COVID-19”.

“There are more delayed presentations of STEMI and probably some out-of-hospital deaths that are not counted as STEMIs, and possibly some more folks who will eventually come in with bad heart failure,” he says.

Following the reports of reductions in primary PCI, both the European Society of Cardiology and the ACC have taken steps to urge the general public to seek medical advice if they experience the symptoms of myocardial infarctions. Both societies stress that hospitals are taking the necessary precautions to reduce the risk of patients contracting COVID-19 while in hospital.

Different treatments and fewer triggers

Another potential reason for why primary PCI cases have gone down is that centres, because of a lack of resources, are preferring to use thrombolysis. Bhatt says that this is an understandable approach when “operating under disaster conditions” as physicians have to “do what they have to do”. But, he states that primary PCI should be the “treatment of choice” for STEMI in places that still have the capacity to provide it.

I hope this pandemic gives us all pause to see how we can make life better for everyone.

I hope it spawns lots of permanent, common sense changes.” think they have COVID-19 and should self-isolate at home. Patients need to be reassured that hospitals are safe and fully operational when it comes to treating cardiovascular emergencies.”

Nervous patients

Garcia et al’s study has been the subject of much discussion on #CardioTwitter, with physicians from both Europe and the USA noting that they have witnessed a drop in primary PCI. Deepak Bhatt (Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, USA) told Cardiovascular News that he too has seen a drop in primary PCI at his centre in Boston since the pandemic began, but said that the drop non-STEMI cases “has been even more notable” than for STEMI. Similar to Garcia et al, Bhatt believes that one of the reasons for these decreases may be that “patients are

For Bhatt, a “more speculative” reason for the drop in cases is that people living under lockdown conditions are now substantially less exposed to myocardial infarction triggers. “Air pollution is a big under appreciated trigger for myocardial infarction, in my opinion, including the commute to work (which can be stressful in other ways). Also, work-related stress I believe is a huge trigger. Sure, there can be home-related stress and, especially financial stress during this epidemic, but on average, I think these pale in comparison to actual on-the-job stress—nothing is quite as bad as a bad boss in terms of generating stress!” Bhatt explains.

Furthermore, like many, he hopes that something positive will come out of this current situation. He notes: “I hope this pandemic gives us all pause to see how we can make life better for everyone. I hope it spawns lots of permanent, common sense changes.”

News in brief

The latest stories from the world of Cardiology

n ACC.20/WCC VIRTUAL: Treatment with aspirin plus rivaroxaban following lower extremity revascularisation in patients with peripheral arterial disease leads to a 15% reduction in the risk of major adverse limb and cardiovascular events when compared with aspirin alone.

For more on this story go to page 8

Marc Bonaca

n STRUCTURAL HEART INTERVENTIONS: Transcatheter aortic valve implantation (TAVI) procedures had a high rate of success and low risk of death or disabling stroke at 30 days in patients with a bicuspid aortic valve, according to research presented by Basel Ramlawi (Valley Health, Winchester, USA) during a late-breaking clinical trial session on day two of the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/ WCC Virtual; 28–30 March, Basel Ramlawi Central Time).

For more on this story go to page 14 n BIBA BRIEFINGS: MitraClip is, by far, the most commonly used device for transcatheter mitral valve repair in Europe. Data from the BIBA MedTech Insights’ Mitral and Tricuspid Monitor shows that out of 10,724 transcatheter mitral devices used in Europe in 2019, 92% were a MitraClip device. This is to be expected as MitraClip is the most well-known device and has the most clinical data.

Of note, Pascal (Edwards Lifesciences)—which, like MitraClip, is a clip-based device—was the second most used device in Europe last year

For more on this story go to page 18

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June 2020 | Issue 57

COVID-19 in the cath lab

Survey provides insights into how to tackle COVID-19 elective backlog Continued from page 1

these figures did change depending on the procedure.

For example, they were, respectively, 58% and 19% for transcatheter valve procedures (including transcatheter aortic valve implantation) versus 25% and 53% for left atrial appendage occlusion. The figures also changed depending on whether the respondents were based in Europe or the USA, with a greater proportion of European respondents not performing any procedures than those in the USA (34% versus 6%).

Given that some areas have now passed the peak of the pandemic, centres in these areas are looking to do elective procedures again. Therefore, the survey asked respondents what measures they felt would be required to clear the backlog of elective procedures. It found that 50% believed there would be a need to increase the number of operating days per week and 34% thought increasing the number of operating hours per day would be necessary. However, 22% felt there was no need for extra measures and the backlog would “clear in time”.

See Figure 1.

Factors to consider when restarting procedures

David A Wood (Centre for Cardiovascular Innovation, St Paul’s and Vancouver General Hospital, Vancouver, Canada) and colleagues have published a joint guidance document in the Journal of the American College of Cardiology about the safe reintroduction of cardiovascular services during the pandemic. The document, which represents the views of several North American societies including the American College of Cardiology (ACC) and the Canadian Association of Interventional Cardiology (CAIC), outlined three areas that must be considered when reintroducing services: ethical considerations; collaboration between regional public health officials, health authorities and cardiovascular care providers to manage the dynamic balance between provision of essential cardiovascular care and responding to future fluctuations in COVID-19 infections and hospital admissions; and the protection of patients and healthcare workers through regions having the necessary critical care capacity, personal protective equipment (PPE), and trained staff available,

and a transparent plan for testing and re-testing potential patients and health care workers for COVID-19.

The Society of Thoracic Surgeons (STS) has also reviewed the steps that need to be taken to reintroduce elective procedures. It hosted a webinar, moderated

by STS president Joseph Dearani (Department of Cardiovascular Surgery, Mayo Clinic, Rochester, USA), on “reactivating cardiothoracic surgery programmes”.

Its global panel included speakers from Europe, South Korea, and USA. According to Domenico Pagano (Department of Cardiothoracic Surgery, University Hospital Birmingham, Birmingham, UK), the secretary general of the European Association for Cardio-Thoracic Surgery (EACTS), restarting cardiothoracic surgery depended on

individual physician on their own. The role of the heart team is more important than ever,” he explained.

Another issue raised during the webinar was testing patients for COVID-19 prior to them coming in for a procedure, with several panellists saying that all patients were tested. Tomislav Mihaljevic (Cleveland Clinic, Cleveland, USA) said that his centre had two testing pathways, with rapid testing for those with acute conditions and a longer test- time for those who were non-acute. “The longer turnaround time [for non-acute patients] is to test 48 hours in advance so that we know the result of the test by the time that they reach the hospital,” he explained. Enrico Ruffini (Department of Thoracic Surgery, University of Torino, Torino, Italy) commented that, of non-acute patients, his

Figure 1: Measures required to clear elective backlog* Will need to increase number of operating days per week

50%

Will need to increase number of operating hours per day

34%

Will need to adjust working practices to optimise efficiency

15%

Re-evaluate treatment plan and use non-interventional treatments

5%

Other

6% *

No need for extra measures

22% 0%

10%

30%

40%

50%

60%

* answers were multiple choice; respondents = 214

Source: BIBA MedTech Insights

a number of things—such as the impact of COVID in the local region and the available resources. He added: “The less the COVID has had an impact on your area, the more you can open up for elective procedures.”

In terms of which patients to bring in for a procedure, Pagano said it was “inevitable” that some patients would be disadvantaged during the pandemic because they would not receive any treatment or would receive the “second-best” treatment. “In my mind, decisions about which patients to treat should not be made by any

hospital triaged patients by phone. He stated: “In case of any possible symptom, of course, we postpone the surgery for two weeks and then we test every patient on admission.”

However, Valerie Rusch (Memorial Sloan Kettering Cancer Center, New York, USA) cautioned that the COVID-19 pandemic was not over. She said: “This infection is not about to disappear any time soon, so it is important to maintain capacity within our operating rooms to operate on COVID patients.”

ESC Congress 2020 to become a completely virtual event The European Society of Cardiology (ESC) is, for the first time in its 70-year history, to hold its annual meeting (ESC Congress) 100% online. The ESC Congress 2020 was to be held between 29 August and 1 September in Amsterdam, the Netherlands, but is now going virtual following a recent announcement from the Dutch government banning public gatherings until 1 September to prevent the spread of COVID-19.

ACCORDING TO A press release, this “cutting-edge” online event will be “extraordinary”. The press release states that the ESC is creating a digital experience “to disseminate the most exciting cardiovascular science in the most engaging formats possible—and featuring key opinion leaders from around the world”.

Features of the meeting include:

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dedicated COVID-19 track showcasing first-hand experience of top experts across the globe; late-breaking trial sessions revealing the most anticipated clinical results; novel research presented in abstracts covering all areas of cardiovascular science; and new ESC clinical practice guidelines introduced and discussed by those who wrote them.

Like the ESC, the EuroPCR organiser

(PCR) has also had to cancel its physical meeting (19–22 May, Paris, France).

According to a statement, the “sanitary and legal environment”—specifically, the current ban in France on public gatherings exceeding more than 5,000 participants—led to the cancellation.

Similar to the ESC, PCR has said it will be providing content online. It has revealed a new initiative (e-Course 2020) that is to run online from 25 June 27 June. The PCR website says that

the course “will be sharing the latest scientific news and best practice for the full benefit of patients worldwide”. The website adds the scientific programme will include online sessions and all content will be available for free for those with a My PCR account.

The pandemic has meant several medical congress organisers have not been able to host physical meetings this year. However, many of them—such as the ESC and PCR—have opted to host an event online (in some format) rather than completely cancel. The team behind the CX Symposium, which was to held in London (UK) between 21 April and 24 April, recently announced that highlights from the CX 2020 programme will be streamed in 10 LIVE sessions over five weeks between 26 May and 25 June. The CX website says: “Mark your calendars for this live digital experience, designed to deliver high-quality vascular education and featuring extensive audience participation, including polling and Techniques & Technologies edited case.”

CX 2020 LIVE 10 sessions 26 May–25 June

LIVESTREAM Tu e s d a y s a n d T h u r s d a y s 16:00–17:20 BST 11:00–12:20 EDT 17:00–18:20 CEST

Aortic Consensus

Peripheral Arterial Consensus

Venous & Lymphatic Consensus

Acute Stroke Consensus

Vascular Access Consensus

w w w. c x s y m p o s i u m . c o m

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June 2020 | Issue 57

COVID-19 around the world

How Egyptian cardiology departments are managing the pandemic Ahmed Bendary Comment & Analysis The COVID-19 pandemic is hitting the world hard. Egypt, the most populous country in the Middle East and North Africa (MENA) region, is no exception. With more than 2,500 confirmed cases and a preliminary case fatality rate of 7% (at the time of writing), the figures in Egypt are alarming, albeit with a relatively benign course compared to what is being seen in the USA and Europe. Ahmed Bendary reviews how cardiology departments in Egypt are handling the virus.

