Cardiovascular News Issue 51—September US edition

Sept

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18 51

MitraClip makes “absolutely no difference” for the prognosis of secondary mitral valve regurgitation The first randomised controlled trial to compare percutaneous edge-to-edge repair (MitraClip, Abbott) with medical therapy alone in patients with secondary mitral regurgitation (to heart failure) has shown no evidence that the percutaneous device provides benefit in terms of prognosis. These findings indicate that regurgitation may be a marker of worse prognosis in heart failure rather than a cause.

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tudy investigator JeanFrancois Obadia (Hôpital Cardiovasculaire, Louis Pradel, Chirurgie Cardio-Vasculaire et Transplantation Cardiaque, Lyon, France), speaking in a Hot Line session at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany), said it was “well established” that there was “a strong correlation between mitral regurgitation severity and prognosis”. He added that while this had led to therapies (both surgical and percutaneous) that aimed to reduce regurgitation, there was no evidence that reducing regurgitation would improve prognosis.

According to Obadia, both European and US guidelines recognise the lack of data in this area and have called for randomised controlled trials. Therefore, the aim of MITRA-FR (Percutaneous repair with the MitraClip for severe functional/secondary mitral regurgitation) was to address this issue and evaluate the safety and efficacy of the MitraClip procedure in a randomised setting. In the study, 307 patients with secondary mitral regurgitation were randomised to receive a MitraClip device (152) or to receive medical therapy alone (152 after three patients were excluded because of problems with obtaining informed consent). The primary endpoint was a composite

Jean-Francois Obadia

of all-cause mortality and unplanned hospitalisation for heart failure at 12 months and secondary endpoints included the individual components of the primary endpoint, death from cardiovascular causes, and survival from major adverse cardiac events (MACE).

In an intention-to-treat analysis, the rate of the primary endpoint was 54.6% for the MitraClip group and 51.1% for the control group; a non-significant difference (p=0.53).

The rates of the individual components of the primary endpoint—allcause mortality (24.3% and 22.4%, respectively) and unplanned hospi-

talisation for heart failure (48.7% vs. 47.4%, respectively)—were similar between groups as were the rates for the other secondary endpoints (cardiovascular death and MACE). A per-protocol analysis, which excluded 14 patients in the interventional group who did not ultimately receive the device, was performed and its results were consistent with the findings of the intention-to-treat analysis.

Obadia said: “We found absolutely no difference in terms of the primary endpoint of all-cause mortality and unplanned hospitalisation; there was not even a trend towards a difference. We performed a subgroup analysis to see if there would be trend somewhere but there was not. Not even when we analysed the results according to severity of regurgitation.”

However, he noted that the study was not powered to detect smaller differences between subgroups (MITRA-FR was only powered to detect a substantial effect in the primary outcome). “Although our overall findings are very strong, we have to be careful about making conclusions about the efficacy of the device for subgroups as they were small. Potentially, future studies could explore the efficacy of MitraClip in selected patients,” he added.

Continued on page 2

Matt Börjesson: Exercise after MI

Page 10

Olaf Wendler: Profile

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More evidence that FFRCT is an effective approach for identifying patients who do not require further intervention

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jarne L Nørgaard (Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark) and colleagues report in the Journal of the American College of Cardiology (JACC) that the use of computer-derived fractional flow reserve (FFRCT, HeartFlow Analysis, HeartFlow) in patients with intermediate stenosis—based on computed tomography (CT) angiography—is effective for differentiating patients who do not require further diagnostic testing or intervention from higher risk patients.

Nørgaard et al have previously shown that FFRCT has “high and improved” diagnostic performance compared with anatomical

interpretation with CT angiography alone.

However, in this new study, they comment: “Clinical outcome data in patients undergoing CT angiogram testing with FFRCT guidance are sparse”. Therefore, the purpose of the present study was to assess the clinical outcomes and safety using a diagnostic strategy including first-line coronary CT angiogram and selecting FFRCT in real-world patients with suspected Continued on page 2

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ESC 2018

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MitraClip makes “absolutely no difference” for the prognosis of secondary mitral valve regurgitation Continued from page 1

MITRA-FR did confirm the findings of previous registries that percutaneous edge-to-edge repair was both a safe procedure and an effective approach for reducing regurgitation; in the interventional group, 76.4% of patients had mitral regurgitation of grade 0+ to 1+ at the time of hospital discharge (all patients had severe regurgitation at baseline).

Concluding his presentation at the ESC Congress, Obadia said that MITRA-FR was designed to answer two key questions: whether MitraClip was safe and whether it was effective in terms improving prognosis. “It was very important that we had a control group as thanks to this control group, we have answered the question about whether the use of MitraClip alters prognosis.

The answer is no. The main cause of worse prognosis in heart failure is probably the underlying pathology and probably mitral regurgitation is more of a marker of worse prognosis than a cause.”

Stephan Windecker (Department of Cardiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital University of Bern, Freiburgstrasse, Bern, Switzerland), acting as the ESC Congress discussant for MITRAFR, said: “To put these findings in context, the MITRA-FR patients were the sickest patients that have been investigated and reported so far. It is notable that both in terms of mortality and unplanned hospitalisation, the event rates were higher than those reported in a registry—usually the reverse is true.” He added that, as the device was shown to be safe and reduce mitral regurgitation, “heart teams are entitled to consider using MitraClip as palliative therapy in selected patients who remain highly symptomatic despite medical therapy.”

Coinciding with the presentation at the ESC Congress, the study was simultaneously published in the New England Journal of Medicine.

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More evidence that FFRCT is an effective approach for identifying patients who do not require further intervention Continued from page 1

stable coronary artery disease.

In the single-centre observational allcomer study, 3,674 symptomatic patients underwent CT angiogram on suspicion of stable coronary artery disease between 2014 and 2016. Of these, 697 patients with intermediate-grade stenosis (75% with stenosis >50%) underwent additional testing with FFRCT or myocardial perfusion imaging.

“The 3D FFRCT model provides computed FFR values in all vessels of the coronary tree ≥1.8mm. The FFRCT result was negative when all values were >0.80 and positive when at least one value was ≤0.80,” the authors explain.

Of 677 with a conclusive FFRCT result, 61% had a value of >0.80 and 39% had a value of ≤0.80. Nørgaard et al comment that patients with values of ≤0.80 were more frequently treated with statins, antiplatelet agents, and beta-blockers six months after CT angiogram than were patients with values of >0.80. “Moreover, in patients with FFRCT ≤0.80, referral to invasive coronary angiogram was associated with higher statin and antiplatelet use when compared with those managed by planned optimal medical therapy alone,” the authors say.

The main finding of the study was that the

rate of the primary endpoint—a composite of all-cause death, myocardial infarction, hospitalisation for unstable angina, and unplanned hospitalisation at up to three years—was not significantly different between patients with <30% stenosis on CT angiogram and FFRCT values of >0.80 (both groups were managed by optimal medical therapy and did not undergo further downstream testing). However, the risk of an adverse event was higher among patients with ≤0.80 who underwent invasive coronary angiogram and significantly higher in patients with values of ≤0.80 but did not undergo coronary angiogram (both groups received optimal medical therapy).

Nørgaard et al say this higher risk was driven by a higher incidence of non-fatal myocardial infarction in the FFRCT values ≤0.80 and no invasive coronary angiogram.

The authors observe that their study “underscores the feasibility of selective FFRCT testing for decision making in patients with intermediate range coronary artery disease determined by first-line CT angiogram in day-to-day clinical practice”.

Coinciding with its publication in JACC, the study was presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany) by Bjarne L Nørgaard.

More than 100,000 people now know hands-only CPR thanks to AHA programme More than 100,000 people have been trained in hands-only cardiopulmonary resuscitation (CPR) since the American Heart Association (AHA) launched its hands-only CPR training kiosk programme in 2016. As part of the programme, which is supported

by Anthem Foundation in the USA, the AHA has placed 30 of these interactive devices in cities across the country.

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he latest kiosk is located at the Indianapolis International Airport (USA), which is now home to two units that provide travellers with an opportunity to learn handsonly CPR. The majority of the handsonly CPR training kiosks are located in high-traffic, public locations, such as airports, across the USA.

AHA leaders, according to a press release, envisioned a self-instructional kiosk employing the latest technology as they considered unique approaches to doubling survival from cardiac arrest, doubling the rate of bystander CPR, and training 20 million people annually in CPR, which are among the organisation’s 2020 goals.

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displays a brief instructional video about hands-only CPR, followed by a practice session and a 30-second test.

With the help of a practice manikin, the kiosk gives precise training feedback about the depth and rate of compressions—factors that influence the effectiveness of CPR. The training session takes about five minutes.

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Research published in the scientific journal Resuscitation showed there was noticeable interest by the public to learn hands-only CPR through the use of the kiosk. During a 32-month period from July 2013 to February 2016, nearly 23,500 visitors tried the device.

Each kiosk has a touch screen that

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Sept

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ESC 2018

18 51

Greater use of PCI for high SYNTAX score patients may explain higher rate of all-cause death with FFR in FUTURE

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The final results of the FUTURE (Functional testing underlying revascularisation) trial indicate that more patients with multivessel disease and a high SYNTAX score (>32) undergo percutaneous coronary intervention (PCI)—as opposed to coronary artery bypass grafting (CABG)—when treatment is guided by fractional flow reserve (FFR) than when it is guided by angiogram. This finding may be why the rate of all-cause death was significantly higher among FFR-guided patients.

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nitial results from the first 836 patients enrolled in FUTURE, according to data presented at the 2016 American Heart Association (AHA) meeting, suggested that FFR-guided treatment (PCI, CABG, or optimal medical therapy) of multivessel disease is associated with a significantly higher rate of all-cause death than is angiogramguided treatment. These results prompted the trial’s data and safety monitoring board (DSMB) to call a halt to the trial (when 938 patients had been recruited).

Therefore, with the final results— which Gilles Rioufol (Interventional Cardiology Department, Hospices Civils de Lyon, Lyon, France) presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany)—the aim was to determine if they confirmed the initial results and to review the potential reasons for the higher rate of all-cause mortality in the FFR group.

According to Rioufol, the goal of FUTURE was to explore the potential of FFR to guide treatment decisions in patients with multivessel disease. He explained that while FFR is already used to guide PCI in patients with multivessel disease, its ability to help to decide among different treatment strategies “remains unknown”. Therefore, Rioufol reported, the study hypothesis posed the question: “In multivessel disease patients, does FFR help to guide treatment strategy (PCI, CABG, or optimal medical therapy) and thereby improve clinical prognosis compared to traditional management?”

In the study, multivessel disease (>50% stenosis) patients with sta-

ble angina or stabilised angina were randomised to FFR-guided treatment or angiogram-guided treatment; all lesions with a FFR of >0.80 (haemodynamically not significant) were disregarded from the analysis. At one year, based on the outcomes of the 938 patients (460 in FFR group and 467 in angiogram group) who were enrolled in the study before it was halted, the rate of all-cause mortality was two-fold higher in the FFR group compared with the angiogram group. Rioufol said: “More than 70% of the deaths, overall, were cardiovascular related. They were not procedural as they occurred later on.”

To better understand these findings, Rioufol and his co-authors performed an intention-to-treat analysis. This showed that there were no significant differences at baseline in either patient characteristics or angiographic characteristics between the two groups. In the FFR group, 43% of lesions had a FFR value of >0.80 and the mean FFR value was 0.77±0.13.

At one year, there were no significant differences in the rate of the primary endpoint—a composite of all-cause death, myocardial infarction, stroke and revascularisation—between the groups at one year or at two years. However, at one year, the rate of all-cause death was still significantly higher in the FFR group: 3.7% vs. 1.5% (p=0.036).

Rioufol et al also found that choice of treatment was different between the groups. In the FFR group, more patients received optimal medical therapy (17% vs. 9%) and fewer patients underwent PCI (71% vs. 79%) compared with the angiogram group (a significant dif-

Gilles Rioufol

ference; p=0.002). However, the rate of CABG was identical (12% in both groups) as was the use of ad hoc PCI (nine out of 10 PCI patients in each group).

In a subgroup analysis, the investigators found that there was two-fold increase risk of major adverse cardiac events (MACE) among patients with stable angina in the FFR group and there was a trend towards worse outcomes for patients with a SYNTAX score of >32.

Additionally, in an exploratory analysis, FFR patients who died had higher SYNTAX scores and had more three-vessel disease than angiogram patients who died. Rioufol observed: “Interestingly, in an all-cause mortality analysis, more FFR patients were treated with PCI and significantly more had a SYNTAX score of >32.”

Concluding his presentation, Rioufol said that the FUTURE trial did “not

challenge” the current use of FFR for PCI guiding (this was not evaluated in the study) but showed that FFR-guided treatment does not improve outcomes in patients with multivessel disease.

“Hypotheses to explain the higher rate of all-cause mortality in the FFR group include a lower than expected rate of CABG in multivessel disease patients, high rate of PCI in severe patients with SYNTAX score >32, and a high rate of ad hoc PCI,” he added.

Patrick Serruys (Imperial College London, London, UK), who was one of the chairs of the late-breaking trial session in which the FUTURE trial was presented, said that the trial was “courageous” but “raised more questions than it answered”. He added that the DSMB should not have been so quick to stop the study, commenting that the higher rate of all-cause mortality could have been a “play of chance” and that the DSMB could have just as easily stopped the trial because of a higher rate of stroke in the angiogram group.

However, Serruys did say that there were “1A” recommendations (i.e. supported by a high level of evidence) that the heart team—specifically, teams that include a surgeon—should be involved in making treatment decisions for patients with three-vessel disease. Agreeing with this view, Rioufol said that he believed that FFR provided important information about functional ischaemia but, in complex patients, “you have to pullback the wire and discuss treatment decisions with the heart team”. He speculated that, in the study, use of FFR may have driven operators to use PCI rather than CABG.

New European guidelines recommend iFR alongside FFR for assessing haemodynamic significance of lesions New European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines for myocardial revascularisation give the use of instantaneous wave-free ratio (iFR, Philips) to assess the haemodynamic significance of lesions (when evidence of ischaemia is not available) a Class I, Level A recommendation. Therefore, iFR can now be used as an alternative to fractional flow reserve (FFR) in the assessment of patients with stable disease and stenosis of intermediate-grade (on angiogram) significance.

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ranz-Josef Neumann (Division of Cardiology and Angiology II, University Heart Centre Freiburg - Bad Krozingen, Bad Krozingen, Germany) and his co-authors write in the European Heart Journal that two recent large randomised trials—DEFINE-FLAIR and iFR-SWEDEHEART—both showed that iFR-guided revascularisation in patients with intermediate-grade stenosis was associated with similar one-year rates of major adverse cardiac events as was FFR-guided revascularisation; in both studies, iFR was also associated with fewer complications than FFR. Neumann et al add the SYNTAX II study has also provided “encouraging outcomes” for the use of iFR. In this study, patients with multivessel disease who underwent

percutaneous coronary intervention (PCI) with contemporary techniques—including the use of lesion assessment with iFR—had significantly better outcomes than the PCI group of the first SYNTAX study (which did not use iFR or even new-generation drug-eluting stents).

Justin Davies (Hammersmith Hospital, Imperial College NHS Trust, London, UK), who developed iFR, told Cardiovascular News: “With the Class 1A recommendation, it is great to see that the ESC has recognised the high level of evidence that now support the use of both FFR and iFR to guide coronary revascularisation.”

In the new guidelines, which were presented at the 2018 ESC Congress (25–29 August, Munich, Germany), the recommendations for revascularisation of non-culprit

lesions in patients with cardiogenic shock undergoing primary PCI have also been revised. The previous recommendation that revascularisation of non-culprit lesions in cardiogenic shock patients undergoing primary PCI “could be considered” has changed to “not recommended”. This follows the results of the CULPRIT-SHOCK trial, presented at the 2017 Transcatheter Cardiovascular Therapeutics meeting, which showed that the 30-day rate of all-cause mortality and renal replacement therapy was significantly decreased in cardiogenic shock patients who underwent culprit-only primary PCI rather than complete revascularisation. The one-year results of CULPRIT SHOCK were presented at this year’s ESC Congress and confirmed the 30-day findings (see page 6 for details).

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Coronary interventions

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All-cause mortality in cardiogenic shock multivessel PCI only increased during first 30 days One-year data from the CULPRIT-SHOCK trial indicate that there is no significant difference in all-cause mortality between cardiogenic shock patients undergoing immediate multivessel percutaneous coronary intervention (PCI) and those undergoing culprit-lesion only PCI. These findings suggest that multivessel PCI is only associated with increased all-cause mortality in the first 30 days after the procedure.

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Holger Thiele

he 30-day outcomes of CULPRITSHOCK, which were presented at the 2017 Transcatheter Cardiovascular Therapeutics meeting and published in the New England Journal of Medicine, showed the rate of the primary endpoint— a composite of all-cause death or renal replacement therapy—was significantly decreased with culprit-lesion PCI: 45.9% vs. 55.4% for the immediate multivessel PCI (p=0.01); a result thought to be driven by an absolute 8% reduction in all-cause death with culprit-lesion only PCI.

Multivessel PCI was also associated with a trend towards more renal replacement therapy. This finding led the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) to revise their recommendations for the use of multivessel disease in cardiogenic shock patients, downgrading multivessel PCI from “should be considered” to “not recommended”.

Writing in the New Journal of Medicine, Holger Thiele (Department of Internal Medicine-Cardiology, Heart Center Leipzig, University of Leipzig, Leipzig, Germany) and colleagues report that the aim of the one-year analysis of the CULPRIT-SHOCK trial was to further explore the safety and efficacy of multivessel PCI in the setting of cardiogenic shock. Therefore, in the present analysis, they reviewed the one-year results of the pre-specified secondary endpoints (allcause death, renal replacement therapy, recurrent myocardial infarction, repeat revascularisation, and rehospitalisation for heart failure).

In CULPRIT SHOCK, 706 patients with acute myocardial infarction, multivessel disease and cardiogenic shock were randomised to culprit-lesion only PCI (351) or immediate multivessel PCI (355). A one-year mortality rate of 50% for patients in the culprit-lesion only

group and 56.9% in the immediate multivessel group (relative risk [RR] 0.88) was observed. However, culprit-lesion only PCI was associated with recurrent infarction rate of 1.7%, vs. 2.1% for multivessel PCI (RR 0.85); repeat revascularisations were also more frequent in patients with culprit-lesion only PCI than in those with immediate multivessel PCI (32.3% and 9.4%, respectively;), as were heart failure rehospitalisations (5.2% vs.1.2%).

Thiele et al note that the study had several limitations, including the fact that the one-year endpoints are exploratory because the trial was powered for a 30-day analysis of the primary composite endpoint. Additionally, the trial was not blinded—allowing for the possibility of residual bias—and investigators were unable to use echocardiography to assess cardiac failure, which would have allowed the exploration of underlying causes for the higher 30-day mortality rate with multivessel PCI and for the higher rate of heart failure rehospitalisations witnessed with culprit-lesion only PCI. Overall, the incidence of heart failure was low in both groups, with a small absolute difference, and the researchers suggested that it could be “a consequence of competing risks”. They explain: “Patients with cardiogenic shock are at an extreme

Higher all-cause mortality with Orsiro at five years than with Xience According to the five-year results of the BIOSCIENCE trial, sirolimus-eluting stents with a biodegradable polymer (Orsiro, Biotronik) have a similar overall safety and efficacy profile as everolimus-eluting stents with a permanent polymer (Xience, Abbott). However, the study also found that all-cause mortality was significantly higher in patients receiving Orsiro and this higher rate was driven by a higher rate of non-cardiovascular deaths (mainly cancer).

