Cardiovascular News 49 – May 2018

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Safety of short-term dual antiplatelet therapy after PCI in acute setting questioned

Mark Spence Valve durability

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TMVI in inoperable patients is feasible but mortality is high at one year

Data from the SMART-DATE study indicate that acute coronary syndrome patients who receive short-term (six months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) have a significantly increased risk of myocardial infarction compared with those who receive it for 12 months or longer. The study investigators report that these findings mean they “cannot conclude” short-term DAPT is safe in patients with acute coronary syndromes.

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riting in The Lancet, Joo-Yong Hahn (Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea) and colleagues explain that they conducted the trial because, at present, identifying the optimal duration of DAPT after PCI in acute coronary syndrome patients is “challenging”. They note that while a recent network meta-analysis suggested shortterm DAPT was not associated with higher rates of myocardial infarction or stent thrombosis, most of the patients enrolled in

that study “had a relatively low risk and the proportion of patients with myocardial infraction was at about 10%”. “Therefore, we sought to investigate whether a reduced six-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT at 18 months after currentgeneration drug-eluting stent implantation in patients with a broad spectrum of acute coronary syndrome,” the authors comment.

Overall, 2,712 patients were enrolled; of these, 1,357 were randomised to receive sixmonth DAPT and 1,355 were randomised to receive 12-month

DAPT or longer. In each group, approximately 38% had STsegment elevation myocardial infarction (STEMI), 31% had nonSTEMI (NSTEMI), and 31% had unstable angina.

Additionally, in each group, a third of patients received an everolimus-eluting stent, a third received a zotarolimus-eluting stent, and a third received a biolimus-eluting stent. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, or stroke.

At 18 months, there was no Continued on page 2

One-year outcome data for transcatheter mitral valve implantation (TMVI), in inoperable patients, indicate most patients who survive the first 30 days after the procedure will be alive at one year.

However, they also show that mortality is high at both 30 days and at one year— with left ventricular outflow tract (LVOT) obstruction as the most important and independent predictor of mortality.

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ayra Guerrero (Division of Cardiology, Evanston Hospital, Evanston, USA) and others write in the Journal of the American College of Cardiology that TMVI, with balloonexpandable valves, in inoperable patients (on compassionate grounds) has been shown to be feasible. However, they note that only shortterm outcome data are available meaning that “long-term outcomes are unknown”. “The present study evaluated the clinical results and function of mitral

prosthesis at one-year follow-up. Our hypothesis was that patients who survive the 30-day procedural period remain stable at one year,” Guerrero et al comment.

Using data from the TMVR in Mitral Annular Calcification (MAC) registry, the authors identified 116 patients with severe mitral annular calcification who underwent TMVI with an aortic balloonexpandable transcatheter heart valve. Of these, 106 were eligible for the one-year follow-up (had the procedure before a Continued on page 2

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Safety of short-term dual antiplatelet therapy after PCI in acute setting questioned Continued from page 1

significant difference in the primary endpoint between groups: 4.7% for six-month DAPT vs. 4.2% for 12-month DAPT (p for noninferiority; p=0.03). However, Hahn et al comment that the non-inferiority margin of 2% “seemed to be wide considering that the actual rate of the primary endpoint was 4.2% with 12-month DAPT or longer DAPT”.

Additionally, myocardial infarction occurred significantly more frequently in the six-month DAPT group than in the 12-month group: 1.8% vs. 0.8%, respectively; p=0.02. To further explore this increased risk of myocardial infarction, Hahn et al performed a post-hoc landmark analysis of the primary endpoint and this showed that the risk of MACCE between six months and 18 months “seemed to be higher” in the six-month DAPT group (p=0.07). Looking at the individual endpoints of this primary outcome, they found that there were no significant differences in the risk of all-cause death between groups “but myocardial infarction occurred more frequently in the six-month DAPT group than in the 12-month or longer DAPT group (p=0.01 for the difference)”. The risk of cardiac death or myocardial infarction was also significantly higher in the six-month DAPT group.

As to why the risk of myocardial infarction was higher in the six-month DAPT group, Hahn et al state that the “most plausible explanation” might be an increase in stent thrombosis in that group after cessation of DAPT but they note that there was not a significant difference in stent thrombosis between groups. The authors add that while their sample size was too small to detect significant differences in events occurring at a low rate (such as stent thrombosis), “exclusive use of a second-generation drugeluting stent with proven efficacy and safety might explain the absence of a significant difference in the rate of stent thrombosis between the two groups”. On the other hand, there was a strong trend of an increased risk of myocardial infarction in the nontarget vessel (p=0.07), which may be the major cause of increased risk of myocardial infarction in the six-month group.

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On the basis of their results, Hahn et al state: “We cannot conclude that short-term DAPT is safe in patients with acute coronary syndrome undergoing PCI with current-generation drug-eluting stents.” They add that, as they did not observe definite harm from prolonged DAPT in terms of mortality or major bleeding, “12-month or longer DAPT should remain the standard of care for these patients despite the improved safety of current-generation drugeluting stents”.

The findings of SMART-DATE differ from the recent DAPT STEMI trial. This study did not find a significant difference in the rate of all-cause mortality, myocardial infarction, any revascularisation, stroke or major bleeding at 18 months between STEMI patients who received DAPT for six months after PCI and those who received it for 12 months. All patients in that study underwent PCI with a second-generation zotarolimus-eluting stent.

However, in DAPT STEMI, patients were randomised to aspirin monotherapy or additional six-month DAPT after receiving DAPT for six months (and being event free)—i.e. unlike SMART-DATE, patients were not randomised at baseline. Additionally, the investigator of that study Elvin Kedhi (Isla Hartcentrum, Zwolle, The Netherlands) did note that further data were needed to confirm the safety and efficacy of short-term DAPT after PCI in STEMI patients.

According to Hyeon-Cheol Gwon (Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea), the corresponding author of the SMART-DATE paper, both DAPT-STEMI and the REDUCE trial (which had similar findings) were underpowered to test the rate of MACCE. He comments: “They adopted revascularisation and bleeding as a part of the primary endpoint, mostly due to small sample size, whereas the SMART-DATE trial is the first trial powered to test MACCE.” Gwon presented the results of the SMARTDATE study during a late-breaking trial session of the 2018 American College of Cardiology Scientific Session (ACC; 10–12 March, Orlando, USA).

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TMVI in inoperable patients is feasible but mortality high at one year Continued from page 1

data lock was imposed). Seventy-seven patients were alive after 30 days and eligible for one-year follow-up, and 49 of them were alive at the one-year follow-up point. This meant that 30-day mortality was 25% and one-year mortality was 53.7%.

Of those alive at one year, there was no significant difference in left ventricular ejection fraction at one year compared with baseline. However, mean mitral valve gradient and mitral valve area significantly improved between baseline and one year.

The authors state that the one-year mortality rate of 53.7% is “concerning” and that “efforts should be made to improve patient selection to achieve better outcomes”. However, they note that most of the deaths that occurred after 30 days were noncardiovascular and, therefore, suggest that “these late events are most likely related to the multiple comorbidities, non-cardiac frailty, and advanced age of these extremely ill patients who had a baseline Society of Thoracic Surgeons score of 15.3%”.

Furthermore, Guerrero et al report: “Landmark analysis after 30 days showed that most patients who survived the 30-day post procedure period remained alive at one year.”

In terms of the predictors of mortality after the TMVI procedure, LVOT obstruction was an independent predictor both at 30 days and at one year. The authors comment: “Efforts should be made to avoid this complication to improve short- and long-term outcomes”. They add that strategies to prevent and treat this complication include pre-emptive alcohol septal ablation performed several weeks before TMVI, percutaneous anterior leaflet laceration, and alcohol septal ablation as bailout treatment. “Another strategy could be the use of self-expanding aortic retrievable devices, which may have the advantage of allowing device retrieval if severe LVOT obstruction occurs after TMVI,” Guerrero et al observe.

They comment that TMVI “might be an alternative for carefully selected high-risk or inoperable patients with limited treatment options” but add that “efforts are required to improve outcomes”.

“The role of TMVI and predictors of outcomes in mitral annular calcification patients treated with TMVI requires further evaluation in clinical trials,” the authors conclude.

Guerrero told Cardiovascular News: “Although we found in this initial experience that TMVI with balloon-expandable aortic transcatheter heart valves in high surgical risk patients with severe mitral annular calcification is associated with high 30-day and one-year mortality, the outcomes improved with experience. There were fewer complications and no need for conversion to surgery in the second half of the experience and a trend towards lower 30day mortality. We also identified the most important predictor of mortality, LVOT obstruction. Avoiding this lethal complication will help improve mortality. I am cautiously optimistic that with improved patient selection and procedural techniques, we can further improve overall outcomes. Further evaluation under clinical trials is needed.”

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Pharmacology

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Personalised approach to choosing antiplatelet therapy for acute coronary syndrome patients may reduce ischaemic and bleeding events A new study suggests that using genotyping—as well as patient characteristics—to choose which P2Y12 inhibitor to use to treat patients with acute coronary syndrome reduces both ischaemic and bleeding events. However, further data are needed to confirm these findings and evaluate the cost-effectiveness of the approach.

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riting in the Journal of the American College of Cardiology (JACC), Francesca Maria Notarangelo (Division of Cardiology, Azienda Ospedaliero-Universitaria Di Parma, Parma, Italy) and others comment that genetic variants of the genes regulating clopidogrel absorption and metabolism, , have been shown “to affect clopidogrel bioavailability, on-treatment platelet reactivity and clinical outcomes”. They add that the aim of the PHARMCLO study, which was also presented at the 2018 American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA), was to test the hypothesis that knowing a patient’s genetic profile of clopidogrel metabolism may lead to more personalised and more efficient antiplatelet therapy.

In the study, patients with acute coronary syndrome were randomised to a strategy of selecting P2Y12 inhibitor through patient characteristics and genotyping or the basis of their characteristics alone.

The authors report: “The genotyping was carried out using the ST Q3 system, a compact platform enabling the laboratory analysis of DNA by means of realtime polymerase chain reaction (PCR). The ST Q3 is designed to as a low entry-cost portable system for foolproof use by unskilled personnel as a point-ofcare instrument.” They add that the primary endpoint was a composite of cardiovascular death and the first occurrence of non-fatal myocardial infarction, nonfatal stroke, and BARC 3 to 5-defined major bleeding within 12 months of randomisation.

Overall, 448 patients were randomised to the genotyping arm and 440 to the patient characteristic alone arm. However, these numbers only represent

24.6% of the pre-specified sample size. “On 18 February 2015, the Ethics Committee of Modena (Italy) required that the trial should be prematurely stopped and all of the patients followed-up as planned because of the lack of in vitro diagnosis certification for the ST Q3 instrument,” Notarangelo et al explain.

Significantly more patients in the genotyping arm received a more potent P2Y12 inhibitor— prasugrel or ticagrelor rather than clopidogrel (7.6%, 42.6% vs. 43.3%)—compared with those in the patient characteristics alone arm (8.4%, 32.7% vs. 50.7%, respectively; p=0.02 for the difference).

Furthermore, significantly fewer patients in the genotyping arm experienced the primary outcome: 15.9% vs. 25.9% for the patient characteristic alone arm (p<0.001). There was also a difference in the

primary endpoint among the subgroup of patients receiving clopidogrel: 24.7% for genotyping vs.

35.4% for the patient characteristic alone (p=0.03).

Additionally, genotyping appeared to be of benefit to patients (regardless of which P2Y12 inhibitor they had been assigned) for the ischaemia components and for the bleeding components of the primary endpoint.

According to the authors, the premature ending of the trial may have affected the results. They say: “Given the premature discontinuation of the study after the enrolment of only 25% of the planned number of patients, it is possible that the observed differences between the two arms may simply be attributable to a chance.” However, they add: “Alternatively, it is possible that the effect size in our sample size may have simply underestimated.”

“Another possible explanation may be related to the percentage of patients receiving clopidogrel or ticagrelor in the standard of care arm. As ticagrelor proved to be more effective than clopidogrel in the PLATO trial, it is possible that some of the benefit observed in our study may have been related to the more frequent use of clopidogrel in the standard of care arm,” Notarangelo et al acknowledge.

The authors conclude: “Our data suggest that a more personalised approach to the selection of antiplatelet therapy may lead to a clinically meaningful reduction in ischaemic and bleeding complications. Future studies of genotype-guided antiplatelet therapy are required to confirm these data and clarify the cost-efficacy of genotyping in the challenging setting of acute coronary syndromes before implementing it in everyday clinical practice.”

Principal investigator Diego Ardissino (Division of Cardiology, Azienda Ospedaliero-Universitaria Di Parma, Parma, Italy) presented the PHARMCLO study at the ACC.

ODYSSEY OUTCOMES trial provides further evidence of benefit of PCSK9 inhibition in high-risk patients after myocardial infarction The ODYSSEY OUTCOMES trial, which was presented at the 2018 ACC Scientific Session, indicates that the use of the PCSK9 inhibitor alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals) in acute myocardial infarction patients with elevated cholesterol— despite maximum tolerated therapy—is associated with a significant reduction in major adverse cardiac events. Last year, data presented at the 2017 ACC Scientific Session found that the PCSK9 inhibitor evolocumab (Repatha, Amgen) reduced cardiovascular outcomes in a similar patient cohort.

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resenting the ODYSSEY OUTCOMES data at the ACC, Ph Gabriel Steg (FACT, French Alliance for Cardiovascular Trials, Hôpital Bichat, AP-HP, Paris, France) reported that proprotein convertase subtilisin-kexin type 9 (PCSK9) is “a validated target for risk reduction in stable atherosclerotic disease” and alirocumab—which inhibits PCSK9— “has been safe and well-tolerated in studies to date”. He added that the hypothesis of the trial was that alirocumab, compared with placebo, would reduce cardiovascular

mortality and morbidity after a recent acute coronary syndrome event in patients with elevated levels of atherogenic lipoproteins despite intensive or maximum-tolerated statin therapy.

In the trial, 18,924 patients who had experienced an acute coronary syndrome and who had inadequate lipid control despite being on high-intensity statin therapy were randomised to receive alirocumab subcutaneously once every two weeks (9,462) or equivalent placebo (9,462). The primary efficacy outcome

was time of first occurrence of coronary heart disease, non-fatal myocardial infarction, or fatal or non-fatal ischaemic stroke, unstable angina requiring hosptialisation—major adverse cardiac events (MACE). Major secondary endpoints included coronary heart disease event, major coronary heart disease event

and cardiovascular event.

Use of alirocumab was associated with a significant 15% reduction in MACE (p=0.0003) and a significant reduction in all-cause death (p=0.026). Steg reported that, according to a prespecified analysis, the effect of the drug on the rate of MACE was more pronounced in patients with low density lipoprotein (LDL) cholesterol levels ≥100mg/dL. In this group, the MACE rate was reduced by 24%. Furthermore, in a post-hoc analysis, the rate of all-cause death was reduced by 29% in patients with LDL cholesterol ≥100mg/dL. Steg commented: “Compared with placebo in patients with acute coronary syndrome, alirocumab 75mg or 150mg subcutaneously once every two weeks targeting LDL cholesterol levels 25– 60mg/dl, was associated with a lower rate of all-cause death, and was safe and welltolerated over the duration of the trial.”

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Post-hoc analysis suggests statin loading dose may benefit STEMI PCI patients Data from SECURE-PCI show that a periprocedural 80mg loading dose of atorvastatin in acute coronary syndrome patients in whom percutaneous coronary intervention (PCI) is planned does not significantly reduce the rate of major adverse cardiovascular events (MACE) at 30 days compared with matching placebo. However, a post-hoc analysis of these data indicate that such a loading dose may provide benefit for patients with ST-segment elevation myocardial infarction (STEMI) who undergo PCI.

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riting in the Journal of the American Medical Association (JAMA), Otavio Berwanger (Institute-Heart Hospital, São Paulo, Brazil) and others report that previous studies have suggested that statin loading doses may provide benefit for patients with acute coronary syndrome. They explain that statins, in this context, “may attenuate the inflammatory cascade and promote stability of coronary lesions vulnerable to rupture”. However, the authors state that the effect of loading doses of statins in patients with acute coronary syndrome is uncertain “because the evidence is limited to studies with low numbers of events and different statin doses and regimens”.

Therefore, the aim of the present study—SECURE PCI (Statins evaluation in coronary procedures and revascularisation) trial—was to assess the effect of loading doses of atorvastatin on clinical outcomes in patients with acute coronary syndrome and planned invasive management.