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ince SARS-Cov-2 was declared to be a public health emergency of international concern by the WHO on 3 January 2020, the Egyptian ministry of health (MOH) has promptly responded by developing a strict protocol for diagnosing and quarantining the suspected cases together with a mass media campaign to increase public awareness. Two toll-free hotlines (105 and 15335) were provided to report any suspected case to health authorities.

Moreover, a dedicated website (Egypt Cares) was launched containing all these educative materials in addition to daily updates about the current Egyptian status.

A partial curfew (from 9pm to 6am) to promote societal distancing was declared by the prime minister on 24 March 2020 and is still active till now (at the time of writing).

Patients with cardiovascular diseases

are more prone to poorer outcomes after COVID-19 infection, with mortality rates reaching up to 10.5%. Importantly, COVID-19 has been linked in some case reports with “direct” myocardial damage, and the interplay between this infection and cardiovascular sequelae remains unclear. Therefore, that cardiology departments in Egyptian hospitals have taken steps forward to protect their patients and healthcare providers amid this crisis is not surprising.

Health workers at risk; cardiology departments ready

Some healthcare providers at a few cardiac centres in Egypt have caught COVID-19 infection. Mohamed Osama, the dean of National Heart Institute (Egypt’s largest governmental cardiac centre), announced on 8 April 2020 the

temporary shutdown of the institute’s admission department (reopened now) after a nurse tested positive for COVID-19. The institute’s director said in a press release that all the institute’s facilities have been sterilised and the 16 medical workers who came in contact with the patient have tested negative for the virus. A cardiac patient and three security guards at the Magdi Yacoub Heart Foundation in Aswan governorate have also been recently diagnosed with the novel coronavirus. The foundation said in an official statement that it took

That cardiology departments in Egyptian hospitals have taken steps forward to protect their patients and healthcare providers amid this crisis is not surprising.” the required precautionary measures at the hospital since the coronavirus emerged in Egypt to ensure the safety of its healthcare workers and patients.

Ahmed Elguindy (Aswan Heart Center) pointed, in an interview with me, to their protocol with Aswan University Hospital for patients with STEMI undergoing primary PCI. Many university hospital cardiology departments have taken precautionary measures as well. At Benha University hospital cardiology department (led

by Khalid El-rabbat), all elective procedures, including non-emergent

Cotton and surgical masks may be ineffective at stopping spread of COVID cough aerosols In Annals of Internal Medicine, Sung-Han Kim (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) and colleagues report that neither surgical nor cotton masks appear to be an effective approach for preventing the dissemination of SARS-CoV-2 from the coughs of patients with COVID-19. They add that further research is needed to determine the effectiveness of cotton and surgical masks in stopping the spread of the virus from asymptomatic or noncoughing patients.

KIM ET AL NOTE that previous research has suggested that surgical masks may be equally as effective as N95 masks at preventing the dissemination of the influenza virus, so surgical masks could potentially be used as an alternative to N95 masks during the current pandemic. However, they add: “The SARS-CoV-2 pandemic has contributed to shortages of both N95 and surgical masks, and cotton masks have gained interest as a substitute.” Therefore, the aim of their study was to evaluate the effectiveness of both surgical and cotton masks in preventing the dissemination of virus particles.

The authors asked four COVID-19 patients, while

in a negative pressure isolation room, to cough five times into a petri dish while not wearing a mask. They were then asked to repeat this process while wearing a surgical mask, and then again while wearing a cotton mask (each time coughing into a different petri dish). “Mask surfaces were swabbed with aseptic Dacron swabs in the following sequence: outer surface of surgical mask, inner surface of surgical mask, outer surface of cotton mask, and inner surface of cotton mask,” Kim et al explain.

They report that the median viral loads after coughs without a mask, with a surgical mask, and with a cotton mask were 2.56 log copies/mL, 2.42 log copies/mL,

echocardiography, have been suspended.

The staff and nurses are being supplied with personal protective equipment (PPE). A dedicated fever room has been established at the hospital emergency department for triaging the acute patients upon presentation (under the supervision of expert pulmonary consultants).

Speaking with Mohamed Sobhy (ex-head of the cardiology department at Alexandria University and current director of International Cardiac Center “ICC” in Alexandria city, Egypt), he said: “We are using telehealth visits now and we are training our staff on using precautionary measure during intubation and mechanical ventilation.” His cardiac centre has not recorded any cases till now, nonetheless “we are restricting visitors of patients to only one for each,” he added.

Major cardiology bodies respond

The Egyptian Society of Cardiology (EgSC) has taken a leadership role by drafting a rapid guidance document for managing cardiac patients during the COVID-19 pandemic in Egypt. Reaching out to Kahlid Shoukry (current president of the EgSC and director of Kobry Elkobba military medical center), he said: “We are working in a close collaboration with the official health authorities to apply this protocol to all governmental hospitals.”

Other important cardiac associations in Egypt shifted to virtual platforms for the purpose of continuous medical education.

Ashraf Reda (chairman and founder of the Egyptian Association for Vascular biology and Atherosclerosis (EAVA) has recently led a webinar for increasing healthcare providers’ awareness about COVID-19 and cardiovascular diseases.

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

and 1.85 log copies/ml, respectively. Furthermore, regardless of the type of mask (surgical or cotton), all swabs on the outside of the mask tested positive for SARS-CoV-2, but most swabs on the inside did not. According to Kim et al, these findings suggest Sung-Han Kim that surgical or cotton masks do not adequately filter SARS-CoV-2 during coughs by infected patients.

The authors comment that while the size and concentrations of SARS-CoV-2 in aerosols generated through coughing are unknown, SARSCoV particles from the 2002–04 epidemic were estimated to be 0.08 to 0.014μm in diameter. They explain that a previous study found that surgical masks did not provide adequate filter performance against aerosols measuring 0.9, 2, and 3.1μm. “Assuming that SARS-CoV-2 has a similar size, surgical masks are unlikely to effectively filter this virus,” Kim et al note.

As to why there was SARS-CoV-2 on the outer surface of the masks but not the inner surface, the authors speculate that this could relate to the “aerodynamic features” of the masks.

Issue 57 | June 2020

Testing for highsensitivity cardiac troponin would be a benefit, not a hindrance during pandemic In response to a recent American College of Cardiology (ACC) review that advocated that troponin should only be measured when a diagnosis of acute myocardial infarction is being considered, Andrew R Chapman (BHF Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, Edinburgh, UK) and colleagues argue in Circulation that highsensitivity cardiac troponin “could actually be an ally in the fight against COVID-19”.

CHAPMAN ET AL NOTE that the rationale for the ACC’s recommendation to not use troponin testing unless an acute myocardial infarction is suspected is on the “basis that troponin elevation in patients with COVID-19 is likely to be multifactorial and less likely to be due to atherothrombotic coronary occlusion”.

However, commenting that circulating cardiac troponin is a marker of myocardial injury, the authors state: “Rather than encouraging avoidance of troponin testing, we must harness the unheralded engagement from the cardiovascular community due to COVID-19 to better understand the utility of this essential biomarker and to educate clinicians on its interpretation for prognosis and clinical decision making.”

COVID-19 perspectives According to Chapman et al, recent studies have indicated that troponin is elevated in one in five patients who have (confirmed) COVID-19 and that the presence of elevated troponin in COVID-19 may be associated with a higher mortality risk. COVID-19 patients with elevated troponin may also be more likely to require ventilation (non-invasive or invasive) and develop acute respiratory distress syndrome. “The observed rate of mortality was 10-fold higher in those with myocardial injury on presentation [and who had elevated troponin],” the authors report. They add: “If clinicians are reluctant to measure cardiac troponin in these patients, the consequences may be to ignore the plethora of ischaemic and non-ischaemic causes of myocardial injury related to COVID-19, which may be directly or indirectly associated with poor outcomes.”

Another benefit of troponin testing, Chapman et al say, is that it is “one of the earliest and most precise indicators of end-organ dysfunction”. “Here, cardiac troponin testing could prompt early initiation of measures to improve tissue oxygenation and perfusion,” they explain.

The authors do acknowledge testing troponin in

Cardiac troponin is the most sensitive and most widely available test to determine whether there is cardiac involvement or not. It does not tell us the mechanism of injury, but it is a good place to start.”

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COVID patients “could increase the need for cardiology consultation and downstream testing, including bedside echocardiography and angiography”. However, they comment: “The recognition of a normal or modestly elevated troponin could conversely reduce the need for cardiac imaging and minimise the risk of exposure to cardiac physiology staff. The role of further investigation must be carefully considered and based on risk to the individual performing the test and the likelihood of informing clinical management.”

Summing up their case, Chapman et al comment that “clinicians must recognise that troponin is not a test for myocardial infarction, and it never was”. They add that the “myth” that it had the ability to detect an acute atherothrombotic occlusion in a coronary artery is limiting physicians’ ability to “evaluate and triage care in critically unwell patients” and argue “we need more, rather than less, information to guide the international response to the COVID-19 patients”. They conclude: “Troponin should be considered an ally and a crucial diagnostic and prognostic aid in what will become even more challenging times.”

Study author Nicholas Mills (BHF Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, Edinburgh, UK), who is an interventional cardiologist and a British Heart Foundation (BHF) funded professor of cardiology, said: “Cardiologists around the world are having to rapidly learn how to assess patients with COVID-19, either because they are being drafted into the general medical service or because these patients are also presenting directly to the coronary care unit with cardiac complications of the condition. Cardiac troponin is the most sensitive and most widely available test to determine whether there is cardiac involvement or not. It does not tell us the mechanism of injury, but it is a good place to start and can help inform the triage of patients to critical care, guide the use of supportive treatments, and facilitate targeted cardiac investigations in those most likely to benefit.”

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June 2020 | Issue 57

ACC.20/WCC Virtual

Aspirin plus rivaroxaban significantly lowers adverse events in peripheral arterial revascularisation Treatment with aspirin plus rivaroxaban following lower extremity revascularisation in patients with peripheral arterial disease leads to a 15% reduction in the risk of major adverse limb and cardiovascular events when compared with aspirin alone.

THE VOYAGER PAD study was presented at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual; 28–30 March, Central Time) and simultaneously published in the New England Journal of Medicine (NEJM). It found that a twice daily dose of 2.5mg rivaroxaban plus low dose aspirin is associated with significantly lower incidence of the composite primary efficacy outcome of acute limb ischaemia, major vascular amputation, myocardial infarction, ischaemic stroke, or death from cardiovascular causes than aspirin alone.

On the principal safety outcome of Thrombolysis in Myocardial Infarction (TIMI) major bleeding there was no significant difference between the therapies. However, rivaroxaban plus aspirin was associated with a significantly higher incidence for the secondary safety outcome of major bleeding.