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riting in the Lancet, Thomas Pilgrim (Department of Cardiology, University of Bern, Switzerland) and others say that, although the higher mortality rates among those receiving biodegradable stents “might be a chance finding”, they add that it warrants further observation during long-term follow-up of ongoing studies.

The single-blind, multicentre, non-inferiority, allcomers randomised trial from Switzerland compared the two stents in patients with chronic stable coronary artery disease or acute coronary syndromes, with a primary endpoint of target lesion failure (a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation). Pilgrim et al found that, of the 2,008 patients who completed five years of follow-up, target lesion failure occurred in 198 (20.2%) of those treated with Orsiro and in 189 (18.8%) of those treated with Xience (p=0.487); there was no significant interaction between treatment effect and time. However, all-cause

mortality was significantly higher in patients treated with biodegradable-polymer stents (14.1% vs. 10.3%; p=0.017)—influenced by non-cardiovascular deaths.

There was no difference in definite stent thrombosis between groups at five years.

Biodegradable polymers are thought to reduce the potential for a polymer-induced chronic inflammatory response, with benefits that may extend beyond the degradation of the polymer. This study is the first to assess long-term efficacy and safety outcomes after the time of complete disintegration of the polymer in a comparison with the best-in-class durable-polymer device.

The investigators comment: “There were no differences in the occurrence of target lesion failure and its individual components of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revacularisation between the stent types in our study. This study extends the clinical evidence on the newest generation of drug-eluting stents combining

risk for death, and if they die early they therefore do not survive long enough for heart failure to develop in the longerterm.” They further speculate that the higher rate of complete revascularisation in the immediate multivessel PCI group may have led to improved ventricular function, resulting in a lower incidence of heart failure among these patients. They add: “Because culprit-lesion only PCI has shown a benefit over multivessel PCI with respect to short-term survival, the risk of heart failure within the first year may be higher with culprit-lesion only PCI than with multivessel PCI.” Thiele et al indicate that the higher incidence of repeat revascularisations in the culprit-lesion only PCI group could be related to the extent of coronary artery disease, the presence of impaired left ventricular function, and the severity of illness in patients with cardiogenic shock, as well as to the trial design, and conclude: “It is unclear whether an even higher rate of revascularisation of non-culprit lesions could have prevented rehospitalisations for heart failure.”

Coinciding with the publication in the New England Journal of Medicine, CULPRIT-SHOCK (one-year) were presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany)

biodegradable polymers with ultrathin-stent platforms.

Although, to our knowledge, our analysis provides the longest available experience of ultrathin strut biodegradable polymer sirolimus-eluting stents, a difference in very late stent thrombosis might become apparent only during extended follow-up beyond five years.”

All-cause death was the only one of 20 outcome parameters to differ significantly between stents, a consequence of the difference in the incidence of death secondary to different types of cancer. Pilgrim et al did not prospectively record a history of cancer at baseline; hence they say “we cannot differentiate between death secondary to pre-existing, recurring, and newly developed cancer in our study population”.

Commenting in the Lancet, Clemems von Birgelen and Paulo Zocca (University of Twente, Enschende, Netherlands) say that, based on existing knowledge and other trial results, “play of chance might be the most plausible explanation for this difference”. They also note that the average age of study participants at around 66 years may have relevance; it was higher than in previous trials with five-year outcomes for all-comers, and age is directly related to an increased risk both of developing cancer and of death.

Also, Birgelen et al add that the results show that “it is desirable to obtain outcome data for novel coronary stents from more than one randomised clinical trial.

Ideally, these trials should originate from different countries so as to increase diversity in study populations.”

Pilgrim presented the results of the BIOSCIENCE at the 2018 ESC Congress.

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Sept

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8

Sept

Dual antiplatelet therapy

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18 51

DAPT score “not generalisable” to a nationwide population

A new study has found that the dual antiplatelet therapy (DAPT) score, which is recommended by both US and European guidelines, did not adequately determine ischaemic and bleeding risk in an unselected patient population. These findings suggest that the score may not be generalisable to real-world populations.

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eter Ueda (Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden) and others write in the Journal of the American College of Cardiology that the DAPT score is used to determine which patients would benefit from receiving DAPT for an extended period—a further 18 months after 12 months’ DAPT without an ischaemic or bleeding event—following percutaneous coronary intervention (PCI). They add that both US and European DAPT guidelines advise physicians to consider using the score when determining duration of DAPT (in patients who have already completed 12 months of DAPT without an event).

However, the authors observe that the score has only been validated using clinical trial populations. Specifically, the score was based on the results of the DAPT study and a large proportion of patients in that study received first-generation drug-eluting stents. “The

performance of the risk score in an unselected real-world patient population receiving contemporary PCI treatment is uncertain,” Ueda et al comment. Therefore, the aim of the present study was to assess the ability of the DAPT score to stratify ischaemic and bleeding risk after 12 months of DAPT and to compare ischaemic and bleeding event rates in this patient population with those observed in the DAPT study.

Using data from the SWEDEHEART registry, the authors identified 41,101 patients who had received DAPT for 12 months without experiencing an ischaemic or bleeding event. Of these, 55% had a “low” DAPT score (<2 points) and 45% had a high DAPT score (≥2 points); according to the decision rule of the score, patients with a score of two or above should receive DAPT beyond 12 months.

Ueda et al report that the DAPT score had a C-statistic of 0.58 for myocardial infarction and stent thrombosis and 0.54

Peter Ueda

for major adverse cardiac cerebrovascular events (MACCE).

They note that patients with a high DAPT score had significantly higher rates of myocardial infarction, stent thrombosis and MACCE than those with a low DAPT score. However, the difference in risk of myocardial infarction and stent thrombosis was largely driven by those with scores of 3 and higher and rates of MACCE did not increase linearly with score level.

“Compared with scores of -1 and -2, event rates were lower at scores of 1 and 2 and significantly increased only at scores of 4 and ≥5,” the authors state.

Furthermore, the score had a Cstatistic of 0.49 for fatal or major bleeding, and the risk of this event between low and high risk groups was similar. Ueda et al observe: “These findings, which remained similar when limiting the analyses to patients receiving new generation drugeluting stents, indicate that the DAPT score is not useful for discriminating bleeding and ischaemic risk.”

After comparing the patient population of the DAPT study with that of the SWEDEHEART registry, Ueda et al found differences in event rates and state: “Notably, rates of fatal or major bleeding in the SWEDHEART registry were roughly one half of those for the GUSTO moderate or severe bleeding in the placebo arm of the DAPT study. Although this could partly be explained by the different bleeding outcome definition used and the potential risk of incomplete registration of events in health registries, the rates of fatal or major bleeding in our study were similar to

those in other coronary patient populations from real-world databases and clinical trials.”

However, the authors note that patients perceived to be at high risk of bleeding in the SWEDEHEART registry may have been prescribed DAPT for less than 12 months (patients in the DAPT study had to receive DAPT for at least 12 months) and, therefore, would not have been included in this present analysis (potentially affecting the results).

Ueda told Cardiovascular News: “Although we could not assess the effect of extended DAPT in patients stratified using the score, our data on discrimination and calibration of the risk score indicate that the ischaemic vs. bleeding risk trade-off seen among high and low-score patients in the DAPT study may not be generalisable to external populations, including the SWEDEHEART Registry. Generalisability, especially with respect to calibration, is a well-known challenge in the area of risk scores.”

Ticagrelor monotherapy approach does not challenge current DAPT approach

The GLOBAL LEADERS trial, simultaneously published in the Lancet and presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany), shows that a regimen of ticagrelor and aspirin for one month after percutaneous coronary intervention (PCI) followed by 23 months of ticagrelor monotherapy is not superior to the current standard approach of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy for 12 months.

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tudy authors Pascal Vranckx (Hartcentrum Hasselt, Faculty of Medicine and Life Sciences, Hasselt University Hasselt, Belgium) and colleagues say that the results “do not support a change in practice at this time”. In an accompanying comment article in the Lancet, Deepak L Bhatt (Brigham and Women’s Hospital Heart and Vascular Centre, Boston, USA) concurs: “Compared with standard treatment, the experimental regimen had no clear benefits and no clear harms either. However, in view of the higher rates of discontinuation, the increased frequency of dyspnoea, and the higher cost associated with the experimental regimen than with the control group, as well as the necessity of twice daily dosing with ticagrelor, aspirin should remain the preferred antiplatelet therapy for secondary prevention.”

Vranckx et al hypothesised that a shorter DAPT regimen might provide a more favourable balance.

GLOBAL LEADERS, an open-label superiority trial at 130 sites in 18 countries, randomised 15,968 patients (1:1) undergoing PCI for stable coronary artery disease or acute coronary syndromes to either aspirin daily plus ticagrelor twice daily for one month, followed by 23 months of ticagrelor monotherapy (7,980) or to standard DAPT (7,988). Standard DAPT, in this study, consisted of aspirin plus

either clopidogrel (stable coronary artery disease) or ticagrelor (acute coronary syndrome) for 12 months, followed by aspirin monotherapy for 12 months.

In the experimental group, 304 (3.81%) participants had died or had had a non-fatal centrally adjudicated new Q-wave myocardial infarction at two years, compared with 349 (4.37%) in the control group (p=0.073). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndrome and stable coronary artery disease (p=0.93). The frequency of major bleeding according to the Bleeding Academic Research Consortium criteria was similar between groups (163 participants [2.04%] in the experimental group and 169 [2.12%] in the control group; p=0.77).

Although the rate of serious adverse events did not differ significantly between the two groups, discontinuation of the treatment regimen was more common in the experimental group than in the control group.

The investigators suggest that this could “stem from the fact that aspirin constitutes the default (background) therapy for patients with established atherothrombotic cardiovascular disease, whereas the experimental treatment strategy has not been established. Additionally, we cannot exclude that pleiotropic effects of aspirin other than the antiplate-

let effect could be beneficial and could have affected the outcome of our trial.”

GLOBAL LEADERS is believed to be the largest trial so far of one month of DAPT with aspirin and ticagrelor followed by ticagrelor monotherapy vs. a standard DAPT regimen after implantation of a drugeluting stent. The trial is also unique in its sole use of ticagrelor, a P2Y12 receptor antagonist, as an antiplatelet regimen rather than aspirin after cessation of DAPT. Also, Vranckx et al comment, GLOBAL LEADERS is the only randomised trial to date in which randomisation was done at PCI and in which two antiplatelet strategies were compared, with up to two years of follow-up. The data, they say, “provided reassuring information with respect to the safety and efficacy of ticagrelor monotherapy”.

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Sports cardiology

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The risks and benefits of exercise after a myocardial infarction MATT BÖRJESSON COMMENT & ANALYSIS In a new position paper, published in the European Heart Journal, the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC) outline recommendations for coronary artery disease patients participating in sport (both for leisure and for competitive reasons). In this commentary, the lead author of the paper, Mats Börjesson focuses on the recommendations concerning patients who have had a myocardial infarction.

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oronary artery disease is the main cause of sudden cardiac arrest/ death in individuals aged more than 35 years old. Regular physical exercise reduces the risk of development and the progression of coronary artery disease, partly by its positive effect on classical risk factors such as hypercholesterolemia, hypertension and diabetes.

However, somewhat paradoxically, high intensity exercise may increase the risk of sudden cardiac arrest (especially during activity) in patients with coronary artery disease; although, the actual incidence of acute events is very low.

Overall, the benefits of regular physical activity outweigh—by far—the increased risk for coronary events triggered by acute, intensive physical activity.

Myocardial ischaemia during exercise is caused by a mismatch in oxygen demand-supply. It may be provoked by an increase in heart rate, blood pressure and subsequent workload, exceeding the threshold of ischaemia, during high intensity exercise. Cardiac events may also be triggered by neuro-hormonal activation, plaque rupture and endothelial erosion in patients with underlying coronary artery disease.

While novel cardiac imaging techniques have proven invaluable in detecting coronary artery disease, they do not provide information relative to the coronary flow and reserve—which are vital to assess the risk of sudden cardiac

death/sudden cardiac arrest associated with exercise. Therefore, different methods of stress testing (e.g. cycle ergometry or treadmill testing), stress echocardiography/MRI/single-photon emission computed tomography (SPECT) and positron emission tomography (PET), play a major role. For the evaluation of competitive athletes with suspected coronary artery disease, maximal exercise capacity should be assessed.

When advising patients with coronary artery disease on engagement in competitive sports, the documented benefits of exercise must be balanced with the potential risk for adverse events. In general, leisure time activity is advised and should be recommended individually (i.e., exercise on prescription) to all those with established coronary artery disease.

Risk stratification

For athletes-patients with proven coronary artery disease, as documented by an earlier clinical event such as a myocardial infarction, or by computed tomography (CT) scan or coronary angiography, advice on sport participation should be based on:1 The extent of the coronary artery disease on angiography The presence of exercise-induced myocardial ischaemia Any exercise induced arrhythmia Evidence of myocardial dysfunction (echo, MRI)

The type and level of sport competition The fitness level of the individual patient The cardiovascular risk factor profile.

Specifically, patients are stratified as having a low probability for exerciseinduced adverse cardiac events if all of the following apply: absence of critical coronary stenoses (i.e. <70%) of major coronary arteries or <50% of left main stem on coronary angiography; ejection fraction ≥50% on echocardiography, cardiac magnetic resonance (MR) or angiography (and no wall motion abnormalities); normal, age-adjusted exercise capacity; absence of inducible ischaemia (symptoms, abnormal blood pressure response) on maximal exercise testing; and absence of major ventricular tachyarrhythmias (i.e., non-sustained ventricular tachycardia, polymorphic or very frequent ventricular extra beat, at rest and during maximal stress testing).1 Conversely, patients can be stratified as having a high probability for exerciseinduced adverse cardiac events if at least one of the above criteria is not fulfilled and/or if having symptoms on exercise.

Recommendations

Patients stratified as low-risk for cardiac events post myocardial infarction can participate in most competitive sports.

Restrictions apply on an individual basis for certain sports with the highest cardiovascular demand (e.g. extreme power and endurance disciplines) and for older patients with coronary artery disease, as the risk of sudden cardiac death during endurance events may be considerably higher in men >60 years old.

In patients stratified as at high risk, post myocardial infarction should be restricted from competitive sport and receive appropriate management. In patients with significant ischaemia during exercise, anti-ischaemic therapy needs to be optimised and revascularisation ought to be performed, if ischaemia prevails. If despite adequate treatment ischaemia cannot be completely resolved, the patient should be restricted from competitive sport and advised on leisure-time activities.

According to the cardiac rehabilita-

“No option” for revascularisation in refractory angina does not mean never

Data from the OPTIMIST (Options in myocardial ischemic syndrome therapy) registry indicate that a quarter (25%) of patients with refractory angina who are initially deemed to be “no option” for revascularisation will go on to have such an intervention.

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riting in Catheterizations and Cardiovascular Interventions, Rahul Sharma, Tim Henry, (Cedars Sinai Heart Institute, Los Angeles, USA and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, USA) and others report that patients with refractory angina—persistent or recurrent symptoms that cannot be controlled by a combination of medical therapy and revascularisa-

tion—are labelled as “no option” if revascularisation with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) does not appear to be feasible. They add that only “limiting and conflicting” data are available for further revascularisation in such patients.

Of the 1,363 patients in the database, from the OPTIMIST programme, 342 (25.1%) underwent revascu-

tion guidelines of the European Society of Cardiology, participation in an exercise programme is recommended for all patients who undergo revascularisation after an acute myocardial infarction.

Exercise should be prescribed in a gradual mode, starting with low-intensity exercise of short duration, progressively and step-wise increased to where the patient is able to perform exercise without limitation. Careful attention to the development of new symptoms, are essential. The duration of the progression is dependent upon the extent of myocardial injury and remodelling. In patients with non-ST segment elevation myocardial infarction (NSTEMI) with complete revascularisation and without remaining ischaemia, exercise can be increased faster to previous levels. More intense training and participation in competition should only be considered after a successful, progressive increase in the exercise load.

Conclusion

The recommendation for patients who have had a myocardial infarction/undergoing percutaneous coronary intervention (PCI) and who have a low-probability of further cardiac events is for them to have a minimum of three months’ rehabilitation before they resume participation in competitive sports. If they are receiving dual antiplatelet therapy (DAPT), because of the risk of bleeding, they should be advised to avoid contact sports.

Advice on eligibility to participate in sport must be combined with recommendations to perform proper warm-up and cool-down procedures and ensure adequate hydration. Patients should also be made aware of the need to be mindful of any symptoms occurring during resumed exercise. Continuous long-term cardiac evaluation, at least annually, is then advised. The risk factor profile should be managed pharmacologically and with lifestyle modifications.

Reference 1. Borjesson et al. Eur Heart J 2018. Epub.

Mats Börjesson is at Department of Neuroscience and Physiology & Sahlgrenska University Hospital, Göteborg, Sweden

larisation within 2.2 years of receiving a “no option” label. Most of these underwent PCI (20.1%), with the remainder undergoing CABG (3.2%) or both (1.8%).

Sharma et al comment: “Patients who were subsequently revascularised had significantly lower mortality than patients who were not (2%/year vs. 4.4% per year; p<0.001).

A paired analysis of baseline and subsequent angiographic records for 181 PCI patients showed that just under half underwent PCI for a new lesion (48%), with 31% undergoing PCI for an existing lesion and 21% for a restenosis. According to a review of five-year survival post revascularisation, patients who required PCI for a pre-existing lesion had higher mortality (23%) compared with those undergoing CABG (15%), those with new lesions (11%), and those with restenosis (11%).

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Section Name

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Structural Heart Interventions

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First US FDA-approved study shows TAVI is safe for low-risk patients The LRT (Low Risk TAVR) trial did not find any significant differences in the rate of all-cause mortality between low-risk patients undergoing transcatheter aortic valve implantation (TAVI) and a historical control group of low-risk patients undergoing surgical aortic valve replacement. LRT is the first TAVI study to have US FDA approved investigational device exemption for low-risk patients.

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riting in the Journal of the American College of Cardiology, Ron Waksman (MedStar Washington Hospital Center, Washington, DC, USA) and colleagues comment that NOTION (Nordic Aortic Valve Intervention)—the only randomised trial to date to evaluate TAVI in low-risk patients—found that TAVI “compared favourably”, in terms of 30-day mortality, with surgical aortic valve replacement in low-risk patients. However, they add that this study also showed that TAVI with an early generation self-expanding device was “associated with significantly higher permanent pacemaker rates and paravalvular aortic regurgitation”.

Therefore, the aim of LRT was to evaluate TAVI, with new-generation devices, in a low-risk US population.

Waksman et al report that, in the study, 200 low-risk patients (STS-PROM score ≤3% and absence of comorbidity that would increase surgical risk) underwent transfemoral TAVI with a balloon-expandable (Sapien 3, Edwards Lifesciences) or self-expanding device (CoreValve, Evolut R, Evolut PRO, Medtronic). The

Ron Waksman

outcomes of these patients were then compared with a historical control group of 719 low-risk patients who underwent surgical aortic valve replacement, with the primary endpoint being all-cause mortality at 30 days.