In the study, 4,191 patients were

randomised to receive two 80mg loading doses of atorvastatin (2,087) or matching placebo (2,104) prior to and after planned PCI. If a patient did not have PCI, they received their second loading dose 24 hours after the first.

The primary outcome was the rate of MACE at 30 days.

Overall, the mean age of patients was 61.8 years and the majority were male (25.9% female). Almost a quarter (24.8%) presented with STEMI, 60.7% with non-STEMI (NSTEMI), and 14.5% had unstable angina. In terms of treatment strategy, 64.7% underwent PCI, 8% underwent coronary artery bypass grafting (CABG), and 27.3% received medical management alone.

All patients were prescribed 40mg of atorvastatin for 30 days, which was initiated the day after the second loading dose. Thereafter, statin use and regimen were defined according to local practice.

At 30 days, there was no significant difference between groups in the rate of MACE: 6.2% for patients in the atorvastatin group vs. 7.1% for the

placebo group (p=0.27). There were no significant differences in any of the components of the primary outcome.

However, in a subgroup analysis, a significant difference in the 30-day rate of MACE was observed in patients who underwent PCI: 6% for atorvastatin vs. 8.2% for placebo (p=0.02). No such difference was observed among patients who did not undergo PCI. Berwanger et al report: “Considering that the reduction in MACE observed in this study occurred early and was related to PCI, the mechanism behind this potential effect is likely not the low-density lipoprotein (LDL) cholesterol reduction.” They add that mechanistic studies have indicated that statins have “important pleotropic effects that can start early after statin initiation, and these effects include regulation of nitric oxide synthesis,

reducing metalloproteinase active and lowering circulating levels of proinflammatory biomarkers”.

Furthermore, in a post-hoc analysis, MACE was significantly reduced in STEMI patients in the atorvastatin group if they underwent PCI (30 of 417 vs. 58 of 448 for placebo; p=0.01).

Again, no significant difference was observed among patients who did not undergo PCI. For patients with NSTEMI, atorvastatin did not provide a significant benefit for either those who underwent PCI or for those who did not undergo PCI. Noting that PCI may result in both local and embolic complications “and also enhancement of inflammatory activity and atherosclerotic plaque instability”, the authors comment that the additional effects (to their lipid lowering effects) of statins have the potential to reduce the risk of clinical events “especially in patients undergoing a coronary intervention”.

“Despite occurring among a post baseline subgroup, the reduction of doses of statin might have a role in modifying adverse atherosclerotic events in patients with acute coronary syndrome undergoing PCI, particularly patients with STEMI. However, this finding requires further investigation,” Berwanger et al comment.

Berwanger presented this study at the 2018 ACC Scientific Session.

C Michael Valentine becomes new president of the American College of Cardiology C Michael Valentine is the new president of the American College of Cardiology (ACC), officially assuming his role at the end of the 2018 American College of Cardiology (ACC) Scientific Session (10-12 March, Orlando, USA). Valentine is a senior cardiologist at the Stroobants Cardiovascular Center of Centra Health (Lynchburg, USA) where he specialises in cardiac catheterisation and intervention, device placement and arrhythmia therapy, clinical quality, leadership and practice development.

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ccording to a press release, he first became involved with the ACC in 1993 and has worked his way up through the leadership ranks, including previously serving on the Advocacy Committee, as Virginia Chapter governor, as Board of Governors chair, treasurer and on the Board of Trustees.

During his year as president, Valentine says he will attempt to achieve several critical goals of the ACC, including guiding the Board of Trustees in delivering and executing the College’s next five-year Strategic Plan, leading the Board in successfully completing the 2018 Strategic Priorities and working with the CEO Selection Committee in choosing the next great staff leader for the college. Valentine is also passionate about advancing member and staff leadership development, partnerships with sister society members and ACC’s International teams around the globe.

He comments: “The ACC has an immensely talented Board and the most dedicated staff of any medical association in the country, now led by Interim CEO Cathy Gates. We have developed new Core Values together that will help us focus on driving strategy and innovation to meet some major challenges and achieve

C Michael Valentine

our new Vision.”

Valentine states he is “very excited” for the opportunities that come with the ACC’s new diversity initiative in shaping how the College will look in the very near future.

Valentine received his undergraduate degree from the University of Georgia and went on to earn his medical degree from the University of Virginia School of Medicine. Valentine completed his medical residency and fellowship in cardiovascular disease at Emory University in Atlanta. After fellowship, Valentine joined private practice in Virginia in 1990. The group ultimately developed into an advanced system, participating in over 90 clinical trials and leading quality and advocacy efforts in the Commonwealth. It became one of the early integrated practice models in the USA, joining Centra Health in 2005.

“Being ACC President is a tremendous honour and privilege, not only for me, but for our group practice and health system at Centra. This recognises the importance and responsibility of community systems to lead with the highest quality care and clinical research.

It also encourages grassroots members who work at the local chapter level to further advance the Mission of the College,” comments Valentine.

Other ACC officers for 2018–2019 are: board of governors’ chair Andrew P Miller; vice president Richard J Kovacs; and treasurer Howard T Walpole Jr.

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Structural Heart Interventions

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TAVI is increasingly seen as the preferred approach for aortic valve replacement in CABG patients A review of the trends in the use and propensity-matched analysis of in-hospital outcomes, published in Circulation: Cardiovascular Interventions, indicates that the number of patients with a history of coronary artery bypass grafting (CABG) undergoing aortic valve replacement is increasing. Furthermore, transcatheter aortic valve implantation (TAVI) is increasingly being used as the preferred approach in this group.

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riting in the journal, Tanush Gupta (Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, USA) and others report that a substantial number of patients requiring aortic valve replacement have previously undergone CABG “because similar risk factors are responsible for the pathogenesis of coronary artery disease and aortic stenosis”.

They add that reoperative cardiac surgery (ie. surgical valve replacement after CABG) is associated with a greater risk of mortality and morbidity, noting that recent European valvular heart disease guidelines advise that both previous cardiac surgery and the presence of intact bypass grafts at risk of damage during redo sternotomy should be seen “as considerations for heart team decision-making between TAVI and surgical aortic valve replacement”.

The aim of the present study was, therefore, to determine if the use of TAVI has increased in patients with prior history of CABG undergoing aortic valve replacement and to evaluate if it was associated with more favourable short-term outcomes than surgery. To achieve this, Gupta et al compared 2012 data from the National Inpatient Sample databases with that from 2014.

Overall, they found that 10.2% of patients with a prior history of CABG underwent isolated aortic valve replacement between 2012 and 2014. “Of the total number of isolated aortic valve replacements, the proportion of those in patients with prior CABG increased from 9.2% in 2012 to 11.4% in 2014 (P trend <0.01),” the authors note.

Study investigator Deepak Bhatt (Brigham and

Deepak Bhatt

Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, USA) told Cardiovascular News that this increase may well relate to patients who previously would have been unable to undergo surgery— because the risk of complications were too high—now being able to receive TAVI. He adds that this is “a great development for those types of patients”.

Of those who underwent aortic valve replacement, more patients underwent TAVI than underwent surgery (59% vs.

41%, respectively). Additionally, the proportion of surgical aortic valve replacement procedures decreased between 2012 and 2014 while the proportion of TAVI procedures increased (p trend <0.001). “In the first quarter of 2012, surgical aortic valve replacement was the predominant modality of aortic valve replacement, whereas by the fourth quarter of 2012, TAVI became the predominant modality of aortic valve replacement in patients with prior CABG, with its utilisation continuing to increase through the last quarter of 2014,” Gupta et al comment.

Bhatt notes the preference for TAVI over surgery in this context is because the “risks of reoperative surgery are much higher than the initial surgery”. He adds: “The patients have already had a median sternotomy and are older at the time of the potential second surgery. Therefore, TAVI is increasingly preferred, and this trend will continue.”

In the study, after propensity matched scoring, the rate of in-hospital mortality was similar between TAVI and surgery patients. Furthermore, the incidence of myocardial infarction, stroke, bleeding, and acute kidney injury were all lower in the TAVI patients. However, the need for a permanent pacemaker was almost two-fold higher in TAVI patients (8.9% vs. 5.4%).

On the basis of these results, Bhatt comments that “in general” TAVI should be seen as the preferred approach to surgery in patients with a history of CABG. However, he comments that the results with surgical aortic valve replacement “were in fact good”. “So if a patient needs concomitant revascularisation that cannot be achieved percutaneously, and if the patient is otherwise a good surgical candidate, surgical aortic valve replacement plus CABG with multivessel revascularisation might also be considered,” he says.

Short-term duration of dual antiplatelet therapy is feasible for patients undergoing percutaneous closure of left atrial appendage Felix Weise (Cardioangiologisches Centrum Bethanien, Frankfurt, Germany) and others report in EuroIntervention that a strategy of six weeks’ duration of dual antiplatelet therapy (DAPT) followed by lifelong aspirin “appears to be a viable alternative” to existing antithrombotic regimens in atrial fibrillation patients who have undergone percutaneous closure of the left atrial appendage.

The short-term DAPT strategy was associated with a lower than expected annual bleeding rate but did not appear to increase the risk of thromboembolic events.

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he authors note that after successful implantation of a left atrial appendage closure device, in patients with atrial fibrillation, a transient antithrombotic regimen should be applied “to avoid device-related thrombosis formation and subsequent embolic events”.

However, they comment: “Uncertainty exists on the optimal antithrombotic regimen as well as the optimal treatment duration.” They note that for the Watchman device (Boston Scientific), two treatment strategies have been put forward: oral anticoagulation plus aspirin for six weeks followed by six months’ DAPT and lifelong aspirin; and six months’ DAPT

followed by lifelong aspirin. “Scarce data from controlled studies are available for alternative devices but it is expert consensus to establish a six-month [duration of] DAPT,” the authors add.

The aim of the present study was to investigate the feasibility of a short-term course of DAPT (six weeks) followed by lifelong aspirin therapy in an all-comers cohort receiving different left atrial appendage closure devices.

Of the 298 patients in the study, almost half (47%) received a Watchman or Watchman Flex device. The Amplatzer Cardiac Plug or Amulet (Abbott) was used in 42% of patients and the

WaveCrest (Coherex Medical) was in implanted in 11% of patients. The mean follow-up was 820±547 days after left atrial appendage closure.

Non procedure-related bleeding events occurred in 4.4% of patients taking DAPT 11±16 days and in 4% of patients after the cessation of DAPT. Weise et al note that while nine patients experienced a major bleed when just taking aspirin, one patient had a fatal gastrointestinal bleed when not taking any antithrombotic medication.

They add that most patients with a non procedure-related bleed had a history of bleeding and most of these had the same type of bleeding, commenting, “Thereof, 82.4% of patients with a gastrointestinal bleed had a prior history of gastrointestinal bleeding”. Furthermore, the annual major bleeding rate was 3.9% and Weise et al observe, “Given the expected bleeding rate of 8.7%, this reflects a reduction of 55.2%.”

Overall, 3.7% of patients had a non procedure-related thromboembolic event.

The authors state: “Most importantly, early DAPT cessation did not lead to a higher

incidence of thromboembolic events. In fact, the first stroke was noted 178 days after DAPT cessation. The observed annual stroke/systemic embolism rate of 1.7% is similar to previous reports such as the PREVAIL study.”

They conclude: “Short-term DAPT for six weeks appears to be a viable alternative for patients after left atrial appendage closure. Age >75 years and renal impairment increase major bleeding events threefold. Therefore, less aggressive antithrombotic strategies in these patient populations deserve investigation.”

Boris Schmidt (Cardioangiologisches Centrum Bethanien, Frankfurt, Germany) told Cardiovascular News: “Bleeding has become the most prevalent complication following left atrial appendage closure; therefore, there is unmet need for risk adapted post implant antithrombotic strategies. Looking at clinical data, both a foreshortened period of antithrombotic medication or reduced intensity seem to work. However, ultimately we need a randomised comparison!”

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Structural Heart Interventions

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“Favourable” in-hospital outcomes for younger patients undergoing TAVI Registry data show younger patients—under 75 years—undergoing transcatheter aortic valve implantation (TAVI) have similar in-hospital outcomes to propensity-matched patients undergoing surgical aortic valve replacement. However while TAVI patients were less likely to have postoperative delirium, they did more frequently need a new pacemaker.

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tudy investigators Holger Eggebrecht (Cardioangiologisches Centrum Bethaniem and AGAPLESION Bethanien Hospital, Frankfurt, Germany) and others write in EuroIntervention that data indicate that TAVI is “at least” non-inferior to surgery for intermediate-risk patients. However, they observed that most studies have focused on older patients, commenting: “Even in the randomised all-comer (low-risk) NOTION (Nordic aortic valve intervention) trial, the mean age was still 79.1 years”. They add that despite the lack of evidence for TAVI in younger patients, “recent registry data have indicated that there is a trend for an increasing number of lower risk and younger patients with symptomatic aortic stenosis to be subjected to TAVI over surgical aortic valve replacement”.

Therefore, in the present study, Eggebrecht et al reviewed data from the Germany Quality Assurance Registry on Aortic Valve Replacement to evaluate the outcomes of younger patients (<75 years) undergoing TAVI (via the transfemoral approach) compared with those undergoing surgery.

Of 6,972 patients aged under 75 in the registry, the majority (82.4%) underwent surgery. While TAVI patients tended to be older and have more comorbidities than did surgical patients, just over half (55.5%) were considered to be low risk for surgery and 28.1% were at intermediate

Holger Eggebrecht

risk—only 16.4% were at high risk.

In a propensity-matched analysis, the mean age of patients was 71.7 years in the surgery group and 71.5 years in the TAVI group (694 patients in each group).

The authors report: “The vast majority of patients were at

low risk, with a logistic EuroSCORE I <10% in 95.5% of surgical aortic valve replacement patients and 86.3% of TAVI patients. Only 0.4% and 1.9% were at high surgical risk, respectively.”

The rates of in-hospital mortality, stroke/transient ischaemic attack, and myocardial infarction were similar between groups. Surgical patients had a three-fold higher rate of postoperative delirium and had a greater need for dialysis than had TAVI patients. However, TAVI patients had more than four-fold increase in the need for a new pacemaker. According to Eggebrecht et al, the rate of new pacemaker after TAVI “remains a concern” and they note that this is particularly the case for younger patients with longer life expectancies, “and thus higher chances of experiencing technical complications of the pacemaker device or its electrodes or developing long-term consequences of right ventricular pacing”.

Additionally, in-hospital stay was shorter with TAVI, and more TAVI patients were discharged to home rather than to another hospital/rehabilitation unit. The authors observe: “This, together with less postoperative delirium and shorter hospital stays, suggest that recovery after the less invasive TAVI procedure was less demanding.”

Concluding, they state: “Further randomised studies are needed in younger patients to confirm these favourable in-hospital results during long-term course.”

Eggebrecht told Cardiovascular News: “These results are very reassuring that TAVI will be the treatment of choice also for younger patients, once the issue of valve durability has been solved.”

Location of tricuspid regurgitation predicts procedural success of percutaneous edge-to-edge repair Supporting the results of previous studies, a new study indicates that percutaneous edge-to-edge repair (MitraClip, Abbott) is a feasible approach for high-risk patients with tricuspid regurgitation.

Furthermore, for the first time, this study provides insight into which patients may benefit the most from the procedure—finding that tricuspid regurgitation jet is a successful predictor.

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riting in EuroIntervention, Philipp Lurz (Department of Cardiology, Heart Center Leipzig—University Hospital, Leipzig, Germany) and others report that several transcatheter techniques and devices have been used in patients with tricuspid regurgitation and have been associated with “promising early feasibility results”.

They add that of these techniques, edgeto-edge repair technique is the one that has been used most often.

Commenting that a recent study “shed light on patients considered for these interventions”, Lurz et al write: “We here report a single-centre experience of 42 patients undergoing edge-to-edge tricuspid repair treatment with complete clinical and echocardiographic 30-day follow-up and, for the first time, provide predictors for procedural success”.

Of the 42 patients, 31 received a combined tricuspid valve and mitral valve repair procedure; 11 underwent

isolated tricuspid repair. The authors report: “Overall procedural success rate—successful clip placement leading to a reduction in tricuspid regurgitation by at least one grade—was 83%. In total, 68 clips were implanted in the tricuspid valve position.”

In both patients who underwent a combined procedure and those who underwent an isolated procedure, significant improvements in New York Heart Association (NYHA) functional class and six-minute walk distance were seen during follow-up (30 days). Of the eight patients (overall) in whom no improvements in NYHA functional class were seen, tricuspid regurgitation remained stable in three patients and changed from “massive” to “severe” in another.

