Cardiovascular News EU

May

Issue

19 53

TAVI moves to the mainstream with new findings in low-risk patients Evidence for the use of transcatheter aortic valve implantation (TAVI) as standard therapy is mounting, with the release of data from two major new studies that demonstrate its role in low-risk patients. Both were presented at a late-breaking trial session at the 2019 American College of Cardiology Scientific Session (ACC 19, 16–18 March, New Orleans, USA) and simultaneously published in the New England Journal of Medicine (NEJM). The studies increase the prospect that TAVI will be approved for these patients.

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ARTNER 3 found a significantly lower risk of onset atrial fibrillation than surgery at 30 days (5% death, stroke and rehospitalisations at one year vs. 39.5% in surgical patients, hazard ratio [HR] 0.10, with transfemoral valve implantation than with p<0.001), a shorter index hospitalisation (three days open surgery among patients who had severe aortic vs. seven days, respectively, p<0.001), and a lower stenosis and who were at low risk for surgery. And the risk of a poor treatment outcome (death or a low Evolut Low-Risk trial determined that, for patients Kansas City Cardiomyopathy Questionnaire [KCCQ] with severe aortic stenosis at low surgical risk, TAVI score, 3.9% vs. 30.6%, respectively, p<0.001). with a self-expanding bioprosthesis was non-inferior Additionally, patients who had transcatheter treatment to surgical aortic valve implantation for death or had more rapid improvement in New York Heart disabling stroke at two years.

Association (NYHA) class, six-minute walk test PARTNER 3 randomly assigned distance, and KCCQ score than 950 patients 1:1 either to surgery patients who had surgery. or to transfemoral placement of a Mack et al also point out that balloon expandable valve (Sapien complications shown to be more 3, Edwards LifeSciences). Average frequent with TAVI than surgery in age was 73 years, and 30% of previous trials occurred with similar patients were female. The primary frequency in both groups in the endpoint was a composite of death, PARTNER 3 study. However, they stroke, and rehospitalisations at acknowledge that, with only one one year. Among the secondary year of follow-up data, the trial does endpoints were new onset atrial not address the issue of long-term fibrillation, need for a new structural valve deterioration. permanent pacemaker, and length “Definitive conclusions regarding of stay. the advantages and disadvantages Michael Mack (Baylor of TAVI as compared with Scott & White Health Heart surgery (with either bioprosthetic Hospital, Plano, USA) and his or mechanical valves) depend coinvestigators describe the on long-term follow-up. In this findings as robust. Multiple trial involving younger, low-risk sensitivity analyses confirmed patients, the protocol requires that TAVI via the transfemoral clinical and echocardiographic route with a Sapien 3 balloon follow-up to continue for at least 10 expandable system was superior years.” to surgery for a composite Evolut was a multinational endpoint of death, stroke, or randomised noninferiority clinical rehospitalisations at one year trial that compared the safety and (8.5% vs. 15.1%, respectively). efficacy of transcatheter aortic Sapien 3 (top); TAVI was also associated with valve replacement with surgical CoreValve Evolut (bottom) Continued on page 2 a significantly lower rate of new

Omar Chehab:

Implications of COAPT Page 12 Adrian Banning:

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Less bleeding with one-month DAPT than standard therapy, with no increased ischaemia

One-month dual antiplatelet therapy (DAPT) followed by 12 months of clopidogrel monotherapy leads to a greater reduction in bleeding events following percutaneous coronary intervention (PCI) than 12-month DAPT, with no increase in ischaemia. Hirotoshi Watanabe (Kyoto University, Japan) announced findings from STOPDAPT-2 at a late-breaking trial session at the 2019 ACC Scientific Session 6–18 March, New Orleans, USA).

HE SAID: “ONE-MONTH DAPT followed by clopidogrel monotherapy provided a net clinical benefit for ischaemic and bleeding events over 12-month DAPT with aspirin and clopidogrel after implantation of a cobalt chromium everolimuseluting stent. The benefit was driven by significant reduction in bleeding events without increase in ischaemic events.”

Current guidelines recommend DAPT, a combination of aspirin and a P2Y12 inhibitor such as clopidogrel, for at least six or 12 months following PCI. STOPDAPT-2, a prospective, open label, multicentre trial, randomised 3,045 participants in 89 Continued on page 2

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TAVI moves to the mainstream with new findings in low-risk patients Continued from page 1

replacement in 1,468 patients with severe aortic stenosis considered to be low risk at 30 days for surgery.

Randomisation was 1:1, and the patients assigned to transcatheter replacement were treated with either CoreValve, Evolut R, or Evolut Pro (Medtronic); the surgical valve was determined at surgeons’ discretion.

Patients were evaluated at baseline, discharge, one, six, 12, 18, and 24 months. Primary safety and efficacy endpoints were a composite of death from any cause or disabling stroke at two years.

The mean age of patients was 74 years and 34.9% were female, with no demographic differences between the two treatment cohorts. At two years, the incidence of death or disabling stroke was 5.3% in the transcatheter group and 6.7% in the surgery group. The 24-month estimated incidence of death from any cause was 4.5% in both groups, and disabling stroke was 1.1% in the TAVI group and 3.5% among patients who had surgery.

No significant treatment by subgroup interactions were observed for the primary endpoint.

Writing in the NEJM, researchers Jeffrey Popma (Beth Israel Deaconess Medical Centre, Boston, USA) et al conclude: “Our study showed that among patients deemed to be at a low risk for death from surgery, TAVI [transcatheter aortic valve implantation] with a selfexpanding supra-annular bioprosthesis was non-inferior to surgery with respect to the risk of death or disabling stroke at 24 months. The estimated 24-month incidence of death from any cause was low (4.5%) in both groups, a finding that reinforced the fact that our study included healthier patients with severe aortic valve disease.”

TAVI was also associated with a lower risk of disabling stroke, acute kidney injury, bleeding events and atrial fibrillation than surgery, but with a higher incidence of aortic regurgitation (3.5% vs. 0.5%) and pacemaker use (17.4 vs. 6.1%). Both therapies provided functional improvement at 12 months, but transcatheter replacement led to better recovery at 30 days. At 12 months, patients who underwent TAVI had lower aortic valve gradients than those who had surgery (8.6mmHg vs. 11.2mmHg) and larger effective orifice areas (2.3cm2 vs. 2cm2).

Speaking to Cardiovascular News, Popma describes the valve haemodynamics as “spectacular”, and said there was a trade-off with pacemaker rates, which he expects to fall: “We only had about 25% of patients who were treated with our newest generation device, and we are still evolving to do better, and we will do better with

lowering the pacemaker rate, no question.”

He hails the trials as “an overwhelmingly positive day for TAVI. This is a huge advance forward.

Both sets of trials had phenomenal results; they had spectacular surgery and TAVI beat that with both of them. Both of these valves perform exceedingly well versus surgery in a low-risk Michael Mack population of patients.”

He says a cross-trial comparison is difficult but although both studies had differing primary endpoints and were set to do different things, there was no real difference between them.

Mack told Cardiovascular News the findings would change risk assessment: “The criteria will now switch from risk for surgery to risk for TAVI, which will primarily be anatomical problems. Patients most appropriate for surgery will be [those with] bicuspid aortic valves, low-lying coronary arteries, inadequate femoral access and significant left ventricular outflow tract calcium. Most younger patients (<65 years) will still stay with surgery until long-term durability questions are answered. I would guess that within a few years, approximately three out of four patients will be treated with TAVI.” And he predicts a change in the indicated options for low-risk patients: “With two randomised trials both being positive, I think it is highly likely that they [transcatheter valves] will be approved later this year.”

His comments are echoed by the investigators of a third study—LRT 1, a prospective multicentre investigator-initiated trial which found that TAVI using commercially available valves is safe and effective in low-risk patients, with low adverse event rates and excellent valve haemodynamics at one year. Ron Waksman (MedStar Washington Hospital Center, Washington DC, USA) presented the data at Cardiovascular Research Technologies (CRT 2019; 2–5 March, Washington DC, USA), and recommended that if its findings were corroborated by the PARTNER 3 and Evolut trials “TAVI should be approved for low-risk patients”.

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Less bleeding with one-month DAPT than standard therapy, with no increased ischaemia Continued from page 1

medical centres in Japan 1:1 to one month of DAPT followed by clopidogrel monotherapy for five years (1,523), or 12 months DAPT followed by aspirin monotherapy for five years (1,522).

The primary endpoint was a composite of cardiovascular death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction (TIMI) major/minor bleeding rates at one year. Major secondary outcomes were an ischaemic composite endpoint and a bleeding endpoint of TIMI major/minor bleeding.

The primary outcome at one year occurred in 2.4% of the one-month DAPT group and 3.7% of the 12-month DAPT group (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.42–0.98, p superiority=0.04). The secondary ischaemic composite outcome at one year was 2% in the one-month DAPT group and 2.5% in the 12-month DAPT group (HR 0.79, 95% CI 0.49–1.29, p noninferiority=0.005). Rates of TIMI major/ minor bleeding at one year were 0.4% vs. 1.5%, respectively (HR 0.26, 95% CI 0.11–0.64, p superiority=0.004).

A second study presented as a late-breaking trial at ACC 19 prospectively randomised 2,993 patients undergoing PCI with an everolimus or sirolimus eluting stent in 33 centres in Korea to either P2Y12 inhibitor monotherapy after three months of DAPT, or to DAPT for 12 months. SMART CHOICE, an open label non-inferiority trial, found that 12 months after the index procedure, for the primary endpoint of major adverse cardiac and cerebrovascular events, P2Y12 inhibitor monotherapy was non-inferior to standard therapy of 12-month DAPT, and monotherapy reduced the risk of bleeding compared to standard therapy. At one year, rates of the primary outcome were 2.9% for monotherapy and 2.5% for those on dual therapy (HR 1.19, 95% CI 0.76–1.85, p=0.46).

Joo-Yong Hahn (Samsung Medical Centre, Seoul, South Korea) said: “Our trial suggests that P2Y12 inhibitor monotherapy after short duration of DAPT is a novel antiplatelet strategy balancing ischaemic and bleeding risk in patients undergoing PCI.”

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4

May

Issue

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Diagnostics

Alert system is safe, quick, and has few complications The AngelMed Guardian implantable device is as safe as using a pacemaker, with comparably low complication rates and less delays in care than reliance on symptoms alone. It also has a higher positive predictive value and lower false positive rate for detecting coronary occlusive events in high-risk patients. Data from an expanded analysis of a prospective randomised trial to assess ST-segment elevation myocardial infarction (STEMI) in patients with coronary disease were simultaneously presented at a late-breaking trial session at Cardiovascular Research Technologies (CRT 2019; 2–5 March, Washington DC, USA) and published online in the Journal of the American College of Cardiology.

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Michael Gibson (Harvard Medical School, Boston, USA), outlined the findings on behalf of the ALERTS (AngelMed for early recognition and treatment of STEMI) investigators.

He said: “The device was safe, and had a complication rate similar to that of pacemakers; there was 96.7% freedom from system-related complications, which in the Bayesian analysis was highly significantly non-inferior to a regular pacemaker [posterior probability >0.999].

The primary endpoint was not met, but in an expanded analysis, in conjunction with the Food and Drug Administration [FDA], there was a higher positive predictive value, and lower false positive rates [with the device], and 42 silent myocardial infarctions [MI] were found.”

Between 30 and 35% of acute myocardial infarction are silent, with atypical chest symptoms, a rate Gibson described as “somewhat shocking”; every 30 minutes of delay in treatment leads to a 7.5% relative increase in mortality, and there is an increased emphasis in getting patients to the cath lab quicker.

But, he said: “The bad news is, that for four decades now, the time from when someone has symptoms to when they get to the hospital has not changed at all. It is about two hours.”

Reasons for this delay can be attributed to the fact that symptoms can be atypical

and may be confused with gastrointestinal problems, or there may not be symptoms.

He said that denial also plays a big role.

And advancing age (>65 years) and a history of either diabetes or myocardial infarction are associated with even greater delays in seeking care.

But, Gibson asked: “What if, instead of a symptom, there was a signal … that said ‘you are having ischaemia and go to the hospital’? That is the basis for this device, the guardian device.”

The AngelMed Guardian System is the size of a pacemaker, and is inserted in the same way to monitor ST segments. Any deviation in ST segments in the absence of an elevated heart rate is indicative of an occlusive event, and triggers an internal and external alarm that tells the patient to seek medical attention.

Participants in ALERTS were acute coronary syndrome patients considered high risk if they had either diabetes, compromised renal function, or a thrombolysis in myocardial infarction risk score >3. Investigators implanted the device in 907 participants and then performed a 14-day stress test to train it to recognise anticipated ST deviation.

Alarms were set for ST elevation without increased heart rate. In the control group (456) the alarm was deactivated for six months; the treatment group (451) had their alarms activated from the onset of

the trial.

He explained: “Half the people had the device turned on, and half the people had the device turned off. This was a real sham controlled study.”

The primary endpoint was cardiac or unexplained death, new Q-wave myocardial infarction, or a symptom-todoor time >two hours for a documented occlusive event. Average age in both groups was about 59 years old, around half of whom had had a myocardial infarction and half had diabetes.

The safety endpoint was met, with 96.7% freedom from complications.

“For the primary prespecified [efficacy] endpoint, the event rates were 4.7% vs.

3.1%. Here, the posterior probability did not achieve statistical significance. But that was looking back seven days. If you capture the silent myocardial infarctions looking back 90 days you do see a significant result.” Additionally, he said: “People got to the hospital quicker, much quicker, with the device; 85% of people got to the hospital within two hours with the alarm being on [compared to] only

the emergency room, what are the odds that you are really having a heart attack?

They were higher if you had the alarming system [25.8% alarms on with or without symptoms vs. 18.2% alarms off symptoms only].” There was also a reduction in the false positive rate, dropping from 0.678 per patient year in the alarms off symptoms only group to 0.164 per patient year in the group with alarms on with or without symptoms. “Two-thirds of the patients coming in a year were false positive symptoms. That level went down to 0.16, to about one quarter of it, with the device. So rather than increase consumption, this actually gave fewer

5% of those who relied on symptoms.”

An expanded analysis looked at the positive predictive value beyond randomisation, in which alarms were on in both control and treatment groups: “That makes about six years of data to compare to the alarms off group. If you came to

false positives; In conjunction with symptoms, it could be more accurate.”

He said: “We can detect these events.

We can get people to the hospital quicker, we can detect silent myocardial infarction; so the science seems to be very well founded.”

Low rates of events in all patients with a negative FFR compared with patients with abnormal FFR values CT

CT

One-year outcomes from the Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (ADVANCE) FFRCT registry show low rates of events in all patients, with less revascularisation and a trend towards lower major adverse cardiac events (MACE), and significantly lower cardiovascular death or myocardial infarction in patients with a negative fractional flow reserve derived from computed tomography (FFRCT) compared with patients with abnormal FFRCT values.

THE PAPER, AUTHORED by Manesh R Patel (Duke University Medical Center, Durham, USA) and colleagues, was recently published in JACC: Cardiovascular Imaging.

In this study, 5,083 patients evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by CT angiography were

prospectively enrolled from 2015 to 2017.

Demographics, symptom status, CT angiography and FFRCT findings and resultant site-based treatment plans, and clinical outcomes at one year were recorded and adjudicated by a blinded core laboratory. MACE, death, MI, and acute coronary syndrome were captured.

At one year, the investigators found that 449 patients

Every 30 minutes of delay in treatment leads to a 7.5% relative increase in mortality.”

did not have follow-up data. Revascularisation occurred in 1,208 (38.4%) with FFRCT ≤0.8 and in 89 (5.6%) with an FFRCT >0.8 (RR 6.87, CI 5.59–8.45; p<0.001).

MACE occurred in 55 patients, 43 events occurred in patients with an FFRCT ≤0.8, and 12 in those with an FFRCT >0.8 (RR 1.81, CI 0.96–3.43; p=0.06).

Additionally, the researchers found that time to first all-cause death or MI occurred in 38 (1.2%) patients with FFRCT ≤0.8, compared with 10 (0.6%) patients with FFRCT >0.8 (RR 1.92, CI 0.96–3.85; p=0.06). Time to first cardiovascular death or myocardial infarction occurred more in patients with FFRCT ≤0.8 compared with FFRCT >0.8 (25 [0.8%] vs. 3 [0.2%]; RR 4.22, CI 1.28–13.95, p=0.01).

Guidelines for management of chest pain using non-invasive imaging pathways are based on shortto-intermediate-term outcomes. Patel et al, therefore, aimed to use one-year data from the international ADVANCE registry of patients undergoing CT angiography to evaluate the relationship of FFRCT with downstream care and clinical outcomes.

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May

Managing the risk of complications in CTO-PCI Jacopo Andrea Oreglia Comment & Analysis Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) is one of the most demanding challenges for an interventional cardiologist. Technological developments have improved efficacy and safety, but complications still occur, and their incidence remains higher than for non-CTO-PCI. Jacopo Andrea Oreglia reviews the typical complications seen in practice.

COMPLICATIONS IN CTO-PCI can be both cardiac and non-cardiac, and prompt recognition is key to managing them without major sequelae.

Common cardiac complications are coronary perforation or rupture, donor vessel injury, collateral channel ischaemia, and loss or entrapment of devices. Of these, coronary rupture or perforation is one of the most feared.

Rupture of the vessel wall happens most frequently during predilatation, stent deployment, or post-dilatation, while collateral rupture or distal vessel perforation may be caused by wire or microcatheter injury. Any rupture or perforation may lead to rapid haemodynamic collapse due to cardiac tamponade. Treatment should

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Coronary interventions

always begin with a rapid balloon inflation proximally, or at the level of the perforation or rupture, to block bleeding. Specific methods, such as the dual catheter technique or the blockand-deliver technique must be used to resolve the issue. A covered stent is usually needed to treat significant lateral vessel rupture, and detachable coils are necessary to treat distal vessel or collateral perforations. Reversal of anticoagulation (that is, protamine)

should be avoided until the guiding catheter, guidewires, or other equipment are in the coronary vessels. If cardiac tamponade occurs, pericardiocentesis must be performed, and IV fluids and vasopressors administered.