Hospital length of stay was significantly shorter in TAVI patients and the rate of postoperative atrial fibrillation was higher in the surgical patients. However, the rates of permanent pacemaker implantation and moderate paravalvular leak were low in both groups—in fact, the rates of pacemaker implantation and moderate paravalvular leak were the lowest seen in all major TAVI studies so far. “This may be explained by the

use of predominantly newer generation balloon-expandable devices in younger patients [approx. six years younger than those of the intermediate-risk populations in PARTNER 2 and SURTAVI] with less aortic annular calcification and less pre-existing conduction system disease, and improved implantation techniques,” Waksman et al comment.

There were no significant differences between TAVI and surgery patients in terms of the primary endpoint, with all 200 TAVI patients being discharged alive within 30 days of the TAVI procedure and zero mortality and zero disabling stroke at 30 days in this group. The authors comment: “It is important to highlight that except for the sponsor (MedStar Washington Hospital Center, Washington, DC, USA), enrolling centres in the LRT trial were not highvolume centres or experienced centres.

As such, these results truly represent contemporary real-world TAVI practice in the USA.” They observe that, unlike for higher risk populations, TAVI may not provide a mortality benefit (over surgery) for low-risk populations. They say, there-

Chronic kidney disease should not be a barrier to TAVI The first study to compare the use of transcatheter aortic valve implantation (TAVI) with conservative management in patients with chronic kidney disease (stage 3–5) indicates that mortality is significantly higher with conservative management.

This suggests that although patients with chronic kidney disease have worse outcomes after TAVI compared with patients without chronic kidney disease, they should still be considered for the procedure.

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ali Steinmetz (Department of Nephrology, Rabin Medical CenterBeilinson Hospital, Petach Tikva, Istrael) and others report in EuroIntervention that current evidence suggests that chronic kidney disease is associated with increased mortality after TAVI. They add that this has led to physicians being hesitant to refer such patients for TAVI, particularly considering TAVI is “associated with exposure to several risk factors for acute kidney injury”. However, the authors observe no study has compared the mortality of

patients with chronic kidney disease undergoing TAVI with those receiving conservative treatment. “We sought to evaluate the effect of TAVI on survival and renal function in patients with stage 3–5 chronic kidney disease and severe symptomatic aortic stenosis compared to conservative management,” Steinmetz et al write.

Using data from their centre (Rabin Medical Center-Beilinson Hospital), the authors identified 198 patients with chronic kidney disease who underwent TAVI and compared them with 162 chronic kidney disease pa-

tients (with aortic stenosis) who received conservative management. The primary endpoint was overall mortality and the second endpoint included estimated glomerular filtration rate (eGFR).

After a mean follow-up of 1.9 years, mortality was significantly lower in the TAVI group: 32.7% vs. 49.5% for conservative management (p<0.001).

Also, in a multivariate cox analysis, conservative management was associated with a hazard ratio of 3.95 for mortality compared with TAVI. Steinmetz et al report that “a Kaplan-Meier survival curve showed signifi-

fore, that the benefit of TAVI for these patients “may be shorter hospital length of stay, swifter recovery, and superior prosthesis haemodynamics”.

Post-surgery haemodynamics were not available for the surgical cohort, so a comparison between the groups could not be made. However, according to the authors, the mean gradient and valve areas seen in the TAVI group of the LRT trial were comparable to those seen in the TAVI arm of the PARTNER 2 Sapien 3 intermediate-risk.

Concluding, Waksman et al write: “TAVI is safe in low-risk patients with symptomatic severe aortic stenosis, with low procedural complication rates, short hospital length of stay, zero mortality and zero disabling stroke at 30 days.”

Waksman told Cardiovascular News: “The LRT study sends a strong signal that TAVI for low-risk patients is a safe and effective alternative to surgical aortic valve replacement for this population with symptomatic aortic stenosis.

We anticipate that the pivotal trials will corroborate the LRT results and FDA will expand the labelling of TAVI for the low-risk population.”

cantly better survival rate for the TAVI group (p<0.001)” in a propensity matched analysis.

At three months, eGFR had increased slightly in patients who underwent TAVI and decreased in the conservative group. By one year, it had further decreased in the conservative group but remained stable in the TAVI group. The authors note that the interaction between eGFR change over time and treatment was “highly significantly” (p=0.01).

According to Steinmetz et al, on the basis of the results of this study, physicians should try to avoid making comparisons between TAVI patients with chronic kidney disease and those without chronic kidney disease. “When evaluating the risk/benefit of TAVI in the presence of chronic kidney disease, one needs to compare the outcome of patients with chronic kidney disease and aortic stenosis post TAVI with those treated conservatively and not to TAVI patients with no chronic kidney

disease,” they comment.

The authors conclude: “These results should encourage both cardiologists and nephrologists to refrain from a priori excluding chronic kidney disease patients from undergoing thorough assessment for TAVI eligibility.” They add further studies are needed to identify characteristics of chronic kidney disease that are associated with survival benefit following TAVI. Steinmetz told Cardiovascular News: “According to our institution’s experience, doctors should not prevent chronic kidney disease patients from undergoing TAVI but they should be aware of the risks of the procedure for these patients—such as contrast nephropathy and acute renal failure. In light of this, every effort (such as intravenous including fluids, 0.9% saline, before and after the procedure) needs to made to prevent a deterioration in renal function and renal function should be assessed at follow-up.”

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Structural Heart Interventions TMVI associated with “excellent outcomes” for valve-in-valve procedures

New results from the TMVR (Transcatheter mitral valve replacement) Registry show that patients with a degenerated bioprosthesis who undergo transcatheter mitral valve implantation (TMVI) have relatively low rates of all-cause mortality (14%) at one year. However, suboptimal procedural outcomes are observed for patients who undergo TMVI for failed annuloplasty rings or for severe mitral annular calcification.

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ung-Han Yoon (Department of Interventional Cardiology, Cedars-Sinai Heart Institute, Los Angeles, USA) told delegates at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany) that TMVI—or “TMVR” as it is called in the USA—was “an emerging alternative treatment” for patients with mitral valve disease who were considered to be at high risk for conventional surgery. He added that as limited data exist regarding the procedural and clinical outcomes of TMVI, he, along with Raj Makkar (Department of Interventional Cardiology, Cedars-Sinai Heart Institute, Los Angeles, USA) and colleagues, initiated the TMVR Registry to evaluate the use of the procedure in patients with degenerated bioprosthetic valves, failed annuloplasty rings, or severe mitral annular calcification.

Data from the registry have already shown (as published in the Journal of the American College of Cardiology) that TMVI for both failed rings and for degenerated bioprostheses is associated with acceptable outcomes in high-risk patients. However, these findings also indicate that procedural complications and mid-term mortality is higher for TMVI in failed rings than TMVI for

degenerated bioprostheses.

At the ESC Congress, Yoon presented outcomes for TMVI in severe mitral annular calcification as well as for failed surgical rings and degenerated bioprostheses. Of 521 patients overall, 322 underwent a valve-in-valve procedure, 141 underwent a valve-in-ring procedure, and 58 underwent TMVI for mitral annular calcification. Patients with mitral annular calcification more frequently had New York Heart Association (NYHA) Class IV heart failure (47% vs. 32% for valve-invalve patients, vs. 26% for valve-in-ring patients; p<0.02) symptoms, whereas the valve-in-ring patients were more likely to have undergone coronary artery bypass grafting (CABG) and have had a prior myocardial infarction. Most patients (90%) underwent TMVI with a Sapien valve (XT/S3, Edwards Lifesciences), with the remaining patients receiving a Lotus valve (Boston Scientific).

Technical success was highest in the valve-in-valve patients (94.4%) and lowest in the annular calcification patients (62.1%). Left ventricular outflow obstruction (LVOT) occurred significantly more frequently in the annular calcification patients—39.7% vs. 5% for valve-in-ring

and 2.2% for valve-in-valve (p<0.001)— which Yoon noted resulted in a higher rate of alcohol septal ablation in this group (12.1% vs. 0.7% for valve-in-ring and 0.6% for valve-in-valve; p<0.01). Need for secondary mitral valve intervention was also highest in this group (22.4% vs. 17.7% for valve-in-ring vs. 10.9% for valve-in-valve; p=0.02), but need for a second valve was highest in patients undergoing valve-in-ring: 12.1% vs. 5.2% for annular calcification vs. 2.5% for valve-in-ring (p<0.001). Additionally, the valve-in-ring patients had the highest rates of moderate-to-severe mitral regurgitation (18.4% vs. 13.8% for annular calcification vs. 5.6% for valve-in-valve; p<0.001).

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At 30 days, mortality was significantly increased in the mitral annular calcification group than in valve-in-ring and valvein-valve groups: 34.5% vs. 9.9% vs. 6.2%, respectively (p<0.001). By one year, valve-in-valve patients had the lowest rate of all-cause mortality than either patients undergoing valve-in-ring or those with annular calcification (14% vs. 30.6% vs.

62.8%; log-rank p<0.001). All-cause mortality was still lowest in patients undergoing valve-in-valve in a landmark analysis of all-cause mortality between 30 days and one year: 8.4% vs. 23% for valve-inring and 43.2% for annular calcification (log-rank p<0.001).

Yoon reported that post procedural moderate or severe mitral regurgitation was associated with increased all-cause mortality in all groups (41.5% vs. 21.4% for mild mitral regurgitation; log-rank p=0.01). He added that compared with valve-in-valve procedures, valve-inring and mitral annular calcification procedures were both—in a multivariate model—independent predictors of allcause mortality.

“There were excellent outcomes of TMVI for patients with degenerated mitral bioprosthetic valves despite high surgical risk, but there were suboptimal procedural outcomes for valve-in-ring and mitral annular calcification procedures,” Yoon told ESC delegates. He added that the higher rates of mid-term mortality for the valvein-ring and annular calcification procedures were because of adverse events and underlying mitral valve disease.

“Optimal patient selection and advanced device technology promise to improve the outcomes of TMVI,” he concluded.

Simultaneous TAVI and left atrial appendage closure is feasible

Thomas S Gilhofer (University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland) and others report in Structural Heart that a combined procedure involving both transcatheter aortic valve implantation (TAVI) and left atrial appendage closure is a feasible approach for aortic stenosis patients with atrial fibrillation and contraindications to oral anticoagulation.

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ilhofer et al note that oral anticoagulation is used to mitigate the risk of stroke in patients with atrial fibrillation but add that it increases the risk of bleeding and this risk “is especially pronounced in contemporary TAVI candidates who are mostly elderly and frail”. They add that some of the differences in prognosis between TAVI patients with atrial fibrillation and those without— i.e. it is generally worse in atrial fibrillation patients—may be attributable to the increased risk of bleeding associated with oral anticoagulation. Therefore, left atrial appendage closure may be an option for atrial fibrillation patients undergoing TAVI; specifically, those who have a relative or absolute contraindication to oral anticoagulation.

The authors write that a previous study has already explored the feasibility of combining TAVI with left atrial appendage closure but write that “different prosthesis in different centres were combined and not compared to a left atrial appendage occlusion group.” Thus, the aim of the present study was to review the feasibility of combining TAVI and left atrial appendage closure procedures using one device type (Lotus and Watchman respectively; both Boston Scientific) and to compare the combined procedure with TAVI alone and with left atrial appendage closure alone.

Of 52 patients enrolled in the study, 19 underwent an isolated TAVI procedure, 23 underwent isolated left atrial appendage

closure, and 10 underwent a combined procedure. Gilhofer et al state that there was not a significant difference in contrast use between the different procedures but acknowledge this finding may relate to their small sample size (previous studies of combined percutaneous approaches have shown an increase in contrast use).

“Our numbers are reassuring in that in there is no alarming increase of contrast dye to be expected by combining TAVI and left atrial appendage closure,” they observe. As to be expected, procedural time was significantly greater in the combined group vs. the isolated TAVI group (82±16.6 minutes vs. 57±18 minutes for TAVI vs. 42.7±16 minutes for the isolated left atrial appendage

closure group; p=0.001).

At the 30-day post procedure follow-up point, no patients had died in either the isolated TAVI group or in the isolated left atrial appendage closure group.

One patient in the combined group died of sudden cardiac arrest on day 28 (two weeks after an event-free hospital stay).

The authors comment: “Our study shows that simultaneous TAVI and left atrial appendage closure procedure using a Lotus vale and a Watchman device is feasible and comparable to both interventions as standalone procedures.” They add that a combined approach avoids the need for a second procedure and also omits the need for lifelong anticoagulation but state that “long-term follow-up will show whether combining TAVI and

left atrial appendage improves the prognosis in high-risk patients with atrial fibrillation”.

Gilhofer told Cardiovascular News: “Reducing the number of procedures performed increases patient comfort and satisfaction and reduces hospitalisations as well as the number of in-hospital days. Despite the limited number of procedures in our study, we were able to show that simultaneous TAVI and left atrial appendage closure with Lotus and Watchman is feasible and comparable to both interventions as stand-alone procedures, although procedural time was higher when both interventions were performed simultaneously. We therefore plea for an open approach to combining percutaneous transcatheter interventions if indicated.”

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Structural Heart Interventions

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Revising the National Coverage Determination for TAVI: The real barrier to care is not volume requirements SCOTT LILLY SATYA SHREENIVAS COMMENT & ANALYSIS Recently the Centers for Medicare and Medicaid Services (CMS) reopened the National Coverage Determination (NCD) for transcatheter aortic valve implantation (TAVI). Much of the discussion has focused on the TAVI and surgical valve volume requirements to start and maintain a TAVI programme. However, in this commentary, Scott M Lilly and Satya Shreenivas argue that the discussion should also review the “two-surgeon” rule as they claim that this is a “more apparent and obstructive barrier” to the care of patients with aortic stenosis than volume requirements.

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hile volume is one correlate of quality, it is an incomplete one. The extent to which these requirements present a barrier to care is a matter of considerable debate.

But as that conversation unfolds, there is a more apparent and obstructive barrier to the care of patients with aortic stenosis within the NCD—namely the two-surgeon rule. Removing this rule immediately would be simpler, occur with the consensus of the care team, and save patient lives.

The original NCD established guidelines for establishing and maintaining TAVI programmes and contained three fundamental elements: The presence of a “heart team” that consists of a cardiovascular surgeon and interventional cardiologist, along with other members that might include specialists in imaging, heart failure, anaesthesia or social work

Institutional volume requirements that include the number of surgical valve replacements, percutaneous coronary interventions, and structural heart disease cases (Table 1).

Two cardiac surgeons to independently evaluate the patient (face-to-face) and provide assessment of patients’ risk for open surgical valve replacement.

The rationale for these elements was to ensure the appropriate and responsible dispersion of TAVI in a manner that maximised quality and minimised the likelihood of off-label use. These elements revitalised the concept of a heart team and were a victory for patient-centred care. These regulations were widely viewed as reasonable and necessary, especially given the environment at the time. TAVI had just been approved for patients deemed to be high or prohibitive-risk for surgical valve replacement,

Table 1: Annual requirements for TAVI programmes Procedures

New TAVI programmes

Existing TAVI programmes

Surgical aortic valve replacement

>50 (>10 high risk)

>20 or > 40 per two years

Cardiac catheterisations

>1,000

>1,000

>400

>400

Percutaneous coronary intervention

and concerns about risk creep necessitated considerable oversight.

While the heart-team approach and the current volume requirements are conventional standards, the requirement for consensus among two surgeons is less defensible. The “two-surgeon” rule often results in an additional clinic evaluation for a patient population that is elderly, often relies on others for transportation, and has a condition with poor shortterm outcomes. Additionally, while it may have been important to prevent risk creep as TAVI was being established, we now know that outcomes with TAVI are comparable to surgical aortic valve replacement for the majority of patients with aortic stenosis. Lastly, this rule has no standard—no other approved procedure or medical therapy requires the consensus of two providers from the same specialty; whether it be organ transplantation, percutaneous ventricular support, or chemotherapy.

To view “access to care” as simply as a function of geographical proximity is short-sighted; it involves the delivery of appropriate, quality care in a timely manner. The delay invoked by current

volume requirements can be measured in the travel time to a TAVI centre, which is measured in hours. The two surgeon rule often requires a second clinic visit—a delay that is measured in days. While the quality implications of TAVI in lower volume centres are established, a geographical hindrance would seem to be less important than a temporal delay.

We should aim to maximise opportunities for timely, high quality care that benefits patients independent of health systems. By removing the two surgeon rule we mitigate the greatest access to care issue for TAVI in the USA and improve the care of patients. This should be the primary focus of the NCD revision, and occur now, even before quality indices for TAVI are vetted for lower volume centres.

Scott M Lilly is at the Department of Medicine, Division of Cardiology, Ohio State University Wexner Medical Center, Columbus, USA; Satya Shreenivas is at The Christ Hospital Heart and Vascular Center/The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, USA.

Novel Ultraseal device is a feasible option for left atrial appendage closure A feasibility study of a novel left atrial appendage device (Ultraseal, Cardia) indicates that the device is associated with a high rate of procedural success and a fast learning curve. It also suggests that the device has an extremely low complication rate.

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aolo A Pagnotta (Humanitas Clinical and Research Institute, Milan, Italy) and others report in the Journal of Interventional Cardiology that European guidelines recommend that left atrial appendage closure be considered in patients with atrial fibrillation who cannot receive oral anticoagulation (because of a high risk of bleeding). Noting that several left atrial appendage closure devices have now been developed, they write that the Ultra-

seal is a novel device that “conforms to left atrial appendage closure anatomy”.

The aim of the present study was to provide an initial assessment of the feasibility and safety profile of the device in patients with non-vavlular atrial fibrillation and contraindications to long-term oral anticoagulation therapy. Therefore, 23 patients were enrolled in the study and received the device.

Pagnotta et al report that mean procedure time was

83 minutes and that “it was progressively shorter in the last procedures (first procedure: 106 minutes; last procedure: 69 minutes)”. They add this indicates a fast learning curve with the device, which they attributed to the device’s “intuitive loading and implantation”. Procedural success was achieved in 21 out of 23 cases (91%) and there were not any other immediate complications.

The authors conclude: “Our results show a promising feasibility and safety profile of the Ultraseal device in patients with non-valvular atrial fibrillation and high risk for stroke but unsuitable for long-term anticoagulation.”

HEMO DYNAMIC The Evolut™ PRO TAVR System.

Large EOAs. Low gradients.

Unsurpassed hemodynamics.

The choice for your patients who can return to an active life. ©2018 Medtronic. All rights reserved. UC201809335 EN 03/2018

INDICATIONS The Medtronic CoreValve™ Evolut™ R and CoreValve™ Evolut™ PRO systems are indicated for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be at intermediate or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality ≥ 3% at 30 days, based on the Society of Thoracic Surgeons [STS] risk score and other clinical comorbidities unmeasured by the STS risk calculator).

The Medtronic CoreValve Evolut R and CoreValve Evolut PRO systems are indicated for use in patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., STS predicted risk of operative mortality score ≥ 8% or at a ≥ 15% risk of mortality at 30 days).