However, according to Lurz et al, no significant change in Minnesota Living with Heart Failure Questionnaire score was observed in either patients who

Philipp Lurz

underwent the combined procedure or those who underwent the isolated procedure. Noting that tricuspid regurgitation remained “severe” in 16% of patients in their study, the authors comment that this finding suggests that “there is room for improvement with respect to technical and procedural aspects during tricuspid regurgitation”.

“Recent data indicate that after minimally invasive mitral and tricuspid valve surgery, tricuspid regurgitation is reduced to grade 2 or less in more

than 95% of cases and, therefore, one should be cautious not to fuel unrealistic expectations when alternative transcatheter options for tricuspid repair are discussed with referring physicians, patients and relatives,” they add.

Additionally, Lurz et al analysed the predictors of success of tricuspid valve edge-to-edge repair—representing the first time that predictors of success of this procedure in this patient cohort have been performed. They found that predominantly non-central tricuspid regurgitation or non-anterospetal tricuspid regurgitation jet appeared as the only significant predictor for procedural failure. The authors comment: “Importantly, in our cohort, clip placement between the anterior and posterior leaflet resulted in unchanged or even increased tricuspid regurgitation in two patients with subsequent clip removal” Concluding their study, they state that future studies are needed “to address the question of morphological assessment for prediction of procedural success.”

Lurz told Cardiovascular News: “Transcatheter edge-to-edge repair of tricuspid regurgitation is a promising technique but requires refinements of patient selection and procedural techniques.”

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ADVERTORIAL

Sentinel Cerebral Protection System provides reassurance to both physicians and patients

Compared with first-generation devices, new-generation transcatheter aortic valve implantation (TAVI) devices—along with iterative approaches in technique and imaging—have partially reduced the documented stroke rates during the procedure. However, the rate of clinically evident stroke is still significant at about 4.4% and this figure does not account for the fact that most studies do not involve a neurologist to assess for the subtle nuances of ischaemic brain injury. This article explores how the use of the Sentinel Cerebral Protection System (Claret Medical) reduces the risk of periprocedural stroke after TAVI—providing reassurance to physicians and patients alike.

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ochen Wöhrle (University of Ulm, Ulm, Germany, Head Interventional Cardiology Research Group) observes that the figure of about 4.4% (based on a weighted average from published studies) only refers to clinically observable stroke, reiterating that even delirium, transient ischaemic attack and non-disabling stroke have consequences for increased mortality—it does not address the risk of silent ischaemia. He comments: “There is a discrepancy between symptomatic stroke identified through clinical examination and silent ischaemia seen via cerebral imaging.

With MRI, the rate of silent ischaemia is much higher—it is actually above 80%.”

Therefore, he uses the Sentinel device (Claret Medical) to not only reduce the risk of clinically overt stroke but to also reduce the risk of silent ischaemia infarcts, which are associated with increased risk of future stroke, cognitive dysfunction, and dementia.

Data from the SENTINEL study found that use of Sentinel was safe and was associated with a 42% reduction in new lesion volume and a significant 63% reduction in clinical strokes at ≤72 hours.1,2 However, as it was a randomised controlled trial, it had a select patient cohort and, therefore, its findings are not necessarily applicable to all patients undergoing contemporary TAVI. To address how Sentinel performs with contemporary TAVI devices, Wöhrle and colleagues independently collected data from 802 prospective patients undergoing TAVI at their centre. They then reviewed outcomes of consecutive patients who had undergone TAVI with the Sentinel device (280) with those who underwent TAVI without the device (522) and performed a propensity matching.3 The primary composite endpoint was all-cause mortality or all stroke according to Valve Academic Research Consortium (VARC)-2 criteria within seven days. Secondary endpoints included technical success of the device.

In the propensity-matched analysis, seven-day all-cause mortality or all stroke occurred significantly less frequently in the group who were protected by the Sentinel device—2.1% vs. 6.8% for patients in whom Sentinel was not used (p=0.01).

Furthermore, use of the device was associated with a significant reduction in the rate of disabling and non-disabling stroke compared with not using the device: 1.4% vs. 4.6% (p=0.03 for the comparison).3 On the basis of these findings, the authors conclude: “In patients undergoing

Jochen Wöhrle

protected TAVI, use of a Sentinel cerebral embolic protection device demonstrated a significantly higher rate of stroke-free survival compared with unprotected TAVI.” In a subsequent patient-level pooled analysis conducted by Wohrle and his colleagues, 1,263 patients from the original study were combined with patients from the SENTINEL study and showed “a significant reduction in the risk of stroke after TAVI with the Sentinel device that was independent of valve type”. He notes that he presented these data at TCT 2017.

Furthermore, Nicholas van Mieghem (Erasmus Medical Center, Rotterdam, The Netherlands) presented data at the 2018 Joint Interventional Meeting (22–24 February, Milan, Italy) that compared Sentinel use in 294 TAVI patients with 453 TAVI patients who did not receive Sentinel.5 Similar to the patient-level pooled analysis presented at TCT, these data showed an 80% reduction in stroke at 72-hours— from 5.1% for unprotected TAVI to 1% for protected TAVI (p<0.01). To further compel the routine use of Sentinel, at the CRT 2018 congress Dr Raj Makkar from Cedars Sinai in Los Angeles showed his real-world TAVR stroke data in 419 patients since his routine use of Sentinel started in June 2017, which also showed a 78% reduction (6.3% in 128 unprotected patients vs. 1.4% in 291

Sentinel CPS device in place

Sentinel protected patients) in clinical stroke in the first seven days post TAVI.6 Aside from assessing the effectiveness of the Sentinel device, another aim of the study by Wöhrle and his colleagues was to identify which patients were at high risk of stroke. According to Wöhrle, at present, knowing which patients will have a stroke after TAVI is difficult. He says: “We have seen patients with a high degree of calcification, as might be expected, have a stroke. But, we have also seen patients without such extensive calcification— therefore, who we did not suspect would have a stroke—have an event. To explore this issue further, in the patient level pooled analysis, Wöhrle performed a multivariate analysis of independent predictors of the risk of stroke after TAVI. Not using Sentinel was the only independent predictor of stroke at seven days. (STS score and non-use of Sentinel were the only independent predictors of the combined endpoint of all-cause mortality and allstroke at seven-days).

Given that lack of use of Sentinel was an independent predictor of stroke, as already mentioned, Wöhrle uses it in all patients.

This not only provides reassurance to the operators but also provides reassurance to the patients. “Patients are concerned about complications and, in particular, they are

concerned about the risk of stroke. Thus, they are happy when we tell them that we use a protection device. In fact, we have patients coming from (northern) areas such as Berlin and Hamburg—we are in the south of Germany—because they know that we use Sentinel when we perform TAVI.” According to Wöhrle, the device is “easy to use” in most patients, but he estimates that about 10% of patients will have difficult anatomies that can make the positioning of the device more complicated.

He does, however, note that using the device in tricky anatomies becomes easier with practice—commenting: “When you use the device in every patient, you build up a lot of experience. We have now done 800 procedures with the device and we now use it in patients in whom we would not have used it two or three years ago.”

References 1. Schaefer U, Interventional Cardiology Review 2017;12( 2):128–32.

2. Kapadia S, Kodali S, Makkar R, et al. Protection against cerebral embolism during aortic valve replacement. JACC 2017; 69: 367–77.

3. Seeger J, Gonska B, Otto M, et al. Cerebral embolic protection during transfemoral aortic valve replacement significantly reduces death and stroke compared with unprotected procedures. JACC Cardiovasc Interv 2017; 10(22): 2297–303.

4. BIBA Medical staff. Study of cerebral protection during TAVI only meets primary efficacy endpoint in adjusted model.

Cardiovascular News 2017; 44: 10 5. Van Mieghem N. JIM 2018 6. Makker R. CRT 2018

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Determining valve durability in the era of TAVI PAUL BRENNAN MARK SPENCE COMMENT & ANALYSIS Transcatheter aortic valve implantation (TAVI) has progressed from being a procedure that was solely reserved for patients who were too high risk for surgery to one that is now being considered for lower risk populations. In this commentary, Paul Brennan and Mark Spence review current definitions of bioprosthetic valve durability and how these can be applied to the durability of transcatheter heart valves.

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he first “in-human” TAVI was performed in Rouen in 2002.

Since then, TAVI has evolved to become an alternative intervention to surgical aortic valve replacement for high-risk patients with severe symptomatic aortic stenosis.1,2 Recent studies have demonstrated the noninferiority of TAVI to surgery in intermediate-risk patients.3,4 The favourable outcomes of the pivotal trials have led to changes in the class of recommendation for TAVI and, alongside improved valve system technology, we have seen the use of TAVI progressively rise over the last 15 years.5 To aid surgeons and patients choosing between surgery and TAVI, a useable definition of aortic transcatheter heart valve durability and structural valve deterioration is required. This will also provide a firm basis for a coherent discourse for clinical investigators.

Long-term outcomes after bioprosthetic surgical valves have been widely published.

Historically, surgical studies have used freedom from reoperation as a primary endpoint, and a marker of structural valve deterioration, without defining the specific haemodynamic or imaging criteria required to diagnose deterioriation.6 In a recent 2015 registry, bioprosthetic aortic valve replacement durability was reviewed in 12,569 patients after implantation of the Edwards Lifesciences Carpentier-Edwards Perimount bioprosthesis between 1982

and 2011. The primary endpoint was time to explant for valve deterioration. In this registry, 354 bioprostheses were explanted during the follow-up period, with 44% attributable to deterioration.

Younger age was a statistically significant risk factor for explant due to deterioration.

Actuarial estimates of risk of explant for deterioration at 10, 15 and 20 years—for patients under 60 years age— were 5.6%, 20% and 45%, respectively. In patients aged 60–80 years, risk of explant for deterioration was 1.5%, 5.1% and 8.1%, respectively, for the aforementioned time intervals.7 Freedom from deterioration, observed in a Hancock II registry in 2010, at five, 10, 15, and 20 years was 99.7%, 97.6%, 86.6% and 63.4% respectively.8 Similar outcomes were seen in a St Jude Medical Biocor registry in 2015, with freedom from deterioration at five, 10, 15 and 20 years being 97.9%, 92.1%, 84.8% and 67% respectively.9 There is, however, a paucity of data with respect to the long-term outcomes of bioprosthetic surgical aortic valve replacement for the patient group for whom TAVI was originally offered.

Several groups have now published five-year outcomes with regards to transcatheter bioprosthetic deterioration.

The Medtronic CoreValve and Cribier Edwards/ Edwards Sapien/ Sapien XT bioprostheses were respectively associated with a 1.4% and 1.67% incidence of deterioration

at the five-year follow-up point.10,11 Structural valve deterioration was defined in both groups using the surgical definition of freedom from re-intervention, and also precise echocardiographic criteria according to the VARC (Valve Academic Research Consortium)-1 criterion.

A systematic review of 8,914 patients, across 13 observational studies, focusing on prognosis after TAVI, found that the pooled incidence rate of deterioration was 28.08 per 10,000 patient years, with 12% of patients experiencing deterioration proceeding to reintervention.12 The current VARC-2 definition of deterioration defines it as valve-related dysfunction or the need for a repeat procedure ≥30 days after TAVI and/or not due to endocarditis. Valve related dysfunction, as assessed by echocardiography, is diagnosed in the presence of a mean aortic gradient ≥20mmHg, a rise in gradient of 10mmHg, a dimensionless valve index <0.35 and/or an effective orifice area of ≤0.9-1.1cm2 and/or the presence of moderate-to-severe regurgitation.13 This definition of deterioration does not include valve thrombosis—an important cause of leaflet restriction and increasing gradient.

Not all patients with an increasing transprosthetic gradient, on echocardiographic follow-up, will be symptomatic or have significant prosthetic valve stenosis; and in this scenario, deterioration is further

characterised as “isolated haemodynamic dysfunction”.

Conversely, patients may demonstrate early anatomical changes, without haemodynamic dysfunction, such as leaflet thickening or reduced leaflet mobility, and this is characterised as “morphological surgical valve deterioration”.14 The term “bioprosthetic valve failure”—applied historically to surgical bioprostheses—differs from deterioration in that while it includes deterioration and the associated clinical consequences, it also extends to valve thrombosis, paravalvular leak and endocarditis.14 Deterioration, currently, remains the focal outcome though, with regards to long-term durability of the aortic transcatheter valve and surgical aortic valve.15 Theoretically, certain procedural-related complications, specific to TAVI, may result in early deterioration—e.g. crimping-related structural damage, paravalvular leak post implantation, potentially resulting in turbulent transcatheter valve flow and a predisposition to accelerated deterioration.

Long-term follow-up after bioprosthetic aortic valve replacement primarily focuses on mortality and structural valve deterioration incidence.

As previously stated, younger age at the time of implantation has historically been associated with increased mortality.

A recent study compared outcomes after mechanical or bioprosthetic aortic and mitral valve replacement, in all eligible patients, between 1996 and 2013.16 Interestingly, in a study population of 9,942 patients, they found that the mortality benefit associated with mechanical aortic valve replacement persisted until 53 years of age, after which there was no statistically significant mortality benefit with mechanical aortic valve replacement. As seen in previous studies, mechanical aortic valve replacement was associated with a statistically significant lower risk of reoperation, at the expense of an increased risk of bleeding

and stroke, when compared to bioprosthetic aortic valve replacement.

Decision making, with respect to valve choice, in younger patients at low-intermediate surgical risk requires a detailed knowledge of the existing literature and available valve technologies. Bagdur et al propose the application of a valve durability (years) to life expectancy (years) ratio when making an informed decision between TAVI and surgery.17 They suggest that we choose a bioprosthesis with a ratio of close to, or greater than, one; i.e. a bioprosthetic valve likely to outlast the longevity of the patient.

Ten-year real world outcomes will provide further insight regarding the long-term performance of the aortic THV in high risk patients. This long term durability data, alongside ongoing clinical trials, will guide clinicians in the application of TAVI for patients at intermediate and low surgical risk.

In summary, predicted aortic bioprosthetic valve durability and structural valve deterioration, alongside a patient-orientated approach, are fundamental guides in the decision making process for patients with severe symptomatic aortic stenosis.

Paul Brennan and Mark Spence are both at the Department of Cardiology, Royal Victoria Hospital Belfast, Northern Ireland References 1. Leon et al. N Engl J Med 2010; 363: 1597–1607.

2. ESC Task Force. European Heart Journal 2017; 00: 1–53.

3. Leon et al. N Engl J Med 2016; 374: 1609–20.

4. Reardon et al. N Engl J Med 2017; 376: 1321–31.

5. Nishimura et al. Circulation 2017; Epub.

6. Rodriguez-Gabriella et al. J Am Coll Cardiol 2017; 70 (8): 1013–28.

7. Johnston et al. Ann Thorac Surg 2015; 99: 1239–47.

8. David et al. Ann Thorac Surg 2010; 90: 775–81.

9. Guenzinger et al. Ann Thorac Surg 2015; 100: 2220–06.

10. Barbanti et al. JACC Cardiovasc Interv 2015; 8: 1084–91.

11. Eltchaninoff. Paper presented at: Transcatheter Valve Therapies (TVT) 2016; June 16–18, 2016; Chicago, Illinois.

12. Foroutan et al. Heart 2017. Epub.

13. Kappetein et al. Eur J Cardiothorac Surg 2012; 42(5): S45–60.

14. Vesely et al. Ann Thorac Surg 1988; 46(3): 302–08.

15. Capodanno et al. Eur J Cardiothorac Surg 2017; 52: 408–17.

16. Goldstone et al. N Engl J Med 2017; 377; 19: 1847–57.

17. Bagur et al. Heart 2017; 103 (22): 1756–59.

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Morphological characteristics may determine benefit of percutaneous PFO closure A new study—presented at the American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA) and published in the Journal of the American College of Cardiology— indicates that patients with “high-risk” patent foramen ovale (PFO), based on morphological characteristics, who undergo percutaneous PFO closure have a significantly lower risk of recurrent stroke than those who received medical therapy alone.

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riting in JACC, Pil Hyung Lee (Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) and others report that “high-risk” PFO—as defined by transoesophageal echocardiography (TEE)—includes size of the PFO, the presence of atrial septal aneurysm, or hypermobility. They add that, in a previous study, they found these factors were useful in predicting the risk of stroke recurrence. “Considering the high prevalence of PFO in the general population and in patients with cryptogenic stroke, transcatheter device closure confined to patients with cryptogenic stroke and characteristic PFO morphology associated with a higher stroke recurrence rate would be a more appropriate approach to enhance the benefits of PFO closure. To test this hypothesis, this multicentre, randomised, open-label trial was performed,” Hyung Lee et al comment.