Although coronary perforations are most dreaded, ischaemic complications, especially within the donor vessel, may be catastrophic. When planning a retrograde CTO-PCI, particular attention should be paid to the donor vessel anatomy and any possible disease.

Even intermediate lesions can cause significant ischaemia when a guidewire and a microcatheter are advanced across them. Injury to the donor vessel may be dramatic, since a vast area of myocardium is jeopardised, and profound ischaemia with hypotension, ECG changes, arrhythmias, or shock may occur.

Anticoagulation control must be checked regularly to avoid donor vessel thrombosis, and a systematic final control angiogram of the donor vessel should be performed before the guidewire is removed from the retrograde system to assess integrity of the collateral circulation, and to rule out possible donor vessel dissections. Also consider treatment of intermediate lesions in the donor vessel, in case a retrograde approach is planned.

Equipment entrapment or loss is another possible complication, and can happen especially in heavily calcific lesions or tortuous vessels. Guidewires

CTO-PCI requires a systematic and disciplined approach. It is a complex procedure.”

may get damaged and stuck and/or break in the lesion or artery. Balloons, stents (or more often, rotablator burrs) may lodge in the vessel, and specific techniques have to be used to remove them.

Most complications can be managed by the interventional cardiologist in the cath-lab, but in rare situations surgical treatment may be necessary. CTO-PCI requires a systematic and disciplined approach. It is a complex procedure, and an awareness of the different steps to be performed is necessary to keep the procedure as safe as possible. Being prepared to deal with any complications that can arise is part of the planning process for CTO-PCI. If a complication occurs, prompt recognition is key in order to avoid major sequelae. Flow-charts simplify and standardise problem-solving techniques to help achieve good outcomes for the patient. Operators should gain confidence in the use of devices such as covered stents, detachable coils, snaring systems, and so on, and understand the compatibility of coils with different microcatheters. Equipment that could be useful to treat a complication (pericardiocentesis tray, coils, covered stents, microcatheters, etc.) should be stored in a special area so that cath-lab staff can access it very quickly.

Complications are rare, but prompt and effective treatment is mandatory; interventional cardiologists should share their experiences and allow others to learn the techniques, tips, and tricks involved, even if they have not yet experienced it for themselves.

Jacopo Andrea Oreglia is head of the interventional cardiology unit at De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy.

Registry data for bioresorbable scaffold Magmaris supports its roll-out into clinical practice Preliminary data from the BIOSOLVE-IV registry are consistent with the favourable safety outcomes seen with the magnesium bioresorbable scaffold (Magmaris, Biotronik) in previous studies (BIOSOLVE-II and BIOSOLVE-III). Investigators Stefan Verheye (Cardiovascular Center ZNA Middelheim, Antwerp, Belgium) and others say that these findings confirm that the device is associated with a low rate of target lesion failure and is safe to use in clinical practice.

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riting in EuroIntervention, Verheye et al report that Magmaris received CE mark approval in 2016 and “it was paramount to test this device in clinical routine to ensure a safe roll-out of this technology”. They add that BIOSOLVEIV is an international, single-arm, multicentre registry conducted in 86 centres. The present study reviewed the first 400 patients (with 425 lesions) enrolled.

Referencing the “predilatation, appropriate vessel sizing, and high-pressure post-dilatation” approach that was advocated for Abbott’s bioresorbable vascular scaffold (Absorb) before it was taken off the market, the authors note that “predilatation using a noncompliant balloon with a 1:1 balloon-to-artery ratio was mandatory”. Furthermore, according to Verheye et al, both pre and post-dilatation was performed in nearly all patients in the study.

At 12 months, the rate of target lesion failure was 4.3%, predominantly by clinically driven target lesion revascularisation. The authors claim that this target lesion failure result was “comparable to the

new-generation, permanent drug-eluting stents”, also observing that no cases of cardiac death were reported.

However, Verheye et al comment: “One definite scaffold thrombosis occurred in our series [10 days after the implant procedure], which is the first definite scaffold thrombosis in the 584 patients published to date”. They state that the thrombosis developed after cessation of dual antiplatelet therapy (DAPT) and, thus, emphasises “that DAPT in the early days after Magmaris implantation is as important as after drugeluting stent implantation”.

“Our outcomes are also within the range of objective performance criteria for new generation stents as postulated by the European Society of Cardiology/ European Association of Percutaneous Cardiovascular Interventions’ task force, namely 2.9% target lesion failure and 0.47% definite stent thrombosis at nine to 12-month follow-up,” the authors write.

They conclude: “The preliminary analysis after 400 patients enrolled in the BIOSOLVE IV real-world registry confirms the safe roll-out of a magnesium-

based bioresorbable scaffold into clinical practice with low target lesion failure rates and only one scaffold thrombosis after DAPT cessation.”

Verheye told Cardiovascular News: “Bioresorbable scaffolds complement our armamentarium, particularly for patients with long life expectancy. To assure patients’ safety, the implantation guidelines should be meticulously adhered to.”

Magmaris

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Patient information

Comics may help patients to better understand coronary interventions A pilot study, published as a research letter in the Annals of Internal Medicine, has found that patients who received comics or “medical graphic narratives” as well as standard informed consent protocols (official consent form and a conversation with a physician) had greater comprehension of the coronary angiography procedure that they underwent and less anxiety than those who only received the standard protocols.

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riting in the Annals of Internal Medicine, Anna Brand (Charité Universitätsmedizin Berlin and DZHK, Berlin, Germany) and colleagues report that the 2018 European guidelines for myocardial revascularisation highlighted the need for “active patient participation and the use of terminology that the patient understands”. However, they add that prior studies have indicated that “a large proportion of patients undergoing coronary interventions do not seem to understand the rationale for treatment and have erroneous perceptions regarding expected benefits”.

According to the authors, comic narratives “may communicate complex health information more clearly” than current approaches to explaining the necessary information. They state that comic-based approaches “allow each patient to acquire and process information at his or her own speed”, adding that “the use of pictures in close juxtaposition with written or spoken text has been reported to increase patients’ ability to understand and recall health information compared with text alone”.

In the study, 121 patients being considered for coronary angiography were randomised to receive standard informed consent protocols (61) or standard protocols plus comics (60). The primary outcomes were understanding of the procedure-related information and periprocedural state anxiety.

Brand et al found that patients who received the comics “had significantly better comprehension, which was attributable to higher scores in all three

subcategories of comprehension items: procedural details, risks, and behavioural measures after procedure”. They also found that after the procedure, periprocedural state anxiety—as assessed by the Spielberger StateTrait Anxiety Inventory— Anna Brand was decreased in patients in the comic group but was increased in patients in the standard protocol alone group, compared with their respective baseline levels. Furthermore, significantly more patients in the comics group felt that they were “well prepared” for cardiac catheterisation: 71.7% vs. 41% for the standard protocols alone group (p=0.01).

“Our pilot trial provides novel proof-of-concept data regarding the benefit of medical graphic narratives as supplementary patient information and consent material before coronary angiography,” Brand et al observe.

They add that larger, multicentre trials are warranted to further assess the advantage of a comic-assisted informed consent approach.

Brand told Cardiovascular News: “In this context, the adage ‘a picture is worth a thousand words’ has proven to be very useful to assist and improve the patient informed consent procedure. More than 93% of the

Editors-in-chief of major cardiovascular journals claim medical misinformation puts “lives at stake” The editors-in-chief of major cardiovascular journals—of both US and European societies—have come together to “sound the alarm” about the dangers of medical misinformation that has been disseminated through the internet, social media, and other platforms. They claim that this misinformation is dangerous, because it leads to patients refusing medication, such as statins, with documented life-saving benefits.

JOSEPH A HILL (Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, USA) and others write in Circulation, and in several other international cardiovascular journals, that medical misinformation “hyped through the internet, television, chat rooms, and social media” has caused many patients to think that the risks of statins are far worse than they actually are and, as a result, they refuse to take the drugs.

“Most patients do not recognise that the benefits of statin use are invisible (‘I did not have a heart attack or stroke

this past year’), whereas the small and typically reversible risks (for example, muscle pain) are readily apparent,” they add.

The authors note that patients rejecting statins is just one example of the effects of medical misinformation, and that another is parents not letting their children be vaccinated following an infamous—and now widely discredited—paper that linked autism to the MMR vaccine.

Furthermore, Hill et al say that some celebrities, actors, activists, and politicians promote false or misleading

Comic narratives may communicate complex health information more clearly than current approaches.” patients completely denied feelings of being not taken seriously by the comic, underlying the high acceptance of this new method (a high percentage of patients had university or a polytechnic degree). Most of the patients gave very positive feedback and welcomed the new informed consent approach.”

medical ideas and claim “not uncommonly” there are people acting with “purely venal motives”.

According to Hill et al, “the strident alarms” by well-known Joseph A Hill people “speaking in absolute terms” exacerbate the problem of medical misinformation, because their words resonate better with the general public than the “nuanced voices” of scientists.

The authors state that scientists “appropriately couch their statements in statistical terms, which may come across to the public as equivocation”.

Hill et al, therefore, have written their editorial to “sound the alarms that human lives are at stake” and call on the media to “do a better job” at avoiding sharing medical misinformation.

“It is unacceptable to posit false equivalents in these discussions [such as the risks and benefits of statins], often done to foster debate and controversy.

It is easy to find a rogue voice, but inappropriate to suggest that this voice carries the same weight as that emerging from mainstream science,” they comment.

In particular, given that misinformation tends to travels faster through social networks than the truth,

Hill et al write that the “purveyors of social media must be responsible for the content they disseminate” and that it is no longer acceptable for these purveyors to “hide behind the cloak of the platform”. They explain that, as editors-in-chief, they “reach out to thought-leading experts to evaluate the veracity of each report” they receive, and “challenge social media to do the same”—“to leverage the ready availability of science-conversant expertise before disseminating content that may not be reliable”.

“Without exaggeration, significant harm, to society and individuals, derives from the wanton spread of medical misinformation. It is high time that this stops, and we lay at the feet of the purveyors of the internet and social media content the responsibility to fix this,” Hill et al conclude.

Hill told Cardiovascular News: “The internet and social media platforms are replete with false information, which does real harm to individuals globally.

We charge the purveyors of these media to take first steps in addressing this enormous problem, and we, in the academic medical community, stand ready to help.”

As well as being published in Circulation, the editorial was also published in the European Heart Journal, the Journal of Electrocardiology, and the International Journal of Cardiology, among others.

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Edwards PASCAL™ Transcatheter Valve Repair System is innovative On February 12, 2019, Edwards Lifesciences received the CE mark for its PASCAL transcatheter valve repair system for managing mitral regurgitation.1 In this article, Cardiovascular News reviews how the system works and speaks to Dr Stephan von Bardeleben (Head of Heart Valve Center Mainz, Center of Cardiology, University Medical Center, Mainz, Germany) about his experience with the PASCAL repair system.

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he PASCAL implant consists of a central spacer that is designed to fill the regurgitant orifice area and with paddles that are intended to maximise coaptation and reduce stress on the native leaflets. The implant also has clasps that allow for independent leaflet capture and offer the possibility to finetune leaflet positioning.2 Furthermore, its 22F delivery system includes independent catheters that enable simplified manoeuvring in three planes, and stabilisers that lock handles in place for procedural ease.

Dr von Bardeleben says the PASCAL repair system is an “innovative step towards treating mitral regurgitation”.

He explains that a major benefit of the central spacer is that the operator does not have to “pull the leaflets of the mitral valve as far together as you would with a conventional surgical approach or already available transcatheter systems”.

He adds that the paddles, which go on the outside of the valve, (“together with the spacer”) help repair the valve in its coaptation deficit and better distribute the forces of the system over a larger area of the native valve leaflets. “That is a very important part of the system,” he notes. Furthermore, the paddles flex on every heart beat “so that the system dynamically flexes as the valve opens and closes”.

According to Dr von Bardeleben, the independent clasping function of the PASCAL repair system also has unique benefits: “We can individually control each side of the clasp mechanism, which is completely new to the market. This means that we can reopen one side of the clasp while keeping the other clasp in its fixed position. This allows you to move the system to the more defective, weaker leaflet, optimise its capture and reclose the system for optimal results.

This independent leaflet capture feature enhances the efficacy of the PASCAL repair system,” he explains.

As with all transcatheter systems, the PASCAL repair system is a less invasive approach for patients. For example, the entry point into the groin is 0.7–0.8cm, whereas the smallest access for a surgeon is 3–6cm (which would be regarded as “a small approach” in surgical terms).

Additionally, the patient is immediately extubated after the procedure (while still in the cath lab) and sent to a normal ward. There is no need for pain medication (unlike with valve surgery), the patient can already be mobilised within 12 hours after the procedure, and they can be discharged after two days.

comments: “In all cases, the PASCAL repair system was easy to implant because of the ease of use, the ability to manoeuvre, the independent clasping, the elongation ability and the contoured paddles.” If heart centres are looking to start implanting the PASCAL repair system, Dr von Bardeleben believes the learning curve depends on the operator’s experience. He notes that, compared with valve surgery, transcatheter procedures are “unique” and imaging training is needed to guide the procedure. “With the PASCAL repair system, the training concept is that you will become an experienced implanter within 15 to 20 procedures if you do not have already advanced experience of implanting transcatheter therapies. But if you have prior experience, you can become very experienced after 10 implants.”

Patient outcomes

Dr. Stephan von Bardeleben

Dr von Bardeleben says, “We make sure there is no bleeding and no issues at the puncture site and then the patient can be discharged. We have even had patients aged 82 years leave two days after implantation. The patient will not see anything from the procedure after one week, not even a scar. They can go back to their normal activity within five days.”

Planning and performing transcatheter valve repair with the PASCAL repair system

The Heart Valve Center Mainz has performed 22 implants of the PASCAL repair system overall—including 13 procedures after the CE mark was granted. In line with the 2017 European Society of Cardiology (ESC) guidelines for valvular heart disease, in its capacity as a heart valve centre of excellence, a multidisciplinary heart team makes the decision about whether a patient is a suitable candidate for undergoing transcatheter repair with the PASCAL repair system.3 Dr von Bardeleben explains: “In our heart team, there is an interventional cardiologist [Dr von Bardeleben], a cardiac surgeon who has experience of performing mitral valve repair, a cardiac imaging specialist, and an anaesthesiologist. Sometimes, we also have a geriatrician or a heart failure specialist.”

Prior to implanting the PASCAL repair system, the Heart Valve Center Mainz heart team assesses the patient to exclude and/or control coronary artery disease. They then use transthoracic and transoesophageal echocardiography to plan the procedure. During the procedure itself, transoesophageal echocardiography is used alongside fluoroscopy (according to Dr von Bardeleben, the ratio is 80% to 20%, respectively). Dr von Bardeleben says that the transoesophageal echocardiography “gives us brilliant images of the mitral valve, which is 5cm to 6cm away from the oesophagus”, adding that the image quality is so good “that it is like a virtual Hollywood movie”. Of note, contrast is not needed, and this makes implanting PASCAL “a soft and harmless procedure for the renal function of the patient”.

The typical patient who receives transcatheter valve repair either has functional mitral regurgitation between 50 and 90 years of age, or is an older patient with degenerative mitral regurgitation disease. However, at the Heart Valve Center Mainz, so far, patients who have undergone transcatheter valve repair with the PASCAL repair system have been between 75 and 92 years of age (with either degenerative or functional mitral regurgitation). Dr von Bardeleben

In his experience of implanting the PASCAL repair system, Dr von Bardeleben has seen an immediate change in patients after the procedure.

“Typically, we see a rise in blood pressure—blood pressure is one of the quality assurance controls—and we also typically see a reduction in pressure in the left atrium by about 6–9mmHg. Using colour Doppler, we observe a reduction in effective regurgitant orifice area.” He adds that, following the procedure, New York Heart Association (NYHA) functional class values “go back by one or two grades” and patients are able to “perform better” without experiencing dyspnoea. “The six-minute walk test is important to evaluate the exercise capacity of the patient. We do a baseline six-minute walk test and patients are usually able to walk 250m. But after the procedure, we see these distances increase by about 40m to 80m.”

When Cardiovascular News spoke to Dr von Bardeleben (April 2019), he had one-month follow-up data for the first five patients with functional mitral regurgitation who received the implant after the CE mark was granted. He says that they are all “doing very well” and have “trace to mild grade residual mitral regurgitation”.

References 1. Cision PR Newswire. Edwards PASCAL Transcatheter System Receives CE Mark. https://prn.to/2ShEB4D (date accessed 5 April 2019).

2. U Schaefer. Early Outcomes from the Multicenter, Prospective Study with the Novel PASCAL Transcatheter Mitral Repair System for Patients with Mitral Regurgitation. DGK 2019.

3. H Baumgartner, V Falk, JJ Bax, et al. 2017 ESC/ EACTS Guidelines for the management of valvular heart disease. European Heart Journal 2017; 38: 2739–91.

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Structural Heart Interventions Reconciling the contrasting findings on MitraClip, and implications for the management of functional mitral regurgitation Omar Chehab Comment & Analysis Last year, the first two randomised controlled trials (RCT) looking at percutaneous edge-to-edge repair (MitraClip, Abbott) for the management of functional mitral regurgitation (MR) were published. MITRA-FR was presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich Germany), and showed no prognostic benefit for MitraClip over medical therapy for functional mitral regurgitation. In contrast, the COAPT (Cardiovascular outcomes assessment of the MitraClip percutaneous therapy for heart failure patients with functional mitral regurgitation) trial, presented at the 2018 Transcatheter Cardiovascular Therapeutics (TCT) meeting (21–25 September, San Diego, California), showed significant benefit in favour of MitraClip over medical therapy for all endpoints, including heart failure hospitalisation and mortality. Omar Chehab discusses the differences between the two randomised trials, and examines the implications for the future management of functional mitral regurgitation.