CONTRAINDICATIONS The CoreValve Evolut R and PRO systems are contraindicated for patients presenting with any of the following conditions: known hypersensitivity or contraindication to aspirin, heparin (HIT/HITTS) and bivalirudin, ticlopidine, clopidogrel, Nitinol (Titanium or Nickel), or sensitivity to contrast media, which cannot be adequately pre-medicated; ongoing sepsis, including active endocarditis; pre-existing mechanical heart valve in the aortic position.

WARNINGS General Implantation of the CoreValve Evolut R and PRO systems should be performed only by physicians who have received Medtronic CoreValve Evolut R or PRO training. This procedure should only be performed where emergency aortic valve surgery can be performed promptly. Mechanical failure of the delivery catheter system and/or accessories may result in patient complications.

Accelerated deterioration of the bioprosthesis may occur in patients presenting with an altered calcium metabolism.

PRECAUTIONS General The safety and effectiveness of the CoreValve Evolut R and PRO systems have not been evaluated in the pediatric population. The safety and effectiveness of the bioprosthesis for aortic valve replacement have not been evaluated in the following patient populations: patients who do not meet the criteria for symptomatic severe native aortic stenosis as defined: (1) symptomatic severe high gradient aortic stenosis — aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient ≥ 40 mmHg; or a peak aortic-jet velocity ≥ 4.0 m/s, (2) symptomatic severe low-flow, low-gradient aortic stenosis — aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient < 40 mmHg; and a peak aortic-jet velocity < 4.0 m/s ; who are at low surgical risk (predicted perioperative mortality risk of < 3%); with untreated, clinically significant coronary artery disease requiring revascularization; with a pre-existing prosthetic heart valve with a rigid support structure in either the mitral or pulmonic position if either the pre-existing prosthetic heart valve could affect the implantation or function of the bioprosthesis or the implantation of the bioprosthesis could affect the function of the pre-existing prosthetic heart valve; with cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support. The safety and effectiveness of a CoreValve Evolut R and PRO bioprosthesis implanted within a failed pre-existing transcatheter bioprosthesis has not been demonstrated.

Implanting a CoreValve Evolut R or PRO bioprosthesis in a degenerated surgical bioprosthesis [transcatheter aortic valve in surgical aortic valve (TAV in SAV)] should be avoided in the following conditions.

The degenerated surgical bioprosthesis presents with: a significant concomitant perivalvular leak (between the prosthesis and the native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g., wire form frame fracture); partially detached leaflet that in the aortic position may obstruct a coronary ostium; stent frame with a manufacturers labeled inner diameter < 17 mm.

The safety and effectiveness of the bioprosthesis for aortic valve replacement have not been evaluated in patient populations presenting with the following: blood dyscrasias as defined: leukopenia (WBC < 1,000 cells/mm3), thrombocytopenia (platelet count < 50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states; congenital bicuspid or unicuspid valve; mixed aortic valve disease [aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)]; moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation; hypertrophic obstructive cardiomyopathy; new or untreated echocardiographic evidence of intracardiac mass, thrombus, or vegetation; native aortic annulus size < 18 mm or > 30 mm for CoreValve Evolut R and < 18 mm or > 26 mm for CoreValve Evolut PRO per the baseline diagnostic imaging or surgical bioprosthetic aortic annulus size < 17 mm or > 30 mm for CoreValve Evolut R and < 17 mm or > 26 mm for CoreValve Evolut PRO; transarterial access not able to accommodate an 18 Fr sheath or the 14 Fr equivalent EnVeo InLine™ sheath when using Model ENVEOR-US/ENVPRO-14-US or transarterial access not able to accommodate a 20 Fr introducer sheath or the 16 Fr equivalent EnVeo InLine sheath when using Model ENVEOR-N-US/ENVPRO-16-US; sinus of valsalva anatomy that would prevent adequate coronary perfusion; moderate to severe mitral stenosis; severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20%; symptomatic carotid or vertebral artery disease; severe basal septal hypertrophy with an outflow gradient.

Prior to Use Exposure to glutaraldehyde may cause irritation of the skin, eyes, nose, and throat. Avoid prolonged or repeated exposure to the vapors. Damage may result from forceful handling of the catheter. Prevent kinking of the catheter when removing it from the packaging. This device was designed for single patient use only. Do not reuse, reprocess, or re-sterilize this product. Reuse, reprocessing, or re-sterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death. The bioprosthesis size must be appropriate to fit the patient’s anatomy. Proper sizing of the device is the responsibility of the physician. Refer to Instructions for Use for available sizes. Failure to implant a device within the sizing matrix could lead to adverse effects such as those listed below. Patients must present with transarterial access vessel diameters of ≥ 5 mm when using Model ENVEOR-US/ ENVPRO-14-US or ≥ 5.5 mm when using Model ENVEOR-N-US/ENVPRO-16-US, or patients must present with an ascending aortic (direct aortic) access site ≥ 60 mm from the basal plane for both systems. Implantation of the bioprosthesis should be avoided in patients with aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) of > 30° for right subclavian/axillary access or > 70° for femoral and left subclavian/axillary access. Use caution when using the subclavian/axillary approach in patients with a patent LIMA graft or patent RIMA graft. For direct aortic access, ensure the access site and trajectory are free of patent RIMA or a pre-existing patent RIMA graft.

During Use For direct aortic and subclavian access procedures, care must be exercised when using the tip-retrieval mechanism to ensure adequate clearance to avoid advancement of the catheter tip through the bioprosthesis leaflets during device closure. For direct aortic access procedures, use a separate introducer sheath; do not use the EnVeo InLine sheath. Adequate rinsing of the bioprosthesis with sterile saline, as described in the Instructions for Use, is mandatory before implantation. During rinsing, do not touch the leaflets or squeeze the bioprosthesis. If a misload is detected, unsheath the bioprosthesis and examine the bioprosthesis for damage (for example, permanent frame deformation, frayed sutures, or valve damage). Do not attempt to reload a damaged bioprosthesis. Do not load the bioprosthesis onto the catheter more than two times or after it has been inserted into a patient. Use the deployment knob to deploy and recapture the bioprosthesis. Do not use the trigger for deploying or recapturing because it could cause inaccurate placement of the bioprosthesis. Once the radiopaque capsule marker band reaches the distal end of the radiopaque paddle attachment (point of no recapture), retrieval of the bioprosthesis from the patient is not recommended. Retrieval after the point of no recapture may cause mechanical failure of the delivery catheter system, aortic root damage, coronary artery damage, myocardial damage, vascular complications, prosthetic valve dysfunction (including device malposition), embolization, stroke, and/or emergent surgery. During deployment, the bioprosthesis can be advanced or withdrawn as long as annular contact has not been made. Once annular contact is made, the bioprosthesis cannot be advanced in the retrograde direction; recapture until the bioprosthesis is free from annular contact, and then reposition in the retrograde direction. If necessary, and the radiopaque capsule marker band has not yet reached the distal end of the radiopaque paddle attachment, the bioprosthesis can be withdrawn (repositioned) in the antegrade direction. However, use caution when moving the bioprosthesis in the antegrade direction. While the catheter is in the patient, ensure the guide wire is extending from the tip. Do not remove the guide wire from the catheter while the catheter is inserted in the patient. Use the handle of the delivery system to reposition the bioprosthesis. Do not use the outer catheter sheath. There will be some resistance when the catheter is advanced through the vasculature. If there is a significant increase in resistance, stop advancement and investigate the cause of the resistance (for example, magnify the area of resistance) before proceeding. Do not force passage. Forcing passage could increase the risk of vascular complications (for example, vessel dissection or rupture). Persistent force on the catheter can cause the catheter to kink which could increase the risk of vascular complications (for example, vessel dissection or rupture). Once deployment is complete, repositioning of the bioprosthesis is not recommended. Repositioning of a deployed valve may cause aortic root damage, coronary artery damage, myocardial damage, vascular complications, prosthetic valve dysfunction (including device malposition), embolization, stroke, and/or emergent surgery. Do not attempt to retrieve or to recapture a bioprosthesis if any one of the outflow struts is protruding from the capsule. If any one of the outflow struts has deployed from the capsule, the bioprosthesis must be released from the catheter before the catheter can be withdrawn. Ensure the capsule is closed before catheter removal. When using a separate introducer sheath, if increased resistance is encountered when removing the catheter through the introducer sheath, do not force passage. Increased resistance may indicate a problem and forced passage may result in damage to the device and/ or harm to the patient. If the cause of resistance cannot be determined or corrected, remove the catheter and introducer sheath as a single unit over the guide wire, and inspect the catheter and confirm that it is complete. Clinical long-term durability has not been established for the bioprosthesis. Evaluate bioprosthesis performance as needed during patient follow-up. Post procedure, administer appropriate antibiotic prophylaxis as needed for patients at risk for prosthetic valve infection and endocarditis. Post procedure, administer anticoagulation and/or antiplatelet therapy per physician/ clinical judgment. Excessive contrast media may cause renal failure. Pre procedure, measure the patient’s creatinine level. During the procedure, monitor contrast media usage. Conduct the procedure under fluoroscopy. The safety and efficacy of a CoreValve Evolut R or CoreValve Evolut PRO bioprosthesis implanted within a transcatheter bioprosthesis have not been demonstrated. However, in the event that a CoreValve Evolut R or CoreValve Evolut PRO bioprosthesis must be implanted within a transcatheter bioprosthesis to improve valve function, valve size and patient anatomy must be considered before implantation of the CoreValve Evolut R or CoreValve Evolut PRO bioprosthesis to ensure patient safety (for example, to avoid coronary obstruction). In the event that valve function or sealing is impaired due to excessive calcification or incomplete expansion, a post-implant balloon dilatation of the bioprosthesis may improve valve function and sealing. To ensure patient safety, valve size and patient anatomy must be considered when selecting the size of the balloon used for dilatation. The balloon size chosen for dilatation should not exceed the diameter of the native aortic annulus or, for surgical bioprosthetic valves, the manufacturer’s labeled inner diameter. Refer to the specific balloon catheter manufacturer’s compliance chart to ensure that the applied inflation pressure does not result in a balloon diameter that exceeds the indicated annulus range for the bioprosthesis. Refer to the specific balloon catheter manufacturer’s labeling for proper instruction on the use of balloon catheter devices.

Note: Bench testing has only been conducted to confirm compatibility with NuMED Z-MED™* and Z-MED II™* Balloon Aortic Valvuloplasty catheters where CoreValve Evolut R and CoreValve Evolut PRO bioprosthesis device performance was maintained after dilation. Data on file.

POTENTIAL ADVERSE EVENTS Potential risks associated with the implantation of the CoreValve Evolut R or CoreValve Evolut PRO transcatheter aortic valve may include, but are not limited to, the following: death myocardial infarction, cardiac arrest, cardiogenic shock, cardiac tamponade coronary occlusion, obstruction, or vessel spasm (including acute coronary closure) cardiovascular injury (including rupture, perforation, tissue erosion, or dissection of vessels, ascending aorta trauma, ventricle, myocardium, or valvular structures that may require intervention) emergent surgical or transcatheter intervention (for example, coronary artery bypass, heart valve replacement, valve explant, percutaneous coronary intervention (PCI), balloon valvuloplasty) prosthetic valve dysfunction (regurgitation or stenosis) due to fracture; bending (out-of-round configuration) of the valve frame; underexpansion of the valve frame; calcification; pannus; leaflet wear, tear, prolapse, or retraction; poor valve coaptation; suture breaks or disruption; leaks; mal-sizing (prosthesis-patient mismatch); malposition (either too high or too low)/malplacement prosthetic valve migration/embolization prosthetic valve endocarditis prosthetic valve thrombosis delivery catheter system malfunction resulting in the need for additional re-crossing of the aortic valve and prolonged procedural time delivery catheter system component migration/embolization stroke (ischemic or hemorrhagic), transient ischemic attack (TIA), or other neurological deficits heart failure cardiac failure or low cardiac output ancillary device embolization individual organ [for example, cardiac, respiratory, renal (including acute kidney failure)] or multi-organ insufficiency or failure major or minor bleeding that may require transfusion or intervention (including life-threatening or disabling bleeding) vascular access-related complications (e.g., dissection, perforation, pain, bleeding, hematoma, pseudoaneurysm, irreversible nerve injury, compartment syndrome, arteriovenous fistula, stenosis) mitral valve regurgitation or injury conduction system disturbances (for example, atrioventricular node block, leftbundle branch block, asystole), which may require a permanent pacemaker infection (including septicemia) hypotension or hypertension hemolysis peripheral ischemia bowel ischemia abnormal lab values (including electrolyte imbalance) allergic reaction to antiplatelet agents, contrast medium, or anesthesia exposure to radiation through fluoroscopy and angiograph permanent disability. n

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Please reference the CoreValve Evolut R and CoreValve Evolut PRO Instructions for Use for more information regarding indications, warnings, precautions, and potential adverse events.

CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician.

The commercial name of the Evolut™ PRO device is Medtronic CoreValve™ Evolut™ PRO System.

710 Medtronic Parkway Minneapolis, MN 55432-5604 USA Tel: (763) 514-4000 Fax: (763) 514-4879 Toll-free: (800) 328-2518

medtronic.com

LifeLine CardioVascular Technical Support Tel: (877) 526-7890 Tel: (763) 526-7890 Fax: (763) 526-7888 rs.cstechsupport@medtronic.com

©2018 Medtronic. All rights reserved.

Medtronic, Medtronic logo and Further, Together are trademarks of Medtronic.

TM *Third party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company.

UC201809335 EN 03/2018

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17

Structural Heart Interventions

“Tricuspidisation” could be a potential approach to performing TAVI in certain patients with bicuspid valves At present, a bicuspid aortic valve is seen as a relative contradiction for transcatheter aortic valve implantation (TAVI) and, thus, surgical aortic valve replacement is the preferred approach in most of these patients. However, surgery is not always possible in some patients with bicuspid aortic valves (e.g. the risk of complications is too great) and, therefore, TAVI may be the only option. When faced with such a patient in a recent case, Danny Dvir (Interventional cardiologist, University of Washington Medical Center, Seattle) performed “tricuspidisation”—turning a bicuspid valve into a tricuspid valve—to ensure TAVI could be performed safely. He talks to Cardiovascular News about the challenge of bicuspid valves and why tricuspidisation may be a potential way of addressing this challenge in some patients.

Will this become more of an issue given that TAVI is increasingly being used in lower risk, younger patients?

What percentage of patients with aortic stenosis have bicuspid valves?

In your recent case, your patient had a bicuspid valve but had to undergo TAVI because she was unable to undergo surgery. How did you overcome this challenge?

Bicuspid aortic valve is a relatively common congenital anomaly. It is estimated that approximately 1–2% of the general population have bicuspid aortic valves. In Asia, bicuspid aortic valves are especially common. People with bicuspid aortic valves are at increased risk for having aortic valve and aortopathies— these include aortic stenosis, regurgitation and dilation of the ascending aorta and aortic dissection. Epidemiologically, the younger the population of patients with aortic stenosis, the higher the rate of them having bicuspid aortic valves.

Below the age of 65 years of age, almost half of patients, by several estimates, with aortic stenosis have bicuspid aortic valves.

How are aortic stenosis patients with bicuspid valves typically treated?

Patients with bicuspid aortic valves that have severe stenosis/regurgitation are conventionally treated with open heart surgery. These surgeries occasionally include replacement of the aorta, when it is dilated. Some of these patients are at increased risk for conventional surgery and are referred for TAVI. These procedures are occasionally more challenging.

Why is it challenging to use TAVI in these patients?

TAVI in bicuspid aortic valves is associated with inferior results. Unfortunately, these patients were excluded from the original large TAVI trials and, as a result, we do not have data comparing surgery and TAVI in bicuspid patients.

However, large registries have suggested that TAVI in bicuspid aortic valves is associated with worse clinical outcomes. These registries mainly included patients treated with first generation devices but not always.

One of the challenges of aortic valve bicuspidity is that it represents a very heterogeneous group of anatomical pathologies. Patients with bicuspid valves not only have many different mechanisms of failure and aortic morphologies, but also their valve characteristics differ significantly by the existence of raphe, and by the amount and location of root calcification. It seems that TAVI is associated with inferior results especially in certain types of bicuspid aortic valves. In these conditions there is a higher risk of paravalvular leak, conduction defects, and annular injury.

Non-circular device expansion is more common in certain bicuspid TAVI procedures and this may lead to worse device durability.

Yes, indeed. As already mentioned, younger patients with aortic valve stenosis are much more likely to have bicuspid aortic valves. This is particularly the case in those younger than 70. Clearly, one of the main obstacles of expanding TAVI towards younger patients is our ability to treat patients with bicuspid aortic valves safely and effectively.

During the last year, I had performed dozens of “BASILICA” procedures.

These are designed to prevent coronary obstruction by slicing a leaflet; a procedure that was developed in collaboration with colleagues at the National Institutes of Health. Extension of this technique to modify certain bicuspid aortic valves by converting them to a common tricuspid anatomy seems to be feasible. In the patient’s case, transforming a bicuspid aortic valve into a tricuspid morphology was performed.

Could the approach you used be replicated to be used in other patients with bicuspid valves undergoing TAVI? Probably, and this was preformed already in other cases; however, we need to study all candidates carefully.

I believe that we need to evaluate the anatomy of each patient with a bicuspid aortic valve that is a candidate for TAVI and consider whether root morphology, amount of calcification

Danny Dvir

and its location could potentially result a higher risk for adverse events following TAVI. If the pattern of calcification could put the patient at an increased risk for adverse events, then aortic root tricuspidisation could be considered.

What further studies in the management of the aortic stenosis patients with bicuspid valves are needed?

There is a lot to learn about TAVI in bicuspid aortic valves. Fundamental aspects, such as device sizing and positioning, are not settled yet. There are already several ongoing large registries inside the large trials, and other registries coming from real-world clinical practice, that will help us learn how to perform these procedures better.

Advanced techniques that can modify bicuspid aortic valves by performing tricuspidisation will probably be applicable to some patients with bicuspid aortic valves, with anticipation of decreasing the risk of adverse events and prolonging device durability. It seems that in some patients just deploying a valve is not good enough and we may want to modify and prepare their valve anatomy before implanting a device.

More than three-quarters of patients have sustained results at very long-term follow-up after percutaneous balloon mitral valve valvuloplasty Rafael A Meneguz-Moreno (Department of Interventional Cardiology, Instituto Dante Pazzanese De Cardiologia, Sao Paulo, Brazil) and others report in JACC: Cardiovascular Interventions that after very long-term follow-up, 75% (i.e three quarters) of patients exhibit sustained results after undergoing percutaneous balloon mitral valve valvuloplasty.

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he authors report that although percutaneous balloon mitral valve valvuloplasty is seen as the gold-standard approach for managing severe symptomatic rheumatic mitral valve stenosis (in patients with suitable anatomy), there is a paucity of very longterm outcome data for patients undergoing the procedure.

“In the present study, we report immediate and very longterm clinical and echocardiographic follow-up results of a large series of consecutive patients who underwent percutaneous balloon mitral valve valvuloplasty,” they write.

Reviewing registry data from their centre, MeneguzMoreno et al identified 1,582 consecutive patients who underwent percutaneous balloon mitral valve valvuloplasty between August 1987 and July 2011. They found that at the very long-term follow-up point (23 years), the incidence of the primary endpoint—the composite of all-cause mortality, need for mitral surgery, and need for repeat percutaneous balloon mitral valve valvuloplasty— was 19.1%.