In the study, of those who presented with cryptogenic stroke and high-risk

PFO, patients were randomised to undergo percutaneous PFO closure (Amplatzer PFO Occluder, Abbott) or medical therapy (60 in each group). The primary endpoint was a composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding during two years of follow-up.

After a median follow-up of 2.8 years, in the intention-to-treat cohort, no events occurred in the PFO group vs. six patients in the medication-only group (p=0.013).

Hyung Lee et al state: “The KaplanMeier two-year cumulative estimate of the probability of stroke was 10.5% in the medication-only group (p=0.0232 for the comparison with PFO closure group), which suggests that the number of people needed to treat to avoid one stroke at two years would be 10.”

Additionally, a per-protocol analysis found that primary events only occurred in the medication-only group and the event-free survival rates were significantly different (p=0.016 for the comparison).

The authors note that, recently, “we have witnessed the dramatic conversion from a negative to a positive outlook with respect to PFO closure. New trials with positive findings have a different study design in terms of medications and follow-up duration”. However, they comment of the trial that showed a benefit for percutaneous PFO closure, only the CLOSE trial had “stringent entry criteria” similar to theirs.

In CLOSE, patients had to have a large interarterial right-to-left shunt or an atrial septal aneurysm. Given that both CLOSE and the present study (DEFENSE-PFO) show no occurrence of stroke in patients who underwent PFO closure, Hyung et al say that their result suggest that “the beneficial effect of percutaneous device closure of PFO can be maximised by adding

the morphologic characteristics of PFO, as evaluated by TEE, to the selection criteria for the procedure.”

They conclude: “We have confirmed that the morphologic characteristics of PFO and the adjacent atrial septa, as evaluated by TEE, are important determinants of the clinical benefit of percutaneous device closure of PFO in patients with cryptogenic stroke.”

Jae-Kwan Song (Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) presented the study at the ACC. He told Cardiovascular News: “I feel it would be better to consider percutaneous device closure of a PFO only in cryptogenic stroke patients with high-risk PFO. Some may say it is too conservative, but I am sure many physicians believe it would be a better strategy considering the cost-benefit aspect.

Although we did not include patients with low-risk PFO, the subgroup analysis of the previous trials (REDUCE and RESPECT) already confirmed that device closure is more favourable in patients with large PFO or PFO with atrial septal aneurysm and not in patients with small PFO, shunt or PFO without atrial septal aneurysm. Thus, I cannot recommend device closure in cryptogenic stroke patients without highrisk PFO.”

3D model could be used to predict paravalvular leak after TAVI A new study presented at the 2018 Society for Cardiovascular Angiography and Interventions (SCAI) Scientific Sessions (25–28 April, San Diego, USA) indicates 3D printing technology could be used to confirm and detect paravalvular leak following transcatheter aortic valve implantation (TAVI). Cardiovascular News spoke to Sergey Gurevich (University of Minnesota, Minneapolis, USA) about the study.

What are the potential consequences of an illfitting valve?

It honestly depends on how you define “ill-fitting”. In my view, an ill-fitting valve is one that offers poor clinical outcomes. For example, many meta analyses and studies show that moderate or greater paravalvular leak—leak around the bioprosthetic valve due to a small size or calcium or poor fit—doubles a patient’s risk of all-cause or cardiac mortality, as well as their risk of hospitalisation at one year.

However, paravalvular leak is not the only adverse outcome of an ill-fitting valve. Complete heart block or conduction disease requiring pacemaker placement is another and occurs in as many as 10–30% of patients, depending on the valve type used.

Historically, earlier generations

of Sapien valves (such as Sapien XT, Edwards Lifesciences) have had higher paravalvular leak rates but lower pacemaker rates (5%), while other valves such as the Lotus (Boston Scientific) have had lower paravalvular rates at the expense of almost prohibitively high pacemaker rates (30%). Companies producing newer generations of these valves have developed various methods of trying to solve these problems. Edwards, for instance, have developed a “sealing skirt” around their second generation valve—the Sapien 3—that has dramatically reduced the rates of greater than mild paravalvular leak. Medtronic has attempted the same with their CoreValve Evolut Pro. Additionally, the shorter profile of the new Lotus valve will hopefully reduce the pacemaker rates to that of other valves (like

the latest generations of Sapien and CoreValve).

Prior to your study, what evidence was available for the use of 3D models for sizing bioprosthetic valves?

The majority of current available data for 3D printing and computer simulations in preprocedure planning for TAVI comes from either case reports or small cohort observational studies of 10–20 patients. There is only a handful of these studies currently in the literature.

What were the aims of your study?

Our aim was to see if we could predict paravalvular leak in patients with TAVI prior to implantation of the valve. To do this, we selected 20 patients

Sergey Gurevich

out of more than 300 that had undergone TAVI at our institution and used their preprocedure multislice computed tomography (CT) images to print 3D models of their aortic root. Sapien TAVI frames were then implanted into these 3D models, which were then scanned using CT, and those digital models were further evaluated for paravalvular leak.

Identified paravalvular leak in those models was then compared with both preprocedure CT images, as well as post procedure transthoracic echocardiogram (TTE) or transoesophageal echocardiography (TOE)

images to identify if the leak on our models matches any identifiable structural problems on CT and Doppler evidence of paravalvular leak. In each case, our paravalvular leak matched what was seen on post procedure TTE/TOE and closely matched calcium location on preprocedure CT. This is also the first 3D printed study using Sapien valves; all prior studies have used selfexpanding valves (CoreValve).

What were the key findings of your study?

We found that 3D printing preprocedure can identify areas of paravalvular leak and that 3D printing can identify aetiology of paravalvular leak.

What are the implications of your study for TAVI?

3D printing preprocedure can identify those patients at risk for paravalvular leak, which can assist in the selection of the right valve size and valve type for that particular patient.

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Five-year data for CoreValve show strong haemodynamic performance New data from the CoreValve US Pivotal Extreme Risk Study and the real-world NOTION trial (Nordic aortic valve intervention Trial)— both of which examined patients with the CoreValve transcatheter aortic valve implantation (TAVI) system (Medtronic) at five years post-implant—were presented at the 2018 American College of Cardiology Scientific Session (ACC, 10–12 March, Orlando, USA).

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H Gustav Thyregod (Heart Center, hese show similar rates of allRigshospitalet, Copenhagen, Denmark), cause mortality (27.7% for TAVI who presented the NOTION data at the vs. 27.7% for surgical aortic valve replacement) and superior haemodynamic ACC, says: “These five-year outcomes of the NOTION data add to the mounting performance for TAVI (mean aortic valve body of longer-term evidence supporting gradient of 8.22mmHg vs. 13.71mmHg the effectiveness of TAVI. We are for surgery) compared with surgery. pleased to see the strong haemodynamic The physician-initiated NOTION trial performance maintained over time without studied an all-comers population of 280 any indication of valve deterioration.” patients at least 70 years old who were Pieter Kappetein, vice president and randomised to surgery or TAVI using the chief medical officer of the Heart Valve CoreValve system. Also presented at ACC Therapies business, comments: “It is were the final five-year results from the remarkable to see patients, whose only CoreValve US Pivotal Extreme Risk Study, aortic valve replacement option was to which enrolled the first US IDE cohort of undergo a TAVI procedure, continue patients ever to be treated with the selfto live an improved quality of life expanding CoreValve TAVI system. five years later. While the Results from the study TAVI therapy continues to continued to show positive show promise in less sick outcomes at five years for patients, it is important to the surviving patients—all acknowledge that the early of whom were deemed to pioneers of this therapy were be facing considerable harm those who truly had very limited or mortality with a surgical treatment options. It is satisfying valve replacement. Patients to see that many of these early implanted with the CoreValve patients continue to do well system maintained a notable with the self-expanding TAVI improvement in quality of life platform, especially as the (mean change from baseline in therapy expands to lowerKCCQ of > 20 points at five risk patients who are years) and sustained low expected to live longer.” mean gradients (7.63mmHg).

CoreValue Evolut Pro

Edwards’ self-expanding Centera TAVI valve now on European market Edwards Lifesciences has received the CE mark for its selfexpanding Centera transcatheter aortic valve implantation (TAVI) valve for severe, symptomatic aortic stenosis patients at high risk of open-heart surgery.

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press release reports that the valve is repositionable and retrievable and can be delivered through a low profile, 14Fr, motorised delivery system. The press release adds that the advice is uniquely packaged with the valve fully preattached to the delivery system, which facilitates simple and rapid device preparation.

The European certification of the Centera valve was based on the CENTERAEU trial, which enrolled 203 high-risk patients at 23 centres in Europe, Australia and New Zealand. Study results presented at EuroPCR 2017 demonstrated high survival rates (99%) and low rates of disabling stroke (2.5%) and new permanent pacemaker (4.9%) at 30 days. In addition, there was a low 0.6% rate of moderate paravalvular leak among patients, and zero incidents of severe paravalvular leak.

All patients in the study were treated via the transfemoral access route with the majority under conscious sedation.

Didier Tchétché (Clinique Pasteur in Toulouse, France) comments: “With the Edwards Centera valve, European clinicians and their patients may now benefit from a self-expanding TAVI option that has demonstrated exceptional clinical safety and performance outcomes in the high surgical risk population. Enhanced design features of the Centera valve, including a motorised handle that enables stable valve deployment, allow for a simpler procedure with compelling outcomes.”

Larry L Wood, Edwards’ corporate vice president, transcatheter heart valves, comments: “Edwards is committed to partnering with clinicians to offer differentiated, best-in-class technologies for transcatheter heart valve therapy.

European certification of the CENTERA valve provides a meaningful treatment option for high-risk TAVR patients when their heart team recommends a selfexpanding device.”

The CENTERA valve is not approved for commercial sale in the USA.

Structural heart interventions

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May

Interview

Profile

Ron Waksman Ron Waksman (MedStar Heart & Vascular Institute, Washington, DC, USA) is the course chairman of Cardiovascular Research Technologies (CRT; 3–6 March, Washington, DC, USA), which this year had Barack Obama as its keynote speaker. Waksman talks to Cardiovascular News about the insights that former US presidents can provide, his career achievements, and what makes CRT unique.

Why did you decide go into medicine and why, in particular, interventional cardiology?

When I was doing military service, I witnessed situations in which some of the soldiers were badly injured; I wanted the capability to treat them and that experience motivated me to go into medicine.

I have always believed that innovation is the key to furthering the field of medicine; therefore, I decided to become an interventional cardiology intern because innovation is an important part of that field.

Who have been your career mentors?

My mentor was Spencer B King, who is one of the founders of interventional cardiology; he actually brought Andreas Grüntzig from Zurich to work at Emory University (where King worked). I feel privileged that many years after this, he offered me a position as an interventional cardiology fellow at Emory.

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

I have been practising interventional cardiology for the past 25 years and during that time, the introduction of stents has definitely been the most important development. That said while they solved a lot of problems, they also created a lot of problems. For example, restenosis.

I believe that my main contribution to the field of interventional cardiology has been designing and developing brachytherapy—using local radiation therapy to treat restenosis.

While I was working at Emory, we designed a clinical trial that enabled brachytherapy to get a stage to which it could be licensed by a company.

This company then put it through the regulatory approval. At the time, brachytherapy was the best solution for patients who had restenosis with metallic stents. Twenty years later, it is still used for some patients who have restenosis after receiving a drug-eluting stent.

Another important development that has occurred during my career has been the introduction of transcatheter aortic valve implantation (TAVI).

Transcatheter therapies are not ending there; we are now hearing about such therapies for the tricuspid and mitral valves.

What are your current research interests?

At present, my main interest is developing a bioresorbable metallic scaffold—Magmaris (Biotronik). I have been working on this for the past 11 years, and I am actively involved in shaping and improving this technology.

I think there are important differences between this scaffold and the polymerisation of L,L-lactide (PLLA) scaffold (Absorb, Abbott). Studies have indicated that device thrombosis with Magmaris are comparable to that of a current-generation drug-eluting stent; therefore, I do not think device thrombosis will be the issue with this device that it was for the PLLA scaffold.

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You are the director of CRT. What makes the meeting unique?

I started CRT 21 years ago. I think people like it because they can listen to a range of topics that will advance their knowledge. Overall, we cover five tracks—from coronary to atherosclerosis and research—and each one is relevant for interventional cardiologists.

Also, we have an impressive faculty list—this year, we had more than 500 faculty members.

Additionally, this year, the meeting was very large as we had 3,139 attendees.

Your belief in the importance of innovation prompted you to go into interventional cardiology. In what ways does CRT support innovation?

We encouraged innovation in several ways. For example, we had a “Technology & Innovation” track and we had an innovations competition. For me, innovation does not have to be a device as it can be an improved technique as well as a novel device.

I think the younger generation of interventional cardiologists are committed to improving techniques.

They want to make things better for patients.

What were the highlights of this year’s meeting?

No doubt that the highlight of this year’s meeting was the first-ever live case to be performed by a femaleonly team of interventional cardiologists, moderated solely by female interventional cardiologists. The case sparked enthusiasm and helped to close the gender gap in the field of interventional cardiology.

The late breaking trials on low-risk TAVI and the new “M” valve for the mitral position were among 12 latebreaking trials that were presented at the meeting. The best innovation was awarded to the 4C technology for mitral valve replacement. Finally the keynote event with President Barack Obama was outstanding and enthused the attendees of the meeting. For CRT, he was the third living president at the meeting. It was the most attended event.

Why did you ask Obama to speak at the meeting?

A few years ago, because CRT takes place in Washington, DC, I decided to start making the keynote speaker a well-known figure from Washington. Therefore, Obama is not the first past US president we have had at CRT. Before that, we have had Clinton and we have had Bush (George W). We also have had people who have run for the presidency. For example, Mitt Romney and Al Gore.

So, we do try to bring true leaders in US politics to learn from them. Obviously, they do not talk about medicine, but they talk about leadership.

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Interview

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I wanted to go to the moon; I want to be an astronaut—I wanted to be a pilot and fly directly to the moon. I found the first moon landing (1969) very inspiring!

We feel having keynote speakers such as these is an opportunity to educate and provide value to the delegates attending CRT. Getting Obama to speak was exciting because he has just finished his time as president. He is still based in Washington, DC, so it was a good opportunity. The interview was in the form of a Q&A and we reviewed his journey from his childhood in Hawaii (where he lived with grandparents) to becoming the first African American president. We also discussed the challenges of bringing up daughters in the White House and, of course, what his

What was your most memorable case?

There is no specific case that I can refer to. During my career I have engaged in thousands of cases many of them complex and heroic. But, whenever I have an opportunity to perform a procedure with a new technology or technique, I feel the thrill of the opportunity that has been given to me in being part of this exciting and rewarding field.

I would say, firstly that they should ask questions. Secondly, if they do not have a passion for interventional cardiology, then they are in the wrong field.

Thirdly, one of the biggest things today is networking via social media, which was not around when I was in med school, and online information. So, they need to be engaged with that.

Fourthly, even if they do not want to get involved with academic writing or research, they need to be keep on top of new data that are coming out.

Ultimately, people coming into the profession need to know that they do not have to accept something as the status quo just because that might be what they have been taught.

What was your childhood dream job?

I wanted to go to the moon; I want to be an astronaut—I wanted to be a pilot and fly directly to the moon.

I found the first moon landing (1969) very inspiring!

Will you be asking the current incumbent of the White House to speak at CRT after his term finishes?

I do not ask individuals when they are actively in position but when he is done with his term, I would love to see him as a keynote speaker! So far we have

Fact File

had three US living presidents as keynote speakers at CRT—obviously we would love to have the fourth one as well!

I think CRT is unique; there is not a meeting like it in the entire world in terms of the keynote speakers that we have. Being based in Washington, DC, we have a lot of connections.

What advice would you give to someone just coming into the profession?

greatest accomplishments and regrets were during his presidency.

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Outside of medicine, what are your hobbies and interests?

Before the era of the internet, I was interested in making and using transistor radios—you could use them to communicate with the rest of the world.

Obviously, you do not use them anymore as there are other means of communication.

Another interest is films—they take you into a whole other world of imagination. You can dream about a whole different life. I found The Shape of Water, directed by Guillermo del Toro, very inspiring.

Films give you the licence to use your imagination.