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n obvious difference between the two trials is their design— COAPT enrolled roughly double the number of patients of MITRA-FR (614 vs. 304), at twice as many sites (78 vs. 37), and follow-up in COAPT was 24 months, compared to 12 months in MITRA-FR. But perhaps the most likely explanation for the difference in outcomes of the two trials lies in patient selection. COAPT applied stricter inclusion criteria, allowing patients with a left ventricular ejection fraction (LVEF) between 20 and 50%, and left ventricular end-systolic diameter of

≤70mm. MITRA-FR included patients with a LVEF of 15–40%, with no limit set on left ventricular size. The criteria for significant mitral regurgitation were also different. COAPT included patients with an effective orifice area of ≥30mm2 and a regurgitant volume of ≥45ml/beat.

MITRA-FR included patients with an effective orifice area of ≥20mm2 and a regurgitant volume of ≥30ml/beat. And, unlike MITRA-FR, COAPT did not include patients with untreated significant coronary artery disease (and patients with significant pulmonary hypertension or right ventricular impairment.

When comparing the patient cohorts,

Lotus Edge becomes third TAVI device on US market

the mean effective orifice area and left ventricular end-diastolic volume (LVEDV) in COAPT was 41mm2 and 101mL/m2, respectively, compared to 31mm2 and 135mL/m2 in respectively MITRA-FR. Hence, COAPT patients had more mitral regurgitation and less left ventricular dilatation than those in MITRA-FR. Therefore, it is possible that the MITRA-FR patients had worse outcomes because the proportion of mitral regurgitation severity to left ventricular function/dimension tipped the balance towards cardiomyopathy being the prognosis-defining issue, rather than the severity of the mitral regurgitation.

Another distinction between the two trials was the uptitration of optimal medical therapy. The MITRA-FR patients were very well medicated in terms of prognostic heart failure treatment, at least matching COAPT when it came to the percentage of patients on angiotensin inhibitors, beta blockers, and mineralocorticoids; 10–12% of MITRAFR patients were on an angiotensin/ neprilysin inhibitor compared to 3–4% of patients in COAPT. In MITRA-FR, the adjustment of medication mimicked realworld practice, and took place gradually after trial enrolment. Whereas, a central eligibility committee determined whether a patient was already on maximal tolerated optimal medical therapy before enrolment in COAPT, and very little adjustment occurred during follow-up.

In terms of procedure safety and durability, the complication rate in COAPT was 8.5% compared to 14.6% in MITRA-FR. The short-term mitral regurgitation reduction with MitraClip was comparable in both trials—this reduction was maintained in COAPT at 12 months (94.8% of patients had ≤grade 2 mitral regurgitation). In MITRA-FR, some echo data were missing, but from available information at least 48 patients in the intervention group had ≥grade 2 mitral regurgitation at 12 months, out of the 138 MitraClip patients.

Finally, follow-up in MITRA-FR was 12 months compared to 24 months in COAPT. A point raised in the discussion that followed the presentation of the COAPT results was that the mortality benefit was observed predominantly more than one year after treatment, which favours the trial with the longer

Boston Scientific has received US Food and Drug Administration (FDA) approval for its Lotus Edge transcatheter aortic valve implantation (TAVI) system. Previously, the only TAVI devices on the US market were Medtronic’s CoreValve and Edwards Lifesciences’ Sapien 3/Sapien XT. ACCORDING TO A press release, the Lotus Edge valve system is the only FDA-approved aortic valve that gives physicians the option to reposition and completely recapture the valve once it has been fully deployed. The valve also features a braided valve frame and an adaptive

follow-up duration.

What are the implications for the management of secondary mitral regurgitation? The fact that we have had two trials with differing designs and outcomes is useful, and many regard them as complementary rather than contradictory. MITRA-FR patients and outcomes more likely reflect realworld practice, whereas COAPT has demonstrated that, in the right patient, MitraClip can have significant and lasting prognostic benefit on top of optimal medical therapy.

COAPT brings into question the notion that mitral regurgitation in the diseased ventricle is a mere bystander and that the prognosis is entirely driven by cardiomyopathy. The marked improvement in survival seen in COAPT patients suggests that mitral regurgitation has an added pathophysiological role in left ventricular deterioration.

Interestingly, the subgroup in COAPT that did not benefit from MitraClip were the 10% of patients with an effective orifice area <30mm2 and a left ventricular end-diastolic volume greater than the median. Going forward, it would be helpful to better understand the pathophysiological relationship between mitral regurgitation and cardiomyopathy, and at what point treating mitral regurgitation can lead to positive remodelling and prognostic benefit.

These trials support the value of guideline-directed optimal medical therapy, resynchronisation therapy, and revascularisation where indicated.

Crucially, what COAPT and MITRAFR tell us is that timely intervention in significant mitral regurgitation can have a substantial additive benefit for a sick patient cohort who currently have a poor prognosis and high hospitalisation rate— ideally, before the pendulum swings away from the mitral regurgitation and towards the cardiomyopathy as the dominant prognosis-defining issue.

We await the results of RESHAPEHF2, the third randomised controlled trial of MitraClip in secondary mitral regurgitation, to see what this will add to the debate.

Omar Chehab is at Guy’s and St Thomas’ NHS Foundation Trust, London, UK.

seal that minimises paravalvular regurgitation or leaking by conforming to the patient’s native aortic valve.

Ian Meredith, executive vice president and global chief medical officer at Boston Scientific, comments: “We are thrilled to offer physicians in the USA and Europe the clinical benefits of the Lotus Edge valve system for the treatment of their high-risk patients with severe aortic stenosis. This system provides physicians a high level of control over the delivery and deployment of the device.”

The company commenced a controlled launch of the valve system in Europe in March, and expects to begin a controlled launch in the USA soon.

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Sapien 3 provides safe and satisfactory access via the transcarotid route The Sapien 3 device (Edwards Lifesciences) can be safely and effectively used in transcatheter aortic valve implantation (TAVI) via the transcarotid approach in patients for whom the transfemoral route is not suitable, according to 30-day results from a multicentre French registry. The authors of the study, published in the Journal of the American College of Cardiology: Cardiovascular Interventions, say: “This descriptive study reports the largest contemporary cohort to date of transcarotid TAVI and demonstrates the safety and efficacy of the transcarotid approach for TAVI with the Edwards Sapien 3 transcatheter heart valve.”

TRANSFEMORAL ACCESS IS the favoured route for TAVI. Although there have been suggestions of a possible role for transcarotid access in patients for whom this approach is precluded, there is very little data on the safety and efficacy of Sapien 3.

The French Transcarotid TAVI registry is a collaborative initiative developed by interventional cardiologists and cardiac surgeons performing transcarotid TAVI. Patient data, including demographics, clinical and procedural characteristics, and outcomes, were prospectively collected between January 2014 and April 2018 from 13 participating centres.

Patients with severe symptomatic aortic stenosis estimated to be at high surgical risk were considered for TAVI, and multimodal vascular imaging was performed to determine the possible approaches. When patient anatomy ruled out transfemoral access, a non-femoral route was considered.

Overall, 6,680 patients underwent TAVI at the 13 centres; 314 patients were treated with the Sapien 3 transcatheter heart valve through the transcarotid approach and included in the study.

Median age was 83 years old, and 63%

were male. One-third of participants had atrial fibrillation, two-thirds had moderate to severe chronic renal failure, and 64% had peripheral arterial disease.

In 91% of patients, transcarotid TAVI was performed under general anaesthesia, and in 73.6% of cases, access was via the left carotid artery. The procedural success rate was 97%. Three annulus ruptures were reported, all of which led to patient death. At 30 days, the rate of major bleeding was 4.1%, new permanent pacemaker 16%, and rate of stroke or transient ischaemic attack was 1.6%.

The 30-day mortality rate was 3.2%, and median hospital stay was seven days.

Pavel Overtchouk, Thomas Modine (both Lille University Hospital, Lille, France) and others acknowledge the limitations of the study, which included possible bias, as “only patients treated with the Sapien 3 device were included”.

Additionally, they say: “Outcomes of this study represent those of tertiary highvolume TAVI centres familiar with the transcarotid approach, thus should be interpreted with caution. Registry data can also be subject to under reporting of complication rates.” And, because follow-up was for 30 days only, they

propose that “more extended followup might provide further insight regarding longterm outcomes”.

The authors also call for further Thomas Modine studies to assess the suitability of other access routes, such as transsubclavian, transapical, and transaortic, and for more extensive data on the safety of transcarotid TAVI in low-risk patients and all-comers to “allow operators to consider this approach regardless of the risk profile”.

The observation of two conversions to open surgery in the registry, attributed

A transcarotid approach could become the first-line alternative for TAVI in selected patients.”

Evolut R superior to surgery at one year in intermediate-risk patients A subanalysis from the SURTAVI trial has found that transcatheter aortic valve implantation (TAVI) with Evolut R in intermediate-risk patients has lower rates of all-cause mortality or disabling stroke than surgical valve replacement 12 months after implantation.

Steven J Yakubov (Riverside Methodist Hospital, Columbus, Ohio, USA) presented data from a propensity-score matched comparison at a late-breaking trial session at Cardiovascular Research Technologies (CRT) 2019 (2–5 March, Washington DC, USA).

The findings have also been published in the Journal of American College of Cardiology: Cardiovascular Interventions.

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e said: “All-cause mortality or disabling stroke at one year were less with TAVI compared to surgical aortic valve replacement. The transcatheter replacement group had less aortic valve or heart failure hospitalisations and less atrial fibrillation than the surgical replacement group at one year, and there was more need for permanent pacemaker implantation in the transcatheter group.”

The randomised SURTAVI trial demonstrated that TAVI using a self-expanding valve is non-inferior to surgical aortic valve replacement for the primary endpoint of all-cause mortality or disabling stroke at two years in patients at intermediate risk. Yakubov explained: “The Evolut R device was approved by the US FOOD and Drug Administration (FDA) as SURTAVI was enrolling patients; as a result, CoreValve was implanted in 84% of the patients in the transcatheter arm of the study, with only the remaining 16% receiving Evolut R. A continued access study was initiated after SURTAVI was fully enrolled to allow analysis of transcatheter implantation using the Evolut

R device in intermediate-risk patients.”

The aim of the SURTAVI propensity-score matched analysis was to compare one-year outcomes with Evolut R in intermediate-risk patients to those from a comparable surgical replacement cohort. Propensity matching on 22 variables allowed comparison between

Evolut R had significantly better valve performance.”

197 Evolut R patients and 197 SURTAVI participants who underwent surgery. Average age was 79 years, and 40% of patients were male. Other matched variables included body mass index (BMI), New York Heart Association (NYHA) classification III/IV, need for revascularisation, peripheral vascular disease, and diabetes controlled by insulin.

At 12 months, combined all-cause mortality and

to excessively tortuous carotid anatomy, led Overtchouk and Modine et al to recommend that “excessive tortuosity of the carotid artery should be considered as a contraindication to the transcarotid approach”, and that “transcarotid access should only be attempted after careful evaluation of its feasibility on preoperative MSCT [multislice computed tomography]”.

They describe the 30-day mortality rate as “acceptable” and “lower than previous observational reports with the transcarotid access in higher risk patients (6% to 7%)”. Stroke and transient ischaemic attack are a major concern when using the transcarotid route, and the researchers suggest the low rate could have been due to the preoperative evaluation, which may have selected patients at lower risk of cerebrovascular events.

Overtchouk and Modine et al propose that a transcarotid approach could become the first-line alternative for TAVI in selected patients where transfemoral access is prohibited: “The Sapien 3 device was safe and effective in our multicentre cohort. The transcarotid approach could be considered as a safe alternative approach for TAVI.”

disabling stroke on a Kaplan-Meier analysis were 4.1% (95% confidence interval [CI] 1.8–9.3) in the Evolut R patients vs. 8.2% (95% CI 5.1–13.1; p=0.08) among patients who had had surgery. Disabling stroke rates alone were 1% (95% CI 0.2–5.6) and 3.1% (95% CI 1.3–6.9; p=0.15), respectively, and there were less aortic valve hospitalisations using Evolute R (4.6% vs.

3.8% with surgery; p=0.33). In other clinical outcomes, the percentage of atrial fibrillation in patients receiving Evolut R was almost half that of those who underwent surgery (18.2% vs. 37.4%; p<0.01), and permanent pacemaker implantation rates were doubled (Evolut R 15.3%, surgery 7.8%; p=0.02).

Additionally, said Yakubov: “Evolut R demonstrated excellent haemodynamic performance. It had significantly better valve performance over surgery at all follow-up visits—baseline, discharge, six months, and one year [p<0.01].”

Among patients implanted with Evolut R, 61.2% experienced either no or trace aortic regurgitation (core lab adjudicated) and 32.9% had mild regurgitation; with 92% of surgical patients having no or trace regurgitation and 7.9% experiencing mild aortic regurgitation.

Evolut R also performed favourably on the outcomes of all-cause mortality and disabling stroke in a comparison of the propensity score matched analysis against the main SURTAVI trial—Evolut R 4.1% versus all TAVI 7.8% and all surgical replacement 8.5%.

Yakubov concluded: “The results for Evolut R TAVI were achieved compared to a propensity-score matched surgical group that had low STS [Society of Thoracic Surgery risk] scores. Advancements in catheter design technology may help drive greater success for intermediate-risk patients with severe, symptomatic aortic stenosis.”

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The Tricento transcatheter heart valve: A novel approach for the treatment of tricuspid regurgitation Stefan Toggweiler Comment & Analysis In this commentary for Cardiovascular News, Stefan Toggweiler writes about how the Tricento device could address the current need in the management of tricuspid regurgitation and more.

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ricuspid regurgitation is a common valvular heart disease that has been directly related to higher morbidity and mortality rates.1 When tricuspid regurgitation is severe, the pressure in the right atrium and the caval veins rises and backflow during systole (the so-called “v wave”) occurs. In this situation, congestion leads to oedema, ascites and, finally, impaired function of the organs, including the liver and the kidneys.

Affected patients may remain asymptomatic for a long time. Over time, right ventricular function may decrease and patients become symptomatic.

However, operative risk in such patients is high and outcomes may be suboptimal.

Therefore, there is a consensus in the community that patients should be identified and treated earlier to improve outcomes and decrease operative risk.

Also, that low-risk procedures may be

a very attractive alternative to surgical treatment in such high-risk, often polymorbid patients.

Following the success of percutaneous

Long-term function of TAVI valves “is excellent” Daniel J Blackman (Department of Cardiology, Leeds Teaching Hospital NHS Trust, Leeds, UK) and others report in the Journal of the American College of Cardiology (JACC) that 91% of patients remained free of severe structural valve degeneration between five and 10 years after receiving a transcatheter aortic valve implantation (TAVI). They note that they have described the largest cohort of patients with echocardiographic assessment of valve function between five to 10 years.

BLACKMAN ET AL write that studies “have consistently shown preserved valve function up to five years after TAVI”. But, they add, structural valve degeneration is usually not seen with surgical valves until five to 10 years post procedure “and data in this

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19 53 treatment of aortic and mitral valve disease, a number of devices have now been developed aiming to repair the tricuspid annulus which has led to mixed outcomes. The tricuspid valve poses many challenges, such as complex variable anatomy, often severely dilated annuli and associated poor right-ventricular function. Therefore, alternative catheter-based concepts such as (bi)caval valve implantation (CAVI) have been utilised and may offer new perspectives in this field.2 CAVI aims to reduce backflow into the caval veins and treat associated congestions of the organs and symptoms of heart failure.

The concept of the Tricento transcatheter heart valve

The Tricento transcatheter heart valve aims to abolish backflow in the venous system to alleviate symptoms associated with tricuspid regurgitation without touching the native tricuspid valve. It consists of a bicaval anchored covered stent with a lateral bicuspid valve element made of thin porcine pericardium leaflets with a low closing pressure.

The Tricento valve aims to abolish the systolic backflow in both the inferior and superior caval veins, addressing the regurgitation of both caval veins with one single implant. The valve is delivered through a 24F delivery system via transfemoral access. Implantation is performed top-down without the need for rapid pacing. The device is fully repositionable and retreivable up to its final release. To account for the marked inter-patient anatomical variability, the stent length and diameter in the current iteration must be custom made.

Following the successful first-in-human implantation, which was performed at our institution in Lucerne hospital, Switzerland, six more implants have been performed.3 From this preliminary experience it can be stated that the procedure is safe and straightforward. The valve was implanted at the target position in all cases. A marked reduction of the v-wave in the caval vein was documented,

timeframe following TAVI are very sparse”. Thus, reviewing data from the UK TAVI registry, the authors sought to “evaluate long-term valve function and to determine the incidence of haemodynamic structural valve degeneration between five and 10 years after TAVI”.

Data were available from 15 UK centres that performed TAVI between 2007 and 2011, with paired echocardiographic data both at baseline and ≥4.5 years post TAVI available for 241 patients. Overall, the median follow-up was 5.8 years, but this extended to six years in 168 patients, seven in 68, eight in 30, and nine in four, and 10 years in two patients.

At five years and four months, one patient who received a 26mm self-expanding valve developed severe structural valve degeneration and was not considered fit for further treatment. No other cases of severe degeneration were reported and only 21 cases of moderate structural valve degeneration were reported.

In the moderate cases, degeneration was observed at a median duration of six years and one month (range four years and 11 months to eight years, and seven months).

Blackman et al comment: “Thirteen (62%) of these patients were treated with the self-expandable valve, and eight (38%) with a balloon-expandable valve.”

potentially translating into improved organ perfusion. Indeed, improvements in kidney function, liver function, appetite and functional status were documented following these implants.

Since the lateral valve element faces towards the interatrial septum, a trans-septal puncture for a left-sided procedure is still possible (for example, the MitraClip, Abbott). Since the native tricuspid valve is not touched, the Tricento valve does not preclude later surgical treatment or additional percutaneous therapies.

The future

Efficacy regarding long-term haemodynamic and clinical outcomes has yet to be proven in prospective studies including a larger number of patients.

The concerns associated with CAVI include the ventricularisation of the right atrial pressure as well as the persistence of atrial and ventricular volume overload, potentially promoting right-ventricular failure and atrial fibrillation. However, in the present limited human experience no such effects were observed.

The question also remains if this procedure can be performed in patients with a pre-existing pacemaker. There are a few concerns with this as there is a possibility of lead migration, a higher risk for an endoleak and the unknown risk of long-term insulation defects of the leads.