The majority (93.1%) of patients, of those who had a

successful procedure, had improvements in New York Heart Association (NYHA) function class within the first year. The authors note in a multivariate analysis, the only predictors of the primary endpoint were NYHA functional class III or IV at baseline, age, and mitral valve area immediately after the procedure.

Meneguz-Moreno et al comment that their study shows that “two decades” after a successful procedure, “more than 75% of followed patients still exhibited sustained results.”

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Profile

Olaf Wendler Olaf Wendler (lead for Cardiothoracic Surgery, King’s Health Partners, and chair of the Heart and Vascular Institute of the Cleveland Clinic London, UK) performed the first transcatheter aortic valve implantation (TAVI) procedure in the UK. He is a course co-director of PCR London Valves and is a keen proponent of the heart team. He talks to Cardiovascular News about the future of TAVI and the potential impact of Brexit on EU nationals, such as himself, working for the NHS.

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

and under conscious sedation. This reduction in procedural trauma, technical experience and patient selection has resulted in a continuous improvement of outcomes.

Who have been your career mentors?

Do you think TAVI has the potential to mirror PCI (for coronary artery disease) and become the default strategy for aortic stenosis (irrespective of a patient’s risk profile)?

I was fascinated by the opportunities to cure, often young patients, with very complex health issues.

I started my medical training with Professor Hans Borst (Medical School Hannover, Hannover, Germany), an eminent leader of cardiac surgery in Germany at the time and a pioneer in aortic surgery. Being a man with strong ethical values, he was an outstanding teacher and role model far beyond the operating theatre and an important advisor throughout my entire medical training.

When Professor Fred Mohr (Heart Center Leipzig, Leipzig, Germany) asked me to join his team to build the Heart Center Leipzig, no one could have predicted that it would be one of the world’s leading organisations for cardiovascular care 20 years later. Professor Mohr demonstrated to me that nothing in cardiac surgery is impossible and also showed a strong link with innovators enables new technology for the benefit of patient care.

Professor Jochen Schaefers (University HomburgSaar, Saarland, Germany) is an extremely skilful cardiovascular surgeon, who polished my surgical skills and personally pushed me to surgical limits. His structured approach to diagnosis and treatment has helped me throughout my career to develop a particular quality of surgical care.

What has been the most important development in cardiothoracic surgery during your career?

I was lucky enough that I was able to become directly involved in the development of TAVI technology and procedures.

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

In 2015, I was the first to implant a spacer-balloon into a human. The patient had ischaemic mitral regurgitation and left heart failure; after the procedure, his heart failure symptoms greatly improved as did his left ventricular function. The improvements meant he was then able to be considered as “low risk” for mitral valve surgery, and he is now living a normal life.

Despite this excellent experience with the device, this spacer technology has not been further developed—the original sponsor did not provide further funding for commercial reasons. However, I strongly believe that this technology could greatly benefit patients with left heart failure in the future and it would be a wasted opportunity from my point of view not to proceed further.

You performed the first transapical TAVI procedure in the UK in 2007. How has TAVI changed since then?

TAVI is nowadays a routine treatment for elderly patients with severe aortic stenosis. While vascular access was initially a major issue due to the size of devices, these days, most procedures are done percutaneously

TAVI is already the default strategy in patients with severe aortic stenosis and who are at high surgical risk. However, so far, all trials have been performed in elderly patients—mainly above 80 years of age.

Before we consider using TAVI in younger patients, we should have a better understanding about the durability of transcatheter heart valves. There is no doubt that, particularly in patients who suffer from impaired mobility, TAVI provides advantages with respect to their time of recovery.

In the USA, the Centers for Medicare & Medicaid Services are in the process of reviewing their national coverage determination for TAVI. Specifically, they are looking at centre and operator volume requirements. What is your view about volume requirements?

There is a lot of evidence from other cardiac treatments that there is a strong relationship between activities and outcomes. However, often it is not differentiated between individual and institutional activities. As a co-author of the latest European guidelines on the management of valvular heart disease, I have addressed this issue when we defined heart centres and heart teams.

We focussed less on procedural numbers, as they are so variant between European countries, but defined clinical infrastructure, governance and working relationships. Key from our point of view is that cardiac surgery is on-site and involved in the interventional treatment of heart valve disease.

In both Europe and the USA, there is a strong emphasis on the need for a multidisciplinary heart team in structural heart interventions. Why is a cardiothoracic surgeon an important part of such a team?

Cardiothoracic surgeons have a tremendous experience with treatment of all kinds of valvular heart disease, not only aortic stenosis. They are also in the best position to determine the surgical risk of patients and to identify the

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I struggle to understand why during this age of globalisation—with all the resultant benefits for scientists—some countries fall back into nationalistic ideas.

most appropriate surgical technique in individual patients.

I strongly believe that if surgeons are aware of the outcomes of interventional techniques, if interventional cardiologists are aware of the outcomes of surgical techniques, and if they work as a functional team, this team is best placed to identify the most suitable treatment option for patients on an individualised basis.

You are the principal investigator of a CE mark trial of a transcatheter mitral valve implantation (TMVI) device.

When do you think we will see the first “TMVI” device come onto the market?

I had, as did many of my colleagues, expected a much faster progress with TMVI when it started. All current TMVI devices face the limitation that they can only be used in patients with a suitable anatomy. Therefore, recruitment of patients is challenging and it has become obvious that the optimal technology still

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Fact File

needs to be developed. At the moment, I think that it will take at least another four years until the first oneyear results of a TMVI US FDA or CE mark trial will be available.

You are a course co-director of PCR London Valves. What big developments in transcatheter heart valve therapies do you think the course will be discussing over the next few years?

We will certainly see more information on the outcome of TAVI in lower risk patients with aortic stenosis.

I also expect more data on transcatheter mitral and tricuspid valve repair devices such as edge-to-edge technology and valvuloplasty. We will also see more development of TMVI technology. However, how much this will change our view on this technology already this year remains to be seen.

Current appointments

Why is it valuable for physicians to become involved in helping to develop conferences such as PCR London Valves?

Medical training

Given that a substantial number of people, such as yourself, working for the NHS are EU nationals, are you concerned about the potential impact of Brexit on the NHS workforce?

Professional memberships and societies

Clinically active physicians know the day to day challenges cardiologists and surgeons face. Their experience enables them to create relevant educational sessions, so that clinically interesting questions can be discussed. Physicians are also crucial to facilitate discussions with the industry, which is particularly helpful when it comes to device development.

From my point of view, I struggle to understand why during this age of globalisation—with all the resultant benefits for scientists—some countries fall back into nationalistic ideas that may isolate them in the future.

However, I am personally not particularly concerned about myself in this respect. Given the large number of highly qualified European Union (EU) medical staff working in the NHS, the UK Government has already taken precautions to support EU nationals working in the NHS and to address future changes.

What was your most memorable case?

One of my most memorable cases was the patient in whom I implanted the spacer into the mitral valve.

Not only because he is a man the same age as me with a lovely character, but also because he was turned down for all established therapies and I could offer him something new and innovative—which finally worked out and turned his life back to normal.

Outside of medicine, what are your hobbies and interests?

I love sailing with my family, particularly in the Caribbean, and we enjoy hiking, mountain biking and skiing in the Alps when we visit our family barn in Austria.

2018–present: Chair of the Heart and Vascular Institute Cleveland Clinic London, London, UK 2016–present: Lead for Cardiothoracic Surgery, King’s Health Partners, London, UK 2004–present: Professor and consultant of Cardiac Surgery, King’s College Hospital, London, UK 1994–1997: Senior registrar, Department of Cardiac Surgery, Heart Centre Leipzig, Germany 1992–1994: Registrar, Department of Cardiology, Siloah Hannover Medical School, Hannover, Germany 1990–1992: House Officer Registrar, Department of Thoracic and Cardiovascular Surgery, Surgical Centre, Hannover Medical School, Hannover, Germany

Fellow of the Royal College of Surgeons of England Society of Cardiothoracic Surgeons of Britain and Ireland (Member of the Adult Cardiac Subcommittee 2014–2017) The Society of Thoracic Surgeons European Association for Cardiothoracic Surgery European Society for Cardiology (Nucleus member of the ESC working group on heart valve disease) German Society for Thoracic and Cardiovascular Surgery (Board Member 2003–2004) German Society for Cardiology Member of the Faculty University of the Saarland/Germany

Clinical innovation

2015: Performed the world’s first implantation of a spacer into a patient with heart failure and functional mitral regurgitation 2011: Performed the first transapical mitral valve implantation in a failing bioprosthesis in the UK, and performed the world’s first transapical TAVI procedure without predilatation in the native aortic valve 2007: Performed the first transapical TAVI in the UK 2006: Performed the world’s first surgical closure of an acute ventricular septal defect using an occluder device and started a pilot trial to evaluate this new technique

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BIBABriefings

TAVI is increasingly being used to treat lower-risk patients

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ata from the BIBA MedTech TAVI Monitor show an increase in the proportion of lower-risk patients undergoing transcatheter aortic valve implantation (TAVI) between Q2 2017 and Q2 2018 in Western Europe. In the second quarter (1 April to 30 June) of this

year, 3% of TAVI procedures were for low-risk patients. Furthermore, 24.5% of all procedures were for intermediate-risk patients (see Figure 1).

However, during the same period last year, only 0.8% and 21.3% of procedures, respectively, were for low- and intermediate-risk patients. At present,

Heart charity launches £30 million award for innovation in cardiovascular disease

The British Heart Foundation (BHF) has launched the “Big Beat Challenge”—a £30 million research award to support projects that identify a significant unmet need in cardiovascular disease or represent an opportunity for innovation in heart and circulatory science or medicine.

A press release reports that the £30 million award will be “one of the largest and most ambitious of its kind” and will provide a challenge to scientists,

Getting to the heart of the complex problems

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ortre Dame News reports that Pinar Zorlutuna (Department of Aerospace and Mechanical Engineering, University of Notre Dame, South Bend, USA) and colleagues are exploring the use of heart cells to create a computer algorithm for solving complex problems.

It adds that The National Science Foundation, in partnership with the Semiconductor Research Corp, is investing US$12 million in new research in the field of “synthetic biology” and that Zorlutuna et al’s project is one of eight that have received an exploratory grant as part of the programme.

According to the news report, the complex problems that heart cells could be used to help solve include managing the US electricity grid or allocating resources in the event of a disaster.

Zorlutuna says: “Cardiac cells are natural oscillators.

They beat spontaneously and, when coupled, they can synchronise to a locked, steady frequency. What we want to find out is if we create a network using these biooscillators, will their natural spatio-temporal dynamics be able to solve complex problems optimally, in less time and using less energy than silicon-based digital computing hardware?”

only the Sapien XT/Sapien 3 (Edwards Lifesciences) and CoreValve Evolut (Medtronic) devices have CE mark approval for use in intermediaterisk patients (they also have US FDA approval for this indication). Although studies of CoreValve and Sapien in low-risk patients are ongoing, neither

clinicians, innovators and entrepreneurs to look beyond incremental gains and accelerate breakthroughs that could transform lives across the globe.

According to the press release, proposals must be transformative, clinically relevant, and with a multidisciplinary approach that could not be achieved without funding on this scale. Furthermore, the “winning team” can come from any country, sector or discipline, working on a scale above and beyond traditional research schemes to achieve a breakthrough in any heart or circulatory disease.

Dream of disappearing device has not disappeared

D

espite the setback that Abbott has had with its bioresorbable vascular scaffold (Absorb), which was taken off all commercial markets last year following negative results (increased target lesion failure at three years vs. Abbott’s everolimus-eluting stent Xience), several companies are still pursuing the idea of a device that eventually biodegrades. At PCR Innovators Day (21 May, Paris, France), Hartlon, Elixir Medical, S-Bahn Medical and Japan Medical Device Technology all outlined their respective bioresorbable scaffolds.

Furthermore, during EuroPCR (22 May—25 May, Paris, France) itself, there was a late-breaking trial session on scaffolds—although, admittedly, most of the studies did focus on Absorb.

The idea of bioresorbable scaffolds are promising because, theoretically, they could overcome some of the limitations of drug-eluting stents. However, the ABSORB trials indicate that, in practice, scaffolds might not overcome these limitations and may have some of their own (i.e. a higher rate of device thrombosis). Time will tell if future generation of scaffolds are able to avoid the

device is currently approved for use in low-risk patients (nor is any other TAVI device).

Overall, the number of TAVI procedures being performed has increased quarter on quarter: from 11,681 in Q2 2017 to 15,152 in Q2 2018 (see Figure 2); an increase of 30%.

The BHF is assembling an international, multidisciplinary, expert advisory panel to oversee the Big Beat Challenge. A call for outline applications will open at the end of this year and close the middle of next year.

Shortlisted applications with the most promising ideas will be given seed funding, and teams will then have around six months to develop their final proposals. These full applications will then be peer-reviewed and the winning research programme recommended by the panel. For more information, see: bhf.org.uk/BigBeatChallenge.

pitfalls of Absorb (such as thick struts) and fulfil their initial promise.

BIBA Briefings

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

The aim of each report is to give an overview of the key information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions. BIBA Briefings cover both percutaneous coronary intervention (PCI) and TAVI. For more information about BIBA Briefings or BIBA MedTech, please contact Elizabeth Sutherst: elizabeth@bibamedical.com

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Protected TAVR™ with SENTINEL® gives you the power to reduce stroke.

The SENTINEL Cerebral Protection System (CPS) was able to capture and remove embolic debris in 99% of TAVR patients, regardless of valve type and patient risk profile.1 In the SENTINEL US IDE, neurologist adjudicated, peri-procedural (≤ 72 hours) stroke rate was reduced by 63% when SENTINEL CPS was used.1

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70%

5%

10%

All-stroke at 7 days

% of Patients

% of Patients

10%

Reduction P = 0.03

Rotterdam Erasmus Medical Center Neurological Events at 72 hrs

80%

5%

Reduction P ≤ 0.01

5.1%

4.6% 0%

1.4% SENTINEL CPS (N = 4/280)

0%

Without SENTINEL CPS (N = 13/280)

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1.0% SENTINEL CPS (N = 3/294)

Without SENTINEL CPS (N = 23/453)

SENTINEL Cerebral Protection System (CPS) INDICATIONS FOR USE: The Sentinel Cerebral Protection System is indicated for use as an embolic protection device to capture and remove thrombus/debris while performing transcatheter aortic valve replacement procedures. The diameters of the arteries at the site of filter placement should be between 9–15 mm for the brachiocephalic and 6.5–10 mm in the left common carotid. CONTRAINDICATIONS • Do not use in patients for whom anticoagulant and antiplatelet therapy is contraindicated. • Do not use in patients with a known hypersensitivity to nickel-titanium. • Do not use in vessels with excessive tortuosity. • Do not use in patients with uncorrected bleeding disorders. • Do not use in patients with compromised blood flow to the right upper extremity. • Do not use in patients who have arterial stenosis >70% in either the left common carotid artery or the brachiocephalic artery. • Do not use in patients whose brachiocephalic or left carotid artery reveals significant stenosis, ectasia, dissection, or aneurysm at the aortic ostium or within 3 cm of the aortic ostium. WARNINGS • Carefully read all instructions and labeling prior to use. Observe all warnings, cautions, and precautions noted throughout these instructions. Failure to do so may result in complications. • Refer to the instructions for use supplied with any interventional devices to be used in conjunction with the Sentinel System for their intended uses, sizing, warnings, and precautions. • The safety and effectiveness of the Sentinel System have not been demonstrated with transcatheter aortic valves other than the SAPIEN XT, SAPIEN 3, CoreValve® , and CoreValve® Evolut R®. • The appropriate antiplatelet/anticoagulation therapy should be administered pre- and post-procedure in accordance with standard medical practice. • Prior to use, the packaging and product should be inspected for signs of damage. Never use a damaged product or product from a damaged package. • Never advance or withdraw the Sentinel System without proper fluoroscopic guidance or against resistance until the cause is determined. Advancing with such resistance may lead to embolization of debris, and vessel and/or device damage. • It is recommended that the patency of the right radial or brachial artery be assessed prior to the introduction of the Sentinel System. • It is recommended that the patient be tested for occlusion of the radial or brachial artery prior to device introduction. • Do not use the device in left radial or left brachial access. • Do not use the Sentinel System to deliver any type of fluid to the patient e.g. contrast media, heparinized saline, etc. due to risk of air embolization and comprise to device performance. • Minimize movement of the Sentinel System after initial placement and stabilize the patient’s right arm by their side. Excessive movement of filters may lead to embolization of debris, vessel and/or device damage. • Do not deploy the filters within a previously repaired artery, an artery that has been used for dialysis purposes, or an AV fistula. • Observe the Sentinel System under fluoroscopy and monitor the patient to verify the filters have not become occluded with debris resulting in slow or no flow. The filters should be recovered if they become occluded or if flow is compromised (See Procedural Use – Retrieval). • Indwell time of the Sentinel System is not to exceed 90 minutes as occlusion could occur, resulting in slow or no flow. • Failure to adequately close off the Flush Ports (Front Handle, Rear Handle) may result in air embolism. • Do not undersize or oversize the filters in relation to the selected vessel diameter. This may result in inadequate vessel wall apposition or incomplete deployment of the filters. (Refer to Sizing Guide, Table 1 in IFU). • Do not apply excessive force to the Sentinel System. This may lead to distal embolization of debris, and vessel and/or device damage. PRECAUTIONS • Do not forcefully bend or reshape the Articulating Sheath of the Sentinel System. This may cause device damage. • A guidewire with excessive stiffness may alter the shape of the Articulating Sheath curve and make cannulation of the left common carotid difficult. • Use of a guidewire with an intermediate coil may result in compromised guidewire movement. • Improper bending of the Sentinel System may damage the catheter. • Do not re-sterilize or reuse on another vessel or patient. ADVERSE EVENTS Possible adverse events associated with Sentinel System use and application procedure include, but are not limited to, the following: • Access site complications • Angina • Aortic dissection • Arrhythmia • Arteriovenous fistula • Atelectasis • Bleeding, operative or post-operative • Cardiac Tamponade • Cardiogenic Shock • Conduction system injury • Congestive Heart Failure (CHF) • Death • Endocarditis • Embolism, including air • Gastrointestinal (GI) bleed • Hematoma • Ischemia (coronary, limb, carotid) • Infection (local or systemic) • Myocardial Infarction (MI) • Nerve injury • Pericardial effusion • Pneumonia • Pulmonary edema • Pulmonary embolism • Respiratory failure • Respiratory insufficiency • Stroke • Vessel injury (e.g., dissection, rupture, perforation, pseudoaneurysm) Adverse events experienced during clinical studies are presented in the Clinical Study Overview section of the Instructions For Use (IFU). Rx Only, CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician.

1. SENTINEL US IDE. Trial data presented at the Sentinel FDA Advisory Panel, February 23, 2017.

2. Seeger J, et al. JACC Cardiovasc Interv. 2017 Nov 27;10(22):2297-2303.

3. van Mieghem N, et al. presented at JIM 2018 and CRT 2018.

Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician. See www.claretmedical.com/ifu for the Indication, Contraindications, Warnings, and Precautions.