Marc P Bonaca (University of

Colorado Anschutz School of Medicine, Aurora, USA) outlined the findings as part of a late-breaking session. He explained that the risks of major adverse limb and cardiovascular events are high in patients with peripheral arterial disease who require lower extremity revascularisation, but there is uncertainty about how effective and safe rivaroxaban is in this context. “In spite of this risk, there are no proven antithrombotic strategies to reduce the risk of limb and cardiovascular outcomes after revascularisation. VOYAGER PAD was designed to address this gap,” he said.

The double blind trial randomised 6,564 patients with peripheral arterial disease who had undergone revascularisation to receive either rivaroxaban 2.5mg twice daily plus aspirin (n=3,286) or placebo plus aspirin (n=3,278). The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and 584 patients in the placebo group. Three-year Kaplan-

Meier estimates of the the rivaroxaban group and incidence were 17.3% in in 17 patients in the placebo the rivaroxaban arm and group (hazard ratio, 0.78; 19.9% in the placebo arm 95% CI, 0.38 to 1.61). Fatal (p=0.009). bleeding occurred in six The incidences of the first patients in each group. five secondary outcomes in The second safety the testing hierarchy were outcome of major bleeding all significantly lower in the occurred in 140 patients rivaroxaban group than in on rivaroxaban versus 100 Marc P Bonaca the placebo group, including patients in the placebo the incidence of unplanned group (5.94% and 4.06%, index limb revascularisation for recurrent respectively; p=0.007). ischaemia (p=0.03). All-cause mortality Bonaca told the online audience: “To was not lower in the rivaroxaban put these results into context, in patients group than in the placebo group with peripheral arterial disease requiring (p=0.34). Therefore, the researchers revascularisation, for 10,000 patients wrote in the NEJM: “In accordance treated for one year with rivaroxaban with the prespecified hierarchical 2.5mg twice daily with aspirin versus testing procedure, the assessment of aspirin alone there would be the the last secondary outcome (venous prevention of 181 first ischaemic events thromboembolism) was considered with the components of [the primary exploratory.” efficacy outcome events]. The cost of this There was no heterogeneity in the would be 29 major bleeds without any efficacy of rivaroxaban plus aspirin excess in intracranial haemorrhage or as compared with aspirin alone for fatal bleeding.” the primary outcome across major Concluding, he said: “In symptomatic subgroups, including those based on peripheral arterial disease after age, sex, and cardiovascular risk factors. revascularisation […] in this population Similarly, there was no heterogeneity on and in this setting, rivaroxaban 2.5mg the basis of qualifying symptoms, type twice daily with aspirin compared to of intervention, ankle–brachial index at aspirin alone significantly reduces this screening, or the presence of critical limb risk. The benefits appear early and ischaemia at index revascularisation. continued over time, with consistent TIMI major bleeding occurred in benefit across subgroups including 62 (2.65%) patients in the rivaroxaban those with critical limb ischaemia and group and 44 (1.87%) patients in the broad benefits included reductions placebo group (p=0.07.). Intracranial in the need for unplanned index limb haemorrhage occurred in 13 patients in revascularisation.”

Renal denervation beats sham control to safely lower blood pressure in patients with untreated hypertension

renal denervation (166) or a sham procedure (165). At the end of three months, the primary efficacy endpoint was the change in average 24-hour systolic blood pressure, adjusted for systolic blood pressure at study entry. The secondary efficacy endpoint was the change in average blood pressure measured in the doctor’s office at three months, adjusted for office blood pressure at study entry. Major adverse safety events were also assessed at three months, including rates of death, stroke, changes in kidney function, or any injury to the arteries surrounding the kidney.

Three months after undergoing renal denervation, patients with untreated high blood For the primary and secondary efficacy endpoints, pressure had statistically significant reductions in average blood pressure over 24 hours the difference between groups was –3.9mmHg for compared with patients who underwent a sham procedure, according to results from the 24-hour systolic blood pressure and –6.5mmHg for SPYRAL-HTN OFF MED pivotal trial presented at the ACC.20/WCC Virtual (28–30 March, office systolic blood pressure, both favouring the renal Central Time) denervation group, with a 99.9% probability that renal denervation was superior to the sham lso, these patients experienced no major devicereduced,” Böhm adds. procedure. or procedure-related safety events through three Böhm et al report in The Lancet: No deaths, strokes, or changes in months, data from the international, prospective, “Catheter-based renal denervation has kidney function occurred during the single-blinded, sham-controlled trial that enrolled at significantly reduced blood pressure in three-month follow-up period, Böhm 46 global study sites show. The findings were also previous studies. Following a positive says. He adds that these results may not published in The Lancet. pilot trial, the SPYRAL HTN-OFF MED demonstrate the total decrease in blood The SPYRAL HTN-OFF MED pivotal trial builds (SPYRAL Pivotal) trial was designed to pressure achieved with renal denervation upon a previous pilot study and was powered to evaluate assess the efficacy of renal denervation given the short follow-up period due to the efficacy of catheter-based renal denervation in the in the absence of antihypertensive ethical and safety concerns that patients absence of medications. “These results show that renal medications.” needed to be restarted on antihypertensive denervation offers an effective alternative approach to The study enrolled 331 patients whose medications. traditional medications that require patient adherence average systolic blood pressure over Michael Böhm “This study establishes renal for reducing blood pressure,” Michael Böhm (Saarland 24 hours was between 140mmHg and denervation as an additional option University Medical Center, Hamburg, Germany), lead 170mmHg. Their average age was 53 years, and 67% beyond exercise or lifestyle modification for patients author of the study, commented in an American College were men. Most were obese, with an average body mass with high blood pressure who are unwilling to take or of Cardiology (ACC) press release. index of 31. Around 5% also had type 2 diabetes. A cannot tolerate medication,” Böhm said, adding that “Furthermore, the findings show that renal condition of enrolment was that patients either had not the study results will be included in an application for denervation lowers blood pressure not just during the been taking any blood pressure-reducing medications or US Food and Drug Administration (FDA) approval of day but also through the night and [in the] early morning had discontinued those medications at least three weeks the renal denervation device used in the trial for the periods when risk is highest for [adverse] clinical events before their blood pressure was measured at study entry. treatment of patients who are not taking blood pressureand the effect of some medications on blood pressure is Patients were randomly assigned to receive either reducing medication.

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June 2020 | Issue 57

ACC.20/WCC Virtual

Genotype-guided therapy after PCI does not hit study target During the Virtual American College of Cardiology/World Congress of Cardiology's virtual scientific sessions (ACC.20/WCC Virtual, 8–30 March, Central Time), Naveen L Pereira (Mayo Clinic, Rochester, USA) said that using genetic testing to guide antiplatelet therapy after percutaneous coronary intervention (PCI) does not reduce the 12-month incidence of ischaemic events by 50%—the prespecified goal of the TAILOR PCI (Tailored antiplatelet initiation to lessen outcomes due to decreased clopidogrel response after PCI) trial— compared with usual therapy (no genetic testing). However, genotype-guided therapy was associated with a 34% reduction at one year.

SPEAKING VIA VIDEO, Pereira reported that clopidogrel, following a PCI procedure, was “the most widely prescribed P2Y12 inhibitor” but added its effectiveness may be reduced in patients who are CYP2C19 loss of function carriers. He explained that patients with this genotype are not able to fully metabolise clopidogrel, which potentially means they may not receive any benefit from the drug and, thus, may be at increased risk of ischaemic events.

Furthermore, Pereira observed that up to 30% of people—rising to 50% in people of Asian heritage—in the USA may have this genotype and, therefore, may be suitable candidates for an alternative antiplatelet agent (such ticagrelor).

Therefore, the aim of TAILOR PCI was to provide an answer to the question: “Does identifying loss of function of CYP2C19 carriers and altering P2Y12 inhibitor therapy based on CYP2C19 genotype reduce ischaemic outcomes in the first 12 months after PCI?” Patients scheduled for PCI were randomised to undergo genotype-guided therapy or conventional therapy. In the genotype group (2,641), those who tested positive for CYP2C19 *2/3* carrier were prescribed ticagrelor after PCI, whereas those tested

negatively were prescribed clopidogrel. All patients in the conventional therapy group (2,635) were prescribed clopidogrel. At 12 months, both groups underwent TaqMan genotyping. Pereira et al then compared (in the primary analysis cohort) outcomes of CYP2C19 *2/3* carrier patients (903) in the genotype-guided therapy group with those in the conventional therapy group (946).

Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy.”

CABG shows 10-year benefit over PCI in left main patients with high SYNTAX score Extended 10-year follow-up has demonstrated that in patients with a high SYNTAX score undergoing left main coronary artery revascularisation, there is a clear prognostic benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). PCI was associated with similar mortality and serious composite outcomes in patients with low to intermediate SYNTAX scores.

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he findings from the MAIN COMPARE registry (Tenyear outcomes of stents versus coronary-artery bypass grafting for left main coronary artery disease) were published in JACC: Cardiovascular Interventions, by Yong-Hoon Yoon (Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, South Korea) et al.

They say: “The adjusted 10year rates of mortality and serious composite outcome were similar after PCI and CABG in patients with low to intermediate anatomic complexity measured by baseline SYNTAX score.

However, CABG showed a clear 10-year benefit over PCI in patients with high anatomic complexity. This study also demonstrates that the SYNTAX score has a significant correlation with mortality and major adverse events in patients who underwent PCI but not in those who

underwent CABG.” Patients with baseline SYNTAX score measurements in the MAIN COMPARE registry were analysed and the 10year rates of all-cause mortality, the composite of death, Q-wave myocardial infarction, or stroke, and target vessel revascularisation after PCI or CABG were compared according to baseline SYNTAX score.

In all 2,240 patients with unprotected left main disease were enrolled in the registry between 2000 and 2006. The SYNTAX score was not available for 660 patients, leaving 1,580 patients for analysis in this study. Of these, 897 patients (56.8%) were categorised into the low- to intermediate SYNTAX score group (34.6% with low score of ≤22, and 22.2% with intermediate score of 23–32); 683 (43.2%) patients were categorised into the high SYNTAX score (≥33) group.

In 897 patients with low to intermediate

The primary endpoint of the study was the composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and severe recurrent ischaemia within one year of the index PCI. Pereira commented that, in the statistical analysis, he and his colleagues assumed an event rate of 6% in the conventional therapy (clopidogrel) patients and an event rate of 6% in the genotype-guided therapy (ticagrelor) group “with a minimum detectable hazard ratio of 0.5 with 85% power”.