Conclusion

The Tricento valve may reflect a promising and safe therapeutic alternative in order to improve heart failure-related symptoms and quality of life for patients with severe tricuspid regurgitation who are not considered suitable to undergo open heart surgery.

References 1. Nath et al. J Am Coll Cardiol 2004; 43(3): 405–09.

2. Lauten et al. Eur Heart J 2014; 35: 1651.

3. Toggweiler et al. EuroIntervention 2018; 14(7): 758–61.

Stefan Toggweiler is the co-chief physician of cardiology and head of interventional cardiology at Lucerne Hospital in Switzerland.

However, according to the authors, the “substantial majority of patients (220; 91%)” did not experience structural valve degeneration.

Furthermore, at follow-up, peak gradient was significantly lower (17.1mmHg vs. 19.1mmHg; p=0.002), the rate of none/trivial aortic regurgitation was increased (47.8% vs. 32.9%; p=0.055), and the rate of mild aortic regurgitation was lower (42.5% vs. 57%; p=0.02) compared with baseline levels. However, there was no change in the rate of moderate regurgitation, and one patient developed severe aortic regurgitation at follow-up.

In terms of different types of TAVI valves, 149 patients received CoreValve (Medtronic) and 80 received Sapien/ Sapien XT (Edwards Lifesciences). “The self-expanding bioprothesis was associated with a fall in peak gradient from baseline to follow-up, and a change in the degree of aortic regurgitation from mild to none/trivial,” Blackman et al comment. No such differences were observed with the balloon-expandable valve.

They conclude: “Long-term TAVI valve function after TAVI was excellent with no increase in gradient of regurgitation at a median follow-up of 5.8 years, up to a maximum of 10 years, and severe structural valve degeneration occurred in <0.5% of patients.”

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A “crackdown” on alternative access for TAVI

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Carlo Di Mario Comment & Analysis The transfemoral approach is—by far—the most desirable access route for transcatheter aortic valve implantation (TAVI) for eligible patients; it was used in the TAVI arm of the recently published PARTNER 3 trial, showing superiority over surgical aortic valve replacement in low-risk patients (see page 1). Results from the National Inpatient Sample Database suggest that transfemoral access is safer and associated with lower in-hospital stay, mortality and costs, compared with the transapical approach. In this commentary, Carlo Di Mario reviews how intravascular lithotripsy may enable more patients to undergo transfemoral TAVI. ADDITIONAL ALTERNATIVE access techniques for TAVI—such as transaxillary, transcarotid and transcaval access—have been refined but have only been studied in small prospective registries. Their generalisability to all TAVI programmes is unlikely because of the demanding learning curve and hesitation on the part of many centres to embark into alternative access TAVI procedures.

The use of intravascular lithotripsy to alter compliance, allowing successful dilatation in calcified infrainguinal peripheral arterial vessels, was reported in a controlled registry. These findings led to the granting of the CE mark and

Food and Drug Administration (FDA) approval for intravascular lithotripsy peripheral balloons up to 7mm in diameter.

Modifying vascular compliance via intravascular lithotripsy in larger suprainguinal vessels, such as the iliac arteries, was initially reported in two cases, and demonstrated feasibility.

A recently published 42-patient registry robustly showed high efficacy in allowing transfemoral access for TAVI after intravascular lithotripsy, maintaining excellent overall procedural outcomes, including vascular events and perivalvular regurgitation. Key highlights from that registry are as follows:

CT reconstruction of left iliac artery, demonstrating severe nearly circumferential calcification with lumen diameters below 5.5mm (A). Infrarenal aorta and iliac axis angiography showing coexistent severe tortuosity (B). Intravascular lithotripsy balloon inflation (4atm) at two different sites (C and D). Successful implantation of a 26mm CoreValve Evolut R prosthesis (E). Final iliac angiography showing no significant dissections (F).

42 consecutive TAVI patients with prohibitive calcified, stenotic femoral-iliac disease received intravascular lithotripsy 100% heavy calcification with a 265.5-degree average maximum arc of calcium >90% access was percutaneous and closed with a percutaneous closure system 100% transfemoral valve delivery success Zero flow-limiting dissections or perforations Zero provisional stenting.

The three main obstacles to using the transfemoral route in TAVI are small vessel diameter, excessive vessel tortuosity and the presence of severe peripheral vascular disease of the iliac and/or the femoral arteries. The presence of severe circumferential arterial luminal calcification is a common finding in elderly patients with

TAVI in bicuspid stenosis provides satisfactory clinical outcomes Transcatheter aortic valve implantation (TAVI) using the current generation of balloon expandable technology leads to acceptable clinical outcomes in the bicuspid anatomy, according to an analysis of the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) TVT Registry. Raj B Makkar (Cedars Sinai Medical Center, Los Angeles, USA) outlined outcomes following TAVI with the Sapien 3 valve (Edwards Lifesciences) in bicuspid aortic stenosis at the American College of Cardiology Scientific Session (ACC 2019; New Orleans, 16–18 March).

M

akkar said: “These data provide an argument for TAVI to be a reasonable alternative for bicuspid aortic stenosis in patients who are intermediate or high risk for aortic valve replacement, and provide a sound basis to conduct a randomised clinical trial in young patients with bicuspid aortic stenosis who are low risk for surgery.”

Up to 50% of patients in the younger population require surgical valve replacement of the bicuspid aortic valves.

Researchers sought to compare outcomes in native bicuspid versus tricuspid aortic valve stenosis following TAVI with the balloon expandable Sapien 3 valve in the

real-world STS/ACC TVT registry.

The study population was 92,236 Sapien 3 TAVIs in the registry between June 2015 and November 2018 at 552 sites; 2,276 were bicuspid Sapien 3 patients, and 79,096 were tricuspid Sapien 3 patients. Following 1:1 propensity matching across 25 covariates including age, gender, body mass index, carotid stenosis, and peripheral arterial disease, 2,691 bicuspid Sapien 3 patients and 2,691 tricuspid Sapien 3 patients remained for comparison.

The primary endpoint was mortality and stroke at 30 days and one year, with secondary endpoints procedural

complications, in-hospital adverse events, post-procedural echocardiographic assessment of the valve, and functional and health status at 30 days and one year. Device success rate was 96.5% in the bicuspid cohort and 96.6% in the tricuspid group (p=0.87), with a conversion to open surgery rate of 0.9% vs. 0.4%, respectively (p=0.03).

Annulus rupture rate was 0.3% vs. 0%, respectively (p=0.02), and 0.4% of bicuspid AS patients needed a second valve, compared to 0.2% of tricuspid AS patients (p=0.16).

Kaplan-Meier estimates of 30-day outcomes for all-cause mortality were

aortic stenosis and often prohibits any consideration of transfemoral TAVI. Intravascular lithotripsy may represent a straightforward technique to preserve the benefits of reduced morbidity and mortality of transfemoral TAVI in patients with calcified peripheral arterial disease.

Additionally, the ease of intravascular lithotripsy and the familiarity of peripheral vascular angioplasty techniques may allow for TAVI centres of varying levels of experience and volume to adopt a strategy of routine intravascular lithotripsy followed by TAVI in carefully selected patients with prohibitive iliofemoral anatomy. Such a pathway could theoretically lead to benefits in quality of life, healthcare cost, and procedural morbidity as compared to referral to traditional alternative access TAVI or surgical valve replacement.

Carlo Di Mario is at Structural Interventional Cardiology, Careggi University Hospital, Florence, Italy.

2.6% among bicuspid patients vs. 2.5 in the tricuspid group (p=0.82), with all stroke at 2.4% vs. 1.6%, respectively (p=0.02). A new pacemaker was required in 9.1% of bicuspid patients vs. 7.5% of tricuspid (p=0.03), and rates of lifethreatening bleeding were low in both groups at 0.1%.

One-year all-cause mortality in the matched cohorts of bicuspid and tricuspid was 10.5% vs. 12% (HR 0.9, 95% CI 0.73–1.1; p=0.31), and one-year stroke was 3.4% vs. 3.1% (HR 1.28, 95% CI 0.91–1.79; p=0.16), respectively.

Haemodynamics were equivalent in both groups, with similar improvement after matching in quality of life metrics of New York Heart Association class and Kansas City Cardiomyopathy Questionnaire.

Makkar said: “This largest real-life registry of all consecutive TAVI with balloon expandable Sapien 3 valve for bicuspid compared to tricuspid was associated with similar survival at 30 days and one year, an increased risk of aortic root injury and conversion to open heart surgery, although overall rate was still low at <1%.”

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Profile

Adrian Banning Adrian Banning (John Radcliffe Hospital, Oxford, UK) initially wanted to fly a Boeing 747 but, aged nine, decided go into medicine instead. He talks to Cardiovascular News about his involvement in both the SYNTAX and the SYNTAX 2 trials, his work in myocardial injury after stenting, and his interest in left main intervention. He also discusses the work of the British Cardiac Intervention Society (BCIS) and the need for better stents/therapies for diabetic patients.

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

I wanted to be a doctor from about age nine. We have no medics in the family but we had a general practitioner come to talk to my fellow students and I at primary [elementary] school. After he left, I told my parents that was what I wanted to be. At medical school, I was initially interested in paediatrics but once I did cardiology, I knew was it my favourite.

My first exposure to interventional cardiology was a revelation. As interventional cardiologists, we get to make the diagnosis, confirm it with imaging and/or physiology and in many cases provide treatment—with stents or valves. That is very unusual within medicine to be responsible for the whole pathway of a patient's care; it is a real privilege.

Who have been your career mentors?

My first boss was Charles Pumphrey at St Georges (London, UK) and I learnt a lot from Roger Hall and Liam Penny in Cardiff (University Hospital of Wales, Cardiff, UK). I was really inspired by my first trip to the Transcatheter Cardiovascular Therapeutics (TCT) meeting (in Washington, DC, USA), and I decided that I would like to perform educational live cases. When I hosted and performed live cases (from Oxford, UK) during the 2010 TCT meeting, I fulfilled an ambition!

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

I can remember the first coronary stent implantation in Cardiff (UK) in 1993. Martin Rothman (previously the London Chest Hospital, London, UK) came to Wales to perform the procedure; 8F guide from the femoral artery on warfarin/aspirin/dipyridamole and dextran infusion.

The patient was an inpatient for five days afterwards, so things have moved on a lot since then! Clearly stents were initially amazing, but then drug-eluting stents seemed revolutionary when they were introduced.

More recently, transcatheter aortic valve implantation (TAVI) has transformed our valve practices—especially now that we are using local anaesthesia and TAVI has become a truly percutaneous technique.

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

I am pleased to say that there have not been too many disappointments. My centre (Oxford, UK) was a major recruiter for the SYNTAX trial, and I remember being disappointed when the one-year results were presented and showed that percutaneous coronary intervention (PCI) was inferior to coronary artery bypass grafting (CABG). However, we went on to recruit the first patient in the EXCEL trial—we ended up recruiting more than 100 patients for the study in Oxford—and I was delighted when improved PCI technologies and techniques meant that, for the first time, the data showed PCI and surgery to have equivalent outcomes (for left main disease).

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You have done substantial work in myocardial injury after PCI. What have been your key findings?

We showed that troponin elevation following stent implantation meant that myocardium was injured and we could not just ignore it. I think understanding this has given us insights into prevention of myocardial injury and this has improved safety and outcomes for patients.

You were the co-principal investigator of SYNTAX 2. What insights did this trial provide in terms of how PCI should be performed?

This trial used a contemporary approach to assessing multivessel disease by combining the use of physiological assessment with a pressure wire and intravascular ultrasound (IVUS) to confirm optimal stent deployment. Together with a third-generation drugeluting stent, we showed that our outcomes are much better than those we achieved in the original SYNTAX trial. We also showed that at two years post-procedure, outcomes with PCI are equivalent to CABG. The “takehome” message is to treat obstructive lesions that are causing ischaemia carefully and effectively, but leave areas of incidental, nonobstructive atheroma alone.

What are your current research interests?

I am still interested in left main and bifurcation intervention, and I am also interested in optimising reperfusion in ST-segment elevation myocardial infarction (STEMI). Our outcomes with stents are good for most patients, but I think there is more we can do for a sizeable minority. We need to identify the patients that are not going to do well with a standard approach at an early stage. We can then find and offer novel therapies that will help. At the moment, we are looking at PICSO (Miracor Medical), which is a coronary sinus device that seems to reduce final infarct size based on our initial non-randomised studies (performed in Oxford, UK).

Given the good outcomes we have seen with current generation drug-eluting stents, have we reached a plateau in terms of improving safety and efficacy with the latest generation stents?

I think the adverse outcomes that occur following stenting are more predictable than many people think and that we still need to improve our technique. Better stents/therapies for patients with diabetes are an unmet need.

As president of the British Cardiac Intervention Society (BCIS), what are your goals for the society?

We have a terrific community of interventional teams in the UK. We need to attract more people to interventional cardiology: nurses, physiologists, radiographers and female doctors. We can do this by showing how much our speciality can offer our patients and what an inspirational community we have. I am also hoping to facilitate the development in the UK for interventional

Outcomes with stents are good for most patients, but we can do more for a sizeable minority.” research. The annual Advanced Cardiovascular Intervention meeting (ACI; 16–18 January 2019, London, UK) is the flagship meeting of the BCIS, and I hope to make it the place to be in the UK, for interventional cardiologists, every January.

What were the highlights of this year’s meeting?

We had three sessions of live coronary cases, which

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Bifurcation Club—I hope they won’t throw me out after Brexit!

What was your most memorable case?

Oliver Ormerod (Oxford, UK) and I implanted the first unprotected left main PCI in Oxford in 1995.

The patient had a blocked right artery, and I remember the uncertainty about what would happen when we blew up the balloon and stent.

Fortunately, the patient did very well and it prompted an interest in left main intervention that I have pursued since then.

What advice did you receive at the start of your career that you now pass on to those whom you mentor?

I am not sure I had too much initial advice from others, but I have learnt that interventional cardiology is hard work and you have to be dedicated, persistent and inquisitive. Reflecting on procedures that do not go so well is really important because adverse outcomes will happen sometimes, and we should try to see if there are things we can do better next time. were excellent. The debates caused a lot of discussion, especially the topic of angiography in patients without ST-segment elevation who present with an out-ofhospital cardiac arrest. On a personal level, I was particularly pleased with the session on helping to attract more women into careers in interventional cardiology.

It was the fulfilment of a year’s project within this area and the presentations and the session were inspirational and thought-provoking.

What impact do you think Brexit will have on the field of interventional cardiology in the UK?

It is very hard to say. In my opinion, there are lots of potential downsides and not many possible gains to Brexit. Interventional cardiology is a worldwide community and I certainly would not want anything to isolate the UK from our friends and partners in Europe.

I am part of the steering committee of the European

What is your view of #CardioTwitter and its potential advantages/disadvantages?

I think I am probably a bit too old to really embrace Twitter! But, the potential is extraordinary. We hope to make bigger use of Twitter at ACI in January 2020—I think I will have to get some youngsters to help me!

What was your childhood dream job (does not have to be a realistic one!)?

Other than medicine, I was intrigued by the law and being a barrister. When I was tiny, I fancied being a Boeing 747 pilot.

Outside of medicine, what are your hobbies and interests?

My wife Anne and daughters Amy and Eve are obviously a huge part of my life—together with Daisy the dog. I enjoy sport, English rugby and cricket. I am a long-suffering fan of Middlesbrough football club.

Current appointments

1999–present: Consultant cardiologist, John Radcliffe Hospital, Oxford, UK 2011–present: Professor of interventional cardiology, Oxford University, Oxford, UK

Medical qualifications

2003: FRCP, Royal College of Physicians of London 2001: FESC, European Society of Cardiology 1997: MD, University of London, London, UK 1990: MRCP UK, London, UK 1987: MBBS, St Georges University of London, UK

Memberships

2015–present: President British Cardiac Intervention Society 2015–present: Board member European Bifurcation Club 2019: EuroPCR Programme Committee 2015–2019: British Cardiac Society Council and Executive 2017–2019: Elected member EAPCI nominating Committee 2018: Chair NHS England Cardiac Improvement Programme Aortic valve disease working group 2018: Chair NHS England High-Cost Tariff Excluded—TAVI devices working group 2017–2018: EAPCI/SCTS Joint Guideline Committee on Revascularisation 2009–2012: European Association of Percutaneous Intervention (EAPCI) Fellowship Committee

Selected publications

Colombo A, Drzewiecki J, Banning AP, et al.

A randomized study to assess the benefit of paclitaxel-eluting stents for coronary revascularization using two different release kinetics in de novo coronary lesions (TAXUS 2).

Circulation 2003; 108: 788–94.

Banning AP, Westaby S, Morice MC, et al.

Comparison of cardiac surgery and paclitaxeleluting stents in nondiabetic and diabetic patients with left main and or 3-vessel coronary artery disease: SYNTAX trial. J Am Coll Cardiol 2010; 55: 1067–75.

Selvanayagam JB, Porto I, Channon K, et al.

Troponin elevation following percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: Insights from Cardiovascular Magnetic Resonance Imaging. Circulation 2005; 111: 1027–32.

De Maria GL, Cuculi F, Patel N, et al. How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous intervention in patients with ST elevation myocardial infarction? Eur Heart J 2015; 36 (45): 3165–77.

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May

Source BIBA MedTech TAVI Monitor

TAVI market continues to grow BETWEEN JANUARY AND December 2018, according to data from the BIBA MedTech TAVI Monitor, 57,935 transcatheter aortic valve implantation (TAVI) devices were used in Western Europe. This represents a 23.9% increase in the number of TAVI unit implants in Western Europe between 2017 and 2018: 46,764 vs. 57,935, respectively. However, there was a 51.4% increase in unit implants between 2016 and 2017: 30,887 vs. 46,764, respectively (difference 15,877). See Figure 1.

Reasons for market growth

A key reason for the growth between 2016 and 2018 likely relates to the expanded indications for TAVI during 2016–2018. In the summer of 2016, both Medtronic and Edwards Lifesciences received the CE mark for their respective devices—CoreValve

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Market insights

and Sapien 3—to be used for intermediate-risk patients. During this time period, based on data from the TAVI Monitor, the proportion of TAVI patients categorised as being at “intermediate risk” did increase. In Q4 (1 October to 31 December) of 2016, there were 10,232 aortic implants in Western Europe. Of these, 20.7% were for intermediate-risk patients.