All trademarks are property of their respective owner. © 2018 Boston Scientific Corporation or its affiliates. All rights reserved. SH-565011-AA

22

Sept

Women in cardiology

Issue

18 51

Non-atherosclerotic spontaneous coronary artery dissection predominantly affects young to middleaged women Data from the Canadian Spontaneous Coronary Artery Disease (CanSCAD) study indicate that the majority of patients with non-atherosclerotic spontaneous coronary artery dissection are young to middle-aged women who present with myocardial infarction.

Furthermore, they indicate that, despite conservative therapy, 30-day survival is good but cardiovascular outcomes (such as recurrent myocardial infarction) can occur.

P

resenting the findings at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany), Jacqueline Saw (Vancouver General Hospital, Vancouver, Canada) said that the first case of spontaneous coronary artery dissection was reported in 1931 but the condition remained “poorly understood” and underdiagnosed”. She added that although “early myths”, such as it being a rare condition, had been debunked, “there remains uncertainties regarding management, predisposing/precipitating causes and outcomes”.

Therefore, the aim of the multicentre observational study was to describe the natural history of non-atherosclerotic spontaneous coronary artery disease, assess the in-hospital and long-term cardiovascular outcomes with the condition, and identify factors associated with these outcomes. Saw and colleagues prospectively enrolled patients if they had new acute non-atherosclerotic spontaneous coronary artery dissection that was documented on angiogram (confirmed by core laboratory). The investigators reviewed the patients’ baseline characteristics, coronary angiograms, in-hospital outcomes, and post discharge outcomes at one, six, 12, 24, and 36 months.

Of the 750 patients included in the analysis, the majority were women (88.5%) and most of these patients were postmenopausal. Overall, the mean age was 51.8±10.2 (age range 24–89 years) with nearly 10%

(9.2%) of patients aged over 65 years. Saw reported that most patients presented with myocardial infarction with 69.9% presenting with non-ST-segment elevation myocardial infarction (NSTEMI) and 29.7% presenting with STEMI; only 0.4% of patients had unstable angina.

“In terms of revascularisation therapy, conservative therapy was used in 84.3% of these patients, 1.5% received fibrinolysis, 14.1% underwent percutaneous coronary intervention (PCI), and 0.7% underwent coronary artery bypass grafting (CABG),” Saw told the ESC audience. She added that the main reasons for performing revascularisation included ongoing chest pain, ongoing ischaemia on ECG, or dissection causing severe stenosis.

Overall, the median rate of major adverse events (MAE) was 8.8% and the median hospital stay was four days. The 30-day rate of major adverse cardiac events (MACE) was also 8.8% with the majority of events occurring within 10 days of discharge. According to Saw, peripartum patients had a significantly higher rate of in-hospital MAE (20.6% vs. 8.2% for non-peripartum patients; p=0.023) and a significantly higher rate of in-hospital high-risk events (23.5% vs. 6.8%; p<0.003).

She said: “Indeed, peripartium status was an independent predictor of both in-hospital MAE and 30-day MACE as was connective tissue disorder.”

Saw concluded: “Spontaneous coronary artery dis-

Jacqueline Saw

section predominantly affected young to middle-aged women and presented with myocardial infarction.

Despite conservative therapy in the majority of patients, in-hospital and 30-day survival was good. However, significant cardiovascular events acrued within 30 days’ post event, including recurrent myocardial infarction, unplanned revascularisation, and stroke/transient ischaemic attack.” She added that as peripartium status and connective tissue disorder were both independent predictors of 30-day MACE, patients with these predictors should stay in hospital for longer than the four days that is typical for patients with spontaneous coronary artery dissection patients.

Saw told Cardiovascular News: “Spontaneous coronary artery dissection has been neglected for decades. It is important to have greater awareness for spontaneous coronary artery dissection as it is a major cause of myocardial infarction in young to middle-aged women. This disease is frequently missed and misdiagnosed.”

Higher rate of acute myocardial infarction during pregnancy linked to increase in older mothers A new study published in Mayo Clinical Proceedings indicates that the rate of acute myocardial infarction among pregnant women increased between 2002–2003 and 2012–2013 (7.1 per 100,000 hospitalisations vs.

9.5% per 100,000 hospitalisations; p<0.01 for trend) and this coincides with an increase in mean age at hospitalisation for labour and delivery.

T

he study also confirms previous findings that advanced maternal age is associated with a higher risk of acute myocardial infarction. Study author Sripal Bangalore (Leon H Charney Division of Cardiology, Department of Medicine, NYU School of Medicine, New York, USA) speaks to Cardiovascular News about the research.

Overall, what was the incidence of acute myocardial infarction among pregnant women?

The incidence was around eight cases per 100,000 hospitalisations.

Why was it important to evaluate the incidence of acute myocardial infarction among pregnant women?

Although the incidence is low, it is important to recognise that the in-hospital mortality in such women with acute myocardial infarction is about 5%. This figure is devastating, particularly given the baby’s life is also at risk.

may be different with a probable higher incidence of spontaneous coronary dissection (where management is less well defined).

If percutaneous coronary intervention with drug-eluting stents is performed, what needs to be considered when prescribing dual antiplatelet therapy?

Why do you think the incidence of acute myocardial infarction has increased over time?

This may be due to the fact that more and more women are becoming pregnant at a later age (i.e. 30s and 40s vs. 20s). Additionally, more women with risk factors for myocardial infarction are becoming pregnant.

Why is there a link between increased maternal age and increased risk of acute myocardial infarction?

Older age during pregnancy may be associated with many of the traditional risk factors for heart disease, such as hypertension, diabetes, and dyslipidaemia. Also, the physiological stress of pregnancy may have a greater impact on older women than in younger woman.

How did the mortality rates compare with non-pregnant acute myocardial infarction patients.

We did not directly compare mortality rates in pregnant women with an acute myocar-

Sripal Bangalore

dial infarction vs. those in non-pregnant people with an acute myocardial infarction. However, in terms of the age groups we are referring to in our study, the rate of mortality associated with acute myocardial infarction was higher than that seen in nonpregnant individuals (in other studies).

How should acute myocardial infarction be managed in pregnancy?

Recognition of myocardial infarction is the first and most important step. There are challenges in the management of acute myocardial infarction in this cohort given the issues with bleeding associated with anticoagulation. Moreover, the pathophysiology of acute myocardial infarction

The risk of bleeding immediately after childbirth should be considered—particularly as the safety of DAPT in lactating women is not known.

What steps can be taken to reduce the risk of acute myocardial infarction in pregnant women?

The key steps are to increase awareness among pregnant women about the risk of myocardial infarction and the need to control risk factors (such as diabetes, hypertension, and hyperlipidaemia) in those who have them. Also, a multidisciplinary approach between a cardiologist and obstetrician is needed for pregnant women who present with an acute myocardial infarction.

Further studies are needed to better define risks, management strategies, and treatment options.

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24

Sept

Patient care

Issue

18 51

“Communication is key” when managing patients who seek discharge against medical advice Chun Shing Kwok (Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK) and others report in JACC: Cardiovascular Interventions that only 0.5% of percutaneous coronary intervention (PCI) patients discharge themselves against medical advice (DAMA). However, they note that the risk of readmission at 30 days is significantly increased in such patients and, therefore, interventions are needed to prevent DAMA in high-risk groups. Study author Mamas A Mamas (Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK) speaks to Cardiovascular News about the findings. as being an inpatient in hospital may prevent them from doing so.

How can the risk of DAMA be reduced in such patients?

Early engagement with the substance abuse team may prevent DAMA, for example, through prescription of methadone during their inpatient stay. Early engagement with mental health services/ psychiatrists may again reduce risk of patients with mental health problems absconding.

Mamas A Mamas

Given that DAMA is an infrequent event in the general patient population, why was it important to evaluate its incidence in patients who have undergone PCI? In a previous study, we observed that DAMA was one of the strongest predictors of unplanned readmissions following PCI. However, prior to the present study, we did not have any literature about DAMA, including its predictors or clinical outcomes, in the PCI setting. From a theoretical standpoint, DAMA may carry quite a poor prognosis—particularly if patients self-discharged prior to receiving dual antiplatelet therapy (DAPT) as they would be at very high risk of stent thrombosis.

In your study, smoking and drug abuse were important predictors of DAMA. Why do you think this is?

Patients with drug abuse problems will also often have a personal history of mental health problems, which is known to predispose to DAMA. Patients with a history of drug abuse may also DAMA in order to use abuse drugs illicitly,

What impact do you think monetary concerns—either because of cost of further treatment or money lost due to not earning—have on the risk of DAMA?

I believe that monetary concerns are very relevant; patients with the lowest income have the highest risk of DAMA.

The risk of 30-day readmission was significantly increased among DAMA. What were the key reasons for this readmission?

The greatest differences between the causes of readmissions for those who discharged themselves before medically recommended and those who did not were seen in the rates of acute myocardial infarction and psychiatric illnesses.

Of those with unplanned readmission at 30 days, DAMA patients were four times more likely to have a neuropsychiatric reason for being readmitted. Such patients often have a history of mental health disorders, so this increased rate of psychiatric disorders is not surprising.

However, twice as many DAMA patients had acute myocardial infarction as the cause of readmission compared

with non-DAMA patients. This is an important finding as it may mean that they discharged themselves prior to receiving DAPT; if there are no mechanisms to get DAPT to them in the community, they will be at high risk of developing stent thrombosis.

Furthermore, the dataset did not capture post-discharge mortality. Therefore, it is entirely possible that patients developed a stent thrombosis and died in the community; as a result, they would not have been picked up by the dataset as a “readmission”.

If a patient wants to be discharged before medically recommended, what can be done to encourage them to stay in hospital?

Communication is key. Understanding their motivation as to why they want to self-discharge may identify the core underlying issues. It is important to communicate to the patient why they are required to remain in hospital and why discharging themselves may increase risks to their health. It is often very useful to get family members on side to support the medical team in continuing the care of their family member.

If a patient cannot be persuaded to stay in hospital, what steps can be taken to reduce their risk of readmission?

The key here is prescription of DAPT and other cardiac medications. Ensuring that patients are given a supply of cardiac medications, either from the hospital or from community pharmacists, is vital. Early engagement with their primary care provider is also important. Often patients can be identified as being at high risk for DAMA,

which may expalin why bare metal stents was used at much higher rates than were drug-eluting stents in the DAMA cohort in our study. So for high risk groups, interventionalists should consider using platforms that only require short DAPT regimens. I think for high-risk DAMA groups, or those patients that are unlikely to adhere to DAPT regimens, it is important to consider the need for PCI. While there tends to be fewer options for patients with acute coronary syndromes (i.e.

PCI is usually necessary), if PCI is not going to provide a prognostic benefit, optimal management should be carefully considered in patients with stable angina (i.e. whether medical management may be a better option for them)

If patient has severe dementia or severe mental health issues (i.e. not capable of making their own decisions), what steps could be taken to make them stay in hospital?

Again, I think that as interventionalists we have to consider whether we should be offering PCI to such challenging patients. Full discussion with family members regarding the need for adherence to DAPT regimens should take place up front and only after this should decisions be taken as to whether PCI would be appropriate in such cases.

What further research in this area is needed?

I think it is important to understand why patients choose to self-discharge post PCI. It is also important to study post discharge outcomes. Our analysis tells us what happens when they are readmitted. What we do not know is how big the black hole is between self-discharge and readmission—many of these patients may not survive their stent thrombosis/cardiac event to be readmitted. I think that this is important and only through such follow-up information will we know the true prognostic impact of DAMA.

Subcutaneous injection of nitroglycerin may be a safe, effective, and economic approach to reducing risk of radial arterial occlusion Yequn Chen (Department of Cardiology, First Affiliated Hospital of Shatou University Medical College, China) and others report in Circulation: Cardiovascular Interventions that subcutaneous injection of nitroglycerin at the radial puncture site in patients undergoing transradial coronary intervention is associated with a significant reduction in radial artery occlusion.

T

he authors comment that comment that while the transradial approach is increasingly preferred over the transfemoral approach in patients undergoing coronary interventions because it is associated with less bleeding, 2.8–11.7% of patients who undergo the transradial approach develop radial artery occlusion “which persists for >1 month in about 60% of these patients”.

Chen et al decided to review the potential of nitroglycerin to reduce the risk of radial artery occlusion because it has been shown to dilate the radial artery without effecting blood pressure. It also been show to prevent radial artery spasm and “act as a nitric oxide donor” (which, in turn, has been show to inhibit vascular thrombosis in a pig model).

In the study, 188 patients were randomised to

receive subcutaneous injection of nitroglycerin (94) when undergoing transradial coronary intervention or receive subcutaneous injection of placebo (94). In the group that received nitroglycerin, radial artery diameter was significantly increased compared with baseline levels (2.48±0.45 vs. 2.45±0.46mm; p=0.003); in the placebo group, radial artery diameter was significantly decreased (2.46±0.49 at baseline vs. 2.41±0.5mm after the procedure; p<0.001). The authors report: “Importantly, the incidence of radial artery occlusion (within 24 hours) was substantially lower in the nitroglycerin-treated group than in the placebo group (5.4% vs. 14.4%; p=0.04)”.

Sept

Issue

Cardiac rhythm management

18 51

25

Re-evaluate use of anticoagulation in patients with atrial flutter A new study, published in JAMA Network Open, indicates that patients with atrial flutter have a lower incidence of stroke than patients with atrial fibrillation who have the same CHA2DS2-VASc score. Given current European guidelines advise that patients with atrial flutter receive the same management, in terms of reducing the risk of stroke, this finding has implications for the use of anticoagulation in patients with atrial flutter—i.e. whether anticoagulation should be prescribed at the same level of CHA2DS2-VASc score as for patients with atrial fibrillation.

A

uthors Yu-Sheng Lin (Division of Cardiology, Depart of Internal Medicine, Chang Gung Memorial Hospital, Chiay, Taiwan) and others report that atrial flutter is similar to atrial fibrillation “in that its incidence increases with age and it contributes to heart failure, stroke, and all-cause mortality”. As result of this, they add, “the pharmacological management of atrial flutter is usually considered to be the same as for atrial fibrillation, especially preventing thromboembolic events”. However, Lin et al note that, despite sharing common risk factors, atrial flutter and atrial fibrillation are associated with different clinical outcomes.

Using data from the Taiwan National Hospital Insurance Research Database, Lin et al identified 219,416 age- and sex-matched individuals. Of these, 188,811 had atrial fibrillation, 6,121 had atrial flutter, and 24,484 had neither (the control group).

Overall, the incidence densities (events per 100 person years) of ischaemic stroke were significantly greater in the atrial fibrillation group compared with the atrial flutter and control groups. Furthermore, while increasing CHA2DS2-VASc score was associated with increasing incidence densities of ischaemic stroke in all three groups, the incidence of stroke associated with a specific level of CHA2DS2-VASc score differed depending on whether the patient had atrial fibrillation or atrial flutter. The authors comment: “The incidence densities of ischaemic stroke at a CHA2DS2-VASc

Yu-Sheng Lin

score of one in the atrial fibrillation cohort was similar to that at a CHA2DS2-VASc score of two in the atrial flutter cohort. Moreover, the incidence densities of ischaemic stroke at a CHA2DS2-VASc score of two in the atrial fibrillation cohort was similar to that at a CHA2DS2-VASc score of four in the atrial flutter group.”

At all levels of CHA2DS2-VASc score, the incidence densities of ischaemic stroke were significantly greater in the atrial fibrillation group compared with the control group but they were only significantly higher in the atrial flutter group (vs. the control group)

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at CHA2DS2-VASc scores five to nine. Apart from CHA2DS2-VASc score zero, the incidence densities of ischaemic stroke were significantly higher in the atrial fibrillation group vs. the atrial flutter group at all score levels.

Lin et al comment that current European guidelines recommend that anticoagulation is prescribed at CHA2DS2-VASc score two or higher (and considered in those with a score of one) in both patients with atrial flutter and those with atrial fibrillation.

Lin told Cardiovascular News: “From this nationwide cohort study, using data from Taiwan’s National Health Insurance Research Database, we found that the incidences of ischaemic stroke in patients with atrial flutter and atrial fibrillation at the same level of CHA2DS2-VASc score were different. During study analysis, we found that 8–10% patients with isolated atrial flutter received anticoagulation therapy and this figure was lower than that in patients with atrial fibrillation. Such prescription behaviour of physicians in clinical practice could be attributed to the belief of low incidence of ischaemic stroke in patients with atrial flutter compared to those with atrial fibrillation.

In fact, according to our findings, this phenomenon make sense. Therefore, our study suggests that further research should be performed to re-evaluate the net clinical benefit of oral anticoagulants in patients with atrial flutter as currently recommended according to level of the CHA2DS2-VASc score.”

Sept

Issue

Research

18 51

26

Female acute myocardial infarction patients experience worse outcomes when treated by male physicians Brad N Greenwood (Carlson School of Management, University of Minnesota-Twin Cities, Minneapolis, USA) and others report in Proceedings of the National Academy Sciences of the United States of America that female patients with acute myocardial infarction who are treated by a male physician have worse outcomes than female patients who are treated by female physicians. They add that this finding may be one explanation for why women historically have worse outcomes than men after a myocardial infarction.

T

he authors comment that, in the medical setting, “gender discordance”—when a physician treats a patient of a different gender to themselves—has been shown to result in lower rapport and patient satisfaction, reduced adherence to preventative care protocols, and weaker patient-physician communications. They add that, given that women are less likely to survive an acute myocardial infarction and that female physicians tend to outperform their male counterparts, “we posit that gender discordance between physician and patients helps to explain why female patients are less likely to survive acute myocardial infarctions”.

To explore this hypothesis, they reviewed outcome data for 581,79 patients admitted emergency departments (with an acute myocardial infarction) in Florida between 1990 and 2010. Greenwood et al comment: “Our decision to focus on emergency department admittances was deliberate, because it creates a discrete interaction between a patient and the attending physicians, allowing for a clear and immediate measure of success. In addition, when patients visit the emergency room, they have little agency over their choice of attending physician, allowing for a quasirandom assignment of physician and patient.”

Overall, the baseline mortality rate was 11.9% but this differed depending on the gender of the patient or physician. The

authors report: “Female patients treated by male physicians were 1.52% less likely to survive than male patients treated by male physicians. This represents an about 12% decrease off the baseline mortality rate.” Furthermore, according to an unmatched sample, patients of any gender were more likely to survive when treated by a female physician. However, Greenwood et al state they also found that “male physicians are more effective at treating female acute myocardial infarction patients when they work with more female colleagues and when they have treated more female patients in the past”.

The authors claim that their results “suggest a reason why gender inequality in heart attack mortality persists”, noting “most physicians are male and male physicians appear to have trouble treating female patients”. As a potential solution to this issue, they recommend increasing the presence of female physicians within the emergency departments given the potential cost of the alternative—“male physicians learning on the job”—to female patients. Greenwood et al explain that mortality may decrease as male physicians treat more female patients but this “comes at the expense of earlier female patients”. They add their study “underscores the need to update the training that physicians receive to ensure that heart disease is not simply cast as a ‘male’ condition.”

Further research, the authors say, could focus on the “role played by residents, nurses, and other physicians who may be present or provide information to the supervising physicians”.