Current appointments

Director, Cardiovascular Research and Advanced Education, MedStar Heart & Vascular Institute, Washington, DC, USA Professor of Medicine, Georgetown University, Washington, DC, USA Associate Director, Division of Cardiology, MedStar Washington Hospital Center, Washington, DC, USA Course chairman, CRT

Prior appointments

2001–2012: Director, Cardiovascular Research and Advanced Education, MedStar Heart & Vascular Institute, Washington, DC, USA 1997–2001: Associate professor of Medicine Georgetown University, Washington, DC. USA 1999–2001: Director, Experimental Angioplasty & New Technologies, Cardiovascular Research Institute

Medical education 1995–1996:

1992–1995:

1988–1991:

1983–1988:

1981–1982:

1981:

Fellowship, Interventional Cardiology, Emory University, Atlanta, USA Fellowship, Cardiology, Emory University, Atlanta, USA Residency, Cardiology, Ein Kerem Hospital, Jerusalem, Israel Residency, Internal Medicine, Mt Scopus Hospital, Jerusalem, Israel Internship, Hillel Yaffe Hospital, Hadera, Israel Medical School Ben Gurion University, Beer-Sheva, Israel

Editorial boards

Editor-in-chief, Cardiovascular Revascularization Medicine Section editor, Journal of Interventional Cardiology Current Editorial Board, Catheterization and Cardiovascular Interventions Editorial board, Structural Heart Journal Editorial board, European Heart Journal Editorial consultant, JACC Cardiovascular Interventions Editorial board, Future Cardiology Editorial Board, Journal of the American College of Cardiology Editorial Board, Journal of Invasive Cardiology

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18

Structural Heart Interventions

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Ticagrelor may be an effective tool for suppressing platelet reactivity after TAVI Speaking at the 2018 Cardiovascular Research Technologies (CRT) meeting (3–6 March, Washington, DC, USA), Victor Alfonso Jiménez Díaz (Cardiovascular Research Unit, Cardiology Department, Hospital Alvaro Cunqueiro University Hospital of Vigo, Vigo, Spain) reported— according to a new study—that ticagrelor could be used to suppress platelet reactivity after transcatheter aortic valve implantation (TAVI).

Therefore, potentially, it could be used to reduce thrombotic and haemorrhagic complications. Cardiovascular News spoke to Jiménez Díaz about the study.

Prior to your study, what evidence was available for reducing the risk of thrombotic and haemorrhagic complications after TAVI?

Improvements in current percutaneous valves have allowed a decrease in the size of the vascular access sheath required to perform TAVI, leading to a safer and more effective vascular haemostasis. This has had a positive impact on the incidence of vascular and haemorrhagic complications.

In addition to this, the refinement in the antithrombotic therapy during the procedure, as well as TAVI technique, have led to a reduction in the incidence of acute ischaemic events. However, the incidence of post-TAVI thrombotic and haemorrhagic complication remains high and, until now, a strategy that provides adequate protection against ischemic events— without significantly increasing the future haemorrhagic risk—has not been defined.

Why did you use platelet reactivity as an endpoint?

Platelet reactivity has been widely studied in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI), and numerous prior studies have linked high platelet reactivity to a greater risk for ischaemic complications, primarily stent thrombosis, while low platelet reactivity has been associated with greater bleeding events.

The advent of more potent drugs with less variability in their effect has had a positive impact on these phenomena.

Taking into account that the recommendation of dual antiplatelet

therapy (DAPT) post-TAVI is based on the knowledge generated from PCI, the measurement of platelet reactivity in patients with severe aortic stenosis who will undergo TAVI and who are currently on the recommended DAPT would be an important parameter to determine its effectiveness in suppressing platelet activity.

To assess for platelet reactivity, you used the VerifyNow assay. What evidence is available for this assay?

All available information comes from patients with coronary heart disease undergoing PCI. Collaborative efforts between groups of American and European researchers have managed to collect and analyse the information available on the use of the VerifyNow assay in more than 20,000 patients with coronary artery disease, demonstrating that high platelet reactivity measured by different platelet function tests, including VerifyNow assay, can be considered a risk factor for post-PCI stent thrombosis and myocardial infarction. Furthermore, in clopidogrel non-responders, they demonstrated that increased-dose strategy does not help to overcome high platelet reactivity to clopidogrel and to improve clinical outcomes. They also found a relation of low platelet reactivity to the risk of bleeding.

Based on their analysis, they provide an optimal range of P2Y12-inhibition that can be considered as a therapeutic window, within which the predicted risk of stent thrombosis and major bleeding is the

Victor Alfonso Jiménez Diaz

lowest after PCI. These same criteria and cutoffs were used in our study.

What were your key findings?

REAC TAVI was a prospective, multicentre, randomised clinical trial that aimed to evaluate the platelet reactivity displayed in patients with severe symptomatic aortic stenosis undergoing TAVI, and the response achieved with the current recommended antiplatelet therapy.

So, patients under aspirin and clopidogrel and with high on-treatment platelet reactivity prior TAVI were randomised to receive ticagrelor plus aspirin vs. clopidogrel plus aspirin for three months following TAVI. We also registered the behaviour of platelet reactivity in those patients who were initially responders to clopidogrel prior to TAVI, through a registry group.

The main findings can be summarised in four key messages: There is a high incidence of high-platelet reactivity in patients with severe aortic stenosis undergoing TAVI treated with clopidogrel, with seven out of 10 patients not being responders to clopidogrel before TAVI. This poor response was maintained during the following three months after the procedure In comparison, nine out of 10 patients treated with ticagrelor achieved optimal platelet anti-aggregation at six hours post-TAVI, reaching 100% at five days and maintaining adequate levels of platelet anti-aggregation in all patients

Cardioband becomes first-ever transcatheter tricuspid system to receive the CE mark Edwards Lifesciences has received the CE mark for its Cardioband tricuspid valve reconstruction system for the treatment of tricuspid regurgitation. The approval means that the system is the first commercially available transcatheter therapy for the treatment of tricuspid regurgitation—in the world as well in Europe.

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he Cardioband tricuspid system is delivered via a transfemoral approach and is designed to reduce tricuspid regurgitation through annular reduction. It enables precise positioning to a patient’s specific anatomy and real-time adjustment with simultaneous confirmation of results. It is the same design and implant technique as is used for the Cardioband mitral system.

Georg Nickenig (Department of Cardiology, University

Hospital, Bonn, Germany) comments: “Although openheart surgical valve repair is practised today, it has not been performed frequently for those suffering from tricuspid regurgitation, despite evidence of increased mortality in these patients. Now with the European approval of the Cardioband tricuspid aystem as the first transcatheter tricuspid therapy, patients can have access to a minimally invasive treatment designed to reduce tricuspid regurgita-

during the three months following the TAVI. More than a third of patients initially responded to clopidogrel become nonresponders after TAVI Additionally, there were no significant differences in the incidence of adverse events, including bleeding events between both treatments at three months of follow-up. The poor response to aspirin was also observed in this population, but only in a small proportion of patients.

Were there any indications that patients in the ticagrelor group had fewer ischaemic events?

There were three major ischaemic events in the study (two strokes and one myocardial infarction), all in patients under clopidogrel. However, the study was underpowered for clinical endpoints, so these results must be taken with caution and need to be confirmed by studies designed specifically for this purpose.

What further studies in this area are needed?

Percutaneous treatment of different valvular heart diseases has been established as the therapy of choice in symptomatic patients rejected for surgery or at high surgical risk.

Its acceptance and application has been fast and broad. The use of an antithrombotic therapy following the procedure is mandatory because thromboembolic complications at follow-up are not negligible. But the current recommended antiplatelet therapy has no support from randomised clinical trials. Additionally, this population of patients is in a very delicate balance between thrombotic and haemorrhagic risk, so the implications in choosing an effective and safe therapy is challenging and of paramount importance.

Therefore, larger scale studies are needed to determine the best antiplatelet treatment to use in this population and its duration after the procedure.

tion and improve their symptoms and quality of life.”

Bernard Zovighian, corporate vice president, transcatheter mitral and tricuspid therapies, says: “We are very pleased to be developing the most comprehensive product portfolio to address both mitral and tricuspid valve disease and to demonstrate continued progress on this robust pipeline of innovative transcatheter therapies for patients in need. The clinical results of the TRI-REPAIR CE mark study with the Cardioband tricuspid system demonstrate the promise of this treatment option for those with tricuspid regurgitation. We are committed to building a significant body of clinical evidence, including the collection of real-world data, on this important new therapy for patients who have few or no other treatment options.”

Data on the Cardioband tricuspid system is due to presented at EuroPCR 2018. The Cardioband system is not approved for commercial sale in the USA.

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Transcatheter mitral valve therapies

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ADVERTORIAL

Edwards Cardiobandâ&#x201E;˘ Mitral Valve Recons annular dilatation In recent years, several transcatheter treatment options have become available in Europe for patients with functional mitral regurgitation considered too high risk for surgery. One of these systems is the Cardioband Mitral System.

Cardiovascular News spoke to Professor Francesco Maisano (University Heart Centre, University Hospital Zurich, Zurich, Switzerland) about the system and why it could be a good option for treating mitral annular dilatation.

Why has Cardioband emerged as a potential treatment option for patients with functional mitral regurgitation and how does it work?

The possibility of reproducing annuloplasty with a catheter procedure is a great advancement in the field of structural intervention. Cardioband has been designed to closely reproduce surgical annuloplasty with the advantages of a minimally invasive approach to annular repair. The Cardioband implant is an adjustable posterior band affixed from commissure to commissure with multiple anchors at the hinge of the posterior leaflet.

Following the fixation of the implant on the annulus, the implant is adjusted under echocardiographic guidance to reduce the annulus and enhance leaflet coaptation. The length of the band can be adjusted bidirectionally and released

in case of excessive annular reduction (to avoid frozen posterior leaflet or valve stenosis).

What is the evidence base for percutaneous annular repair for patients with functional mitral regurgitation?

The Cardioband Mitral System has been studied in a feasibility trial for CE mark acquisition in Europe [the system received CE mark in September 2015]. In my opinion, the results suggest percutaneous annular repair reduces mitral regurgitation in patients with functional mitral regurgitation and heart failure patients to a degree that is comparable toâ&#x20AC;&#x201D;if not better thanâ&#x20AC;&#x201D;that achieved with surgical annuloplasty. The reduction of mitral regurgitation was substantial and is in line with a reproducible reduction of annular dimension, which remain stable

throughout one year.

Can percutaneous annular repair be used to complement other mitral therapies?

Yes, the main advantage of percutaneous annular repair is it allows future complementary procedures such as leaflet repair or valve replacement to be performed if needed. Preserving the native valve anatomy is especially important in cases of mixed and complex aetiologies.

The Cardioband implant interacts only with the annulus, meaning it does not obstruct the future possibility of repair or replacement.

How does mitral annular dilatation affect the mitral valve? For example, can it lead to mitral regurgitation?

Mitral valve annular dilatation is one factor behind mitral regurgitation, and is

Francesco Maisano

almost invariably present in all patients.

In some cases, it is primary (e.g. annular dilatation in patients with chronic atrial fibrillation), and in other cases it is the consequence of left ventricular remodelling (e.g. annular dilatation in patients with functional mitral

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Transcatheter mitral valve therapies

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struction Systemâ&#x20AC;&#x201D;Reliably addressing regurgitation). Most of the patients I see in my clinic with mitral regurgitation have annular dilatation.

What are the current approaches to treating mitral annular dilatation?

There are several surgical rings (almost 50 different types), as well as several direct and indirect transcatheter annular repair systems under investigational and commercial use.

To date, in my opinion, Cardioband is the only available transcatheter device to perform annular repair with consistent and substantial annular remodelling. Other systems can only partially remodel the annulus and, thus, have to be considered palliative treatments with limited applicability.

Why might percutaneous annular repair be an effective treatment option for annular dilatation?

When dilatation is the problem, then transcatheter annular repair is actually superior to surgery as it can deliver the same treatment through a minimally invasive approach. There are no incisions, no heart lung machines, no ischaemia, andâ&#x20AC;&#x201D;most importantlyâ&#x20AC;&#x201D;it is performed on the beating heart.

This allows for adjustment of annular reduction and real-time confirmation of procedural results.

What evidence is available for managing annular dilatation with percutaneous annular repair?

Cardioband is the only available transcatheter device to perform annular repair with consistent and substantial annular remodelling.

Cardioband Mitral System

Data are only available for the Cardioband Mitral System; in my opinion, the only device to reliably address annular dilatation.

What further evidence is needed for the management of mitral dilatation?

We need a head-to-head comparison with other repair procedures, and we need to

define the ideal timing for this procedure.

Different from MitraClip (closing the door to other interventions) or replacement (consequences of the prosthesis), percutaneous annular repair has the potential to be implemented and applied in the early phase of congestive heart failure with functional mitral regurgitation, to try to obtain a greater prognostic benefit and induce reverse remodelling.

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May

Cardiac rhythm management

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New-onset atrial fibrillation after CABG significantly increases the risk of death and stroke in left main patients New data from the EXCEL trial, which found that percutaneous coronary intervention (PCI) was non-inferior to coronary artery bypass grafting (CABG) at three years in patients with left main disease, indicate that CABG patients have a significantly increased risk of new-onset atrial fibrillation than do PCI patients. Furthermore, these data show that patients with new-onset atrial fibrillation have a significantly increased risk of death and stroke both at 30 days and at three years.

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riting in the Journal of the American College of Cardiology, Ioanna Kosmidou (Clinical Trials Center, Cardiovascular Research Foundation, New York, USA) and others report that new-onset atrial fibrillation is a “common complication” after CABG and that preoperative atrial fibrillation is a predictor of long-term mortality and morbidity after CABG, for left main disease. However, they add that the effect of new-onset atrial fibrillation on outcomes following either CABG or PCI in patients with left main disease is unknown. Therefore, they reviewed data from EXCEL—Evaluation of Xience vs. coronary artery bypass surgery for effectiveness of left main revascularisation—to determine the predictors, incidence, and outcomes of new-onset atrial fibrillation in patients with left main disease undergoing either PCI or CABG. Of 1,905 patients in the EXCEL study overall, 1,812 did not have atrial fibrillation at baseline. Of these, 893 underwent CABG and 919 underwent PCI. Kosmidou et al comment: “New-onset atrial fibrillation developed at a mean of 2.7±2.5 days after revascularisation in 162 patients (8.9%), including 161 of 893 (18%) CABG-treated patients and one

of 919 (0.1%) PCI-treated patients (p<0.0001).”

They note that by the time of hospital discharge, the atrial fibrillation had resolved in 85.8% of patients (including those who had undergone cardioversion).

At 30 days, the risk for the composite outcome of death, myocardial infarction, or stroke was significantly higher in patients with new-onset atrial fibrillation than those without. The risk of this endpoint was also significantly increased at three years in patients with new-onset atrial fibrillation: 19.3% vs. 12.8% for patients with new-onset atrial fibrillation (p=0.02).

According to the authors, the increased risk of cardiovascular death associated with new-onset atrial fibrillation was driven by stroke-related and heart failure related death.

A multivariate analysis showed that older age, greater body mass index (BMI), and reduced left ventricular ejection fraction (LVEF) were all independent predictors of new-onset atrial fibrillation in patients undergoing CABG. However, Kosmidou et al observe that the C-statistics for the correlations between these risk factors and new-onset atrial fibrillation were modest and they comment: “Many patients who may benefit from CABG have these characteristics.”

The authors suggest that while the increased periprocedural risk of new-onset atrial fibrillation should be recognised in patients with the aforementioned risk factors, they should not be seen as a barrier to performing CABG. “Rather than avoiding CABG in these patients, effective preoperative and postoperative measures (prophylactic beta-blockers or amiodarone) should be considered to prevent the post-surgical occurrence of new-onset atrial fibrillation,” they write.

Study investigator Gregg Stone (Clinical Trials Center, Cardiovascular Research Foundation, New York, USA) told Cardiovascular News: “These data demonstrate that the markedly increased risk of atrial fibrillation after CABG compared to PCI should be one of the issues that are discussed with the patient and taken into account when deciding upon the optimal revascularisation therapy for complex coronary artery disease. Further studies are essential to examine whether more intensive surveillance to detect AF and recurrent arrhythmias after CABG and more aggressive therapies when atrial fibrillation occurs, including anticoagulation, left atrial appendage occlusion, and ablation may improve outcomes after CABG in patients with postoperative atrial fibrillation.”

Wearable cardioverter defibrillator reduced total death but not sudden cardiac death after myocardial infarction The first randomised controlled trial of a wearable cardioverter defibrillator (LifeVest, Zoll) did not find that the device significantly reduced the risk of sudden cardiac death in the immediate period (three months) after a myocardial infarction.