However, in Q4 of last year, 30.3% of 15,113 devices implanted were for intermediate-risk patients. Of note, the proportion of procedures for low-risk patients also increased between Q4 2016 and Q4 2018: 0.7% vs. 4.5%, respectively. See Figure 2.

This is of particular interest given the recent data from the PARTNER 3 and Evolut Low Risk Trial studies (see page 1). These studies showed, respectively, that Sapien 3 was superior to and CoreValve was noninferior to surgical aortic valve

ACC to tackle patient and provider access to novel therapies The American College of Cardiology (ACC) has launched a new initiative that leverages prospective clinical registry data and partnerships—spanning the pharmaceutical and medical device industry, health plans, employers, clinicians and patients—that aims to reduce the administrative burden associated with ensuring the most vulnerable heart disease patients have access to medications that can save their lives.

Source BIBA MedTech TAVI Monitor

replacement in low-risk patients; therefore, they will probably lead to these devices being approved for use in low-risk patients (in both European and US markets). If/when these devices are approved (possibly this year), the TAVI market is set to grow further as a result.

Other changes to the market between 2016 and 2018 include Edwards Lifesciences bringing out the self-expanding Centera valve last year and Boston Scientific acquiring Symetis (and thus, the Acurate neo valve) in 2017.

The introduction of Centera has not greatly affected Edwards’ market share—if anything, it slightly decreased (45.5% in 2016 to 43.8% in 2018)—but the acquisition of Symetis led to an increase in Boston Scientific’s share: from 7.4% (2,290 of 30,887) in 2016 to 10.6% (6,158 of 57,935).

This increase is despite Boston Scientific having withdrawn its Lotus/ Lotus Edge valve from the market in 2017. In April 2019, the company reported that it is planning a controlled relaunch of the device on to the European market and has received

AS PART OF the initiative, the ACC will work with likeminded stakeholders to proactively identify and address the behavioural and system challenges that clinicians and patients face in prescribing novel therapies.

Once fully implemented, the initiative will prospectively leverage data from ACC’s National Commissioning Data Repository (NCDR) hospital and outpatient registries, such as the PINNACLE registry, to help clinicians, practices and/or health systems identify which patients are at highest risk of an additional myocardial infarction and which are eligible for newer therapies that could lower their risk. The initiative will provide insights into physician treatment patterns (e.g. adjusting patient doses, following up with lab tests and patient panel intensity) and patient factors (e.g. social determinants, medication burden, comorbidities, etc). These insights will help practices understand how to address access barriers.

Additionally, the ACC and its partners will pilot ways to implement cost-effectiveness through price reductions, reduce administrative burden through

Food and Drug Administration (FDA) approval for it; Boston Scientific also hopes to receive the CE mark for the next generation of Acurate neo (Acurate neo 2) and subsequently launch that on to the market.

Therefore, Boston Scientific’s market share may further increase after these products become available.

BIBA Briefings BIBA Briefings is a new platform that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America. The platform also reviews data and news.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact Merveille Anderson: merveille@bibamedical.com.

policy and automation, support patient activation and adherence through mutual goal-setting and actionplanning, and optimise the right therapy through the targeting of specific high-risk patient cohorts.

ACC CEO Timothy W Attebery comments: “Advancing quality, equity and value of cardiovascular care is a strategic priority for the College and key to optimising cardiovascular care and outcomes. Changing the narrative around the administrative burden that physicians face in prescribing medications and authorising cardiac procedures is one giant step towards achieving this vision. We are working with external stakeholders across the healthcare industry, including medical societies, pharmaceutical companies, employers and pharmacy benefit managers, to implement a more targeted approach to saving lives.”

The ACC will begin announcing specific programmes and partnerships in the coming months that build on the groundwork that has already been laid towards improving access and put into action initiatives that directly help physicians and patients.

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May

Challenges of conducting a randomised clinical trial to prove the impact of mechanical circulatory support in cardiogenic shock Andreas Schäfer Comment & Analysis Mechanical circulatory support is frequently used to stabilise patient haemodynamics in desperate situations of circulatory failure to increase and maintain end organ perfusion.1 Of the available devices, the percutaneous micro-axial Impella (Abiomed) additionally provides a unique mechanism of left ventricular unloading.2 By reducing wall stress and increasing oxygen delivery, this might in itself be beneficial.3 In this commentary, Andreas Schäfer reviews the difficulties of evaluating the effectiveness of the system.

CARDIOGENIC SHOCK represents a combination of patient conditions ranging from hypotension after acute myocardial infarction to out-of-hospital cardiac arrest often treated with multiple inotropes and/or mechanical circulatory support.1,4 It is challenging to differentiate patients in cardiogenic shock within the window of opportunity for treatment that might benefit from mechanical support from patients in the “haemometabolic state” who already have irreversible organ injury despite normalisation of haemodynamic parameters.5 Randomised trials play an important role in the assessment of therapies and innovative treatment options but present

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several logistic and methodological challenges.4,6,7 Therefore, evidence on the impact of mechanical support in cardiogenic shock based on randomised controlled trials is limited and currently mainly registry data and historical comparisons are available.7

Trial enrolment in cardiogenic shock

Given the low incidence rate of cardiogenic shock (approximately <10% of patients with acute myocardial infarction), slow enrolment has been observed in randomised trials with mechanical assist devices.4,6,8,9 Additionally, patients with cardiogenic shock have a high mortality and

Prevalence of multiple organ failure among cardiogenic shock patients has steadily increased Between 2000 and 2014, in the USA, the percentage of patients with acute myocardial infarction cardiogenic shock (AMI-CS) who developed multiple organ failure increased from 15.7% to 45.5%.

SARASCHANDRA VALLABHAJOSYULA (Department of Cardiovascular Medicine, Mayo Clinic, Rochester, USA) and colleagues write in the Journal of the American College of Cardiology that only “a small incremental benefit” has been seen in the AMI-CS population in recent years, despite shorter door-to-balloon times and greater use of coronary angiography. They speculate the lack of a greater mortality benefit may relate to the proposed

procedural risks, often due to the presence of multiple comorbidities and extensive coronary disease.2,7,10,11 Considering the emergent conditions in the setting of myocardial infarction and cardiogenic shock, obtaining consent from the patient is often impossible and seeking informed consent from the patient’s next of kin may cause additional delay.6,12,13 Also, the investigator-driven exclusion of study candidates that are expected to benefit from mechanical support may impact recruitment (selection bias).4 Last, but not least, it is important to conduct such randomised controlled trials in sites where experienced physicians and personnel are available 24/7 to make sure that mechanical support can be implanted at any time in optimal technical conditions.14 The exact definition of the targeted patient cohort by inclusion and exclusion criteria impacts both sample size and inclusion rate. A broad definition may increase the enrolment of patients in the trial but will also dilute the treatment effect and, thus, increase the sample size and potentially compromise identification of the beneficial effects of mechanical support. However, narrowing the inclusion criteria to exclude patients such as those with severe brain injury (for example, following out-of-hospital cardiac arrest) may help to assess the impact of the targeted device but requires strict adherence to the protocol and severely reduces monthly inclusion rates.

Appropriate definition of inclusion- and exclusion criteria, early identification of eligible patients, on-the-spot randomisation and subsequent enrolment in a trial with immediate initiation of support during an emergency situation presents a significant challenge.6

Outcome

Due to the life-threatening nature of cardiogenic shock and the known correlation of haemodynamic stability and maintained end organ perfusion

“haemometabolic” model for the evolution of AMI-CS “wherein the initial haemodynamic insult subsequently evolves into a metabolic insult, resulting in persistent hypoperfusion and multiorgan failure”. Vallabhajosyula et al note “there are limited data on the burden of multiorgan failure in AMI-CS in modern practice”. “We hypothesised that patients with AMI-CS have evolved into a more complex population with greater organ failure and that multiorgan failure would be associated with higher in-hospital mortality,” the authors add.

Using data from the National Inpatient Sample, Vallabhajosyula et al identified >nine million patients who had been admitted to a US hospital with AMI between 2000 and 2014. Of these, 444,253 (4.6%) also had CS. Of those with AMI-CS, 64.3% had non-cardiac organ failure and 31.9% had multiple organ failure.

The authors observe: “There was a steady increase in multiple organ failure during the study period (15.7% in 2000 to 45.5% in 2014) with a concomitant decline in admissions with single organ or non-organ failure.”

They add that the increase in multiple organ failure “can be explained by the increase in overall comorbidity and acuity of patients present with AMI”. “Due to the rapid improvement in care from ischaemic heart disease due to primary prevention and aggressive revascularisation, it is possible that the spectrum of AMI-CS patients presenting

with positive clinical outcomes, it is expected that mechanical support may affect the prognosis. Accordingly, the primary outcome of most randomised trials has been short- and long-term mortality. Overestimating the impact of primary haemodynamic stabilisation on mortality in cardiogenic shock can lead to false estimations when defining the potential effect size. Hence, calculating the sample size required to detect a significant difference in mortality probably contributes to underpowered study designs and thus inconclusive study results.15

Conclusion

The conduct of randomised controlled trials is an important element to scientifically understand emerging technical and therapeutic developments and verify their clinical relevance. As shown, the success of such studies depends on numerous aspects and requires dedicated compliance during execution.

Running a trial with highly unstable patients in cardiogenic shock adds additional challenges from a logistic and ethical point of view. Using highly specific technology limits the number of specialised sites capable of conducting such trials.

Andreas Schäfer is at the Department of Cardiology and Angiology, Centre for Internal Medicine, Hannover Medical School, Hannover, Germany.

References 1. Rihal et al. J Am Coll Cardiol 2015; 65 (19): e7–e26.

2. Basir et al. Am J Cardiol 2017; 119(6): 845–51.

3. Basir et al. Catheter Cardiovasc Interv 2018; 91(3): 454–61.

4. Thiele et al. Eur Heart J 2015; 36(20):1223–30.

5. Kapur et al. AHA Scientific Sessions 2018.

6. Ouweneel et al. Int J Cardiol 2016; 202: 894–96.

7. van Diepen et al. Circulation 2017; 136(16): e232–68.

8. Goldberg et al. Circulation 2009; 119(9): 1211–19.

9. Sieweke et al. Eur Heart J Acute Cardiovasc Care 2018.

Epub.

10. Schwarz et al. Med Klin Intensivmed Notfmed 2016; 111(8):715–22.

11. Harjola et al. Eur J Heart Fail 2015; 17(5): 501–09.

12. Goldberg et al. Am J Cardiol 2004; 94(11): 1373–78.

13. Dickert et al. BMJ 2015; 351: h3791.

14. Henriques et al. Am Heart J 2014; 167(4): 472–79.

15. Hochman et al. N Engl J Med 1999; 341(9): 625–34.

to hospital has systematically shifted during this study period,” they explain.

Vallabhajosyula et al also found that patients with organ failure less frequently underwent angiography and/or percutaneous coronary angiography (PCI) than those without organ failure; the reasons for this were less clear than those for why there has been an increase in the prevalence of multiorgan failure. They comment: “The bidirectional relationship between organ failure and revascularisation highlights the need for a multidisciplinary approach to decision-making in these patients to improve clinical outcomes.”

In-hospital mortality was increased in patients with organ failure—it was 1.3 and 2.2 higher, respectively, in patients with single and multiple organ failure— compared to those without organ failure. And overall in-hospital mortality for AMI-CS remained relatively stable since 2008, despite a steady decline in previous years. Commenting that the prevalence of multiorgan failure started to increase around 2008, Vallabhajosyula et al state: “Taken together, these findings might suggest that any mortality benefit derived from early revascularisation might be offset by multiorgan failure in AMI-CS”. However, they add that their data need to be interpreted with caution and further evaluation in “carefully designed prospective studies” is required.

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We need to embrace digital education and adapt it to improve patient care— reflections from the European Society of Cardiology Xavier Rosselló Dipak Kotecha Comment & Analysis Recent years have seen many advances in education for cardiologists, but little attention has been paid to the impact of new technologies, particularly digital platforms and social networking. Digital education is evolving so rapidly that most patients, clinicians, and institutions have had little time to digest the changes. The 5th European Society of Cardiology (ESC) Education Conference, held at the European Heart House in Sophia Antipolis (France) in 2018, addressed the challenges and opportunities in training digital cardiologists. In this commentary, Xavier Rosselló and Dipak Kotecha look at what the ESC is doing to embrace digital education.

THE ESC IS a not-for-profit professional organisation representing 57 countries, and the annual education conference brings together national directors of training with youth and patient representatives. The main

outcomes of the conference have been summarised at https://doi.org/10.1093/ eurheartj/ehy884, reflecting on six domains: social media, apps, online resources, remote assessment, educating patients and defining reliable information.

Major challenges identified in social media were the digital divide between younger and older professionals, and the inability to control some social media content. However, the highly interactive nature of these resources can facilitate scientific exchange of knowledge, and provide a broad dissemination of educational material.

Mobile applications are frequently used at a patient’s bedside (for example, to calculate risk scores) and for “onthe-job” education, although finding reliable content that is up-to-date can be tricky, and privacy and confidentiality present further difficulties. But, there is potential to develop multitasking apps for real-time collaboration to enhance professional discussions, and to produce patient-tailored content to complement self-care and adherence to therapy.

The use of online resources, web-based education, and clinical case galleries is limited by time constraints, and by the difficulty of finding high-quality content. This provides an opportunity for an agency such as the ESC to provide unbiased educational content (in contrast to industry supported learning), assist in continued e-learning, and promote “micro-learning” to improve basic skills.

Remote assessment is still developing in many countries across the ESC, and is hampered by a lack of homogeneous structured learning programmes across countries. However, there is now evidence of a greater acceptance of the need for curricula that can transcend national borders (https://doi.org/10.1093/ eurheartj/ehy058).

Educating patients through digital means has many potential advantages—it

One in five US patients with atherosclerotic cardiovascular disease cannot pay their medical bills

A review, published in the Journal of the American College of Cardiology, of the financial hardship associated with atherosclerotic cardiovascular disease (such as coronary heart disease, myocardial infarction, angina, and stroke) indicates that one in five patients are unable to pay medical bills related to their condition. Furthermore, of those who are unable to pay medical bills, at least one third are at risk of receiving inadequate medical care such as cost-related medical nonadherence.

J

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avier Valero-Elizondo (Center for Outcomes Research and Evaluation, New Haven Health, New Haven, USA) and others write that atherosclerotic cardiovascular disease (ASCVD) “is not only the leading cause of mortality and morbidity in the USA, but it is also responsible for the highest healthcare costs for a single class of disease”. They add that even people with the condition who are insured are inadequately protected against financial hardship “due to the high costs of insurance, including deductible, copays, and coinsurances”. However, Valero-Elizondo et al note that national estimates of burden of financial hardships related to medical bills among patients with ASCVD are lacking. Thus, to address this issue, they reviewed data for non-elderly (age 18–64 years) patients with ASCVD from the National Health Interview Survey.

Of 6,160 patients with self-reported ASCVD, 2,741 (45%) said that they were part of families that experienced financial hardship from medical bills.

Furthermore, 1,229 (18.9%) said that they were unable to pay their medical bills at all. As to be expected,

in a stratified analysis, uninsured and low-income individuals had the highest burden of financial hardship related to medical bills.

Additionally, of those who were not able to pay medical bills, most experienced at least one of the following consequences: financial distress (worry), food insecurity, or cost-related medical adherence. In fact, 22% experienced two of these consequences and 19% experienced all three consequences (20% experienced one of these consequences); only 38% reported

Insurance coverage is critical to protect against financial burden from unexpected medical bills, but the current structure falls short.”

can improve shared care approaches and make clinical practice more patientcentred. There is still much to be done in this field, and the ESC is moving swiftly forward with patient forums and committee representation, as well as specific projects in cardiovascular diseases, such as atrial fibrillation (https://doi.org/10.1093/europace/ eux299).

Defining reliable information online can be problematic, and publication and industry biases add an extra layer of complexity specific to medical education.

Better approaches are also needed to protect users, and to provide solutions to prevent or deal with online harassment.

The way we deliver and receive education is undergoing intense transformation. Although digital technologies have massive potential, they come at a price—there is a direct impact on patient care, and many challenges have to be faced for these tools to further improve medical education. A modern day cardiologist needs to be able to use digital tools for clinical practice, teaching and training, and interacting with patients. To promote digital cardiologists of the future, curricula and methods for training need to be adapted to reflect the expectations of the new digital era.

Xavier Rosselló is at the Centro Nacional de Investigaciones Cardiovasculares Carlos III, Complutense University of Madrid, Spain.

Dipak Kotecha is at the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, UK.

experiencing none of these consequences.

While uninsured patients had the highest burden of financial hardship related to medical bills, most (76%) patients who reported being unable to pay their medical bills were actually insured. Valero-Elizondo comments: “Our study underscores the fact that, although insurance coverage is critical to protect against risk of financial burden from unexpected medical bills, the current insurance structure falls short in protecting from financial hardship.”

They conclude that the current US healthcare system “fails to protect a significant proportion of nonelderly atherosclerotic cardiovascular disease patients from financial hardships and its dire consequences”.

Valero-Elizondo told Cardiovascular News: “We firmly believe that this problem not only resides at the policy level; sure, we need to address it, but the change needs to come from all of us. We are all in this together.

So, as physicians (and part of healthcare provider teams), we need to find better and more efficient ways to talk to our patients about their financial troubles/ worries, either by screening them early in their disease path, or talking to those already in our care. Two of the main reasons we decided to study ASCVD is because it is highly preventable and there are a myriad of treatment options that can help the patients navigate their disease without having to go bankrupt.

“As for patients and their families, we strongly advise you to talk to your healthcare provider. It may be uncomfortable at first, but this is the way to mitigate many (present or future) expenditures. At the end of the day, healthcare providers need to increase cardiovascular prevention efforts, and all of us— healthcare providers and patients (and their families) need to get this conversation started.”