At one year, the primary endpoint occurred in 4% of patients in the genotype-guided therapy group versus 5.9% in the conventional therapy group. This meant that genotype-guided therapy was associated with a non-significant 34% relative risk reduction in ischaemic events—meaning that TAILOR PCI did not meet its primary endpoint (which hypothesised that there would be a 50% reduction). However, a prespecified sensitivity analysis showed a statistically significant 40% reduction in the total number of events per patient receiving genotype-guided treatment compared with patients who received standard treatment. Additionally, a post-hoc analysis suggested that the benefit of genotyope-guided therapy is greatest within the first three months, with a nearly 80% reduction in ischaemic events compared with conventional therapy. The rates of bleeding were similar between groups.

Pereira commented: “Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately onethird fewer adverse events in the patients who received genetically guided treatment compared with those who did not.”

He added that, as the first three months after PCI is when patients are most at risk of ischaemic events, the observed 80% reduction “suggests that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period.”

score, 633 (71%) underwent PCI, and effect of contemporary PCI and CABG in 264 (29%) underwent CABG. Among patients with left main disease according 683 patients with high score, 186 (27%) to anatomic complexity measured by underwent PCI, and 497 (73%) underwent SYNTAX score”.

CABG. In an accompany comment, Bernard The researchers found that in patients Chevalier (Institut Cardiovasculaire Paris with low to intermediate SYNTAX Sud, Massy, France) says the investigators score, the adjusted 10-year risks for should be congratulated, particularly death and serious composite outcome “considering the paucity of follow-up data were similar between the PCI group and beyond five years”. However, he suggests the CABG group. However, in patients that the “central role in the decisionwith high SYNTAX score, PCI was making process” played by angiographic associated with a higher risk for death evaluation by means of the SYNATX (p=0.048) and serious composite outcome score is “outdated”, describing it as only (p=0.123) compared to CABG. In each one of the criteria to be considered by the revascularisation group, conventional heart team. tertiles of SYNTAX score had Corresponding author Duka differential prognostic impact Woo Park (University of Ulsan on 10-year clinical outcomes College of Medicine 88, Seoul, in the PCI arm, but not in the South Korea) also underlined CABG arm. the need for an overview. He Limitations were that the told Cardiovascular News: study was observational “The SYNTAX score is not and should be considered Duk-Woo Park sole factor used to decide hypothetical and hypothesis optimal revascularisaton. generating only, and the findings are Therefore, further factors such as clinical, subject to selection bias. Additionally, anatomical, and/or physician or patient 30% of the total study population was preferences should be considered in heartexcluded because baseline SYNTAX team discussions.” score measurement was not available, and And he stressed: “Our study might have clinical outcomes of bare metal stents or novelty to evaluate the SYNTAX score in first-generation drug eluting stents were left main revascularisation during longevaluated in the PCI arm. Therefore, say term follow-up beyond 10 years, data Yoon et al, further evaluation through for which are still limited. Assessment extended follow-up of the EXCEL and of the discriminative value of SYNTAX NOBLE trials using contemporary score was limited in the recent EXCEL generation DES “may provide more and NOBLE trials, and therefore, further compelling evidence on the long-term study is required.”

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June 2020 | Issue 57

Interview

Profile

Vinod H Thourani Mitral and tricuspid valve technologies, aortic valve replacement, and the value of the heart team are among the issues that Vinod Thourani (Marcus Valve Center, Piedmont Heart Institute, Atlanta, USA) tackles, as he reflects on his career for Cardiovascular News and addresses key areas for future research.

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

My father was a non-invasive cardiologist in a small town in rural South Carolina for more than 30 years, so my interest in the heart started when I was about 10 years of age; I would shadow my dad in his office and the local hospital, and observe him during his clinics, on rounds in the hospital, performing electrocardiograms (ECGs) in the office, and performing cardiac echocardiograms. I remember thumbing through his textbook The Heart by J Willlis Hurst, at that time. This led me to become interested in cardiology.

I went to Emory University School of Medicine (where Hurst was based) for that reason in 1990. After gross anatomy in my first year of medical school, I then switched from cardiology to cardiac surgery. My interest in transcatheter or percutaneous valve technology developed during my 11 years of residency. I wanted to be able to provide a patient with the option of open, minimally invasive, or transcatheter aortic and mitral valve therapies. This would allow me to have the most equipoise in my approach to the management of these complex patients. In addition, when I started my practice in 2005, there were very few surgeons in the country who specialised specifically in valvular heart disease.

Who were the biggest influences on your early career?

My dad was a major influence, allowing me to pursue cardiovascular medicine. In medical school, David V Feliciano, a well-known trauma surgeon, was my earliest clinical mentor. He instilled in me the pursuit of comprehensive patient care, from preoperative management, operational efficiency, to attentive postoperative care. He also had a superb command of anatomy and an attention to detail that I still attempt to emulate to this day. Moreover, Feliciano instilled in me the importance of the highest ethical levels of performing clinical research.

I have been fortunate that I have had phenomenal, equally important, cardiac surgical and cardiology mentors. Robert Guyton, whom I first met as a second year medical student at Emory University, was instrumental in my development as a clinical cardiac surgeon, and led my pursuit in academic affairs. During my 15 years of practice, Michael Mack, a surgeon from Dallas, Texas, and Joseph E Bavaria, from the University of Pennsylvania, have been my confidants and mentors in the art of medicine and surgery, and in my continued research endeavours. It would be remiss not to mention Martin Leon, an interventional cardiologist from Columbia University, who has mentored me in my continued pursuit for research excellence. He has encouraged me to aim high in terms of what we can do as clinicians, particularly in research.

His level of acumen and persistence for the highest level of investigation in the performance of sophisticated research trials remains one of my academic goals.

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

Without a doubt, it is the management of severe, symptomatic aortic stenosis with the advent of

transcatheter aortic valve implantation (TAVI). I performed my first TAVI in 2006 with the team at Emory University, including interventional cardiologists Vasilis Babaliaros and Peter Block, and cardiac surgeon Robert Guyton. The technology was in its infancy then, but it has now become one of the most disruptive technologies of our time. It has allowed us to advance the treatment of aortic stenosis to multitudes of patients that had no other option.

What are your current research interests?

I am interested in continuing the pursuit for new TAVI technologies, but also in innovating pathways for mitral and tricuspid valve technologies. I was fortunate to come back to Atlanta in October 2019. With our current team at the Marcus Valve Center in the Piedmont Heart Institute in Atlanta, Georgia—interventionalists Chris Meduri, Vivek Rajagopal, and Pradeep Yadav, and surgeons W Morris Brown, James Kauten, and Federico Milla—I believe we are well on our way to making major advancements in these technologies. Furthermore, our echocardiography and computed tomography imaging team is world class, including Mani Vannan, Sara Mobasseri, and Venkat Polsani among others. I am very honoured to be part of this incredible and worldclass team.

I am spending an enormous time on the study of new devices in the mitral and tricuspid valve space, which may include transcatheter and minimally invasive techniques. I also continue to focus on decreasing morbidities in TAVI and surgical aortic valve replacement procedures.

It is quite ironic that it takes a pandemic for us to slow down and smell the roses.�

What do you feel has been your biggest contribution to interventional cardiology?

My biggest contribution is that we have proven that surgeons and cardiologists can work seamlessly together as a heart team: that barriers that once existed can be torn down to lead to a team collaboration that produces exemplary care for patients. We have to be careful not to get lost in the technology, but to ensure that we concentrate on the highest level for quality patient care that we can provide. This can be on a local level at the hospital, but also on a national level with our respective societies like the American College of Cardiology (ACC), American Heart Association (AHA), Society of Thoracic Surgeons (STS), and the American Association for Thoracic Surgery (AATS).

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

In the management of aortic valve disease (both aortic stenosis and regurgitation), I believe that we still are unsure how to predict who will or will not do well.

The idea of utility and futility needs some more precision. Also, the area of treatment of moderate aortic stenosis. In the mitral and tricuspid space, I believe we have much more to learn about which is the optimal therapy. The complexity and toolbox needed for the management of these valves is highly complex, and I believe we are just scratching the surface for those patients. Lastly, future research on the untreated population of valvular surgery is in its infancy and will be important to ascertain.

Now that TAVI can be used for lowrisk patients, what factors should be considered when deciding between TAVI and surgery?

I think anatomical considerations are very important.

In the low-risk trials there were certain patient populations that were excluded, including those who were very young (and may need a mechanical valve), those with bicuspid aortic valves, and those with

Issue 57 | June 2020

Interview

13

Fact File

Current appointment

October 2019–present: Bernie Marcus chair of the Department of Cardiovascular Surgery, Piedmont Healthcare and the Marcus Heart Valve Center, Atlanta, USA

Past appointments

August 2017–October 2019: Chairman, Department of Cardiac Surgery, MedStar Health (Washington Hospital Center and Union Memorial Baltimore Hospital Programs), Washington, DC and Baltimore, USA; Professor of Surgery, Georgetown University School of Medicine, Washington, DC, USA August 2017–October 2019: Executive Committee, MedStar Heart and Vascular Institute, Washington, DC, USA August 2017–October 2019: Medial Board and Perioperative Goverance Council, MedStar Washington Hospital Center, Washington, DC, USA 2005–2017: Assistant, Associate, and then Professor of Surgery and Medicine, Emory University School of Medicine, Atlanta, USA

Selected postgraduate training

severe left ventricular outflow calcium, to name a few.

I think one of the most important is that it should be a heart team decision that is presented to the patient.

What impact has the COVID-19 pandemic had on your practice?

The pandemic has had a major effect on our personal and professional lives. While I am profoundly saddened by the countless of deaths, it has allowed me to appreciate my close friends and family even more.

It is quite ironic that it takes a pandemic for us to slow down and smell the roses. I have been keeping up with my patients who are still of need of heart surgery and will continue to advocate the right time for their interventions.

What are the implications of COVID-19 for the management of patients with structural heart disease?

The pandemic has definitely affected those with structural heart disease. With most of the country not performing elective procedures for the past four to six weeks [at time of writing], that has left many patients at home with severe valvular disease and the resultant shortness of breath. This has been in response of the need to protect these patients from coming to the hospital for the risk of infection, but also to allow enough personal protection equipment for those infected with the virus admitted in the hospital.

What are your hobbies and interests outside of medicine?

I love spending time with my family, playing tennis, watching moves, and anything to do with the beach [pre social distancing]. I also love to travel internationally to experience different cultures and point-of-views, it allows me to think out of the box.