However, the trial did indicate that it was associated with a significant reduction in total mortality.

P

resenting the data at the 2018 American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA), Jeffrey Olgin stated that the risk of sudden cardiac death is high after myocardial infarction but studies suggest that there is “no benefit from early implantable cardioverter defibrillator (ICD) therapy”.

He added that current US guidelines recommend that ICD therapy is not used for “at least 40 days post myocardial infarction and at least 90 days post revascularisation”. Therefore in the immediate period after myocardial infarction, patients at increased risk of sudden cardiac death (i.e. patients who may later require an ICD) are unprotected in this respect.

Olgin told delegates at the ACC that, in addition to ICDs not being indicated in the immediate post-myocardial infarction period, left ventricular ejection fraction (LVEF) may recover in this three month period, making a permanent ICD implant unnecessary in those patients in whom the LVEF recovers. Thus, the aim of the VEST study was to answer the question of whether a wearable cardioverter defibrillator (i.e. LifeVest) could “reduce

sudden death mortality in the immediate post myocardial infarction period (<90 days) in patients with reduced left ventricular ejection fraction as a bridge to evaluation for ICD”. He explained that the LifeVest was a “washable interchangeable garment” that had self-gelling defibrillator electrodes, dry electrodes, a rechargeable monitor and battery pack, and response buttons.

In the study, 2,302 patients were randomised to wear the LifeVest (1,524) and receive optimal medical therapy or optimal medical therapy alone (778).

The mean follow-up time was 84.3±15.6 days and the primary outcome was sudden cardiac death and death because of ventricular arrhythmias. Secondary outcomes included total mortality and non-sudden death, cause-specific death, and non-fatal outcomes.

Although there was a lower sudden death rate in the wearable cardioverter defibrillator group compared to the control group, this difference was not statistically significant (1.6% vs. 2.4%, respectively; p=0.18). Additionally, there was no significant difference in the rate of non-sudden death (1.4 vs.

2.2%, respectively; p=0.15). However,

Jeffrey Olgin

the device was associated with a reduction in all-cause death: 3.1% for LifeVest vs. 4.9% for optimal medical therapy alone (p=0.04).

According to Olgin, possible misclassification of sudden death may explain why the difference in sudden cardiac death was not significant but total death was—“reducing the power for sudden death outcome but not total mortality”. He told Cardiovascular News, that to better identify cause of death, “one would have to do autopsies which is not feasible”.

He adds: “Thus an endpoint of total mortality may be a better outcome in

this situation because it does not rely on determining cause of death.”

Another reason why the LifeVest reduced total death but not sudden cardiac death may be because it provides additional protection beyond sudden death—Olgin says this may relate to defibrillation of ventricular fibrillation.

Speaking at the ACC, he concluded: “Prescribing the wearable cardioverterdefibrillator is reasonable to protect high-risk patients with a low left ventricular ejection fracture postmyocardial infarction until evaluation for an ICD at 40–90 days.”

At the European Heart Rhythm Association (EHRA) congress (18–20 March 2018, Barcelona, Spain) Johannes Sperzel (Department of Cardiology, Kerckhoff Heart Centre, Bad Nauheim, Germany) said that during the VEST trial, patient adherence had been low (median wear time was 18.1 hours) and that—even though the primary outcome was not reached—the wearable cardiac defibrillator was a feasible bridging therapy for treating patients at risk of ventricular tachycardia or ventricular fibrillation, especially during their evaluation for implantable cardioverter device implantation.

Responding to this viewpoint, Olgin observes “clearly the device only works if worn, so the more wear time the better the outcome,” but notes that it is “easy to use”.

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Patient care

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Take care from start to finish: Avoiding radial artery occlusion IAN C GILCHRIST COMMENT & ANALYSIS Root cause analysis of radial occlusion points to vessel trauma. An ultrasound study by Costa et al demonstrated that in the setting of a 6Fr vascular sheath placed into the radial artery, 100% of the arteries manifested traumatic injury.1 Dissection, haematoma, and pseudoaneurysm were seen in the majority of patients, yet only 4% showed intraluminal thrombus in these heparinised patients. This finding suggests that traumatic vessel injury rather than primary thrombus is the underlying problem. In this commentary, Ian C Gilchrist looks at the causes of radial occlusion and how to avoid the complication.

T

he advent of dorsal radial access and the observation that radial artery occlusion tends to be limited to the dorsal branch rather than extension into the radial proper highlights the dominant role the vessel wall injury has in initiating the radial artery occlusion process.2 How can radial artery damage be limited? Use the smallest sheath needed to do the job! As one moves down a French size, each jump reduces the baseline radial occlusion rate by about 50%. Therefore if one has a 5%

occlusion rate at 6Fr, using 5Fr will result in a 2.5% occlusion rate—and 4Fr sheath would result in a 1.25% rate. The number of attempts at access (how many needle sticks) is a measure of trauma and minimising the need for multiple needle sticks also results in less radial occlusion. Ultrasound technology and micropuncture needles all curtail trauma at the time of access. Finally, the use of hydrophilic sheath technology that facilitates a smooth entry into the radial artery probably adds to reducing trauma.

Sheaths in small arteries, such as the

radial, usually produce radial spasm that further enhances blood stasis and thrombosis. Antispasm regimens, also referred to as “cocktails”, and analgesia to reduce sympathetic tone may counter some of the spasm. The most important addition is heparin, or its equivalent, at a therapeutic dose on the order of 5,000U. Full dose heparin has been shown superior to lesser regimens or no anticoagulation. Oral anticoagulants have not been shown to substitute for this protective effect afforded by systemic anticoagulation. Heparin likely controls thrombosis both early on around the sheath before its removal and then along the acutely injured artery and the entry site during haemostasis.

At the conclusion of the case, haemostasis techniques affect the potential for ultimate radial artery occlusion. Zip bands were quick, but their mechanism of action probably resulted from thrombus-driven occlusion.

Pancholy et al coined the term “patent haemostasis” to describe an approach to haemostasis that maintains luminal flow without extra-vascular extravasation.3 It is a “Goldilocks” approach of “not too tight, not to lose, but just enough” pressure on the radial entry site to maintain flow without resulting bleeding.

What can be done if, despite all the best efforts, there appears to be radial artery occlusion after haemostasis?

Bernat et al have demonstrated that

application of occlusive pressure to the ipsilateral ulnar will often result in rapid resolution of an acute radial occlusion.4 While mechanical disruption of thrombus may be possible, this appears to have the risk of distal embolisation into the finger tips that is not a welcome complication.

Putting this all together, radial artery occlusion can be and should be reduced to less than 1%. Using the best sized sheath for the procedure, careful cannulation with a micropuncture needle under ultrasound guidance, pharmacologic control of thrombus formation, patent haemostasis at the conclusion of the procedure, and ulnar compression for bailout in the case of acute radial occlusion, the net loss of radial arteries can be minimised to the point that most will remain available for use in the future. Radial artery catheterisation is the way to proceed for procedures suitable for the vessel’s size.

It is a low-risk access point, but care is needed to maximise its long-term use.

References 1. Costa et al. Circ Cardiovasc Interv 2016; 9 (2): e003129.

2. Kiemeneij. EuroIntervention 2017; 13(7): 851–57.

3. Pancholy et al. Catheter Cardiovasc Interv 2008; 72(3): 335–40.

4. Bernat et al. Am J Cardiol 2011; 107(11): 1698–701.

Ian C Gilchrist is at Pennsylvania State University, College of Medicine, Heart & Vascular Institute, M.S. Hershey Medical Center, Hershey, USA. He spoke about this topic at the CRT 2018 (3–6 March, Washington, DC, USA)

Cardiogenic shock patients would benefit the most from reducing contact-to-balloon time Data from the FITT-STEMI (Feedback intervention and treatment times in ST-segment elevation myocardial infarction) trial indicate that reducing the time between first medical contact and the initiation of angioplasty (balloon time) to less than 90 minutes would lower mortality for all STEMI patients. However, these findings also indicate that patients with cardiogenic shock would receive the greatest benefit from reducing this timeframe.

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arl Heinrich Scholz (Department of Cardiology, Medizinsche Klinik I, St Bernward Hospital, Hildesheim, Germany) and his fellow investigators sought to evaluate the prognostic significance of treatment delays between the first medical contact and coronary reperfusion in patients with cardiogenic shock and/or out-of-hospital cardiac arrest. They report in the European Heart Journal that while door-to-balloon time is known to be a predictor of outcomes after percutaneous coronary intervention (PCI), less is known about the prognostic value of contact-to-balloon time—particularly in patients with cardiogenic shock and/or out-of-hospital cardiac arrest whose medical needs (such as resuscitation) may lead to delays in this timeframe.

Using data from FITT-STEMI, Scholz et al identified 12,675 PCI patients who received PCI within ≤360 minutes of first medical contact. Of these, 10,766 had neither cardiogenic shock nor out-of-hospital cardiac arrest, 369 did not have cardiogenic shock but did have out-of-hospital cardiac arrest, 699 had cardiogenic shock but not out-of-hospital cardiac arrest, and 831 had both cardiogenic shock and out-of-hospital cardiac arrest.

Overall, in-hospital mortality was lower among patients who had a contact-to-balloon time of <90 minutes compared with those with a timeframe of >90 minutes (3.9% vs. 12.2%; p<0.0001). Scholz et al report: “A particular high risk of death was observed in the group of

patients with contact-to-balloon times ranging from 150 minutes to 190 minutes, as one-fifth of all patients out of this group died after PCI”.

Regardless of the contact-to-balloon time, patients with cardiogenic shock and/or out-of-hospital cardiac arrest had much mortality than patients without these factors. The authors note that they observed “pronounced beneficial effects” when patients with either cardiogenic shock or out-of-hospital cardiac arrest were treated within 90 minutes of the first medical contact. “By reducing the contact-to-balloon time to less than 90 minutes, one additional life could be saved out of five patients treated with cardiogenic shock. However, this number needed to treat

was much higher in stable patients (one life additionally saved out of 53 patients),” Scholz et al comment.

Furthermore, the authors found that every 10 minute in contact-to-balloon time “resulted in 3.31 additional deaths” per 100 PCI-treated patients with cardiogenic shock but no out-of-hospital cardiac arrest. They state: “This treatment delay-related mortality was significantly higher as compared with the two groups of out-of-hospital cardiac arrest patients with shock and without shock, as well as haemodynamically stable patients.”

Scholz et al conclude that their data indicate that efforts to shorten time to PCI therapy should be applied to “all STEMI patients”, adding that patients with haemodynamic instability “may benefit most from future improvements in STEMI treatment protocols”.

Scholz told Cardiovascular News: “We believe that quality improvement measures with standardised data registration, systematic analysis and interactive feedback—which are all important components of the FITTSTEMI study protocol—should be implemented in local treatment networks in order to maintain a long-lasting impact on mortality in all STEMI patients. Continuous quality checks ensure that all professionals engaged in the treatment of STEMI patients will work together in order to shorten treatment times and impact on the survival especially in high-risk patients presenting with shock or out of hospital cardiac arrest.“

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More non-cardiac death explains higher rate of post-PCI mortality in females According to a new study, the higher rate of all-cause mortality after percutaneous coronary intervention (PCI) in females relates to an excess of non-cardiac death. Furthermore, the study shows that the causes of non-cardiac death in women after PCI are different from those of men.

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laire E Raphael (Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA) and others report in Circulation Cardiovascular Interventions that the reason why women have higher long-term mortality after PCI compared with men “has been uncertain”.

They note that the potential reasons may relate to the fact that women, generally, are older and have greater comorbidity when they undergo PCI than when men do or may relate to “undefined sex-specific factors”.

Additionally, the authors observe, previous studies reviewing sex differences after PCI focused on all-cause mortality rather than cause-specific mortality. “Causespecific mortality represents a more useful synthesis of baseline risk factors than allcause mortality because it enables separation of the influence of cardiac and non-cardiac death,” they comment.

Thus, they performed a single-centre study “using rigorously ascertained cause-specific mortality” to evaluate longterm trends in causes of death in women compared with men after PCI, examine the effect of baseline risk on final cause of death to determine whether there is a sex-specific biological factor, and determine specific causes of death in women and men.

Using data from the Mayo Clinic PCI

registry, the authors reviewed data from 16,280 men and 6,847 women who underwent PCI between 1991 and 2012.

They found that in an unadjusted analysis, all-cause mortality was significantly higher in women and this excess was because of non-cardiac deaths. Similar to findings of previous studies, Raphael et al found that across three time periods (1991–1997, 1998–2005, and 2006–2012) “there was a temporal shift from predominantly cardiac death to predominantly non-cardiac death in both sexes”. They add that this shift may “in part” be related to the increased use of secondary prevention measures that has been observed in both sexes.

After adjusting for age and comorbidities, the shift from predominantly cardiac death to non-cardiac death remained. However, in this adjusted analysis, the incidence non-cardiac death was no longer higher in women. There was also no significant difference in the incidence in cardiac death between men and women.

In the contemporary era (2006–2012), the cumulative five-year incidence of myocardial infarction/sudden cardiac death was similar in men and women. However, Raphael et al note “nominally more women died of heart failure”. They add that, in terms of non-cardiac death, women were

Rajiv Gulati

more likely to die of chronic diseases while men more were likely to die of cancer. The authors observe: “After adjustment for age and baseline comorbidities, there was no difference in heart failure or chronic disease deaths between the sexes; however, the higher rates of cancer in males compared with females remained.”

Acknowledging that the differences in causes of non-cardiac death between men and women after PCI “likely result from differences in baseline risk in women and men”, Raphael et al comment that they “do suggest sex-specific differences in long-term healthcare needs after PCI”.

“Although women had higher unadjusted rates of all-cause mortality compared with men, this is because of an excess of noncardiac than cardiac deaths with no evidence of a sex-specific biological factor,” the authors conclude.

Study author Rajiv Gulati (Department of Cardiovascular Diseases, Mayo Clinic,

Rochester, USA) told Cardiovascular News that why women who undergo PCI tend to be older and have more comorbidity than men who undergo PCI is “not really known”. However, he says that possible explanations include coronary artery disease beginning later or becoming severe/ symptomatic later in women; or women not coming to medical attention or not being referred for invasive studies, until later than men. Regarding the fact that non-cardiac death was behind the increased mortality in women, Gulati comments: “By virtue of an older age at presentation, more noncardiac comorbidities would have been accumulated thereby increasing the risk for non-cardiac death. We have to remember the issue of competing risks—everyone has to die of something. “ In terms of preventing non-cardiac death in both men and women, he says that the focus should still be preventative cardiac deaths. “While cardiac death risk has declined, there are continued opportunities for improvement. These might include strategies to increase uptake and use of secondary preventative medications that already have proven prognostic benefit, use of newer therapies in lipid and heart-failure management, and pursuit of completeness of revascularisation.

Stressing improved lifestyle measures such as tobacco avoidance, improved diet and levels of activity will likely also have an effect at reducing non-cardiac deaths (certain cancers) as well as cardiac deaths,” Gulati observes.

Women are still less likely to receive high-intensity statin therapy after myocardial infarction New data show that, after a myocardial infarction, significantly fewer women than men fill a prescription for high-intensity statin therapy. These findings are despite initiatives aimed at reducing historic sex differences in guideline-recommended therapy.

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anne AE Peters (The George Institute for Global Health, University of Oxford, Oxford, UK) and others report in the Journal of the American College of Cardiology that “historically, women have been less likely than men to receive guideline-recommended statin therapy for the secondary prevention of myocardial infarction”.

They add a large meta-analysis of individual participant data of randomised controlled trials have demonstrated that the benefits of more-intensive vs. less-intensive statin therapy, among patients with a history of vascular disease, are similar between men and women. Furthermore, 2013 US guidelines on managing cholesterol do not make sex-specific recommendations on statin dosage.

Noting that “substantial efforts”, such as Go Red for Women, have been made to reduce sex differences in cardiovascular disease, Peters et al comment it is unknown whether these efforts (as well as the guidelines) have reduced the gap between men and women regarding the differences in high-intensity statin therapy. “Moreover, although the overall uptake of high-intensity statins in secondary prevention has increased substantially in recent years, sex differences in the use of high-intensity statin therapy following a hospital admission for myocardial infarction have not been assessed in detail,” they add.

The aim of the present study, therefore, was to review contemporary use of high-intensity statin therapy following a myocardial infarction in men and in women. The

authors also sought to “identify factors associated with the underutilisation of high-intensity statins among women.”

Using data from US commercial and government health insurance databases, they identified 39,256 women and 49,000 men who filled a statin prescription for statin therapy following hospital discharge for myocardial infarction.