Greenwood told Cardiovascular News: “I think this study calls attention to the issue that the medical community has been grappling with, and making strides on, for a while: differences in patient presentation and making sure all patients get the care they need. I think what is critical to emphasise is the importance of understanding the diversity of the patient community and ensuring that the physician pool is diverse as well. The mechanism is particularly tricky in this setting, and we need to be careful here. Since it is

a secondary data study, pinning down the exact mechanism is hard. There are several possible explanations. For example, gender concordance often facilitates communication between the patient and the physician, meaning that men might not be getting the signals they need from female patients. Alternatively, women may feel more comfortable advocating for themselves with a female physician. Further, since heart disease is often cast as ‘male’ condition, male physicians might not pick up on the atypical presentation symptoms women more often show (or at least not to the degree that female physicians do).

But, like I mentioned, these are speculative and we need deeper work to dive in and figure out what is going on.”

Invasive strategy provides better outcomes for very elderly patients with NSTEACS A study in EuroIntervention indicates that very elderly patients—mean age 84.3 years— with non-ST-segment elevation acute coronary syndromes (NSTEACS) who undergo invasive therapy have a lower rate of cardiac events compared with those who undergo a conservative approach. Additionally, the association between the rate of cardiac events and type of therapy was different according to the frailty status of the patient.

Cardiovascular News spoke to study author Albert Ariza-Solé (Hospital Universitario de Bellvitge, Barcelona, Spain) about the findings.

Prior to your study, what evidence was available for the management of NSTEACS in frail elderly patients?

Evidence regarding this topic is scarce, since frail elderly patients are often excluded from clinical trials. There are three recent clinical trials addressing the role of an invasive strategy in elderly patients with NSTEACS and they show conflicting results. However, information about frailty and other components of a geriatric evaluation were not available in these studies, so it is difficult to know how those patients were selected.

Therefore, we believe that our study provides novel and interesting data about the potential impact of an invasive strategy in very elderly patients with NSTEACS according to their frailty status.

Do you think perceived old age/frailty dissuades people from performing invasive interventions in elderly patients?

Yes, absolutely! Registries consistently show a strong association between the degree of frailty and a lower likelihood of undergoing an invasive strategy during admission.

In your study, how did you assess frailty?

We used a very quick and easy to tool to assess frailty in the acute setting—the FRAIL scale. It is a five-item interview based evaluation that can be easily performed in less than one minute.

What were the key findings of your study?

In our opinion, the most important finding from our study is that an invasive strategy during the admission was associated with a lower incidence of reinfarction, need for coronary revascularisation or cardiac mortality at six months in this cohort of unselected very elderly patients with NSEACS from routine clinical practice. Additionally, the benefit of an invasive strategy was different according frailty status—suggesting a lower impact on outcomes in elderly patients with stablished frailty criteria.

How did they differ?

While an invasive strategy during the admission was associated with a significantly lower incidence of the primary outcome in the whole cohort, this association was not significant in patients with established frailty.

Based on the available evidence, which elderly NSTEACS patients would benefit the most from an invasive strategy?

We believe that, taking into account these data, most robust or “prefrail” elderly patients with NSTEACS should undergo an invasive strategy. In contrast, patients with established frailty criteria and disability should undergo an individualised approach.

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The “absolute priority” is to develop onco-cardiology guidelines to help clinicians In a “Call to action”, published in the Journal of American College of Cardiology, Tochi M Okwuosa (Division of Cardiology, Rush University Medical Center, Chicago, USA) and others outline the challenges of “cardio-oncology”, including whether “onco-cardiology” is a more accurate term. Okwuosa talks to Cardiovascular News about the issues discussed in the paper.

What is “cardio-oncology”?

It is the study, prevention and treatment/management of cardiovascular diseases resulting from cancer and/or cancer therapy.

Why is there a need for “cardiooncology”?

Cardiovascular disease is the number one cause of death in the USA; cancer is a very close second.

Therefore, when cancer patients have cardiovascular disease, it is a combination that could lead to significant morbidity and mortality.

Also, cancer patients are living longer as a result of progress in cancer therapies; and after secondary malignancy, cardiovascular disease is the major cause of death in cancer patients and survivors. Furthermore, some of the chemotherapeutic drugs, radiation therapies, and even newer targeted therapies that help patients become cancer-free can cause significant cardiovascular toxicities that could sometimes last a lifetime; in some cases, they can lead to significant cardiovascular morbidity and death. There are many cardiovascular problems linked with cancer therapies, such as arrhythmias, coronary artery disease, myocardial infarction, heart failure, hypertension/hypotension, autonomic dysfunction, valvular heart disease, pericardial diseases, and so on.

Cancer therapies may also cause or exacerbate certain cardiovascular risk factors (e.g. tyrosine-kinaseinhibitor-induced significant hypertension). Because the risk of heart disease from cancer treatment can last a lifetime, and cancer therapy is necessary for those that have the diagnosis, proper peri- and post-treatment monitoring is essential for cancer patients and survivors.

Why might “onco-cardiologist” be a better name than “cardiooncologist”?

While a cardio-oncologist signifies an oncologist involved in care of cardiac patients (one might imagine an oncologist specialising in cardiac cancers); the name “onco-cardiologist” better defines the subspecialty in question—usually a cardiologist dedicated to

managing cancer patients with heart disease.

What are the challenges of being a cardiologist who practises as an “onco-cardiologist”?

There are various challenges to this subspecialty as detailed in our paper, mostly related to being caught in between two different and important medical subspecialties with somewhat different priorities and patientcare focus. Additionally, the novelty of the field with current limited recognition presents its own challenges dealing with billing and training/education.

If working as a onco-cardiologist, what are the difficulties of linking up with colleagues working in the same field?

The difficulty lies in the fact that there are few (but it is growing) practising in this field of medicine. That being said, we now have cardio-onco networks through social media; and we also have newly-established national cardio-onco conferences/meetings in which onco-cardiologists can talk and exchange ideas. Hopefully, we are connecting better.

When treating a cancer patient (or a patient with a history of cancer), what are the specific considerations?

The type and prognosis of the cancer.

This includes whether it is metastatic or not; the agent and sort of treatment being used for the cancer (the need for chemotherapy, targeted therapy, surgery and/or radiation); cardiovascular comorbid conditions that might affect treatment; prior therapies for prior cancers that could also portend present or future cardiovascular consequences; and drug interactions between cancer and cardiovascular drugs.

All of these factors may affect planned cardiovascular procedures such as transoesophageal echocardiogram (TOE) or car-

diac catheterisation with possibly percutaneous coronary intervention (PCI).

Given the lack of guidelines in this area, what are the priorities for developing guidelines?

The absolute priority is to help guide clinicians. The American College of Cardiology (ACC) is working on this, and we are also trying to get the American Heart Association (AHA) involved. The challenge in doing this lies in the myriad of treatment modalities for very many different types of cancers affecting various organ systems.

What are the key priorities for research in this area?

Risk prediction of those at risk for cardiovascular morbidity/mortality for certain cancer therapies—that would also depend on the type of cancer/cancer therapy, effective cardiovascular prevention and management strategies of cardiovascular complications of these treatments.

What do you hope the take-home messages of your call to action will be?

The demand for the onco-cardiologist will only increase as expanding treatment options for cancer patients are leading to more cures and longer survival measured in years. As the growing population of cancer survivors age, the cardiac side-effects of therapy can be expected to compile with common comorbidities. We hope a call to action would entail coalitions to help develop guidelines to aid clinicians in the practice; set up protocols for education and formalised training for trainees; engage trainee interest in this important subspecialty; inform physician groups and academic centres on the importance of this subspecialty to instill willingness to invest resources to better care for these patients; enlighten insurance companies and health management systems on the nuances of the field to allow for easier coding and billing in order to better test and manage patients and cancer survivors with cardiovascular concerns secondary to cancer/cancer therapies; and encourage a focus on patient education and empowerment for improved cardiovascular health as cancer survivors.

Tochi M Okwuosa

No difference in MACE between drugcoated balloons and drug-eluting stents for de novo lesions in small vessels

The 12-month results of the BASKET-SMALL 2 study, which was presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany), indicate that use of a drugcoated balloon (SeQuent Please, B Braun) to treat de novo lesions in small vessels is associated with a similar rate of major adverse cardiac events (MACE) as contemporary drug-eluting stents.

I

n the study, 758 patients with de novo lesions in small vessels (≤3mm) were randomised to undergo percutaneous coronary intervention (PCI) with a drug-coated balloon or a second-generation drug-eluting stent. The primary endpoint was the rate of MACE at one year; the rate of the primary endpoint was 7.6% for the drug-coated balloon group vs. 7.5%

for the drug-eluting stent group (a nonsignificant difference).

Simultaneous to its ESC presentation, BASKET-SMALL 2 was published in the Lancet. Study author Bruno Scheller (Clinical and Experimental Interventional Cardiology, University of Saarland, Homburg/Saar, Germany) comments: “There was no acute and subacute vessel occlusions in

the drug-coated balloon group, proving the safety of the standalone drugcoated balloon procedure, provided the lesion is carefully prepared. After one year, ‘drug-coated balloon’ only has the same event rate as modern drug-eluting stents, which so far has been regarded as the standard of care for this indication. Additionally, the absence of a permanent implant

may provide a long-term benefit of drug-coated balloon therapy compared with stent implantation, which will be investigated in the long-term observation of the study.”

Gerd Wacker, senior vice president of B Braun Vascular Systems, comments: “With the new clinical evidence, SeQuent Please can be considered as a reasonable ‘implant free’ alternative to drug-eluting stents for a good number of patients with coronary artery disease.”

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Sept

Market watch

Product News Bayer announces new licensed indication for use of Xarelto in patients with coronary artery disease

Siemens Healthineers seeks to help healthcare providers by making it easier to take advantage of the unique diagnostic information provided by cardiovascular MRI. Xarelto, co-administered with aspirin, is indicated in the The first Magnetom Sola Cardiovascular Edition European Union (EU) for the prevention of atherowill be installed at the Marienhospital Gelsenkirchen, thrombotic events in adult patients with coronary artery Germany, in the coming months. Christoph Jensen (head disease at high risk of ischaemic events. of Cardiology, Marienhospital Gelsenkirchen, Germany) The European Commission (EC) has says: “That is why it is important for us to approved a combination of have a faster and high-quality cardiac Xarelto (rivaroxaban) 2.5mg imaging system that will reliably deliver twice daily plus low dose the information we need to assist our aspirin once daily for the decision-making.” prevention of atherothromPhilipp Fischer, general manager botic events in adult patients Cardiology at Siemens Healthineers, with coronary artery disease says: “We think there is huge potential at high risk of ischaemic in incorporating cardiovascular MRI in clinical Xarelto events. treatment pathways and making a significant differThe EU approval is based on data from the COMence to patient care. Magnetom Sola Cardiovascular PASS study, the largest phase III study with rivaroxaban Edition incorporates our very latest technologies with (27,395 patients), which showed that the rivaroxaban the specific aim of providing the maximum diagnostic vascular dose, 2.5mg twice daily, plus aspirin 100mg information in cardiovascular examinations. This leads once daily reduced the risk of the composite of stroke, to faster, more reliable, and definitive diagnoses for a cardiovascular death and heart attack by 24% (relative larger number of patients with underlying ischaemic, risk reduction) compared with aspirin 100mg once daily structural, and arrhythmogenic conditions. This in turn alone in patients with coronary artery disease and/or enables us to deliver vital outcome-related information peripheral arterial disease. for therapy decisions and thereby optimise patient treatDerek Connolly, consultant interventional cardioloment pathways. The patient benefits from fast access to gist at Birmingham City Hospital, (Birmingham, UK) the right treatment, avoiding the need for unnecessary and COMPASS trial investigator comments: “Cardioexaminations or procedures. Not only can this reduce vascular diseases are one of the leading causes of death cost, it may also improve the treatment outcome, which in the UK, and coronary artery disease and peripheral is in the interests of both the patient and the healthcare artery disease represent a major public health burden— provider.” despite many advances in the area of cardiovascular Christoph Zindel, senior vice president and general care, coronary artery disease and peripheral arterial manager Magnetic Resonance at Siemens Healthineers, disease have remained an area of unmet need. Even with notes: “Magnetom Sola Cardiovascular Edition reprecurrently available treatments for secondary prevention, sents a further milestone in the systematic development patients remain at an unacceptably high risk of thromof MRI for cardiovascular diagnostics and treatment. Its botic events which can lead to disability, loss of limb innovative applications can cut examination times down and death. This was the biggest study of rivaroxaban to to 20 minutes and clarify a broad range of clinical quesdate, and now that it is licensed for these conditions, it tions in cardiology. The many options it offers in tissue provides UK clinicians with a new option for treating characterisation make Cardiovascular MRI an essential coronary artery disease and peripheral arterial disease.” element on the path to precision medicine. This is why Lars Bruening, CEO Bayer UK & Ireland, says: “The we, as market leader in MRI, developed this edition.” story and momentum behind the COMPASS data continues to grow—from the study being stopped one year CE mark and US FDA approval for early for overwhelming efficacy, the presentation of the RadialSeal introducer kit results themselves at the European Society of CardiolInteger Holdings has received US FDA and CE mark apogy congress last year, and now to this exciting news proval for its new radial access introducer, RadialSeal. from the European Commission. Ten years ago this OcAccording to a press release, the RadialSeal introducer tober saw Bayer just starting out on the Xarelto journey kit is founded on Integer’s core technology platforms with the first indication in orthopaedics—and this year in guidewires and haemostatic introducers. The press we welcome our eighth indication for the management release states that the kit further strengthens its portfolio of patients with coronary artery disease and peripheral of high quality access products available for distribuarterial disease in the UK. It is especially exciting to see tion by medical device companies in the interventional the continuing impact that Xarelto will have on patients cardiology and peripheral vascular space. with peripheral arterial disease, most of whom have Payman Khales, president of Integer’s cardiovascuconcurrent coronary artery disease, as it has been many lar division, says: “RadialSeal was designed with two years since a new medical therapy has been proven in performance goals in mind: optimal treatment flexibility this high risk patient population.” provided by a thin walled sheath design that minimises Following the licence approval across Europe, the outer diameter while maximising inner diameter, and new indication will be submitted to the National Inease of sheath insertion through smooth transitions stitute for Health and Care Excellence (NICE) and the and hydrophilic coating. Given the currently limited Scottish Medicines Consortium (SMC) for review for number of viable offerings in the thin-wall introducer routine reimbursement across the UK. segment of the growing radial access market, RadialSeal addresses the needs of medical device manufacturers Siemens Healthineers showcase seeking to strengthen their product portfolios with high Magnetom Sola Cardiovascular Edition quality and innovative access devices.”

At the 2018 European Society of Cardiology (ESC) Andrew Senn, vice president of product solutions, Congress (25–29 August, Munich, Germany), Siemens notes: “We set out to build upon our proven haemostatic Healthineers launched Magnetom Sola Cardiovascuintroducer and guidewire technologies to develop a lar Edition—a 1.5 Tesla magnetic resonance imaging robust radial introducer portfolio ranging from 4Fr to (MRI) scanner that is specifically designed for car6Fr to address the needs of the interventional cardiolodiovascular examinations. A press release reports that gists,” said. “The thin wall sheath design increases ra-

Issue

18 51 dial access options, especially for patients with smaller arteries, while the smooth transitions and tip, combined with a hydrophilic coating, lessen friction to potentially reduce the risk for vessel trauma and spasm.”

Infraredx launches Makoto intravascular imaging system and Dualpro IVUS+NIRS catheter in Japan Infraredx has announced the Makoto intravascular imaging system, and accompanying Dualpro intravascular ultrasound and near-infrared spectroscopy (IVUS+NIRS) catheter, is now available in Japan. The launch follows a Spring 2018 limited market release, which included more than 10 hospitals in Japan.

A press release states that the Makoto intravascular imaging system and Dualpro catheter is the only technology on the market to identify vessel structure and plaque composition using IVUS+NIRS. Its launch follows market approval from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) in August 2017.

Dualpro is the only imaging catheter on the market equipped with extended bandwidth IVUS technology.

By emitting and carefully processing a broad band of frequencies, the Dualpro IVUS is designed to provide the best-in-class image resolution without compromising depth of field. Data collected from the NIRS technology are translated into a Chemogram, which the press release describes as an easy-to-interpret, colourcoded map to identify lipid core plaque (LCP) that can help distinguish between stable plaque and dangerous LCP. Coupled together, IVUS+NIRS aims to give cardiologists with unparalleled insights into the role LCP plays in heart disease.

There are several global landmark studies—including the Lipid-Rich Plaque (LRP) study, currently underway—which underscore the importance of identifying LCP for the prediction, and ultimately prevention, of serious heart attacks. Results of the prospective, multicentre LRP study, along with a US market launch of the Makoto imaging system and Dualpro IVUS+NIRS catheter, are anticipated in 2H 2018. The technology is currently the only FDA-cleared dual-modality catheter and imaging system indicated for the detection of LCP. Takashi Kubo (Wakayama Medical University, Wakayama, Japan), says: “In Japan, we rely heavily on intravascular imaging during percutaneous coronary intervention; so much so that is has become the standard of care, with approximately 90% of angioplasty procedures employing intravascular imaging. The Makoto imaging system and Dualpro catheter is the next generation of imaging technology, providing superior deliverability and lesion crossing ability as well as best-in-class image resolution to easily identify the degree of stenosis and plaque burden.”

Jason Bottiglieri, president and CEO, says: “Infraredx is proud to announce the release of the Makoto intravascular imaging system and Dualpro IVUS+NIRS catheter in Japan, the world’s largest imaging market.

IVUS+NIRS technology has the potential to dramatically change the field of interventional cardiology. Two unique modalities in one catheter provide cardiologists twice the information of other imaging catheters, helping to inform personalised treatment decisions. We thank our parent company Nipro for its significant role in advancing our commitment to the diagnosis and management of coronary artery disease.”

Makoto

32nd EACTS Annual Meeting

Milan, Italy

18-20 October 2018

To find out more or to register for the event visit:

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Raising Standards Through Education and Training

Fundamentals in Cardiac Surgery: Part III

Surgical Management of Valve Disease in Children

1-5 October, Windsor, UK

21-22 October, Bergamo, Italy

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Congenital Heart Disease

1-3 November, Berlin, Germany

13-16 November, Windsor, UK

Professional Leadership

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26-27 November, Windsor, UK

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Raising Standards Through Education and Training

www.eacts.org/educational-events/programme

32

Sept

Studies

Clinical News Twenty thousand patients have now been treated with RenalGuard therapy

RenalGuard Solutions has announced the treatment of 20,000 patients with RenalGuard for the prevention of contrast-induced nephropathy. A press release reports that the system, which is currently used in Europe and other countries that recognise the CE mark, is designed to reduce the incidence of contrast-induced nephropathy found in the millions of at-risk patients undergoing cardiovascular imaging procedures by managing real-time fluid balance in conjunction with interventional procedures involving contrast media.

The press release adds that a number of studies have demonstrated RenalGuard’s ability to protect patients from AKI following catheterisation procedures when compared to the standard of care.

Bjoern Andrew Remppis (Herz- und Gefässzentrum, Bad Bevensen, Germany) says: “Our hospital has treated over 700 patients with RenalGuard Therapy, and has established a pathway to ensure patients with chronic kidney disease are identified and receive appropriate treatment. In many cases, patients display a broad range of diuretic efficiency and fluid balance within hours. Our institution is happy to have an option for patients that circumvents contrast media, which are associated with worsening kidney function. We will continue to look to RenalGuard as an important therapy in the field of cardio-renal medicine and are intrigued at the potential of this valuable tool for automated negative volume management in heart failure patients.”