2006 (two months): Transcatheter and Minimally Invasive Valve Fellowship, Fuwai Hospital, Beijing, China and Leipzig Heart Center, Leipzig, Germany March 2003 (two weeks): Visiting cardiothoracic surgery fellow, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA March 2003 (two weeks): Visiting cardiothoracic surgery fellow, Toronto General Hospital, Toronto, Canada 2004–2005: Administrative chief resident, Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, USA 2002–2004: Resident in Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, USA

Medical education

1990–1994: Doctor of Medicine, Emory University School of Medicine, Atlanta, USA 1986–1990: Bachelor of Science (Biology), Furman University, Greenville, USA

Selected societies

2019–2020: President, Southern Thoracic Surgical Association 2020–2021: President, Heart Valve Society

June 2020 | Issue 57

14

Structural Heart Interventions High success rate for TAVI in bicuspid aortic stenosis patients

Transcatheter aortic valve implantation (TAVI) procedures had a high rate of success and low risk of death or disabling stroke at 30 days in patients with a bicuspid aortic valve, according to research presented by Basel Ramlawi (Valley Health, Winchester, USA) during a late-breaking clinical trial session on day two of the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/ WCC Virtual; 28–30 March, Central Time).

T

hese were the conclusions of the Evolut Low Risk Bicuspid Study, which evaluated the safety and efficacy of the Evolut (Medtronic) TAVI system in bicuspid aortic valve patients at low surgical risk for early mortality. “These findings point to a potentially less invasive treatment for patients who otherwise would undergo open heart surgery due to their anatomical valve structure,” said Ramlawi, a co-primary investigator of the study who presented the data at the meeting. “We feel confident that these primary early outcomes provide additional evidence that the Evolut TAVI platform is a suitable treatment option for patients with bicuspid valves who have previously been left out of TAVI trials.”

Bicuspid aortic valve disease is an abnormality of the aortic valve resulting in the patient having two functional valve leaflets instead of the more common three leaflets (tricuspid). Often bicuspid patients are younger than tricuspid patients (median age of 70 in the study).

Ramlawi noted that TAVI is the standard of care in patients at intermediate or higher risk of early surgical mortality. The procedure has recently been shown to be non-inferior to surgery in low-risk patients, Ramlawi said but adding that the pivotal trials have excluded patients with bicuspid aortic valves, “due to anatomic issues, as well as technical concerns about implantation”.

The prospective, multicentre study involved 150 patients with severe bicuspid aortic stenosis at low risk of 30-day mortality who underwent TAVI at 25 centres across the USA. Patients were treated with the Evolut R (23, 26, 29, 34mm) or the Evolut PRO (23, 26, 29mm) self-expanding, supra-annular, repositionable valves. Those included in the study had a bicuspid aortic valve anatomy confirmed by multislice computed tomography. Patients under

TAVI with a supraannular, selfexpanding valve in low risk bicuspid patients achieved excellent early results, consistent with annular sizing, with 95% device success, low mortality and stroke.”

the age of 60 years were excluded from the study, as were those with significant ascending aortopathy requiring surgical repair, or an ascending aorta diameter of less than 4.5cm.

Thirty-day follow-up was completed in 147 of the Basel Ramlawi participating patients. The primary safety endpoint assessed was death or disabling stroke at 30 days, and the primary efficacy endpoint comprised device success involving the absence of procedural death and correct positioning of one valve in the proper location, as well as absence of moderate or severe total aortic regurgitation at 18 hours to seven days.

The study showed low rates of all-cause mortality or stroke at 30 days (1.3%) with a low rate of serious procedural complications, and no annular rupture or aortic dissection. .

Results from the study showed positive outcomes at 30 days, with a 95.3% device success rate and a low rate of serious procedural complications including no annular ruptures or aortic dissection. In addition, results from the study showed: Low rate of all-cause mortality (0.7%) Low rate of disabling stroke (0.7%) Exceptional haemodynamics with low mean AV gradients (7.6±3.7mmHg), and large effective orifice area (2.3±0.7cm2) No incidence of moderate or severe paravalvular leak Low rate of major vascular complications (1.3%) High utilisation of the Evolut 34 mm (41.6% of patients in the study were implanted with this larger valve size) New pacemaker rate (15.1%) was lower than in the Evolut Low Risk Trial.

Summarising his findings, Ramlawi said: “TAVI with a supra-annular, self-expanding valve in low risk bicuspid patients achieved excellent early results, consistent with annular sizing, with 95% device success, low mortality and stroke at 30 days of 1.3%, and low risk of aortic insufficiency with no moderate or severe aortic insufficiency in this population.”

Ramlawi said that the study was limited by the fact that all patients received TAVI, rather than providing a randomised comparison between TAVI and open-heart surgery. In addition, the study was conducted in medical centres that perform a high volume of TAVI procedures, and it is unclear whether a similarly high success rate would be achievable in centres with less TAVI experience.

Positive 12-month results for next-generation Watchman FLX

Boston Scientific has announced positive 12-month results from the PINNACLE FLX clinical trial assessing the safety and efficacy of the next-generation Watchman FLX left atrial appendage closure device for patients with non-valvular atrial fibrillation. Presented as a late-breaking clinical trial at HRS 2020 Science (a virtual event), the study evaluated performance of the device as an alternative to oral anticoagulation therapy, including nonvitamin K antagonist oral anticoagulants, for stroke risk reduction.

THE PROSPECTIVE, NON-RANDOMISED PINNACLE FLX trial included 400 patients in the USA with non-valvular atrial fibrillation who were eligible for anticoagulation therapy to reduce the risk of stroke but had an appropriate rationale to seek a non-pharmaceutical alternative. The trial met its primary safety endpoint—defined as occurrence of a major procedure-related complication within seven days following the procedure or time of hospital discharge, whichever was later—with a low adverse event rate of 0.5%. The study also met its primary effectiveness endpoint, with data demonstrating a 100% rate of effective left atrial appendage closure at 12 months’ post-procedure with peridevice flow <5mm.

Data from the trial also demonstrated an implant success rate of 98.8% and that no patients experienced peri-procedural death, device embolisation or pericardial effusion requiring cardiac surgery, all of which is favourable in the context of previous clinical studies according to a press release.

Additionally, 96.2% of patients were able to discontinue oral anticoagulation following their 45-day follow up. Secondary endpoints from the PINNACLE FLX study, including the occurrence of ischaemic stroke or systemic embolism, will be reported after 24 months of patient follow-up.

Shephal Doshi (Providence St John’s Health Center, Santa Monica, USA), the study’s co-principal investigator, comments: “We believe the next-generation Watchman FLX technology contributed to the excellent overall clinical performance seen in this study, notably the very low rate of safety events and high rate of effective closure. In fact, we saw that 90% of patients showed absolutely no detectable leakage around the device at their 12-month follow up, which compares favourably to the rates of peri-device flow observed in the PROTECT-AF and PREVAIL trials with the predicate Watchman device and may translate into improved long-term clinical outcomes.”

Boston Scientific plans to further evaluate the Watchman FLX device for patients with non-valvular atrial fibrillation via continued enrolment in the ongoing OPTION trial— comparing the device to oral anticoagulants in patients who also undergo a cardiac ablation procedure—as well as in the CHAMPION-AF clinical trial, which will study a broader anticoagulant-eligible patient population to evaluate the device against non-oral anticoagulation for embolic stroke prevention.

Ian Meredith, global chief medical officer, Boston Scientific, comments: “We are pleased with the performance exhibited by the next-generation Watchman FLX device in the PINNACLE FLX study, which mirrors positive European physician experience to date.”

Structural Heart Interventions

Issue 57 | May June2020 2020

Approval of Tendyne TMVI device means physicians now have a portfolio of options for treating mitral regurgitation Abbott made history in January when it became the first company in the world to receive market approval for a transcatheter mitral valve implantation (TMVI) device. Its Tendyne system now has a CE-mark indication for the management of patients with mitral regurgitation who cannot undergo mitral valve surgery or percutaneous edge-to-edge repair (MitraClip). TMVI devices have been in the pipeline for years but, until now, none have been commercially available. In this interview, Nicolas Dumonteil (Clinique Pasteur, Toulouse, France) talks to Cardiovascular News about what the approval of Tendyne means for the management of patients with mitral regurgitation.

Why do you think it has taken so long to get a TMVI device on to the market?

Despite being one of the most common heart valve conditions, mitral valve disease is complex and patient anatomy varies. The mitral valve’s dimensions and features require bigger valves with a more involved design than those for the aortic valve, for example. Therefore, ensuring the proper concept, validating it in preclinical studies, and then completing the initial feasibility study for CE mark approval took some time. Bringing a device to market that was safe and efficient in reducing mitral regurgitation, which Tendyne achieves with some unique features, was important.

By having a device such as Tendyne, which is fully repositionable and retrievable during implantation, physicians have the best possible treatment options for their patients requiring a valve repair/replacement. The CE mark approval means that physicians no longer have to ask whether they

can treat a patient with severe mitral regurgitation but, instead, can now consider how best to treat them.

What do you think is different about the design of Tendyne that meant it did not encounter the challenges seen with other TMVI valves that have not made it to market?

The device has an innovative (and unique) anchoring and fixation system with a tether and apical pad, which can be adapted to a broad range of patient anatomies. The quality of the delivery catheter supports the simplicity of the procedure—making it safe, reliable and reproducible.

Left ventricular outflow tract obstruction is a feared complication with TMVI. How can the risk of this be reduced?

Although left ventricular outflow

Antiplatelet drugs increase risk for TAVI patients with atrial fibrillation In the POPULAR TAVI trial, patients with atrial fibrillation who took oral anticoagulants alone after undergoing transcatheter aortic valve implantation (TAVI) had a lower rate of bleeding complications without an increased risk of clotting-related complications, compared to patients who took antiplatelet medication in addition to oral anticoagulants.

THE NEW STUDY was presented at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual; 28–30 March, Central Time). Lead author Vincent J Nijenhuis (St. Antonius Hospital, Nieuwegein, the Netherlands) gave the presentation. The study was simultaneously published in the New England Journal of Medicine.

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tract obstruction is a feared device, and we will continue complication, its determinants to assess Tendyne as an option are quite well understood. to treat patients experiencing Therefore, in almost all the debilitating symptoms cases, it is anticipated rather of mitral regurgitation. We than noticed after valve are committed to providing implantation. And if there is a a rigorous evaluation that high risk of this complication, Nicolas Dumonteil will hopefully demonstrate we can cancel the procedure. the safety and efficiency of However, the question is how can the Tendyne in a larger population risk of left ventricular outflow tract obstruction be reduced to expand the In your view, how does TMVI range of anatomical feasibility for TMVI? sit alongside transcatheter The risk will be reduced with prosthesis mitral valve repair? Is it frame design refinement and an even an alternative therapy or a deeper understanding of anticipation of complementary one? this issue during screening (based on Both TMVI and transcatheter mitral valve computed tomography). repair have a successful track record and a place, but the best treatment option What safety and efficacy data ultimately depends on the condition of the are available for Tendyne? patient and their anatomy. While some Clinical data from the Tendyne global patients may qualify for transcatheter early feasibility study demonstrated repair, others may need a full excellent procedural safety. A key replacement. TMVI has to be understood finding from the study was that 98.9% as part of a portfolio of therapies in the of Tendyne patients experienced mitral hands of physicians. regurgitation elimination at discharge, which was sustained through one year in Do you think TMVI has the this patient population. potential to develop in the

What further safety and efficacy data are needed for the valve?