Peters et al comment: “After adjustment for demographic characteristics comorbidities, and healthcare use, the womento-men risk ratio for high-intensity statin use were 0.91 in the total population of statin users, 0.91 among those with no prior statin use, 0.87 among those with low/moderateintensity statin use, and 0.98 among those with prior highintensity statin use (p for interaction by prior statin use and dosage <0.001).”

According to the authors, the sex differences were largest among those without prior statin use and those with prior low/moderate intensity use “suggesting that women are less likely than men to get uptitrated or less likely to initiate highintensity statin therapy post myocardial infarction”.

The sex differences were also larger among the youngest and oldest patients. This finding, Peters et al state, is “concerning” because the “oldest are at the highest risk, whereas young women have recently been shown to have the slowest rate of decline in cardiovascular disease rate in the United States”.

Furthermore, they note that there was no evidence of diminishing of the sex differential in the use of highintensity statin post myocardial infarction following the

2013 guidelines, commenting: “In the overall population, the women-to-men risk ratio ranged from 0.94 in 2007 to 0.91 in 2015.”

Peters et al discuss several reasons for the reasons why women are still less likely to receive high-intensity statin therapy after a myocardial infarction. This includes the fact some studies have suggested that women are more likely to experience side-effects from statin therapy from men, but data from six randomised controlled trials indicate that muscle symptoms (a known side-effect of statin therapy) was slightly higher in women in both placebo and statin groups. “These suggest that the risk for statin-associated muscle symptoms should not be a barrier to prescribing high-intensity statin therapy to women,” the authors comment.

Concluding, they write: “The factors attributable to these sex differences need to be elucidated. Increased awareness of the benefits of high-intensity statins is needed to reinforce the use of high-intensity statins among women with a prior myocardial infarction.”

Peters told Cardiovascular News: “The discrepancies in high-intensity statin use may explain, at least in part, why mortality rates for women with a history of heart disease and stroke are higher than for men. Our research suggests some deaths could be prevented if the guidelines on treatment with high-intensity statins were adhered to.”

She adds: “We need further research to understand the barriers to guideline-recommended treatment in women.

There is clearly more work to be done to raise awareness of the benefits of high-intensity statins for both women and men who have experienced heart attacks, in order to eliminate these disparities.”

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Product News Following FDA approval, Resolute Onyx 2mm becomes smallest stent on US market

thrombosis and no cardiac death at 12 months.

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, comments: “Furthering our core objective of developing technologies that address unmet patient needs, the introduction of the Resolute Onyx 2mm drug-eluting stent allows physicians to expand treatment options for patients with smaller vessels.

The Resolute Onyx drug-eluting stent is an incredibly deliverable product that incorporates various design enhancements enabling physicians to optimise treatment for a wide range of patients.”

Fifty US centres are now using Claret Medical’s Sentinel cerebral protection system

Core Wire Technology

Designed specifically for small vessels, the Resolute Onyx 2mm drug-eluting stent has received US FDA approval and, consequently, has been launched on to the US market.

According to a press release, the device is now the smallest sized drug-eluting stent on the US market. It is designed to help interventional cardiologists treat patients with coronary artery disease who have small vessels—which are often untreatable with larger stent technologies during percutaneous coronary intervention (PCI).

The first—and only—2mm drug-eluting stent size available in the USA, the press release reports, the newly approved stent joins the Resolute Onyx 4.5mm and 5mm drug-eluting stents to provide physicians with the broadest drug-eluting stent size matrix available. The press release states that the Resolute range of device means that there are options for treating patients with the smallest coronary vessels to the largest, from the simplest of anatomies to the complex. Additionally, the stent is engineered with the lowest crossing profile of any drug-eluting stent (less than 1mm) enabling exceptional deliverability. Once delivered, the Resolute Onyx 2mm drug-eluting stent is engineered to expand from 2mm to the maximum labelled expansion diameter of 3.25mm.

The Resolute Onyx drug-eluting platform is the first-and-only stent to feature Core Wire Technology, an evolution of Continuous Sinusoid Technology (CST). CST is a unique Medtronic method of stent manufacturing, which involves forming a single strand of cobalt alloy wire into a sinusoidal wave to construct a stent. Core Wire Technology enables thinner struts while maintaining structural strength and visibility.

Matthew J Price (Scripps Clinic in La Jolla, USA), national principal investigator of the RESOLUTE ONYX 2.0 mm clinical study that supported the recent FDA approval, comments: “Patients with lesions in small vessels or complex vasculatures can present unique challenges for physicians during PCI procedures.

The Resolute Onyx 2mm drug-eluting stent is an extremely deliverable stent that, when needed, can be post-dilated to 3.2mm to treat lesions in difficult-toreach areas of the heart.”

The Resolute Onyx 2mm drug-eluting stent is supported by the RESOLUTE ONYX 2.0 mm Clinical Study, which was presented at the 2017 EuroPCR annual meeting and simultaneously published in the JACC: Cardiovascular Interventions. In the study, the Resolute Onyx DES met its pre-specified performance goal with low target lesion failure (5%), low target lesion revascularisation (2%), no episodes of stent

Since it received FDA clearance in June 2017, the Sentinel cerebral protection system (Claret Medical) has become an emerging standard of care in the USA to protect patients from the risk of stroke by capturing and removing debris associated with transcatheter aortic heart valve implantation (TAVI) before it travels to the brain.

A press release reports that the system has been adopted by 50 US centres as part of its controlled rollout.

According to the press release, Sentinel has been shown to significantly reduce the risk of stroke in the first three days after TAVI by more than 60%. It is the first and only FDA-cleared device that captures and removes debris that is dislodged ubiquitously during TAVI before it can travel to the brain and potentially cause neurological and neurocognitive damage, regardless of the TAVI system used or a patient’s risk profile.

Hemal Gada (Pinnacle Health, Harrisburg, USA) led a presentation of clinical benefits of the Sentinel System at a Centers for Medicare and Medicaid Services (CMS) Town Hall meeting (13 February) as part of the device’s approval process for gaining a New Technology Add-on Payment (NTAP) under the Medicare hospital inpatient prospective payment system (IPPS).

Gada comments: “During the TAVI procedure, we must remember that we liberate a wide spectrum of debris from the hostile aortic arch and the aortic valve complex due to the atherosclerotic nature of this disease.

Some of the liberated debris is several millimetres in size, and can travel to the brain and cause ischaemic brain damage or stroke, as demonstrated by outcomes from the SENTINEL US and SENTINEL ULM trials.”

He adds that, at his centre, they have adopted the system as “the standard of care to protect our patients during every TAVI case”, noting they have had a “significant improvement in neurologic outcomes” since they started using the system in July 2017.

Azin Parhizgar, CEO of Claret Medical, says: “The rapid adoption of Sentinel in the USA is the result of a strong and consistent evidence base from multiple clinical studies, a superb safety profile, a highly effective training program and the inherent ease of use of the Sentinel technology. We have seen the Sentinel being used in all or the majority of TAVI cases in the centres that have adopted it, reflecting physician belief in the patient benefits of protected TAVI.” The company also announced that Stacy Enxing Seng, a 30-year medical technology leader, has joined its board of directors. She is currently a venture partner with Lightstone Ventures and a member of the board of directors for a variety of public and private companies, including The Fogarty Institute for Innovation. Enxing Seng’s extensive experience includes leading Covidien’s vascular division and ev3, as well as a variety of management roles with Boston Scientific, SCIMED Life Systems, Baxter

Healthcare and American Hospital Supply.

“We are thrilled to have a medtech veteran of Stacy’s caliber join our board. Her deep experience and successful legacy of growing innovative, emerging companies will be invaluable as we expand the company’s commercial operations globally, while remaining focused on delivering the key patient benefits that Protected TAVI offers,” comments Parhizgar.

CE mark for HeartStitch’s transapical access and closure device

A press release reports that HeartStitch transapical access and closure device provides safe and effective percutaneous transapical access for structural heart procedures and reliable closure. The suture-based technique is designed to emulate surgical closure without the need for open heart surgery or limited thoracotomy access when repairing structural heart defects in the left heart.

According to the press release, the HeartStitch technology for transapical access and closure has received significant attention from interventional cardiologists after the recent publication of the NobleStitch Italian clinical study publication in the peer reviewed EuroIntervention journal this month.

The NobleStitch data demonstrated the safety and effectiveness of placing sutures percutaneously in the heart. This success in the patent foramen ovale space has launched an increased interest in suture-based solutions that eliminate the need for open surgical procedures by giving physicians a tool that can allow access though a percutaneous puncture directly in to the heart without an incision and then use sutures to safely close the hole.

Anthony Nobles, chairman, CEO and chief clinical specialist of HeartStitch, states: “The CE mark approval is another major step in the continuing process of establishing HeartStitch in the market as an innovator in the field of structural heart repair. We strive and will continue to deliver to physicians a line of suture-based closure, repair and remodelling devices which provide the quality they demand for their patients with the ease of use they have been seeking. The ability to access the left ventricle to treat structural heart defects without surgery is a major step forward for HeartStitch. We expect to bring this product to market this fall in Europe and will follow with USA thereafter.”

Yuri Pya of the National Cardiac Research Center, Astana, Kazakhstan, who was the first in the world to perform this procedure using suture-based solution comments: “I am very excited about this technology and see great potential for our minimally invasive structural heart procedures. The device is revolutionary, allowing interventional procedures to be performed safely and effectively.”

Abiomed receives FDA approval for Impella CP with SmartAssist and Optical Sensor

Abiomed has received US FDA premarket approval (PMA) for its Impella CP heart pump with SmartAssist, using an optical sensor. At the forefront of innovation, according to a press release, these advances in technology and software are designed to improve productivity, ease of use, and patient management to ensure optimal patient care.

The addition of Impella CP with SmartAssist represents the next generation for heart recovery products and includes the following features: Simplified Patient Management: Advanced software and new optical sensor improves understanding of real-time, exact positioning for the Impella heart pump and allows for repositioning without the need for imaging equipment.

Integration of Clinical Data Informatics on Impella Console: Real-time informational displays of Left Ventricular Pressure (LVP), End-Diastolic Pressure (EDP) and Cardiac Power Output (CPO) provides optimal support for patients.

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Product News Ease of Use: Faster set-up with fewer steps and connections simplifies patient management for physicians, cath lab staff and ICU staff. New steps further reduce start time by 15%, which is critical for emergency patients in cardiogenic shock Abiomed has already received CE marking approval in the European Union to market Impella CP with SmartAssist. To date, more than 60 patients at three sites have been treated with Impella CP with optical sensor.

Abiomed submitted more than 60 engineering reports and full technical specifications for this expanded PMA approval, which were approved by the FDA. To date, the clinical data informatics has been tested on the Abiomed Impella Controller on 38 patients at two hospitals in the USA. Over the next fiscal year, Abiomed will launch the Impella CP with SmartAssist through a controlled roll-out at hospital sites with established heart recovery protocols. A simple upgrade to Abiomed’s existing installed base will be performed on the routine service cycle.

William O’Neill, medical director, Center for Structural Heart Disease, Henry Ford Hospital, USA: “The ability to view fundamental haemodynamic data such as LVP, EDP and CPO directly on the Impella console provides critical information for clinical decision-making. Additionally, access to data and realtime pump position improves efficiency for nurses and physicians in the ICU and CCU.” Michael R Minogue, president, chairman and chief executive officer of Abiomed, says: “Through innovation and research, our clinical team will use SmartAssist to help our customers achieve our goal to improve outcomes and enable heart recovery for every patient.”

FDA approves the world’s smallest mechanical heart valve

The US FDA has approved the Masters HP 15mm rotatable mechanical heart valve (Abbott), which a press release says is the world’s smallest mechanical heart valve. It adds that valve is designed to treat the babies and toddlers in need of a mitral or aortic valve replacement. This dime-sized new valve is the first and only paediatric mechanical heart valve developed for newborns and infants.

According to the press release, prior to the approval of Masters HP, surgeons could only use a range of larger-sized valves to replace a paediatric heart valve that could not be repaired and larger valves are often not suitable given the smaller size of children’s hearts.

Therefore for children who have a poorly functioning valve that cannot be repaired, a valve replacement procedure using the 15mm mechanical heart valve is now an option.

Kirk R Kanter (Emory University School of Medicine, USA), comments: “In my practice, I want to be able to provide a treatment option that works for a critically ill child when a largersized valve may not be suitable. The approval of this smaller paediatric mechanical heart valve provides surgeons with a much-needed option for treating these vulnerable, high-risk children.”

The approval of Abbott’s new Masters HP 15mm rotatable mechanical heart valve was primarily based on the results of a clinical trial, which enrolled paediatric patients five years of age or younger who had a diseased, damaged or malfunctioning heart valve. Jonathan M Chen (Seattle Children’s Hospital Heart Center, Seattle, USA) was the first physician in the trial to implant the Masters HP 15mm valve in a paediatric patient.

Michael Dale, vice president of Abbott’s structural heart business, comments: “There is an urgent need for the smallest babies and children who need a suitable

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replacement valve in order to survive. Abbott’s new mechanical paediatric heart valve is a life-changing technology for the smallest paediatric patients, giving them a better chance at a long, healthy life with a fully functioning heart.”

Sapphire II PRO becomes US’s first and only 1mm coronary balloon

Cardiovascular Systems has announced that the US FDA has granted 510(k) clearance for the OrbusNeich 1mm Sapphire II PRO coronary balloon. The approval means that the device is the first and only 1mm coronary balloon available in the USA. In January, CSI announced it is the exclusive US distributor of OrbusNeich balloon products.

At launch, CSI will offer both the 1–4mm Sapphire II PRO and the 2–4 mm Sapphire NC Plus non-compliant coronary balloons on a limited basis. The company anticipates that OrbusNeich’s full balloon product portfolio will become available in the USA throughout 2018 and 2019.

David E Kandzari (Piedmont Heart Institute, Atlanta, USA) principal investigator for the Sapphire II PRO US clinical study, says: “As physicians, we have continued to advance techniques and expand access to interventional cardiology procedures. As a result, the patients we are treating today have become increasingly complex, with more challenging lesions and anatomy, and with more difficult clinical indications. With its exceptionally low profile and deliverability, the Sapphire II PRO is an important new tool to enable us to better treat the patients we serve.”

Scott Ward, CSI’s Chairman, President and Chief Executive Officer, notes: “Offering the Sapphire II PRO 1.0mm coronary balloon—the smallest, FDAcleared coronary balloon on the market—is critical for physicians treating highly complex coronary lesions.

As the market leader in coronary atherectomy, the 1mm balloon complements our orbital atherectomy system as we continue providing advanced solutions for treating the complex and high-risk indicated patient.”

CE mark for 2.5mm Fantom Encore bioresorbable scaffold

Fantom

According to a press release, Reva Medical has received the CE mark for its 2.5mm Fantom Encore bioresorbable scaffold and that the scaffold has been implanted for the first time. Matthias Lutz (Universitätsklinikum Schleswig-Holstein, Kiel, Germany) implanted the scaffold, which has—the press release notes—a marketleading 95-micron strut profile.

Fantom Encore has been designed to offer a thinner strut profile compared with the original Fantom without compromising strength or visibility under x-ray. Like the original Fantom, Fantom Encore is made from Tyrocore—Reva Medical’s proprietary tyrosine-derived polymer designed specifically for vascular scaffold applications. Additionally, Fantom Encore leverages the same antiproliferative drug (sirolimus), scaffold design,

and balloon delivery system as Fantom. The press release states Reva Medical achieved a thinner profile without compromising strength or X-ray visibility by developing improved polymer processing and manufacturing techniques.

Lutz comments: “Fantom Encore has the thinnest strut profile of any available bioresorbable scaffold in the 2.5mm diameter size. A thinner profile can improve easeof-use during the implant procedure and vessel healing following the procedure. My experience with Fantom Encore was a successful implantation procedure, and it was easy to see with x-ray. Bioresorbable scaffolds have the potential to improve long-term outcomes compared with metal drug-eluting stents and are an important treatment option for my patients.”

Reva Medical will begin initial commercial introduction of the 2.5mm size of Fantom Encore at select centres while it pursues CE mark of the 3mm and 3.5mm diameter sizes. It expects to launch the entire Fantom Encore product line later this year. Reggie Groves, CEO of Reva Medical, notes: “Approval of Fantom Encore is a significant milestone in bioresorbable polymer and scaffold technology. Reva developed a novel polymer, Tyrocore, and then used it to create a bioresorbable scaffold with the most advanced features available: X-ray visibility and a 95-micron profile.