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May

Polymer-free stents have similar performance profiles, except in diabetes

A pooled data analysis comparing the Cre8 amphilimus-eluting stent (Alivmedica) and the BioFreedom biolimus-eluting stent (Biosensors) demonstrates similar safety and efficacy for the devices, with possible differences in treatment effect for patients with diabetes mellitus. Describing a combined investigation into two multicentre observational studies in Italy in Circulation: Cardiovascular Interventions, the researchers say: “BioFreedom and Cre8 have favourable and comparable safety and efficacy profiles in real-world all-comer patients undergoing percutaneous coronary revascularisation.” Also, they add: “Cre8 might provide a clinical benefit in diabetic patients.”

POLYMER-FREE DRUG-ELUTING stents have performed positively in comparisons with bare metal stents and with durable-polymer drug-eluting stents.

But to date there have been no direct comparisons of safety and efficacy between different polymerfree drug-eluting stents.

The study population came from two singlearm studies conducted at 22 Italian centres—the ASTUTE (Amphilimus Italian multicentre registry), and the RUDI-FREE (Polymer free biolimuseluting stent implantation in all-comers

population). ASTUTE enrolled all patients undergoing Cre8 implantation, and RUDI-FREE enrolled all patients undergoing BioFreedom implantation.

The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularisation. Propensity score matching compared safety and efficacy outcomes in 1,280 patients (640 matched pairs) treated with BioFreedom or Cre8.

At one year, target lesion failure occurred in 4% of BioFreedon and 4.2% of Cre8-treated patients (hazard ratio [HR] 0.98, 95% CI 0.57–1.70). Risks of cardiac death (2% vs. 2.1%, HR 1.03, 95% CI 0.47–2.26), target vessel myocardial infarction (0.8% vs. 0.3%, HR 1.89, 95% CI 0.50–6.80), target lesion revascularisation (1.5% vs. 2.2%, HR 0.74, 95% CI 0.34–1.62), and definite/probable stent thrombosis (0.9% vs. 0.8%, HR 1.17, 95% CI 0.36–3.81) were comparable in patients treated with BioFreedom and Cre8.

A differential treatment effect by diabetes mellitus status was observed, indicating a benefit of Cre8 in patients with diabetes mellitus (p interaction=0.003).

Summarising the findings, Mauro Chiarito, Giulio Stefanini (Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy) and their co-researchers say: “BioFreedom and Cre8 are characterised by a similar performance as indicated by comparable risks of the primary endpoint target lesion failure at one year. Device effectiveness and safety profiles of BioFreedom and Cre8 are similar, as indicated by low and comparable rates of target lesion failure and stent thrombosis at one year.”

They cite the potential benefits of polymer-free drug-eluting stent as an “extremely short” dual antiplatelet therapy duration, which might Giulio Stefanini

New anticoagulants and stopping aspirin early after PCI in atrial fibrillation patients leads to lower bleeding rates Patients with atrial fibrillation (AF) who have had recent acute coronary syndrome or percutaneous coronary intervention (PCI) and are on P2Y12 inhibitor therapy have less bleeding and fewer hospitalisations with an antithrombotic regimen that includes apibaxan but not aspirin, than with one that includes a vitamin K antagonist (VKA), aspirin or both, with no significant difference in the number of ischaemic events. Findings from the AUGUSTUS trial were presented at a late-breaking trial session at the American College of Cardiology Congress (ACC 2019; 16–18 March, New Orleans, USA) and simultaneously published in the New England Journal of Medicine (NEJM).

WRITING IN THE NEJM, Lopes et al say: “AUGUSTUS confirms the safety and efficacy of apixaban, as compared with a VKA, at a dose recommended for patients with AF, and shows that the effect of avoiding aspirin on the incidence of bleeding events seems to be even greater than the benefit of using apixaban instead of a VKA.” The authors point out that, although two previous trials have evaluated standard or reduced doses of non-VKA oral anticoagulants (NOACs) without aspirin in patients with AF who were undergoing PCI and found lower rates

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of bleeding than with VKA regimens that included aspirin, “Neither trial was designed to assess whether the lower incidence of bleeding was due to the use of standard or reduced doses of the NOAC or to the removal of aspirin therapy.” As a result, Lopes et al say, “We conducted the AUGUSTUS trial … to assess the safety and efficacy of standard dose apixaban as compared with a VKA and of low-dose aspirin as compared with placebo, on a background of concomitant P2Y12 inhibitor therapy for six months in patients with AF and recent acute coronary syndrome or PCI.”

provide a clinical advantage in the management of patients at high bleeding risk. Moreover, the reduced risk of polymer-related local inflammatory reactions and neoatherosclerosis could lead to a lower risk of thrombotic events over the longer term.

Efficacy and safety was consistent across all major subgroups in the analysis, except for patients with diabetes mellitus: “The observed significant interaction between treatment effects and diabetes mellitus status suggests that the use of Cre8 might be more favourable in patients with diabetes mellitus, and the use of BioFreedom in patients without diabetes.”

This may be accounted for by the method of drug release in Cre8, which has a mixture of sirolimus with long-chain fatty acids, possibly leading to enhanced cellular uptake in patients with diabetes mellitus. But the researchers could not rule out selection bias as the cause.

Among other limitations were baseline imbalances in the matched population despite the use of propensity score-matching, the small sample size which may have led to type II error, and the study was inadequately powered to evaluate rare events such as stent thrombosis.

Chiarito and Stefanini et al point to the optimal performance of BioFreedom and Cre8 in terms of both efficacy and safety. Rates of target lesion failure, its individual components, and stent thrombosis compared favourably with those observed in recent large-scale randomised trials and all-comers registries on other contemporary drug-eluting stents at one-year followup. These findings are undoubtedly “reassuring” regarding the use of BioFreedom and Cre8 in everyday clinical practice.

Nonetheless, the researchers warn that “any comparisons of event rates between observational and randomised studies should be interpreted with caution”.

They say that a propensity score matched analysis “cannot replace an adequately designed randomised trial. Therefore, our findings should be considered as hypothesis generating.”

AUGUSTUS was an international prospective randomised controlled trial with a two-by-two factorial design; patients were randomly assigned to receive apixaban or a VKA (open label) and to receive aspirin or a matching placebo (double blind) for six months.

Primary outcome was major or clinically-relevant non-major bleeding.

Secondary outcomes included death or hospitalisation and a composite of ischaemic events. Among the inclusion criteria were age ≥18 years, and persistent, permanent, or paroxysmal AF, as well as planned long-term use of an oral anticoagulant. Patients who were taking oral anticoagulants for another condition were excluded, as were those with severe renal insufficiency.

From September 2015 to April 2018, 4,614 patients were enrolled at 492 sites in 33 countries. Patient characteristics were similar across groups, with a median age of 70.7 years, and 29% were female. Stroke and bleeding risk were assessed by the CHA2DS2VASc score (reflecting the risk of stroke among patients with AF who are not receiving oral anticoagulation) and the HAS-BLED score (reflecting the risk of bleeding among patients with AF who are receiving anticoagulation therapy).

Researchers found no significant interactions between the two randomisation factors on the primary or secondary outcomes. Major or clinically-

relevant non-major bleeding occurred in 10.5% of the apixaban group and 14.7% of the VKA group (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58– 0.81; p<0.001 for both non-inferiority and superiority), and in 16.1% of those taking aspirin compared to 9% on placebo (HR 1.89, 95% CI 1.56–2.24; p<0.001). Rates of death or hospitalisation were lower in the apixaban group (23.5%) than in those on a VKA (27.4%, HR 0.83, 95% CI 0.74–0.93; p=0.002), with a similar incidence of ischaemic events. Rates of death or hospitalisation and of ischaemic events was similar across both the aspirin and placebo groups.

AUGUSTUS investigator Robert F Storey (University of Sheffield, Sheffield, UK) told Cardiovascular News the findings would “substantially improve the balance of safety and efficacy of antithrombotic therapy in AF patients requiring PCI. The AUGUSTUS study shows for the first time that a NOAC is clearly superior to VKAs such as warfarin in this setting.

Furthermore, it shows the extent of the increased bleeding hazard when aspirin is continued along with an oral anticoagulant and a platelet P2Y12 receptor antagonist. These findings will drive practice towards preferentially using a NOAC such as apixaban in these patients and, in those who have a low risk of stent thrombosis, stopping aspirin within the first week after PCI.”

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May

Renal denervation lowers blood pressure compared to sham procedures A meta-analysis of sham controlled randomised trials looking at catheter-based denervation of the renal arteries to lower blood pressure in uncontrolled hypertension has found that renal sympathetic denervation (RSD) effectively reduces blood pressure. The findings were published in the Journal of the American College of Cardiology.

PARTHA SARDAR, HERBERT Aronow (Brown University, Providence, USA) et al say: “RSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.”

Conflicting results have been found in previous randomised trials on the effectiveness of the therapy to lower blood pressure. Sardar et al performed an updated study-level meta-analysis of all available sham-controlled randomised trials to evaluate the effect of RSD on blood pressure in patients with uncontrolled

hypertension. Five databases—PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and CINAHL—were searched from inception until 30 June 2018 for studies with ≥50 patients that compared catheter-based RSD with a sham control. The authors used random effects meta-analysis to calculate summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CI).

Six trials with 977 patients were analysed; 582 subjects were randomised to RSD and 395 to sham procedure. Mean patient age was 52.8–64.5 years, and median follow-up was two to six months. Three secondgeneration trials in the analysis were designed and performed with greater attention to newer technology, and procedural technique and patient selection (SPYRAL HTN-ON MED, SPYRAL HTN-OFF MED, and RADIANCE HTN SOLO). More than half (54.7%) of the patients in the meta-analysis were from the SYMPLICITY HTN-3 trial, and five of the trials used radiofrequency energy for renal denervation, while one used ultrasound.

The analysis found that the reduction in 24-hour ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than for those treated with a sham procedure (WMD -3.65mmHg, 95% CI -5.33 to -1.98; p<0.001).

When compared with the sham group, RSD was also associated with a significant decrease in daytime ASBP (WMD -4.07mmHg, 95% CI -6.46 to -1.68; p<0.001), office systolic blood pressure (WMD -5.53mmHg, 95% CI -8.18 to -2.87; p<0.001), 24-hour ambulatory diastolic BP (WMD -1.71mmHg, 95% CI -3.06 to -0.35; p=0.01), daytime ambulatory diastolic BP (WMD -1.57mmHg, 95% CI -2.73 to -0.42; p=0.008), and office diastolic BP (WMD -3.37mmHg, 95% CI -4.86 to -1.88; p<0.001).

There was also a significantly greater reduction in daytime ASBP with RSD in second-generation

trials than in first-generation trials (6.12mmHg vs.

2.14mmHg; p interaction=0.04), although the interaction was not significant for 24-hour ASBP (4.85mmHg vs.

2.23mmHg; p interaction=0.13).

The evalution was subject to the usual restrictions common in meta-analyses, including the pooling of data from trials with different study protocols and varied patient characteristics. Additionally, follow-up was short term, at two to six months, and some of the trials were designed for proof-of-concept and not powered for efficacy endpoints. The authors also point out: “Medical adherence was not objectively measured in some trials.

The present findings are suggestive of effect in both adherent and non-adherent populations but cannot confirm the benefit of renal denervation among patients with higher drug adherence.”

They also say that, as five of the six trials included used catheters delivering radiofrequency energy, it was not possible to perform subgroup analysis on the basis of catheters using other modalities of RSD. The authors suggest larger trials, incorporating a design consistent with the second-generation trials in the meta-analysis, should be performed to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension. They add: “Based on our analysis, future large trials should include longer follow-up, be powered for efficacy endpoints including clinical outcomes, and incorporate objective measurement of medical adherence.”

Aronow told Cardiovascular News: “We believe the findings from our meta-analyis should restore hope.

We found that renal denervation caused significant blood pressure reduction, and that the reduction was even more pronounced in newer second-generation studies which optimised patient selection, improved upon the technology, and modified the endpoint under consideration. This is an exciting time in the treatment of hypertension—one of the most common, yet difficult to treat, conditions.”

Majority of cath labs feel burdens of PCI public reporting outweigh benefits Nearly two thirds (64.3%) of cath lab staff believe that the financial and admistrative burdens of meeting percutaneous coronary intervention (PCI) public reporting requirements are not outweighed by the potential benefits in terms of improving quality of care. The median institutional costs to meet public reporting requirements are US$100,000–200,000 and interventional cardiologists spend a median time of five to 10 hours per week on these requirements.

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ishi K Wadhera (Richard A and Susan F Smith, Smith Center for Outcomes Research in Cardiology, Cardiovascular Division, Beth Israel Deaconess Medical and Harvard Medical School, Boston, USA) and others report in the Journal of the American College of Cardiology that the aim of PCI public reporting (of mortality rates) programmes in the USA is “to incentivise physicians and institutions to improve care and to provide patients with information to make informed decisions about where to seek care”. However, they add that the evidence suggests such programmes have “not clearly led to improvements in quality of care or patient outcomes”.

“Consequently, some physicians and policymakers have expressed concern that reporting may impose a significant financial and administrative burden on physicians and hospitals without

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improving care,” Wadhera et al comment.

Given little data for the financial and admistrative burdens associated with public reporting are available, the aim of the present study was to survey Massachusetts cath labs that participate in public reporting programmes about these burdens. Of 24 cath labs contacted, 15 responded. The authors state: “Respondents were more likely to be from cardiac catheterisation laboratories at large hospitals (>400 beds; 53.3% vs.

0%) and teaching institutions (53.3% vs. 22.2%). In addition, respondents more often had cardiothoracic surgery available onsite (73.4% vs. 44.5%) and higher mean annual PCI volumes (491 vs. 314).”

They found that the median estimated range of annual institutional costs to meet state public reporting requirements was US$100,000–200,000 (range

Robert Yeh

US$0–50,000 to >US$300,000), the median number of full-time equivalent staff employed to handle public reporting requirements was one (range 0.5–2.75), and the median time spent by an interventional cardiologist to meet the requirements was five to 10 hours per week (0–5 hours to >20 hours per week).

Of note, according to Wadhera et al, “most respondents felt that the potential benefits of PCI public reports to quality of care and healthcare transparency did not weigh the administrative and/or financial burden (64.3%)”.

The authors observe that the “little evidence” that public reporting leads to improving outcomes has prompted debate about the value of the public reporting programme, adding that survey data suggest “patients undergoing PCI are unaware of and rarely use publicly reported information”. Additionally,

public reporting, Wadhera et al state, “has pushed physicians to avoid high-risk but indicated PCIs”.

Summarising the findings of the survey, the authors write: “Our study raises concerns that this policy, which has not clearly improved patient outcomes, has also imposed financial and administrative burdens on physicians and institutions. As public reporting continues to expand nationally under the American College of Cardiology, it will be important to ensure these efforts are efficient and do not result in excessive cost and administrative burden to physicians and institutions.”

Senior author Robert Yeh (Cardiovascular Division, Beth Israel Deaconess Medical and Harvard Medical School, Boston, USA) told Cardiovascular News: “Many cath labs have robust internal quality improvement programmes that include reviewing adverse events and challenging cases that may have a more positive impact on care quality than public reporting policies do, so it is not clear that these policies add anything more than administrative and financial burden. Here is a case where an alternative to public reporting, namely a strong cath lab quality assurance programme, already exists. There is of course no free lunch, since even these internal quality insurance programmes need to be well resourced, have an effective physician champion, and be backed by organisational leadership in order to succeed.”

May

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Final analysis of MOMENTUM 3 confirms superiority of HeartMate 3 to HeartMate II The final results of MOMENTUM 3, published in the New England Journal of Medicine, show that the HeartMate 3 left ventricular assist device (LVAD) is superior to the HeartMate II LVAD regarding stroke-free survival or reoperation. Additionally, use of the HeartMate 3 (vs. HeartMate II) would prevent two strokes and 6.8 bleeding events per 10 patients treated.

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andeep R Mehra (Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, USA) and others report that HeartMate 3 has been engineered “with blood-flow pathways, friction-free movement, and intrinsic pulsatility to reduce shear stress and stasis of blood”. They add that they have previously reported six-month and twoyear data from MOMENTUM 3, which compared HeatMate 3 with HeartMate II (both Abbott), but these were from smaller cohorts (294 and 366 patients, respectively). “We now provide the final report of efficacy and safety endpoints in the full trial population [1,028 patients],” the authors comment.

In the study, patients with advancedstage heart failure were randomised to receive HeartMate II (an axialflow device) or HeartMate 3 (a centrifugal-flow intrathoracic device).

The composite endpoint was the two-year rate of disabling stroke-free survival or reoperator to replace or remove a malfunctioning device. The principal secondary endpoint was pump replacement at two years, with other secondary endpoints including rehospitalisation, functional status, and quality of life.

Of 1,028 patients, 516 received HeartMate 3 and 512 received HeartMate II. At two years, 76.9% of the HeartMate 3 patients were alive and free from

disabling stroke or free from reoperation to remove a malfunctioning device vs.

64.8% of patients with a HeartMate II device. Mehra et al write: “The non-inferiority criterion (p<0.001) and superiority criterion (p<0.001) were met.” Furthermore, at two years, significantly fewer HeartMate 3 patients underwent pump replacement than HeartMate II patients: 2.3% vs. 11.3%, respectively (p<0.001).

In terms of safety outcomes, there were 70 cases of suspected or confirmed pump thrombosis with the axial-flow pump and seven with the centrifugal-flow pump.

The rate of disabling stroke was 5% for HeartMate 3 vs. 7.5% for HeartMate II (p=0.008). Mehra et al report: “We calculate that for every 10 patients who received the centrifugal-flow pump rather than the axial-flow pump, 2.2 pump-

thromboses (3.6 gastrointestinal bleeds) were averted over a two-year period.”

They note the previous findings of MOMENTUM 3 had suggested lower stroke rates with Heart Mate 3 but these were “interpreted cautiously, since only the rates of disabling stroke were favourably influenced. In the population in the current analysis which was three times as large, we found lower rates of both haemorrhagic and ischaemic strokes and a lower rate of disabling stroke.”

Concluding, they say: “The Centrifugal-flow HeartMate 3 LVAD was associated with a less frequent need for pump replacement than the axial-flow HeartMate II LVAD and was superior to the axial-flow pump with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device.”