This valve was evaluated in the context of the aforementioned study in highly selected centres, with conservative inclusion/exclusion criteria. We are now focusing on a post-approval study of the

same way that TAVI has—that is, expand into different risk populations until it becomes a standard therapy for all?

Yes, I hope it will follow the same pathway, requiring of course a robust and rigorous scientific validation with controlled trials comparing the device with other therapies.

I hope TMVI will follow the same pathway as TAVI, requiring of course a robust and rigorous scientific validation with controlled trials comparing the device with other therapies.”

The study is the first randomised trial designed to assess the safety of oral anticoagulants alone, as compared to using antiplatelet drugs alongside oral anticoagulants for managing TAVI complication risks in these patients.

Nijenhuis said: “This study helps physicians to better understand the risks of adding antiplatelet therapy to oral anticoagulants—namely, that doing so leads to more bleeding without reducing the rate of ischaemic events. I think once physicians are aware of this, they will not treat patients undergoing TAVI so aggressively, leading to better outcomes.”

In focusing on patients with atrial fibrillation, the trial sought to address how best to balance the risk of clots against the increased risk of bleeding that comes with any anticoagulant or antiplatelet therapy.

Researchers enrolled 313 patients with atrial fibrillation, undergoing TAVI at 17 sites across Europe.

Half were assigned to take oral anticoagulants alone and half took the antiplatelet drug clopidogrel for three months after TAVI in addition to oral anticoagulants.

At 12 months, those taking oral anticoagulants alone were significantly less likely to have bleeding complications than those who took oral anticoagulants plus clopidogrel, meeting the trial’s prespecified primary endpoint. The first primary endpoint, all bleeding as assessed with the Valve Academic Research

Consortium (VARC) definition, occurred in 21.7% of those receiving only oral anticoagulants and 34.6% of those receiving clopidogrel. The second primary endpoint, non-procedural bleeding as assessed with the Bleeding Academic Research Consortium (BARC) criteria, occurred in 21.7% of those receiving only oral anticoagulants and 34% of those receiving clopidogrel.

This reflects a 43% reduction in the rate of bleeding complications among those taking oral anticoagulants alone.

In a secondary analysis, patients taking oral anticoagulants alone did not show an increased risk of clotting-related complications, meeting the trial’s prespecified secondary endpoint for non-inferiority. A composite of cardiovascular death, ischaemic stroke and heart attack occurred in 13.4% of those receiving only oral anticoagulants, and 17.3% of those receiving clopidogrel, while a composite of those outcomes plus non-procedural bleeding occurred in 31.2% of patients receiving only oral anticoagulants and 45.5% of patients receiving clopidogrel.

“The results suggest it would be beneficial to not give clopidogrel—in fact, it is safer because it does not lead to as many bleeding events,” Nijenhuis comments.

The researchers are now assessing antiplatelet management in patients without atrial fibrillation in a separate cohort of the ongoing POPULAR TAVI study.

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June 2020 | Issue 57

MedTech Insights

Source: BIBA MedTech Insights Mitral and Tricuspid Monitor

Newer generations of MitraClip associated with greater reduction in mitral regurgitation than previous version At the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual; 28–30 March, Central Time), D Scott Lim (University of Virginia, Charlottesville, USA) reported that mitral regurgitation ≤1+ was achieved more frequently with MitraClipNTR or with MitraClipXTR (both Abbott) than previously observed with the first-generation MitraClip device. He added that MitraClipXTR was associated with greater reduction in mitral regurgitation than was MitraClipNTR in patients with more complex anatomies.

LIM SAID THAT no core-lab adjudicated data on patients with primary mitral regurgitation had been reported since the EVEREST II trials, which evaluated the first-generation MitraClip device. He added that, over the last four years, four new generations of MitraClip have come onto the market: MitraClipNTR (2016), MitraClipNTX (2018), MitraClipXTR (2018), and MitraClipG4 (2019).

Therefore, Lim commented, the primary objective of the present study, was to report on “real-world, echo core lab and clinical events committee adjudicated outcomes in patients with significant primary mitral regurgitation treated with next-generation NTR and XTR systems in the 1,000 plus patient global EXPAND study”. Lim added that, compared with the first-generation device, MitraNTR has an improved delivery system while MitraClipXTR had “longer arms with an improved delivery catheter system”.

In the study, Lim et al reviewed data for 422 patients with primary or mixed mitral regurgitation aetiology.

Of patients with primary mitral regurgitation, 46.2% received the MitraClipXTR device, 34.8% received MitraClipNTR, and 19% received both—meaning the XTR device

was more frequently used to treat primary mitral regurgitation than was the NTR device. Choice of device was at the operator’s discretion but Lim commented: “Early on, a group of core members of the study got together and issued their recommendations. So for patients with greater flail whipping and for those with longer leaflets, it was advised to use the longer clip arms [MitraClip XTR]. Conversely for those with more restricted leaflets, the shorter arms of the NTR system was seen as more beneficial; it was also seen as more beneficial for patients with functional aetiologies, particularly those with more restrictive pathologies. Lastly, for patients with smaller mitral orifice areas, we thought the NRT would be superior.”

Furthermore, of those who received a MitraClipXTR device, 73.7% had severe mitral regurgitation (≥3+) versus 26.3% who had moderate mitral regurgitation (≤2+). By comparison, of those who only received an NTR device, 47.6% had moderate disease versus 52.4% who had severe disease.

Overall, according to echo core lab adjudicated analysis, mitral regurgitation reduction to none/trace was achieved in 27.7% of patients,

Source: BIBA MedTech Insights Usage and Attitudes survey

reduction to ≤1+ was achieved in 86.9%, and reduction to ≤2+ was achieved in 97.3% of patients at 30 days. Lim noted: “Mitral regurgitation reduction to ≤1+ at 30 days was numerically greater in EXPAND compared to the prohibitive risk cohort from prior EVEREST studies [53.6%].”

Furthermore, after comparing outcomes of the MitraClipXTR with those of the MitraClipNTR, he reported: “Greater mitral regurgitation was achieved using the MitraClipXTR in complex anatomies.”

“The study represents the first contemporary report of echo core lab and clinical events committee adjudicated 30-day clinical outcomes in patients with primary mitral regurgitation treated with nextgeneration NTR and XTR MitraClip devices. Approximately one third of patients had a complex mitral valve anatomy that reflects the difference in patients treated in the real world in comparison to past clinical trials,” Lim stated.

Summing up the results, he said: “The EXPAND study confirms the safety and effectiveness of the next-generation MitraClipNTR/XTR system in primary mitral regurgitation contemporary, real-world setting.”

Use of MitraClip in clinical practice

MitraClip is, by far, the most commonly used device for transcatheter mitral valve repair in Europe. Data from the BIBA MedTech Insights’ Mitral and Tricuspid Monitor shows that out of 10,724 transcatheter mitral devices used in

Europe in 2019, 92% were a MitraClip device. This is to be expected as MitraClip is the most well-known device and has the most clinical data. Of note, Pascal (Edwards Lifesciences)—which, like MitraClip, is a clip-based device—was the second most used device in Europe last year.

This is despite it only receiving the CE mark in February 2019. See Figure 1.

MitraClip is also most used transcatheter mitral valve device in the USA: of 5,626 implanted overall last year, 94% were a MitraClip. Again, this is to be expected; particularly as it is the only such device that has US Food and Drug Administration (FDA) approval. However, a short BIBA MedTech Insights survey, into the usage and attitudes of physicians performing transcatherter mitral valve repairs, did have a surprising finding. This indicates that the COAPT trial appears to have had a greater impact in Europe than in the USA. The COAPT trial indicated that transcatheter mitral valve repair with MitraClip was associated with significant reductions in the rate of heart failure hospitalisations at two years for the management of secondary mitral valve regurgitation.

The trial subsequently led to MitraClip receiving FDA approval for this indication (previously, it only had approval for primary mitral valve regurgitation). In Europe, MitraClip already had market approval for secondary mitral valve regurgitation.

However, according to the survey, only 16% of US respondents said that the trial affected their practice versus 58% of European physicians. See Figure 2.

BIBA Briefings

BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments.

For editorial enquiries, please contact Dawn Powell: dawn@bibamedical.com For sales enquiries (including BIBA MedTech Insights), please contact Merveille Anderson: merveille@bibamedical.com

Issue 57 | June 2020

Market watch

Product News

TriClip

CE mark for transcatheter system that uses same clip technology as MitraClip

Abbott has received the CE mark for its TriClip transcatheter tricuspid valve repair system. It can, therefore, be used as a non-surgical treatment for people with a leaky tricuspid valve in Europe and in other regions where the CE mark is recognised. A press release reports that TriClip leverages the same clipbased technology as MitraClip, which is CE marked for transcatheter mitral valve repair, but has a differentiated delivery system designed specifically for delivery to the tricuspid valve.

The TriClip procedure repairs the tricuspid valve without the need for open-heart surgery. The device is delivered to the heart 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. This approach is designed to allow the heart to pump blood more efficiently, relieving symptoms of tricuspid regurgitation and improving a person’s quality of life.

According to a press release, the CE mark for TriClip follows positive six-month data from Abbott’s pivotal TRILUMINATE study examining the edge-to-edge repair technique using TriClip (published in The Lancet in November 2019). The study demonstrated that TriClip reduced severity of tricuspid regurgitation and was associated with strong improvement in functional capacity and in quality of life at six months.

With the CE mark designation, Abbott’s TriClip device is the first minimally invasive, clip-based tricuspid valve repair device to be commercially available in the world. Abbott has now brought to market three therapies for structural heart disease: MitraClip for mitral valve repair, Tendyne for mitral valve replacement; and now TriClip to treat the tricuspid valve.

Georg Nickenig (Department of Cardiology, University Hospital, Bonn, Germany), lead investigator of the TRILUMINATE trial, says: “Patients suffering from severe tricuspid regurgitation are extremely ill and have very few treatment options. Abbott’s TriClip could profoundly impact how physicians treat these patients. The therapy is backed by data proving safety and performance, durability, and improved patient quality of life.”

Michael Dale, senior vice president of Abbott’s structural heart business,

comments: “Tricuspid regurgitation is a highly prevalent, yet seldom treated disease, which is why this approval is a significant milestone for the healthcare community. TriClip has the potential to fill a treatment gap and transform how doctors are able to help people with tricuspid regurgitation. Our clipbased technology provides clinicians a life-changing, proven safe, simple, and effective option to treat people suffering from a crippling and life-threatening disease.”

TriGUARD 3 given CE mark for embolic protection during TAVI

European CE mark has been awarded to the TriGUARD 3 cerebral embolic protection (CEP) device from Keystone Heart, a Venus Medtech Company.