“To date, we have received very positive feedback from our Fantom customers. We expect that Fantom Encore will deliver the next level of performance as we expand commercialisation of our bioresorbable scaffolds.”

Terumo receives CE mark for Ultimaster Tansei drug-eluting stent

Terumo has received the CE mark for its Ultimaster Tansei drug-eluting stent. Building on the Ultimaster stent, a press release reports, the Ultimaster Tansei features optimised technology that will benefit clinicians and their patients worldwide.

Granting of the CE mark indicates that the product satisfies the requirements Ultimaster Tansei of relevant EU directives and can be marketed throughout Europe.

Terumo will launch Ultimaster Tansei in Europe in May 2018, and expand in other countries (Middle East, Latin America, and Asia) sequentially.

The original Ultimaster drug-eluting has extensive real-world clinical data, having been studied in a population of over 40,000 patients. It has proven long-term safety and efficacy, as demonstrated in the global clinical trial programme that encompassed a wide range of different patient’s conditions, complex anatomy, and challenging procedures.

According to a press release, the next-generation drug-eluting provides enhanced pushability and excellent kink resistance with a stainless steel tapered core wire at the exit port and advanced shaft technology. With Ultimaster Tansei, Terumo hopes to introduce a durable yet flexible tip, specially developed for stent application. The press release notes that this innovation will improve the deliverability of the whole stent system considerably.

Hikaru Samejima, president, Cardiac and Vascular Company of Terumo, comments: “Ultimaster is a trusted brand being used by cardiologists daily in procedures around the world. With Ultimaster Tansei we will optimise our proven technology even further for better clinical outcome.” He adds: “Tansei is the Japanese word for ‘diligent’ or ‘dedicated’.

Mastering complexity has never been simpler. Nearly three-quarters of the cardiologists are seeing in their daily practice fall into the ‘complex’ category. With Ultimaster Tansei we want to simplify their job, giving them the opportunity to focus on their patients and not their tools”.

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Clinical News Using iFR over FFR saves US$896 per patient per year

Economic data from the DEFINE FLAIR clinical trial indicate that using instantaneous wave-free ratio (iFR) provides one-year average cost savings of US$896 per patient compared with a strategy of using fractional flow reserve (FFR). The data were presented at the 2018 American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA).

DEFINE FLAIR is a randomised, controlled, single-blinded comparison of clinical outcomes and cost efficiencies of iFR and FFR-guided interventions of 2,492 patients in 49 centres across Europe, Asia, North America, and Africa. The study conducted its comparison of iFR vs. FFR using pressure guide wires and equipment from Philips.

With an average saving of nearly US$900 per patient per year, the study found that iFR offers a total procedure cost saving of approximately 10% per patient over FFR. Additionally, patients treated with the use of an iFR-guided revascularisation strategy had fewer coronary artery bypass graft procedures and fewer subsequent revascularisations. Previous data from DEFINE FLAIR released in 2017 found that iFR-guided treatments reduced procedure time by 10% vs. FFR-guided treatments, while reducing patient discomfort by 90%. The pivotal DEFINE FLAIR study continues to illustrate the advantages of iFR and the superior value it delivers to clinicians and hospital administrators.

Manesh Patel (Duke Heart Center, Duke University School of Medicine, Durham, USA), says: “The findings from DEFINE FLAIR continue to demonstrate the benefits of iFR—showing that an iFR-guided treatment offers proven outcomes, reduced costs and procedure time, and enhanced patient comfort compared to FFR. iFR is not only a faster diagnostic solution, but it also offers the advantage of significantly reduced patient discomfort. By implementing an iFR programme at a hospital, this solution can deliver the clinical outcome benefits of physiology-driven PCI, while reducing annual health care costs significantly across the organisation.”

Since the introduction of the hyperaemia-free iFR modality in 2013, a press release reports, iFR has been studied in nearly 15,000 patients and is used in more than 4,100 catheterisation labs across the world.

“The DEFINE FLAIR study has provided further clinical validation of iFR and how it is improving the lives of patients and physicians. An iFR-guided strategy has now been shown to improve patient outcomes and reduce costs for the treatment of coronary artery disease in comparison to an FFRguided strategy. This is a significant step in our journey to help clinicians decide, guide, treat and confirm the right therapies for their patients, while reducing costs,” comments Christopher Barys, Business Leader of Philips Image Guided Therapy Devices.

New trial of Symplicity Spyral approved

Medtronic has announced US FDA approval to begin an investigational device exemption (IDE) pivotal trial to evaluate its Symplicity Spyral renal denervation system in patients with hypertension.

The SPYRAL HTN pivotal trial is part of the broader SPYRAL HTN global clinical programme—a multiphased clinical study strategy aimed to establish the safety and efficacy of renal denervation to lower

blood pressure.

The SPYRAL HTN Pivotal Trial is a 1:1 randomised, sham-controlled study to investigate the renal denervation procedure in up to 433 patients at 50 sites in the USA, Europe, Australia, and Japan.

The trial will investigate the blood pressure lowering effect and safety of renal denervation in the absence of medication. The primary efficacy and safety endpoints in the trial are 24-hour blood pressure at three months and incidence of major adverse events through one-month post-randomisation.

In addition to the results from the SPYRAL HTN-OFF MED trial and the initiation of the SPYRAL HTN pivotal trial, new data from the first 80 patients enrolled in the prospective, randomised, sham-controlled SPYRAL HTN-ON MED trial will be presented during the late-breaking clinical trial session at EuroPCR 2018 (22–25 May, Paris, France). This latest phase of the SPYRAL HTN global clinical programme will report the initial safety and efficacy of renal denervation six months following the procedure in patients with uncontrolled hypertension despite ongoing drug therapy.

The study’s principal investigator David Kandzari, director of interventional cardiology and chief scientific officer, Piedmont Heart Institute in Atlanta, USA, says: “We are entering a new era for blood pressure control with data from a rigorous sham controlled trial showing that renal denervation significantly lowered blood pressure in the absence of antihypertension medications.”

Raymond Townsend, director of the Hypertension Program at the Hospital of the University of Pennsylvania, a professor of Medicine in the Perelman School of Medicine at the University of Pennsylvania (USA), and co-principal investigator in the trial, comments: “We understand the renal denervation procedure much better than we did just a few years ago, and our growing body of clinical evidence strongly suggests that this unique procedure can positively impact patients with high blood pressure.”

Approved for commercial use in more than 50 countries around the world, the Symplicity Spyral system is limited to investigational use in the USA and Japan.

Study of next-generation JenaValve device completes enrolment

JenaValve

A press release reports that successful patient enrolment in the CE mark study of the nextgeneration JenaValve pericardial transcatheter aortic valve implantation (TAVI) system—using the Coronatix transfemoral delivery catheter—for the percutaneous treatment of severe aortic stenosis has

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been completed. The JenaValve pericardial TAVI system is an investigational device in the USA and internationally.

The JenaValve system is proprietary and differentiated from prior technologies, comprising the Everdur pericardial aortic valve with locatorbased technology designed for more predictable implantation, combined with the new 18Fr compatible Coronatix transfemoral delivery catheter.

According to the press release, the optimised TAVI system has now been used to treat 10 patients across three sites in Germany and New Zealand.

Technical success for those procedures was 100%, with no reported adverse events and no moderate or higher paravalvular leakage reported.

The CE mark study is an international, prospective, non-randomised, single-arm trial of the JenaValve pericardial TAVI system for the treatment of severe aortic stenosis in patients who are at increased risk for conventional surgical valve replacement.

The German national principal investigator, Hendrik Treede (Halle University, Halle, Germany), says: “The novel JenaValve transcatheter valve may address the ongoing clinical needs for these patients. Specifically, early experience with this innovative transcatheter heart valve demonstrates low permanent pacemaker rates, negligible mean pressure gradients across the valve and no significant paravalvular leaks. Additionally, the new transfemoral system enables rapid, safe, and reliable delivery of this new valve.”

Chief executive officer at JenaValve Victoria CarrBrendel comments: “We were already extremely pleased with the initial clinical results of our nextgeneration TAVI valve, Everdur. Now, the most recent implants using the optimised delivery system have shown significantly improved ease of use and performance. We have invested a substantial amount of intellectual know-how, capital and time to develop the Everdur valve and Coronatix delivery catheter, and they are exceeding our expectations.

We look forward to expanding our clinical development programmes and building on this initial body of clinical evidence to eventually improve results, quality of life and survival among patients with these very serious conditions.”

JenaValve expects to complete patient enrolment by mid-2018 at clinical sites in Germany, The Netherlands, New Zealand and the USA. It anticipates CE mark approval by the end of 2018.

Enrolment complete in CT imaging substudy of leaflet mobility with Sapien 3 in low-risk patients

Edwards Lifesciences has announced that enrolment is complete in the computed tomography (CT) imaging substudy within the PARTNER 3 trial of the Sapien 3 valve.

This randomised substudy is examining leaflet mobility of both the Sapien 3 valve and surgical heart valves in low-risk patients undergoing valve replacement for the treatment of severe aortic stenosis.

According to a press release, enrolment in the PARTNER 3 main study of the Sapien 3 valve in low-risk patients had already been completed. The company anticipates that data from the PARTNER 3 trial will be presented at the 2019 American College of Cardiology Scientific Session and expects to receive FDA approval for the indication late that year.

Additionally, Edwards is studying the Sapien 3 Ultra system as part of a single-arm multicentre trial of up to 30 intermediate-risk patients. These data will be used to supplement the European regulatory filing for the Sapien 3 Ultra system. Edwards now expects that the European launch of the Sapien 3 Ultra system will occur later this year.

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Mar

Companies

Industry News Medtronic appoints Laura Mauri as vice president, Global Clinical Research & Analytics

Medtronic has announced that Laura Mauri—interventional cardiologist and clinical researcher at the Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School— will join the company as vice president, Global Clinical Research & Analytics.

According to a press release, she will direct the company’s dynamic global clinical research strategies that leverage her widely recognised clinical trial leadership and deep domain expertise in medical technology evaluation and clinical research methodology.

Mauri will lead the development of novel analytical and data science solutions at Medtronic to address the expanding global requirements for clinical evidence for our products. She will also lead initiatives supporting the value-based healthcare strategies that Medtronic is pioneering to meet the growing broad-based stakeholder demand for outcomes accountability. She will officially assume this role on 1 September 2018 and report to Rick Kuntz, chief medical and scientific officer.

Omar Ishrak, chief executive officer of Medtronic, says: “We are excited to welcome Dr Mauri to Medtronic. She is an accomplished front-line clinician, and widely recognised academic clinical researcher and medical thought leader. Her scientific and clinical expertise will greatly contribute to our ability to fulfil our mission to alleviate pain and restore health.”

Mauri has served as chief scientific officer of the Harvard Clinical Research Institute. Her research regarding new medical device effectiveness has helped shape clinical evaluation of new medical technologies, providing a greater understanding of the interactions between medical devices, general clinical practice, and concurrent pharmaceutical therapies. She has led clinical trials to evaluate novel medical devices and pharmaceuticals, and is an expert in trial design, strategy and data analysis. Her

innovative work has also influenced international medical guidelines and has been published in the New England Journal of Medicine, among other highimpact medical journals, and is presently a senior associate editor for Circulation, contributing to the editorial oversight of the journal’s content.

“Dr Mauri is a highly respected physician and researcher who has served as a principal investigator on multiple major clinical studies and has generated novel original research in clinical trial methodologies. She will allow us to expand our scientific strategies for evidence development and to explore new frontiers in data science.

In today’s dynamic healthcare landscape, including the trend toward value-based healthcare, innovative leaders such as Dr Mauri assure we continue to be on the leading edge of medical technology and healthcare solutions,” Kuntz comments.

LivaNova to buy TandemLife

LivaNova has entered into an agreement to acquire TandemLife, a privately held company focused on advanced cardiopulmonary temporary support solutions. A press release reports that the Pittsburgh-based company offers four product systems, all built around a common pump and controller.

It adds that these systems—including the extracorporeal life support and percutaneous mechanical circulatory support systems—are complementary to LivaNova’s strong offerings in cardiac surgery.

LivaNova has agreed to pay up to US$250 million for TandemLife.

Upfront costs total US$200 million, with up to US$50 million in contingent considerations based on regulatory milestones. The deal is projected to be modestly accretive in 2018 and is expected to close in the first half of 2018 (subject to approvals and other customary closing conditions).

With the TandemLife portfolio, hospitals can deploy a versatile platform consisting of a single pump and controller upon which all of the company’s products operate. This simple platform creates ease

of use for clinicians and offers mobility for patients. Each TandemLife system may include a pump, an oxygenator and cannulae for comprehensive, acute cardiac, pulmonary or cardiopulmonary care. The TandemLife system provides cardiopulmonary support through veno-arterial extracorporeal life support.

For patients experiencing respiratory dysfunction, TandemLung provides pulmonary support through veno-venous extracorporeal life support. ProtekDuo and TandemHeart provide advanced percutaneous mechanical circulatory support for right heart support and left heart support, respectively.

Damien McDonald, LivaNova’s CEO, comments: “We are pleased to enhance our cardiac surgery product offerings with TandemLife’s complete portfolio of advanced cardiopulmonary support products. Use of extracorporeal life support and percutaneous mechanical circulatory support systems is on the rise, and technological advancements have made products easier to use and more efficacious, leading to growth in the number of hospitals capable of performing these advanced procedures.

We will leverage our customer base and global infrastructure to increase penetration in the USA and to expand geographically.”

Since inception in 1996, TandemLife products have been used in more than 5,000 patient cases. TandemLife is currently maintaining a multicentre clinical registry and is sponsoring studies for its main indications.

HeartFlow enters into licensing agreement with Cedars-Sinai for AutoPlaque technology

HeartFlow has entered into a licensing and technology transfer agreement with Cedars-Sinai in Los Angeles (USA) for AutoPlaque technology—a software tool used to detect and characterise coronary artery plaque based on coronary computed tomography (CT) angiography images.

A press release reports that HeartFlow plans to use the AutoPlaque technology in its efforts to provide plaque assessment in future products, providing physicians with more information to help diagnose patients with coronary artery disease and determine optimal treatment pathways.

According to the press release, results

of the EMERALD (Exploring the mechanism of the plaque rupture in acute coronary syndrome using coronary CT angiography and computationaL fluid dynamics) study, which were presented at EuroPCR 2016, demonstrated that the HeartFlow FFRct analysis—together with an assessment of coronary plaque—may help predict which coronary plaques are most likely to rupture. The HeartFlow FFRct analysis is a first-of-its-kind non-invasive technology that provides a personalised 3D model of the heart to help clinicians diagnose and treat patients with suspected coronary artery disease.

John H Stevens, president and CEO of HeartFlow, says: “In addition to assessing lesion-specific physiology, understanding and characterizing coronary artery plaque is important in determining the most appropriate treatment path for patients with suspected coronary artery disease. The power of utilising the AutoPlaque tool in the HeartFlow analysis may accelerate our ability to analyse and characterise plaque in coronary arteries. HeartFlow is committed to looking beyond our initial FFRct offering to additional novel products that can help clinicians address other important clinical factors in the diagnosis and treatment of coronary artery disease and develop solutions that we believe will benefit patients who may be most at risk for acute coronary syndrome.”

Rome hospital to participate in European DuraGraft registry

The European Hospital in Rome has become the first site in Italy to participate in the DuraGraft European Registry clinical trial. The registry will assess the clinical benefits of treatment with DuraGraft—a one-time intraoperative treatment designed to reduce the risk of vascular graft disease and graft failure in patients treated with coronary artery bypass grafting (CABG).

In many cases of CABG, in the time between removal and implantation, the graft is stored in the operating room without nutrients and oxygen supply—potentially increasing the risk of ischemia reperfusion injury and graft failure. DuraGraft is designed to mitigate oxidative stress, support energy needs of the cells during the anaerobic ischaemic period, and support vasomotor function of the graft during storage and prior to implantation.

Calendar of events 04—06 June

21—23 June

25–29 August

Manchester, UK

Chicago, USA

Munich, Germany

www.bcs.com

www.crf.org/tvt

www.escardio.org

13—16 June

27—30 June

09–11 September

Vancouver, Canada

Frankfurt, Germany

London, UK

http://meetings.ismics.org/

www.csi-congress.org

www.pcronline.com/Courses/PCR-London-Valves/PCR-Lon-

BCS Annual Conference 2018

ISMICS 2018

meetings.ismics.org

Issue

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TVT 2018

CSI 2018

ESC

PCR London Valves

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