For every 10 patients that received the centrifugal-flow pump, 2.2 pumpthromboses were averted over a two-year period.”

Mandeep R Mehra

No significant difference between immediate and delayed angiography with respect to survival at 90 days Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of ST-elevation myocardial infarction (STEMI), a recent study found that a strategy of immediate angiography was not shown to be better than a strategy of delayed angiography with respect to overall survival at 90 days.

THE RESULTS OF the Coronary Angiography after Cardiac Arrest (COACT) trial, authored by Jorrit S Lemkes (Amsterdam University Medical Center VUmc, Amsterdam, The Netherlands) and colleagues, were recently published in the New England Journal of Medicine.

Lemkes and colleagues begin by noting that ischaemic heart disease is a major cause of out-ofhospital cardiac arrest, which is a leading cause of death in Europe and the USA. “Despite advances in the field of resuscitation and intensive care management,” they comment, “the outcome in patients after cardiac arrest remains poor.”

The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. Specifically, the authors note that data from randomised trials are lacking, and observational studies have shown conflicting results

29

Our findings do not corroborate previous observational studies which showed a survival benefit with immediate coronary angiography.”

regarding the effect of immediate coronary angiography and PCI on outcomes in this patient group.

The authors found that at 90 days, 176 of 273 patients (64.5%) in an immediate angiography group and 178 of 265 patients (67.2%) in a delayed angiography group were alive (odds ratio 0.89; 95% confidence interval [CI], 0.62 to 1.27; p=0.51). Additionally, the median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36).

They note: “The results of the trial did not show a significant difference between the two treatment groups in the primary endpoint of survival at 90 days.” In addition, they found no significant differences between the groups in the remaining secondary endpoints.

In this randomised, multicentre trial, Lemkes and colleagues assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurological recovery. All patients underwent PCI if indicated.

The primary endpoint was survival at 90 days.

Secondary endpoints included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit.

According to the authors, “Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favoured treating patients who had a presumed better prognosis with a strategy of immediate angiography,” they concluded.

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May

Product News

FDA approves Orsiro for use in the USA

The US Food and Drug Administration (FDA) has approved Biotronik’s drugeluting stent, Orsiro. A press release states that Orsiro is the first and only ultrathin drug-eluting stent to outperform the clinical standard (Xience, Abbott).

The device received CE mark in 2011 and has been used to treat >one million patients worldwide to date.

According to the press release, the BIOFLOW-V trial demonstrated significantly lower rates for target lesion failure and target vessel myocardial infarction at 12 months with Orsiro compared with Xience in a large, complex patient population (1,344). At two years, treatment with Orsiro further improved event rates in comparison to Xience, including a significant reduction in target lesion revascularisation and spontaneous myocardial infarction.

The two-year results—presented at the 2018 Transcatheter Cardiovascular Therapeutics meeting (TCT; 21–25 September, San Diego, USA) and published in the Journal of the American College of Cardiology—showed a 37% lower target vessel failure rate in favour of Orsiro (7.5% vs. 11.9% target lesion failure rate; p=0.015), a 47% lower ischaemia-driven target lesion revascularisation rate, and a 70% lower rate of spontaneous myocardial infarction (landmark analysis 31 days to two years follow-up).

David Kandzari (Piedmont Heart Institute, Atlanta, USA), BIOFLOW-V US principal investigator, says: “Orsiro has set a new standard for safety and efficacy clinical endpoints, including statistically lower target lesion revascularisation and target vessel myocardial infarction rates. BIOFLOW-V data are the best clinical outcomes witnessed with a modern drug-eluting stent. It was largely thought that efficacy findings were unsurpassable, but Orsiro proves we can further reduce event rates with meaningful innovation.”

For use in percutaneous coronary intervention (PCI) procedures, the cobalt chromium metal stent elutes sirolimus via Biolute—Biotronik’s biodegradable polymer coating. Beneath the biodegradable layer is proBio, a passive coating on the bare metal surface, designed to reduce nickel ion release. The Orsiro stent system provides ultrathin stent struts without compromising radial strength, and a low crossing profile for easier lesion cross in complex PCI. It is available in 52 sizes ranging from

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Device approvals

2.25–4mm in diameter and lengths up to 40mm, the longest available in the USA. Ryan Walters, president at Biotronik, states: “The FDA approval of Orsiro changes the dynamic of what had become a highly commoditised drug-eluting stent market. We designed Orsiro for use even in challenging cases with features that make it unlike any other drug-eluting stent in the world. Hospital administrators now have available a drug-eluting stent that shows improved clinical event rates and interventionalists can rely on Orsiro’s deliverability to treat complex lesions and challenging subgroups to achieve unprecedented patient outcomes. Patients, physicians and health systems deserve the best, and that is exactly what we are bringing to the US market.”

indicated to reduce mitral regurgitation in certain patients with degenerative mitral regurgitation.

The MitraClip is inserted in a minimally invasive procedure through the femoral vein in the leg and guided into the heart’s left ventricle where it grasps the two leaflets of the mitral valve, clipping them together to reduce the backflow of blood.

Bram D Zuckerman (Division of Cardiovascular Devices, the Center for Devices and Radiological Health, FDA), says: “Expanding the approval of this device to heart failure patients with significant secondary mitral regurgitation, who have failed to get symptom relief

CE mark for PASCAL mitral valve repair system

Edwards Lifesciences now has CE mark for its PASCAL transcatheter mitral valve repair system. According to a press release, the system is designed for reduction of mitral regurgitation while respecting the native anatomy.

It features contoured, broad paddles to maximise coaptation of the mitral leaflets, and a central spacer that fills the regurgitant orifice area. The delivery system, the press release notes, allows for independent leaflet capture and the ability to optimise leaflet position.

Konstantinos Spargias (Hygeia Hospital, Athens, Greece), who is an investigator in the multinational prospective CLASP study of the PASCAL system, says: “The PASCAL system is uniquely designed for optimised valve leaflet capture and coaptation, and to help operators achieve their ultimate goal of safe and effective mitral regurgitation reduction for their patients.”

Bernard J Zovighian, Edwards’ corporate vice president, transcatheter mitral and tricuspid therapies, notes: “Mitral valve disease is complex, varied and prevalent, and patients are in significant need of multiple safe and effective therapies to treat debilitating symptoms that can lead to a high rate of mortality. The introduction of the PASCAL system to clinicians and patients in Europe provides a differentiated, minimally-invasive therapy to address the needs of patients with mitral regurgitation.”

MitraClip can be used to treat secondary mitral regurgitation in the USA

The US FDA has approved a new indication for percutaneous edge-to-edge repair (MitraClip, Abbott), allowing its use for the reduction of moderateto-severe or severe secondary mitral regurgitation in patients who are already receiving optimal medical therapy. When first approved in 2013, the MitraClip was

MitraClip

from other therapies, provides an important new treatment option. Careful evaluation by a team of specialists is essential to determining whether a particular patient is an appropriate candidate for this procedure.”

The approval of the new indication is based on a study of 614 patients with heart failure who had moderate-to-severe or severe secondary mitral regurgitation and were randomly assigned to get either continuation of their optimised medication treatment plus the MitraClip (MitraClip group) or continuation of their optimised medication treatment only (control group). The risk of being rehospitalised for heart failure symptoms was reduced by approximately 47% in the MitraClip group compared to the control group. Additionally, the risk of death within two years was decreased by approximately 37% in the MitraClip group compared to the control group.

About 6.5 million American adults live with heart failure, a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen. A small percentage of these patients also have moderate-to-severe or severe secondary mitral regurgitation, increasing the risks and complicating the treatment of their heart failure. With this new approval, this small percentage of patients could be indicated as candidates for treatment with the MitraClip device when combined with optimal medical therapy.

Watchman FLX left atrial appendage closure (LAAC) device in Europe.

Patients with atrial fibrillation (AF) are five times more likely to suffer a stroke than someone with a normal heart rhythm.1 In people with non-valvular AF, data suggest that more than 90% of stroke-causing blood clots that come from the heart are formed in the left atrial appendage.2 The Watchman left atrial appendage occlusion devices are intended to reduce the risk of stroke in people with non-valvular AF. “The Watchman device has been implanted in more than 75,000 patients worldwide and we are pleased that this next-generation technology has been granted European regulatory approval so that we can offer it to patients and clinicians throughout Europe,” said Kevin Ballinger, president, Interventional Cardiology, Boston Scientific. “The robust clinical evidence and successful commercial outcomes of the Watchman device to date reinforce the value of this procedure for all appropriate patients.”

The new Watchman FLX device was designed for simplified implantation to fit a wider range of patients, from those with simple to the most complex anatomies.

The device allows for implantation flexibility to customise placement with a fully enclosed and rounded frame and by offering physicians the ability to fully recapture and reposition the device during the procedure. Furthermore, the frame of the new device is designed to enhance sealing within the left atrial appendage.

Boston Scientific has begun a limited market release of the Watchman FLX device in Europe and expects to expand commercialisation to additional sites in the second half of 2019. The company also plans to begin enrolling European patients in a post approval registry in the coming months. In the USA, the Watchman FLX device is an investigational device and not available for sale.

CardioCel 3D and VascuCel receive regulatory approval in Europe Admedus has received CE mark for its CardioCel 3D product portfolio and its next-generation collagen bioscaffold VascuCel in Europe. According to a press release, this regulatory approval is an important step forward as the company continues to increase global sales of its adapt tissue technology and to create future value through the rollout of its novel 3D technology.

The press release reports that the CardioCel 3D product portfolio is the world’s first and only shaped and proven fully acellular collagen bioscaffold. It is

CE mark for Watchman FLX left atrial appendage closure device

Boston Scientific announced it has received CE mark and initiated a limited market release of the next generation

CardioCel 3D

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Product News designed for highly complex congenital defect repairs and enables cardiac surgeons to achieve a more natural shape during aortic arch reconstruction; combined with the unique clinical benefits of calcification resistance, which is one of the most significant problems that clinicians face post procedure.

Admedus intends to commence the first phase of its commercial launch of CardioCel 3D later this month, initially working with selected European key opinion leaders already familiar with the clinical benefits of Adapt tissue technology. In the subsequent phase, there will be a broader peer-to-peer education programme to benefit more patients.

Tomasz Mroczek (Department of Paediatric Cardiac Surgery, University Children’s Hospital, Jagiellonian University Medical College, Kraków, Poland) says: “After our initial positive experience with Adapt, we are excited to have the choice of these 3D shaped products that will produce better reconstructions for complex aortic arch repair surgeries.”

Wayne Paterson, CEO of Admedus, says: “Obtaining CE mark approval for the 3D portfolio is a further endorsement of the medical need and effectiveness of our 3D-shaped collagen bioscaffold; a world first technology with proven anticalcification properties and zero DNA. The approval of the 3D portfolio in Europe further reinforces the company’s focus on global strategic growth with geographic expansion into key markets and portfolio expansion of ADAPT tissue technology products.”

US physicians can now use Resolute to treat chronic total occlusions Medtronic has received US FDA approval of its Resolute drug-eluting stent platform—including the Resolute Onyx and Resolute Integrity—for the treatment of patients with coronary artery disease who have de novo chronic total occlusion. Chronic total occlusions are considered to be more difficult to treat with percutaneous coronary intervention (PCI) than non-chronic total occlusions because of a greater risk of complications.

According to a press release, the expanded indication was supported by data from the PERSPECTIVE study, a single-centre, observational study of 183 patients with chronic total occlusions who underwent a stent procedure with the older-generation Resolute Integrity.

Results showed that patients treated with the Resolute device exhibited low rates of repeat revascularisation (1.1%), cardiac death (2.2%) and minimal stent thrombosis (0.6%) at one year.

David Kandzari (Piedmont Heart Institute, Atlanta, USA), principal investigator in the PERSPECTIVE study, comments: “Revascularisation of chronic

total occlusions presents physicians with many challenges—both regarding procedural technique and tools—given the patient and disease complexity. In part because of these challenges, chronic total occlusion remains undertreated in interventional cardiology. The newest-generation, thin-strut Resolute Onyx, in particular, is well-suited to address the procedural challenges of deliverability and conformability, with now demonstrated excellent early and late safety and efficacy.”

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, states: “This expanded indication will allow physicians the option to treat these more complex chronic total occlusion cases with the Resolute Onyx, which has shown strong clinical performance across a variety of vessel sizes and anatomies.

Medtronic is committed to helping interventional cardiologists better treat the tough, complex coronary cases that have historically required more invasive treatment options, such as coronary artery bypass grafting.”

is a one-of-a-kind procedure planning environment for structural heart interventions that provides physicians with unique insights to evaluate device sizing and positioning preoperatively using novel computational modelling and simulation technology. The current release includes workflows for transcatheter aortic valve implantation (TAVI) and left atrial appendage (LAA) occlusion procedures.

The press release states that FEops HEARTguide helps to assess the risk of potential complications by preoperatively simulating multiple treatment scenarios in terms of device sizing and positioning, both for TAVI and LAA occlusion procedures. Within the TAVI workflow, it is also possible to plan TAVI procedures for patients with bicuspid aortic valve stenosis—the incidence of which is increasing with the shift towards treating low-risk patients.

Furthermore, the press release explains, FEops HEARTguide

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US FDA approve SSO2 therapy for the management of myocardial infarction

TherOx has received US Food and Drug Administration (FDA) premarket approval for its SuperSaturated Oxygen (SSO2) therapy. A press release reports that it provides interventional cardiologists with the first and only FDA-approved treatment beyond percutaneous coronary intervention (PCI) to significantly reduce muscle damage in myocardial infarction patients.

The press release adds that SSO2 therapy delivers hyperbaric levels of oxygen directly to the ischaemic heart muscle immediately after the coronary artery has been successfully opened

by PCI (angioplasty and stenting).

It is indicated for patients who have the most serious kind of myocardial infarctions—left anterior descending STsegment elevation myocardial infarction (STEMI), which is also known as the “widowmaker”—treated within six hours

iVascular receives CE mark for Navitian microcatheter

After receiving the CE mark for the device, iVascular launched its Navitian coronary microcatheter on to the market. A press release reports that the microcatheter can be used to facilitate, guide and support a guidewire while accessing the coronary system, the exchange of guidewire and injection of radiopaque contrast media or saline solutions.

It adds that Navitian was specifically designed to achieve a desirable navigation in cases of chronical total occlusions, and that the microcatheter stands out for its superior crossability and exceptional penetration capacity due to the internal and external conical transition. Other features include: Complete braided pattern that provides exceptional flexibility, pushability and resistance to kinking Hydrophilic coating Hydrax Plus having high trackability for small and tortuous arteries Internal polytetrafluoroethylene (PTFE) layer facilitating the movement of the guidewire during exchange Sizes 135cm and 150cm, guidewire compatibility 0.014inch.

Lluis Duocastella, CEO of iVascular, comments: “At iVascular, we work continuously for the improvement of today’s therapies, to achieve the best benefit for the patient.”

CE mark for the FEops HEARTguide

FEops has received CE mark approval for its FEops HEARTguide. According to a press release, FEops HEARTguide

FEops HEARTguide

cloud-based procedure planning environment uses advanced personalised computational modelling and simulation to provide clinicians and medical device manufacturers with first-ever insights into the interaction between transcatheter structural heart devices and specific patient anatomy—preoperatively. The current release includes TAVI and LAA occlusion workflows. Such insights have the power to accelerate research and development of novel device-based solutions, as well as ultimately help to improve clinical outcomes in real-world hospital settings.

Cameron Dowling (St George’s Hospital, London, UK) states: “FEops HEARTguide gives our team increased confidence to perform TAVI in the most challenging of aortic valve anatomies.” Additionally, Ole De Backer (Rigshospitalet, Copenhagen, Denmark) notes: “I have the strong hope and belief that preprocedural planning with FEops HEARTguide will transform percutaneous LAA closure into an even more safe and more efficient procedure for patients with non-valvular atrial fibrillation and contraindications for oral anticoagulant therapy.”

of symptom onset. SSO2 therapy is adjunctively administered immediately following successful stent placement, with no delay in PCI treatment.

Gregg W Stone (Columbia University Medical Center, New York, USA) says: “Even after angioplasty with stenting, many heart attack patients suffer from irreversible damage to the heart muscle, which carries a poor prognosis in terms of mortality and the potential for future heart failure. SuperSaturated Oxygen is the only therapy shown in a pivotal randomised trial to reduce infarct size in patients with large anterior myocardial infarction, offering the potential to further improve outcomes in these high-risk patients despite successful primary angioplasty.”

According to the press release, SSO2 therapy has been shown in multiple randomised prospective clinical trials to consistently and safely reduce infarct size in anterior acute myocardial infarction patients and thereby improve outcomes.

A pivotal randomised controlled trial demonstrated a 26% relative reduction in infarct size compared to PCI alone.

Additional clinical trial data show left ventricular stability at 30 days with no deleterious enlargement.

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Clinical News Innovative cardiovascular systems announce first use of its next-generation Emblok embolic protection system in European feasibility study Innovative Cardiovascular Solutions (ICS) has announced the first clinical use of its next-generation Emblok embolic protection system in patients undergoing transcatheter aortic valve implantation (TAVI) procedures in its European feasibility study. The cases were successfully performed by primary investigator Federico De Marco (Policlinico San Donato, Milan, Italy).

The Emblok system is designed for use in TAVI and other structural heart procedures, which are associated with an increased risk of neurological events compared to conventional surgery due to embolic debris that is liberated throughout the procedure. A press release reports that the next-generation Emblok system is the first embolic protection system to fully protect the cerebral, abdominal and peripheral vasculature with complete circumferential aortic coverage to capture and remove the liberated embolic debris throughout the entire TAVI procedure.

In addition to offering protection to more patients, according to the press release, the next-generation Emblok system provides protection throughout the entire TAVI procedure. The embolic filter deploys before the TAVI catheter enters the aorta and remains deployed until the TAVI catheter is removed.

De Marco comments: “I am excited to have one embolic protection system I can use across nearly all my TAVI patients to provide complete protection during the entire TAVI procedure. There is nothing like it on the market.”