According to the company, TriGUARD 3 is the only CE marked product designed to cover and protect all three major cerebral aortic arch vessels. It consists of a Nitinol frame and dome-shaped mesh deflector that is delivered transfemorally and designed to “self-position” in the aortic arch. This design, says Keystone Heart, allows the TriGUARD 3 CEP device to conform to a variety of patient anatomies.

Chris Richardson, Keystone Heart president and chief executive officer, says: “Taking into consideration the devastating impact of stroke, we are pleased to bring this important technology to patients undergoing any transcatheter heart procedure. The introduction of the TriGUARD 3 CEP device in Europe provides physicians the only commercially available device that is designed to protect all three cerebral vessels.”

The device is designed to minimise the risk of cerebral damage by deflecting embolic debris away from cerebral circulation during transcatheter aortic valve implantation (TAVI) and other transcatheter heart procedures. Keystone Heart recently completed the REFLECT trial, a pivotal randomised study of the TriGUARD 3 CEP device, and says it is currently finalising data analysis ahead of a planned marketing application to the US Food and Drug Administration (FDA). Keystone Heart is a medical device company that develops and manufactures devices for structural heart interventions.

FlexNav

Abbott receives CE mark for FlexNav delivery system

Abbott has received CE mark in Europe for the new FlexNav delivery system for the company’s Portico transcatheter aortic valve implantation (TAVI) system. A statement from the company says that with the approval, physicians implanting Portico can benefit

from improved delivery, flexibility and navigation during implantation, even in complex cardiac anatomies.

The press release states that clinical experience with the FlexNav delivery system has yielded positive outcomes for patients to date. Data presented at the Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in September 2019 showed that within the Portico US IDE study, patients who received a Portico valve implanted with the FlexNav delivery system saw no deaths, no strokes and low rates of major vascular complications and new permanent pacemaker implants after 30 days.

Abbott says the new FlexNav delivery system demonstrates its commitment to developing new tools for doctors to treat patients requiring TAVI. The approval and launch of the FlexNav delivery system follow first global implants in a clinical study of Abbott’s next generation Navitor TAVI system, recently conducted by a clinical team led by Lars Sǿndegaard, (Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark). Sǿndegaard also serves as coprincipal investigator for the trial.

Based on physician feedback, says Abbott, it developed the FlexNav delivery system to incorporate more stability, predictability and placement accuracy into the TAVI procedure.

“Within the field of TAVI, delivery systems often do not receive the attention of the evolving technology of the valves themselves, but improvements to a delivery system can result in substantial benefits to patients,” says Neil Moat, chief medical officer of Abbott’s structural heart business. “If we look at the total TAVI procedure, innovation around both the valve itself and also how it is delivered during an implant are both central to improving outcomes.”

FDA Breakthrough Device Designation for novel heart failure therapy

VisCardia has been granted Breakthrough Device Designation from the US Food and Drug Administration (FDA) for its implantable VisONE system, which is designed for the treatment of moderate-to-severe heart failure with reduced ejection fraction and preserved ventricular synchrony. A press release reports that VisONE has now completed the first phase of the Breakthrough Devices programme by being designated to provide for more effective treatment of a life-threatening or irreversibly debilitating disease.

During the second phase of the programme, the FDA will expedite premarket reviews of VisCardia’s IDE(s) as well as the subsequent premarket approval (PMA) application to request approval to commercialise the device in the USA. The FDA Breakthrough Device Program is a two-phase process intended to help patients receive more timely access to

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breakthrough technologies.

The VisONE technology, according to the press release, recruits the diaphragm by applying stimuli synchronously with the cardiac cycle which improves the blood flow through a weak heart by modulating the pressures within the chest. A recent European, multicentre, pilot trial demonstrated that patients improved their quality of life, physical performance and haemodynamic measurements when implanted with a VisONE device and followed for one year. VisCardia believes that expanding the size of the patient population studied to date will further illustrate the clinical benefit of this technology and lead to a minimally invasive therapy that will make this under-served patient population feel better and remain physically independent longer.

Peter Bauer, CEO of VisCardia, comments: “As we continue to support scientific presentations at international meetings, this partnership with the FDA will expedite our entrance into the US medical device market through the design and implementation of an initial IDE study. We are proud to have Lee Goldberg, section chief of the Advanced Heart Failure Program at the University of Pennsylvania, to serve as our US principal investigator and Michael Mirro, chief academic research officer at Parkview Health and clinical professor of Medicine at Indiana University, as our medical director to assist us in identifying future clinical sites and implementing the next phase of our clinical research.”

LivaNova can modify indications of its cardiopulmonary products to help address COVID-19 LivaNova has announced that several of its cardiopulmonary products can now be used in the USA for extracorporeal membrane oxygenation (ECMO) therapy for more than six hours, per guidance issued by the US Food and Drug Administration (FDA) on 6 April, to temporarily expand the availability of devices to address the coronavirus (COVID-19) pandemic.

This guidance is intended to remain in effect during the COVID-19 public health emergency declared by the US Department of Health and Human Services (HHS), including any renewals made by the HHS secretary. Product indications for use have been modified accordingly for the following LivaNova products and product lines: S5 heart-lung machine TandemHeart pump and controller TandemLung oxygenator

Damien McDonald, CEO of LivaNova, comments: “During this critical time, LivaNova is committed to helping patients impacted by the COVID-19 pandemic in every way we can. We are pleased to offer cardiopulmonary and advanced circulatory support products and therapies that may benefit patients in need and will continue to work with health authorities to help fight this pandemic.”

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June 2020 | Issue 57

Studies

Clinical News

Resolute Onyx

Medtronic shares positive results of Onyx ONE Clear Study

Medtronic has announced positive results of the Onyx ONE Clear Study that evaluated the Resolute Onyx drugeluting stent (DES) in high bleeding risk (HBR) patients with one-month dual antiplatelet therapy (DAPT) in the USA and Japan. Results from the study were shared virtually at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual).

The study met its primary endpoint of cardiac death or myocardial infarction by beating a performance goal derived from contemporary one-month DAPT trials at one-year post-procedure.

“Despite the high-risk population, we observed a low rate of ischemic outcomes after DAPT discontinuation at one month,” Ajay Kirtane, professor of medicine at Columbia University Irving Medical Center (New York, USA), lead investigator and presenter of the data at ACC.20, said in a press release issued by Medtronic. “These data, in conjunction with the randomised data from the Onyx ONE Global randomised controlled trial, offer additional clinical evidence of one-month of DAPT for appropriately selected patients treated with the Resolute Onyx DES.” The prospective, multicentre, singlearm study included highly complex HBR patients in the USA and Japan who were treated with one-month DAPT (the combination of aspirin and an anti-clotting medication) following PCI with Resolute Onyx and were clear of any adverse events and were DAPT compliant at one month.

Patients in the Onyx ONE Clear study were pooled with similar patients treated with Resolute Onyx from the Onyx ONE Global Study, totalling approximately 1,500 patients that were included in the primary endpoint analysis. The Onyx ONE Clear study’s primary composite endpoint of cardiac death or myocardial infarction was 7%, beating the pre-specified performance goal of 9.7% at one-year post-procedure.

The rate of stent thrombosis stood at 0.7% at one year. The performance goal was based on short-DAPT studies.

The Onyx ONE Clear Study was designed to complement the Onyx ONE Global Study, results of which were recently published in the New England Journal of Medicine.

“Onyx ONE Clear demonstrates our commitment to providing the clinical evidence of greatest interest and benefit to the interventional cardiology community,” said Dave Moeller, vice president and general manager of the Coronary and Renal Denervation business, which is part of the Cardiac and Vascular Group at Medtronic.

“We hope these data will support our submission to the FDA for a one-month DAPT indication for high-bleeding risk patients treated with Resolute Onyx.”

To date, more than 22,000 patients have been studied in Medtronic sponsored and funded clinical trials that have addressed DAPT duration, the company said in its press release.

Resolute Onyx DES was approved in the USA in 2017 and is not currently indicated for high bleeding risk patients on one-month DAPT.

Shockwave completes enrolment in study of coronary intravascular lithotripsy

Shockwave Medical has completed enrolment in its US Food and Drug Administration (FDA) Investigational Device Exemption (IDE) study— DISRUPT CAD III—for the use of intravascular lithotripsy (IVL) for the management of heavily calcified coronary arteries. A press release reports that the investigational Shockwave IVL system with the Shockwave C2 Coronary IVL catheter, which has been granted Breakthrough Device Designation by the FDA, is an innovative therapy designed to fracture problematic calcium using sonic pressure waves in order to facilitate stent delivery, deployment and optimal expansion.

DISRUPT CAD III is a prospective, multicentre, single-arm, global IDE study to demonstrate the safety and effectiveness of the Shockwave coronary IVL system with the Shockwave C2 coronary IVL catheter in de novo, calcified, stenotic, coronary arteries

prior to stenting. The study enrolled 384 patients, exceeding the minimum requirement of 372 patients, per the a priori statistical plan agreed by the FDA. Patients were enrolled at 47 global sites in the USA, France, Germany, and the UK. The study is assessing freedom from major adverse cardiac events (MACE) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness endpoint is procedural success defined as stent delivery with a residual stenosis less than 50 percent and without in-hospital MACE. The study chairman is Gregg W Stone (Icahn School of Medicine, Mount Sinai, New York, USA). The co-principal investigators of the study are Dean Kereiakes (The Christ Hospital Heart and Vascular Center and the Christ Hospital Research Institute, Cincinnati, USA) and Jonathan Hill (Royal Brompton Hospital, London).

Hill says: “We eagerly await the opportunity to share the DISRUPT CAD III results with the global interventional community later this year. IVL has been a significant advance for our management of calcified lesions in

Shockwave system

Europe and I am excited about the potential for the technology to have a similar impact in helping patients across the USA.” Doug Godshall, president and CEO of Shockwave Medical, states: “Despite the global challenges of COVID-19, the CAD III investigators, research staff and site monitors have done an outstanding job in bringing this important study to a timely conclusion. Based on recent collaborative interactions with the FDA, it is our expectation that the pre-market approval will be submitted in the third quarter of this year, with US device approval anticipated in the first quarter of 2021, consistent with previous guidance.’’

Shockwave C2 Coronary IVL catheters are commercially available for the treatment of de novo coronary artery disease in Europe and select other geographies; they are limited to investigational use in the USA.

BIOFLOW-DAPT trial enrols first patient in one-month evaluation of DAPT in high bleeding risk group

Biotronik has announced that the first patient has been enrolled in the BIOFLOW-DAPT randomised controlled trial, which aims to assess the safety and efficacy of the Orsiro Mission drug-eluting stent, in combination with one-month dual antiplatelet therapy (DAPT), for the management of patients at high risk of bleeding. A press

release reports that Henning Kelbæk, Sjaellaands (University Hospital, Roskilde, Denmark), successfully performed the first implantation.