Jim Dillon, CEO, RenalGuard Solutions notes: “We are very pleased by the positive response in the medical community in Europe towards the use of RenalGuard in high-risk patients undergoing cardiovascular procedures.

This is a huge milestone for the product, the company, and our patients.”

RenalGuard Solutions demonstrated RenalGuard Therapy at the 2018 annual meeting of the European Society of Cardiology (ESC; 25–29 August, Munich, Germany; Booth G400) and at the 2018

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Transcatheter Cardiovascular Therapeutics (TCT) meeting (21–25 September, San Diego, USA; Booth 823)

Enrolment in FAST-FFR trial completed early

CathWorks has announced that its FAST-FFR trial is fully enrolled ahead of schedule. The trial is designed to evaluate efficacy of the CathWorks FFRangio system in terms of sensitivity and specificity when compared to conventional invasive fractional flow Reserve (FFR). Enrolment in the trial began on 27 September 2017 and enrolment of all 382 patients was completed just eight months later on 7 June 2018.

A press release reports that the FFRangio system is non-invasive and performed intra-procedurally, during coronary angiography. It is designed to enable physicians to objectively and cost-effectively determine if percutaneous coronary intervention (PCI) is indicated, without an additional intervention during the course of a routine diagnostic angiography. The FAST-FFR trial is being conducted at 10 cardiovascular centres around the world using various coronary angiography platforms. These sites include: OLV Aalst, Belgium; Rabin Medical Center, Israel; Rigs Hospital CPH, Denmark; St Francis Hospital, USA; University of Erlangen, Germany; Stanford University, USA Share Zedek Medical Center; Columbia University, USA; HaSharon Medical Center, Israel; and University of Pennsylvania, USA William F Fearon (Stanford University Medical Center, Stanford, USA) is the FAST-FFR trial principal investigator. He says: “As interventional cardiologists, we want objective multivessel physiologic measurements to make PCI decisions, which can be performed easily and with as low risk and cost as possible. We look forward to the data analysis and understanding how CathWorks FFRangio System data compares to pressure wire-derived FFR.” Jim Corbett, CathWorks CEO, comments: “Early enrolment of the FASTFFR trial population confirms interventional cardiologists’ excitement about cost-effectively adding a new level of objectivity in PCI decision-making.”

Following the completion of trial

FFRangio demonstration

enrolment, CathWorks announced that it has submitted its FFRangio system to the US FDA for review and 510(k) market clearance. Corbett says; “The FAME trials clearly demonstrated the clinical and economic value of FFR in PCI decision-making. We are confident that the CathWorks FFRangio system meets a real need for patients and physicians, and we expect the system to make non-invasive, wire-free FFR possible in coronary angiograms; reducing wire-related risks and costs.”

PRECLUDE study of Caisson TMVI system concludes

LivaNova has announced the conclusion of the PRELUDE feasibility study for its Caisson transcatheter mitral valve implantation (TMVI) system. The PRELUDE first-in-human study evaluated the company’s TMVI system to treat moderate to severe mitral regurgitation using a transseptal approach. Following the positive patient outcomes from the PRELUDE study, a press release reports, the company will now focus on enrolling patients in the INTERLUDE CE mark trial and finalising the protocol for the US pivotal trial, ENSEMBLE, with the US FDA. Principal investigator of the PRECLUDE study, Mathew Williams (NYU Langone Health, New York, USA), says: “Patients with moderate to severe mitral regurgitation are often too sick for traditional open-heart surgery. We saw encouraging outcomes in patients within the PRELUDE trial. Follow-up results showed positive acute valve performance, which was maintained over time, along with improved quality of life.” He adds: “We are pleased to continue our TMVI research with the INTERLUDE trial.”

The INTERLUDE trial will be conducted in North American and European centres with enrolment completion expected by 2020.

Safety and efficacy results of REDUCE study published in International Journal of Cardiology

The manuscript “Safety and efficacy of the Reducer: A multicentre clinical registry— REDUCE study” has been published in the International Journal of Cardiology.

In this study, the safety and effectiveness of the Reducer (Neovasc)—a CE-marked medical device designed for the treatment of refractory angina—was evaluated using a real-world cohort of 141 patients in three high-volume medical centres in Milan (Italy), Tel Aviv (Israel) and Antwerp (Belgium).

The researchers aimed to evaluate the efficacy of the Reducer in improving quality of life and reducing symptoms of angina pectoris in 141 consecutive patients suffering from coronary artery disease and chronic refractory angina. The safety endpoint of the study was to evaluate the rate of successful Reducer delivery and deployment in the absence of any devicerelated events.

The investigator demonstrated that treatment with the Reducer was very safe and significantly reduced the severity of angina

Reducer

as measured by the Canadian Cardiovascular Society classification (CCS)—from a mean at baseline of 3.05±0.53 to 1.63±0.98 at follow-up (p<0.001). Overall, results show that 81% of the patients experienced improvement in their angina severity by at least one CCS class, and 45% of the patients became free of any limiting angina as they improved by two or more grades in their CCS class. All parameters of quality of life as measured by the Seattle Angina Questionnaire improved significantly (p <0.001). These benefits translated into a significant reduction in the mean number of anti-ischaemic drugs prescribed (2.37± 0.97 vs. 2.17±0.95; p= 0.003).

Fred Colen, Neovasc’s president and chief executive officer, comments: “The publication is another ‘real-world’ non-randomised study that demonstrates clinical results in an additional 141 enrolled patients, that are remarkably consistent with the results of the COSIRA randomised sham-controlled clinical trial. This recent manuscript published in the International Journal of Cardiology is a testament to the benefits of the Reducer as a safe device, which can provide substantial qualify of life improvements in patients with refractory angina, who do not have other suitable treatment alternatives. We are very pleased to have this data published in such a highly-regarded journal.”

Cerner and Duke Clinical Research Institute collaborate on new app for calculating cardiac risk

Cerner has collaborated with Duke Clinical Research Institute to develop the atherosclerotic cardiovascular disease (ASCVD) Risk Calculator app, which is designed as a tool to increase communication between a patient and their doctor about ways to live a healthier life and risk factors for heart disease and stroke.

The app helps healthcare providers estimate 10-year and lifetime cardiovascular disease risk for patients based on information such as age, race, sex, blood pressure, cholesterol levels, smoking status and diabetes status.

Cerner and Duke Clinical Research Institute worked together to develop the software through the Cerner Open Developer Experience (code) that encourages innovators to build apps that advance the health care industry. Through Cerner’s open source code, doctors from Duke Clinical Research Institute provided clinical direction to create an app that could be embedded within Cerner’s electronic health record (EHR) for each patient. Cerner wrote, maintains and hosts the Risk Calculator under an open source license.

To facilitate shared decision-making

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Clinical News between the person and their doctor to guide treatment decisions, the app was designed to factor in a person’s willingness to take action to improve their health and the risks and benefits of potential therapies. Pierre Elias (Columbia University, New York, USA), a former medical study at Duke University School of Medicine (Durham, USA), comments: “Guidelines from the American College of Cardiology and American Heart Association now emphasise using the 10-year calculator to identify adults for statin therapy. We wanted an app that would make it easier for clinicians to calculate risk at the point of care. Whether it is the primary care clinic or a cardiologist’s office, I cannot tell you the number of times this can get missed when there are so many other problems to manage. Making it faster and easier to get news you can use leads to better patient care.”

Kevin Shekleton, vice president and distinguished engineer at Cerner, states: “This collaboration demonstrates how the healthcare industry can come together to develop and continually improve an app that has the ability to save lives by the power of SMART on FHIR open source standards. We developed this ASCVD Risk Calculator for our client hospitals and health systems, but open source lets any health care organisation leverage the technology to help people live healthier lives.”

The ASCVD Risk Calculator app is available to providers in the SMART App Gallery and the Cerner Open Developer Experience (code) App Gallery.

Patient enrolment in US early feasibility study of Everdur TAVI device initiated

JenaValve has announced initiation of patient enrolment in its early feasibility study (EFS) of its next-generation JenaValve pericardial transcatheter aortic valve implantation (TAVI) system using the Everdur device and Coronatix transfemoral delivery catheter at NewYork-Presbyterian/ Columbia University Medical Center (CUMC), New York City, and MedStar Washington Hospital Center, Washington, DC (both USA).

A press release reports that the study is investigating the JenaValve system for the minimally invasive treatment of patients with symptomatic, severe aortic stenosis and symptomatic, severe aortic regurgitation for whom open surgery is an extreme or high risk. The feasibility study is a prospective, single-arm study of the system being conducted at several centres of excellence in the USA under an FDAapproved investigation device exemption (IDE). It is part of a larger, ongoing CE Mark clinical program investigating the system for the same indications at centres in Europe and New Zealand.

According to the press release, the JenaValve system is proprietary and differentiated from currently available TAVI devices due to the Everdur valve

33

NEW locator-based technology—designed to enable anatomically-correct, predictable implantation using the new 18Fr equivalent Coronatix transfemoral delivery catheter. Enrolment has been completed for the aortic stenosis CE mark clinical programme and is ongoing for the aortic regurgitation CE mark clinical programme.

The executive chair of the JenaValve clinical development programme Martin Leon (CUMC, New York, USA) says: “Both myself and my CUMC colleagues, Susheel Kodali and Torsten Vahl, are extremely pleased to be the first US physicians to treat patients with the new JenaValve TAVI system. The first procedures for both aortic stenosis and aortic regurgitation patients demonstrated the system’s ease of use and potential that the Everdur valve may be an important addition to the transcatheter valve products. In particular, the JenaValve TAVI technology enables TAVI treatment for patients with severe aortic regurgitation who are at increased surgical risk that until now have not had a suitable transcatheter option in the USA. We look forward to continuing our work with the JenaValve clinical and product development teams to expand the study of its TAVI technology in the USA.”

All congress resources in one online library New platform Enhanced search function Year round access

Positive one-year results for Interatrial Shunt Device

One-year follow-up data from the REDUCE LAP-HF I clinical study of the Interatrial Shunt Device (IASD, Corvia Medical) demonstrate shunt patency (blood flow from the left to right atrium) for all participants who received the implant. The IASD is the world’s first transcatheter device for heart failure with preserved and mid-range ejection fraction.

Data was presented in the late-breaking scientific session at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany)

by Ted Feldman (Evanston Hospital, Evanston, USA). REDUCE LAP- HF I is a prospective, double-blind, mechanistic study of 44 patients randomised to IASD or sham control. Primary study endpoints at 30 days included effectiveness of the IASD as measured by exercise pulmonary capillary wedge pressure (PCWP) reduction compared to sham control, and procedural safety as assessed by major adverse cardiovascular, cerebral, or renal events (MACCRE). The study met its primary endpoint.

The one-year results demonstrate shunt patency (blood flow from the left to right atrium) for all participants who received the implant. Results further showed that the IASD is safe, improved quality of life and is associated with favorable trends in heart failure hospitalisation and reduction in New York Heart Association (NYHA) heart class. As well as being presented at the ESC, the results were published in JAMA Cardiology.

Watch the sessions you missed or replay the ones you like at your convenience More than 84,500 cardiovascular slide sets, videos and abstracts from the ESC family of congresses www.escardio.org/365

ESC 365 is supported by Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer Alliance, and Novartis Pharma AG in the form of an educational grant.

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Industry News Boston Scientific closes acquisition of Claret Medical

Boston Scientific has announced that it has recently closed its acquisition of Claret Medical, which developed and commercialised the Sentinel cerebral embolic protection system—the only device cleared in the USA and Europe to protect patients against the risk of stroke in transcatheter aortic valve implantation (TAVI) procedures.

The company also announced that the US Centers for Medicare and Medicaid Services (CMS) granted a New Technology Add-on Payment (NTAP) designation for the Sentinel system as part of the federal fiscal year 2019 Inpatient Prospective Payment System (IPPS). The NTAP designation, awarded to new medical devices determined to substantially improve the diagnosis or treatment of Medicare beneficiaries, will be effective on October 1, 2018.

Kevin Ballinger, president, Interventional Cardiology, Boston Scientific, comments: “The Sentinel System is an exciting platform technology designed to reduce the risk of procedure-related stroke in TAVI and other left-heart and endovascular procedures, and is an increasingly important consideration for patients and physicians as the TAVI indication expands to treat a younger patient population. The recent CMS NTAP designation underscores the clinical value of the Sentinel System and will allow for accelerated adoption of this adjunctive therapy amongst structural heart centres.”

Boston Scientific announced a definitive agreement to acquire Claret Medical on July 20, 2018 for $220 million in upfront cash with an additional $50 million payment for reaching a reimbursementbased milestone, which has been fulfilled with the recent NTAP designation.

ClearFlow awarded group purchasing agreement for the chest drainage products category with Premier

ClearFlow has been awarded a group purchasing agreement—chest drainage contract: Contract # PP-OR-1561—for the chest drainage products category with Premier. A press release reports that the PleuraFlow ACT System is indicated for use following cardiothoracic surgical procedures and chest trauma. Its Active Clearance Technology is designed to proactively inhibit and disrupt clot formation inside the chest tube to reduce the likelihood of chest tube occlusion.

The press release adds that improving drainage by maintaining chest tube patency has been shown to improve patient outcomes reducing the incidence of common complications such as pleural, pericardial effusions and new-onset postoperative atrial fibrillation.

Premier is a healthcare improvement company, uniting an alliance of approximately 3,900 US hospitals and 150,000 other providers to transform healthcare.

With integrated data and analytics, collaborative supply chain solutions and advisory and other services, Premier aims to enable better care and outcomes at a lower cost.

Paul Molloy, CEO of ClearFlow, states: “ClearFlow is proud to now be able to bring its Active Clearance Technology devices to Premier members under these new arrangements with one of the country’s leading GPOs. ClearFlow’s founding principles are directed toward improving patient outcomes and lowering the total cost of healthcare for all participants in the medical eco-system and these principles closely align with the membership objectives of the Premier organisation.”

FDA sends letter warning about mortality and risks with the Syncardia TAH-t Companion 2 Driver

The US FDA has sent a letter to transplant surgeons and cardiologists about the Syncardia temporary Total Artificial Heart (TAH-t) Companion 2 Driver. The letter states the final results of the post-

Syncardia device

approval study of the system indicate that it is associated with a higher stroke rate than a previous generation of the driver (the Circulatory Support System [CSS] Console). Therefore, the FDA is now recommending that transplant surgeons and cardiologists “carefully consider” the final results.

According to the letter, the FDA previously apprised the healthcare community about interim results comparing C2 Driver System patients to CSS console patients.

On 15 June 2015, the FDA posted a letter indicating that interim data suggested a higher mortality rate for a subgroup of patients requiring pre-implant circulatory rescue interventions when using the C2 Driver System. On 26 October 2016, the FDA posted an update about the continued increased mortality rate for a subgroup of patients requiring pre-implant circulatory rescue interventions when using the C2 Driver System as well as additional interim study results that indicated a higher risk of neurological adverse events for C2 Driver System patients. On 25 September 2017, an update informed the health care community of a higher rate of cerebrovascular accidents (stroke) for C2 Driver System patients.

The letter goes on to detail the final mortality and stroke results from the postapproval study. These results show that survival for patients initially supported with the C2 Driver System was significantly lower than survival for patients initially supported with the CSS Console at three months and six months’ postimplant, and the study’s non-inferiority

hypothesis was not met.

Furthermore, the letter notes, there was a higher mortality rate at six months’ postimplant for C2 Driver System patients who did not require pre-implant circulatory rescue interventions (such as intraaortic balloon pump or extracorporeal membrane oxygenation) compared with those who received the CSS console— even though at three months’ post-implant the mortality rates were similar. For the subgroup of patients who did require preimplant circulatory rescue interventions, the final results confirm the previously communicated finding of a higher mortality rate with the C2 Driver System at three months and six months’ post-implant.

Additionally, the stroke rate (a secondary endpoint) for patients initially supported with the C2 Driver System was statistically significantly higher than the stroke rate for patients initially supported with the CSS Console at three months and six months’ post-implant. Other neurological adverse event rates were similar between the two groups.

The FDA letter states: “The information provided in this letter is meant to assist physicians in understanding the performance of the TAH-t using the C2 Driver System as seen in the postapproval study. We recognise that the CSS Console is no longer available as a driver option for TAH-t patients, and that consequently, physicians may determine that the C2 Driver System is the most appropriate option for patients with severe biventricular failure in need of mechanical circulatory support.”

Calendar of events 18–20 October

10–14 November

Milan, Italy www.eacts.org/educational-events/eactsannual-meeting

Chicago, USA https://professional.heart.org

EACTS 2018

22–24 October

27th European Cardiology Conference Rome, Italy https://cardiologyconference.cardiologymeeting.com/

AHA Scientific Sessions

05–08 December

EuroEcho-Imaging Milan, Italy https://bit.ly/2xeZLZI

2019 14–16 February

JIM 2019

Milan, Italy https://jim-vascular.com/

02–05 March

20–23 May

SCAI 2019

Las Vegas, USA http://www.scai.org/

21–24 May

EuroPCR 2019

CRT 2019

Paris, France

Washington, DC, USA http://www.crtmeeting.org/

https://www.pcronline.com/Courses/EuroPCR

16–18 March

ESC Congress 2019

ACC.19

New Orleans, USA https://accscientificsession.acc.org/

31 August–04 September Paris, France www.escardio.org/Congresses-&-Events/ESCCongress

Vascular & Endovascular

Challenges Update 15–18 APRIL 2019 MONDAY–THURSDAY OLYMPIA GRAND • LONDON • UNITED KINGDOM

Aortic Challenges

Peripheral Arterial Challenges

Venous Challenges

Acute Stroke Challenges

Vascular Access Challenges

and introducing

Abstract submissions open WWW.CXSYMPOSIUM.COM/ABSTRACTS

SUBMISSION DEADLINE: 28 OCTOBER 2018

EDUCATION

INNOVATION EVIDENCE

STRUCTURAL HEART THERAPIES

INNOVATION at Heart *

REPRISE III showed

Mild or Greater PVL is a PREDICTOR OF STROKE LOTUS™ Aortic Valve showed a

4x LOWER rate of Mild or

Greater PVL at 30 days

10.7

% vs.

LOTUS

58.3

%

Evolut R / CoreValveTM (P < 0.001)

See the full REPRISE III clinical data set at bostonscientific.com/LOTUSEdgeClinical LOTUS VALVE SUPERIOR TO EVOLUT R / COREVALVE Primary effectiveness endpoint (1 year): Composite of all-cause mortality, disabling stroke, moderate or greater PVL. LOTUS Valve = 15.8% vs. Evolut R / CoreValve Platform = 26.0%. Superiority P < 0.001.

LOTUS VALVE NON-INFERIOR TO EVOLUT R / COREVALVE Primary safety endpoint (30 days): Composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2/3 kidney injury, major vascular complications. LOTUS Valve = 20.3% vs.

Evolut R / CoreValve Platform = 17.2%. Non-inferiority P = 0.003.

CAUTION: The LOTUS Edge™ Aortic Valve System is an investigational device. Limited by U.S. law to investigational use only. Not available for sale. © 2018 Boston Scientific Corporation or its affiliates. All rights reserved. SH-560903-AA