R Kevin Plemmons, CEO of ICS, says: “The prior generation demonstrated excellent performance, however we saw an opportunity to modify the device dimensions to be suitable for even more patients. The next-generation Emblok system is appropriate for 97% of all TAVI patients, whereas other commercial embolic protection devices may not be suitable for all anatomies.”

The entire system is 11F and allows both the embolic filter and integrated pigtail catheter to be deployed through a single femoral access site. The Emblok system is available for investigational use only and is not approved for sale.

The company plans to begin its US early feasibility study later this year. Study endpoints will include acute cerebral embolic burden and major adverse cardiac and cerebrovascular events (MACCE) at 30 days.

(HVAD) system (Medtronic) as destination therapy shows that targeted blood pressure management helped reduce serious strokes. The HVAD system is a left ventricular assist device (LVAD) that is designed to increase the amount of blood that circulates through the body in patients with advanced heart failure.

According to a press release, the retrospective analysis used data from both the ENDURANCE and ENDURANCE supplemental randomised trials. In the latter trial, patients received optimal blood pressure management. Presented at the 2019 International Society for Heart and Lung Transplantation (ISHLT) Scientific Sessions, the researchers found that: freedom from disabling stroke at two years was 91% in the HVAD cohort.

Survival was significantly higher for HVAD patients who experienced a nondisabling stroke compared to patients who had a disabling stroke (76% vs.

29%, p<0.0001, one-year post-stroke event). For patients receiving the control device, survival was also greater in patients with non-disabling compared to disabling strokes (71% vs. 17%; p<0.0001).

In patients who experienced a stroke of any severity, those receiving the HVAD pump tended to have a lower stroke-related mortality rate than patients receiving the control device (17% vs.

27%; p=NS).

The current analysis demonstrated a 23% reduction in total strokes, a 36% reduction in disabling strokes, and a 39% reduction in stroke-related mortality in patients in the ENDURANCE supplemental HVAD arm compared to those in the original ENDURANCE trial HVAD arm.

In the ENDURANCE supplemental trial, a total of 465 patients were randomised in a 2:1 ratio to receive the HVAD system or a control device, i.e. an alternative LVAD approved by the US Food and Drug Administration (FDA) for destination therapy. A prespecified blood pressure management strategy was applied to patients in the HVAD arm in an effort to reduce the stroke rate seen in earlier trials.

Jeffrey Teuteberg, section chief of Heart Failure, Cardiac Transplantation,

Targeted blood pressure management helps to reduce strokes in patients with HVAD An analysis of the impact of stroke severity in patients receiving the HeartWare Ventricular Assist Device

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HeartWare Ventricular Assist Device

and Mechanical Circulatory Support, and associate professor of medicine at Stanford University (Stanford, USA), comments: “This analysis shows that stroke severity is an important determinant of outcomes, and the use of the HVAD system with a guidelines-based blood pressure management strategy can, in addition to reducing overall stroke rates, reduce the occurrence of disabling stroke and improve survival in patients who experience strokes. We also found that patients with a stroke in the HVAD cohort had better survival than those who received the control device. These results reinforce the importance of blood pressure management with the HVAD for end-stage heart failure patients.”

To further confirm the safety and effectiveness of the HVAD system in “real-world” clinical practice, Medtronic has initiated two studies: The Destination Therapy post-approval study (DT PAS) and the Apogee study, which will look at how to improve patient outcomes through best practices in blood pressure management, anticoagulation/antiplatelet therapy, and implant procedure.

The DT PAS is a prospective, observational study of 300 newly implanted destination therapy patients at approximately 50 US sites, which will follow patients up to five years.

The primary objective is long-term, complication-free survival over two years. Apogee is a prospective, observational, multisite study involving DT PAS patients who consent to an additional heart failure management protocol and data collection for one year.

The primary objective is to understand how blood pressure management, anticoagulation/antiplatelet therapy and implant procedures affect the 12-month rate of overall major adverse events, including infection, bleeding, device malfunction, stroke or death.

The studies are led by co-principal investigators Nader Moazami (Heart Transplantation and Mechanical Circulatory Support, NYU Langone, New York, USA) and Jennifer Cowger (Mechanical Circulatory Support Program at Henry Ford Health System, Detroit, USA).

Peregrine catheter demonstrated 100% procedural success in postmarket clinical trial

The Peregrine system infusion catheter (Ablative Solutions) has demonstrated 100% procedural success in the Peregrine post-market clinical trial, new data presented during a late-breaking session at the 2019

Cardiovascular Research Technologies (CRT) meeting (2–5 March, Washington, DC, USA) attest.

The Peregrine post-market study is a European multicentre, open-label trial that evaluated the safety and performance of the CE marked Peregrine System infusion catheter using alcohol as a neurolytic agent in 45 patients with systemic hypertension.

The efficacy endpoint of the study was met, with a reduction in mean systolic 24-hour ambulatory blood pressure of 11mmHg (±14mmHg; p<0.001) at six-month follow-up. Additionally, the average reduction in systolic office blood pressure was 18mmHg (±21mmHg; p<0.001). Antihypertensive medications were unchanged in 73% and reduced in 23% of patients at six months. The study demonstrated 100% procedural

Peregrine

success, and the safety endpoint was met in 96% of patients. Two patients had major adverse events of periprocedural access site pseudoaneurysms, with major bleeding in one patient. There were no deaths or instances of myocardial infarction, stroke, or transient ischaemic attack.

“The Peregrine post-market study showed efficient nerve ablation with the CE marked Peregrine catheter, resulting in significantly sustained reduction in both systolic and diastolic blood pressure at six months, with the vast majority of patients not requiring an increase in the number of antihypertensive medications during this time,” says Felix Mahfoud, of Saarland University Hospital, Homburg, Germany.

The Peregrine system infusion catheter has received a Certificate of Conformity and has been CE marked for the infusion of a neurolytic agent (for example, alcohol) to achieve a reduction in systemic blood pressure in hypertensive patients. Designed to be performed in a short and straightforward procedure with minimal sedation required, the Peregrine catheter is engineered to target nerves known to influence the body’s regulation of blood pressure. The delivery of a neurolytic agent—dehydrated alcohol in this study—directly to the space outside of the renal artery is intended to block the overactive signalling of the sympathetic nerves, a press release explains.

The investigational Peregrine kit, which includes the Peregrine system infusion catheter (Peregrine catheter) and Ablative Solutions dehydrated alcohol, will be investigated in the TARGET BP clinical programme, which comprises two clinical trials. The global TARGET BP I trial in centres in the USA and the European Union is a

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Clinical News blinded, randomised, sham-controlled study which will evaluate the safety and efficacy of the Peregrine kit in the treatment of patients with uncontrolled hypertension and who are taking two to five antihypertensive medications.

Patient enrolment in the Target BP I trial is anticipated to begin soon. The recently initiated TARGET BP OFF-MED trial in the EU is a proof-of-concept, blinded, randomised, sham controlled study evaluating the safety and effectiveness of the Peregrine kit for the treatment of patients with uncontrolled hypertension who are not taking antihypertensive medications.

“Based on early clinical results using the CE-marked Peregrine catheter, we are excited to be embarking upon the pivotal TARGET BP I clinical trial of the investigational Peregrine kit to evaluate safety and efficacy when used in the treatment of patients with uncontrolled hypertension in conjunction with antihypertensive medications,” says David Kandzari, co-principal investigator of the TARGET BP I trial, and director of Interventional Cardiology and chief scientific officer at Piedmont Heart Institute in Atlanta, USA. Ablative Solutions recently announced a US$77 million round of financing to complete clinical trials in support of US and EU regulatory submissions for the company’s minimally invasive renal denervation technology.

Northwestern’s Center for Heart Valve Disease, Chicago, USA), the principal investigator for the study at Northwestern, says: “If proven effective, Eko’s platform could be a much simpler, lower cost way to identify patients with heart disease. We are looking to support and advance work that broadens access to the best diagnostic tools in healthcare, regardless of whether a patient lives in the city or a more rural area. Deep learning provides that expert knowledge, regardless of a patient’s location.”

Connor Landgraf, CEO of Eko, states: “One of the biggest problems in healthcare is that general practitioners so often miss heart murmurs that if found earlier would allow patients to get treatment before problems arise.

Northwestern is known for their work in valvular heart diseases and together we are working on AI technology that will detect the two most prevalent valve diseases with the sensitivity of a cardiologist. The results of this study will work to bridge the gap for general practitioners and early detection of these life-threatening conditions.”

PhaseBio receives FDA breakthrough therapy designation for PB2452 for the reversal of the antiplatelet activity of ticagrelor

PhaseBio Pharmaceuticals has announced that the US FDA has granted breakthrough therapy designation Northwestern Medicine for PB2452—a novel reversal agent and Eko partner to for the antiplatelet improve valvular drug ticagrelor. heart disease Breakthrough therapy screening using designation is designed machine learning to expedite the algorithms development Northwestern Medicine and review Bluhm Cardiovascular of promising Institute is pioneering the new drugs use of artificial intelligence for serious or (AI) for cardiac screening in life-threatening a new study of Eko’s cardiac conditions, monitoring platform. The when study aims to demonstrate that preliminary Eko’s digital stethoscopes and clinical AI algorithms can interpret evidence heart sounds accurately to indicates that help screen for pathologic the drug may heart murmurs and valvular demonstrate heart disease. substantial Eko's cardiac Eko is funding the study of improvement monitoring platform the AI systems at two sites, with over existing the plan to enrol 1,000 patients, 800 therapies on one or more clinically of them at Northwestern. The clinical significant endpoints. trial is part of the Bluhm Cardiovascular According to a press release, the Institute’s new Center for Artificial breakthrough therapy designation for Intelligence, where Northwestern’s PB2452 was supported by phase 1 trial cardiovascular clinical programme works results, in which PB2452 achieved with early innovators in AI, develops immediate and sustained reversal of new products, and trains physicians in ticagrelor’s antiplatelet effects. The this new field through Northwestern results from this trial were recently University McCormick School of published in the New England Journal Engineering and Applied Science’s of Medicine and presented in a featured Masters programme in AI. clinical research session at the 2019 James Thomas (director of the American College of Cardiology (ACC)

Scientific Session (16–18 March, New Orleans, USA).

John Lee, chief medical officer of PhaseBio, says: “Breakthrough therapy designation for PB2452 highlights the critical unmet need for a therapy to reverse the antiplatelet activity of ticagrelor, which is widely prescribed to patients with acute coronary syndrome or a history of heart attack. The results from the phase 1 clinical trial of PB2452 demonstrated immediate and sustained reversal of the antiplatelet activity of ticagrelor, which could mitigate bleeding concerns associated with use of ticagrelor.

Breakthrough therapy designation supports our goal of making the first approved reversal agent for ticagrelor available to patients and physicians as soon as possible. We look forward to working closely with the FDA throughout the expedited development process.”

MedAlliance granted breakthrough device designation from US FDA for its sirolimus-coated balloon

MedAlliance has been granted breakthrough device designation from the US Food and Drug Administration for Selution—a sustained limus release drug-coated balloon catheter for the treatment of coronary disease. The FDA breakthrough device programme is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide MedAlliance with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.

A press release reports that Selution’s technology involves unique microreservoirs made from biodegradable polymer intermixed with the antirestenotic drug sirolimus. These microreservoirs provide controlled and sustained release of sirolimus. Extended release of sirolimus from stents has been demonstrated to be highly efficacious in both coronary and peripheral vasculatures. MedAlliance’s proprietary cellular adhesive technology, according to the press release, enables the microreservoirs to be coated onto balloons and adhered to the vessel lumen when delivered via an angioplasty balloon.

Jeffrey B Jump, chairman and CEO of MedAlliance, comments: “MedAlliance is honoured to have been selected for the FDA’s breakthrough device programme, which will allow US patients timely access to new technologies with the potential to provide safer and more effective treatment.”

The press release states that MedAlliance is the first and only company able to deliver sirolimus in a drug-coated balloon with an extended release profile similar to that of a drugeluting stent. Preclinical animal data show therapeutic levels of sirolimus in tissue for greater than 60 days, and first-in-human clinical trial results in

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peripheral arteries demonstrate a late lumen loss of 0.19mm.

The FDA received the MedAlliance request to designate Selution as a breakthrough device in January 2019.

The proposed indications for use included improving luminal diameter, after predilatation, in treatment of coronary artery in-stent restenosis for stenotic lengths up to 36mm with reference vessel diameters of 2.25–4.5mm.

New Australian research ~ and development partnership aims to innovate heart failure care

Biotronik, the University of Newcastle, Australia, and the John Hunter New England Local Health District have partnered to shape a future heart failure care model. A press release reports that investments by the Australian government and Biotronik have “kicked off” the partnership, recognising the importance of evolving standards of care in line with the latest technological advances.

The partners will create a digital testbed that addresses the changing needs in heart failure treatment. With this testbed, according to the press release, future care models can be tested in a real-world clinical setting. Results will help to determine how digital resources and developed processes most benefit different heart failure groups.

Among others, the research project will specifically assess the best strategies to improve access to and delivery of cardiac care to patients living in rural and remote areas. These patients often need to travel long distances and frequently experience delays in receiving health care due to geographical isolation and limited specialist medical services in rural areas.

For example, ways of integrating cardiac remote monitoring into a virtual heart failure service model will be tested to examine the value for patients living close to or far from the clinic, with and without cardiac implantable devices.

Aaron Sverdlov (John Hunter Hospital, Newcastle, Australia; University of Newcastle, Newcastle, Australia) comments: “We want to identify the concepts that lead to the best outcomes and most cost-effective delivery of healthcare when treating heart failure patients. This partnership would allow us to combine our clinical and research expertise with technological innovations to design, test and evaluate best value strategies for improving the cardiovascular health of our community.”

Current standards of care are based around the device that treats heart failure and accompanying services, which generally not integrated within the heart failure service. In contrast, future care models could involve integrated services and solutions that generate new insights.

Jan Ewert, managing director of Biotronik Australia and New Zealand says: “Biotronik works with the public sector to tackle complex health problems like heart failure. We believe in bespoke instead of ‘off-the-shelf’ solutions. The respective healthcare provider should be in full control of the solution and be able to scale it as it sees fit.”

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Industry News TAVI company Tioga Medical closes US$15 million in series A financing

Tioga Medical—a newly formed Shifamed portfolio company—has announced the closing of its series A preferred stock financing, raising a total of US$15 million. According to a press release, Tioga Medical was founded to provide physicians and patients with an elegant transcatheter valve implantation (TAVI) experience that is procedurally simpler and less invasive than current mitral or tricuspid approaches—many of which require transapical access, intricate device sizing regimens, and/or excessive bulk in the ventricles. The financing was led by The Capital Partnership (TCP), with significant participation from Cormorant Healthcare Fund, AMED Ventures, and Shangbay Capital. The funds will be used to advance Tioga Medical’s preclinical and clinical development programs.

Mike Dineen, president and CEO of Tioga Medical, comments: “We are extremely pleased to close this round of financing with such strong support from our investors. This round allows us to build a world-class team and dramatically accelerate the progress of our novel mitral valve and delivery system before

we leverage the technology for the tricuspid application.”

Micro Interventional Devices enters strategic alliance with Oscor

Micro Interventional Devices chairman, president and CEO, Michael Whitman, and Oscor president and CEO, Thomas Osypka, are pleased to announce a strategic alliance that leverages each company’s unique strengths and capabilities to further develop and commercialise innovative solutions to structural heart disease, specifically, Micro Interventional Devices’ MIA— minimally invasive annuloplasty— technology.

According to a press release, Micro Interventional Devices designs, develops and commercialises proprietary, percutaneous technologies solving unmet needs in structural heart disease. Oscor designs, develops, manufactures and markets a variety of highly specialised implantable devices for neuromodulation, cardiac rhythm management and structural heart disease, as well as ancillary delivery systems and accessories. Additionally, it offers its extensive portfolio of intellectual property to its customers under Contract

Manufacturing or original equipment manufacturer (OEM) branding.

Under the terms of this agreement, Micro Interventional Devices acquires a non-exclusive worldwide licence to Oscor’s patented catheter technology and in turn, Oscor receives exclusive manufacturing rights to Micro Interventional Devices’ MIA devices. The synergy accelerates Micro Interventional Devices’ corporate development and provides access to a world-class backend organisation with an established regulatory and distribution network.

In conjunction with the strategic alliance, Micro Interventional Devices is closing a US$20 million series D round of financing led by Oscor. Also participating are Originate Ventures, Life Sciences Greenhouse, Ben Franklin Venture Partners, and other existing Micro Interventional Devices shareholders. In this transaction, Micro Interventional Devices debt will convert to series D preferred stock. Oscor CEO, Thomas Osypka will join Micro Interventional Devices’ board of directors (effective March 2019).

Micro Interventional Devices will use the proceeds to complete its ongoing STTAR clinical trial. STTAR, the study of transcatheter tricuspid annular repair, is studying MIA’s safety and efficacy in the percutaneous (less invasive) treatment of tricuspid and mitral regurgitation.

Tricuspid and mitral regurgitation affects an estimated 12 million people worldwide. Eight patients have already

been enrolled in the STTAR trial to date, with encouraging results.

Scott Gottlieb resigns as head of US FDA

The commissioner of the US Food and Drug Administration (FDA), Scott Gottlieb, unexpectedly resigned after serving just under two years in the post.

He announced his intention to stand down in a letter to Alex Azar II, the secretary of the Department of Health and Human Services, the FDA’s parent agency, on 5 March 2019. Gottlieb says the decision is due to the fact that he wants to spend more time with his family.

In an interview with The Washington Post, he says: “It was a very hard decision”, calling this posting “the best job I will ever have”. He continues: “I am leaving because I need to spend time with my family. I get home late Friday, work on weekends and come back to Washington on Sunday. I did the job 100%.”

Gottlieb took up the position in May 2017 and has presided over a number of important initiatives, including the development of the new 510(k) pathway for device clearances.

“All of us at the Department of Health and Human Services [HHS] are proud of the remarkable work Commissioner Gottlieb has done at the FDA,” Azar comments in a statement. “He has been an exemplary public health leader, aggressive advocate for American patients, and passionate promoter of innovation.

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