The press release adds that BIOFLOW-DAPT is a prospective, multicentre randomised controlled trial with a planned enrolment of up to 1,948 patients at more than 80 study sites. Eligible patients with high risk of bleeding will be randomised 1:1 to receive either Orsiro Mission or Resolute Onyx (Medtronic). The trial’s primary endpoint was a composite rate of cardiac death, myocardial infarction and definite or probable stent thrombosis assessed at 12 months.

Marco Valgimigli (Department of Cardiology, Inselspital, Bern, Switzerland), principal investigator of the study, says: “The use of DAPT therapy following stent implantation is critical for the prevention of coronary stent thrombosis and other major adverse events. Until today, clinical results have been controversial in defining the optimal DAPT therapy for an often under-represented patient group that faces an increased risk of cardiovascular events. Our study will help us determine the optimal DAPT duration in this challenging population undergoing percutaneous coronary intervention (PCI) with the newly launched Orsiro Mission drug-eluting stent.”

Additionally, Biotronik has also announced that data from the TICO trial show that patients with acute coronary syndrome treated with Orsiro benefit from stopping aspirin three months after stenting and continuing only with ticagrelor monotherapy. Yang Soo Jang (Yonsei Cardiovascular Research Institute, Seoul, Korea) presented the results at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual, 28–30 March, Central Time).

The trial is the first randomised, controlled trial to demonstrate the safety and efficacy of a shortened DAPT regimen of three months followed by ticagrelor monotherapy in patients with acute coronary symptom treated with Orsiro. Primary endpoint results of the 3,056 acute coronary syndrome patients enrolled showed significantly lower rates of net adverse cardiac events (3.9% versus 5.9%; p=0.01) in patients discontinuing aspirin three months after PCI and continuing with ticagrelor only, compared to patients following a conventional DAPT therapy for 12 months. The difference seen in the primary endpoint was mainly driven by significantly lower rates of major bleeding (1.7% versus. 3.0%, p= 0.02) favoring the ticagrelor monotherapy arm Alexander Uhl, president Vascular Intervention at Biotronik, comments: “The TICO study not only provides valuable insights into the treatment of acute coronary syndrome patients, but further underscores Orsiro’s clinical performance with low stent thrombosis and target vessel revascularixation rates in both arms.”

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June 2020 | Issue 57

Companies

Industry News Ventilator manufacturers unite to training alliance and create app for frontline workers

A press release reports that several of the world’s ventilator manufacturers have formed a Ventilator Training Alliance (VTA) and partnered with Allego to create a mobile app that frontline medical providers can use to access a centralised repository of ventilator training resources. The manufacturers include Dräger, GE Healthcare, Getinge, Hamilton Medical, Medtronic, Nihon Kohden, and Philips.

The VTA app—powered by learning and readiness platform provider Allego— connects respiratory therapists, nurses and other medical professionals with ventilator training resources from alliance member companies.

According to the press release, the resources include instructional howto videos, manuals, troubleshooting guides, and other ventilator-operation expertise critical to helping responders treat patients suffering from COVID19-related respiratory distress.

The app is provided at no cost to medical professionals.

To download the Ventilator Training Alliance

knowledge hub application, visit the Apple App store or Google Play store, or click here to access the hub from any Web browser. Content on the VTA app can be accessed on iOS and Android device, even in environments with little to no WiFi access, or from a web browser. The app provides healthcare professionals multi-language closed captioning and mobile background audio when multitasking.

Patrick Berges, chair of the VTA and vice president of commercial capabilities, which is part of the Minimally Invasive Therapies Group at Medtronic, says: “We can help overcome this pandemic by collaborating across companies, agencies and industries to deliver smart solutions that add value and reduce stress for frontline healthcare heroes when every minute matters. This training alliance is a great example of that collaborative spirit. Being able to share content from a variety of ventilator manufacturers all in one place ensures that hospitals can quickly access information they may need to accelerate putting life-saving ventilators to use.”

Pi-Cardia closes a US$27 million financing round led

by Sofinnova Partners

Pi-Cardia has closed a US$27 million round of financing, led by Sofinnova Partners. A press release reports

that Pi-Cardia’s Leaflex catheter performs mechanical scoring of valve calcification, restoring leaflets’ mobility and improving valve haemodynamics.

The Leaflex catheter is designed to be a cost-effective, durable standalone treatment. It can be used for patients who are not planning to undergo a transcatheter aortic valve implantation (TAVI) and it can be a means to defer TAVI in patients who may be too young for the procedure.

The Leaflex catheter can also be a preparatory step for improving the outcome of TAVI in heavily-calcified and bicuspid aortic valves. Last year, Pi-Cardia successfully completed its First-in-Human studies, demonstrating acute safety and feasibility. The new financing will now enable the company to demonstrate the therapeutic effect of aortic valve scoring over time, through parallel clinical trials in the USA and Europe.

Anne Osdoit, partner at Sofinnova Partners, comments: “We are excited to join Pi-Cardia as an investor to help leverage the Leaflex in building a significant new market for aortic valve repair. The aortic valve market is expected to reach US$9 billion over the next few years, and there is an ever-growing number of patients for whom physicians would prefer to avoid replacing the valve if they had a safe and effective way to defer disease progression.”

Golan, Pi-Cardia’s CEO and founder, states: “Now, as we follow with admiration our fellow physicians and healthcare teams, working day and night to save lives in this COVID-19

crisis, we are ever more committed to driving healthcare innovation forward.

With our very promising early results, we are now ready to move to the next stage and establish the long-term safety and efficacy of Leaflex as a standalone treatment for patients with aortic stenosis. We have an ambitious plan ahead of us, and we are dedicated to making Pi-Cardia’s technology the next revolution in the treatment of structural heart disease.”

Proximo Medical named as commercialisation partner for Elucid Bioimaging

Proximo Medical has announced a partnership with Elucid Bioimaging, a developer of diagnostic image analysis software used to assist in the detection and treatment of myocardial infarction and stroke. A press release states that Elucid Bioimaging’s technology, vascuCAP, is the only US Food and Drug Administration (FDA)-cleared, histologically-validated software for evaluation of atherosclerotic plaque stability from a single computed tomography (CT) angiography to inform the risk of a cardiovascular event and treatment selection.

Blake Richards, CEO, Elucid Bioimaging, says: “VascuCAP uses machine learning to analyse CT scans of arteries and automatically quantify and classify the type of atherosclerotic plaque. This information, along with key measures of the artery’s structure, leads to significant improvements in accurately predicting events and informing optimal intervention,procedure planning.

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.

2020 29 August–1 September ESC Congress Virtual

www.escardio.org/Congresses-&Events/ESC-Congress

23–27 September TCT 2020 Miami, USA www.crf.org/tct

August 2019

no:

Maisa Francesco

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ers Stakehold updated welcome erage CMS cov for TAVI updated

ed an have welcomination (NCD) Stakeholders ge Determ re Covera for Medica National US Centerss (CMS) on from the id Service valve implantation & Medica matic aortic transcathetertreatment of sympto decision the saying the (TAVI) in stenosis, s.

at r aortic valve access to service the statement Stephan Windecke nnouncing will improve it will Paris, France), Switzerland) in June that (20–24 May, y Hospital, Bern, consistent ANNOUNCED through coverage of TAVI are surgical (Bern Universit THE CMS procedure e outcomes that when furnished cover the favourabl suggesting ent (CED) continue to choice said: “The spectrum, developm Administration to guide the entire risk with evidence US Food and Drug the basis to ent.” changes across the to a n is no longer valve replacem has . In addition, and according risk estimatio and surgical aortic evidence proved indication ents for hospitals e (FDA)-ap between TAVIexplained: “The available trials in the l volume requirem TAVI programm to r landmark the procedura begin or maintain a Windecke now with and providers s to by two recent provide us highfor hospitals physician been extended population which flexibility g TAVI. from extreme of the allow greater low-risk patient picture, ranging for performin ces said: The aim nsive meet the criteria Edwards Lifescienents and a comprehe ate-, to low-risk patients.” available release, the se ed requirem In a press are risk, intermedi , he said, is to “synthesishifts can be the modernis n process “We believe ed patient evaluatio PCR statement this, three paradigm help ensure . From more streamlin ents that may from evidence” making enhancem suffering ul meaningf to the decision- the benefits more patients identified. ed that CMS access for these relates are encourag equitable SAVR: “Becausewe applied The first of stenosis. We a quality measure focused TAVI and ion that severe aortic in towards process betweent, the risk stratificat score volume, l moving to Surgery] r is open , not procedura is no are so consisten[Society of Thoracic Windecke TAVR in the outcomes Stephan to provide STS risk for surgeryin the on patient y and valve using the increased hospitals eligible life expectanc at very young patients , patients at evaluating categorise based upon rather to identify in a statement be, if we look Rather than al valve and is to be its support risk, we should USA.” : “That should longer useful. ially a mechanic that also indicated coverage policy allows ate, and low durability characteristics Medtronic years], preferent In patients the new specially extreme, intermedi and anatomical patients [<50 aortic stenosis. etic valve. The clinical decision-making saying it “believes access to TAVI—e in case of look at the to guide the ile still te patient prosthesis age, a bioprosth l patients for appropria rural communities—wh centres and 65 years of of individua two procedures.” in the best are above ents for for patients between these heart team will identify with rigorous requirem the patients, maintaining the therapy.” more mixed Secondly, individual the default providing it a option for SAVR as operators s have given Christ Hospital, treatment to now, ral TAVI replacing of patients: “Up therapy s (The Some physician important transfemo was the Satya Shreeniva out: “It is vitally 2 a greater number response. on page therapy for low-risk patients surgery d in those Continued ti, USA) pointed considere in be to notCincinna by default, In the was only and TAVI not be possible. actually of choice, 2 on page surgery would emerge where Continued patients where scheme will any patient being t future, a with too-distan and surgery will be reversed, candidate the question to be a TAVI is not possible.” d a priori that choice, considere to cases whereto prosthetic valve being reserved relates paradigm The third

A

t oo-distan In the not-t patient any future ... priori idered a will be cons candidate.” to be a TAVI

8–10 October 34th EACTS Barcelona, Spain

2021 30 January–2 February STS annual meeting Austin, USA

www.eacts.org/annual-meeting/

22–24 November PCR London Valves London, UK

https://sts2021.com/

www.pcronline.com/Courses/PCRLondon-Valves

11–13 February JIM Milan, Italy

www.jim-vascular.com/

27 February–2 March CRT 2021 National Harbor, USA www.crtmeeting.org/

20–22 March ACC.21 Alanta, USA accscientificsession.acc.org/

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