Cardiovascular News Issue 54—August 2019 US edition

August 2019 | Issue 54 Francesco Maisano:

Transseptal puncture

Page 12

Partha Sardar and Herb Aronow:

Josep Rodés-Cabau:

Profile

Renal denervation

Page 18

Page 24

PCR statement on TAVI signals Stakeholders a “paradigm shift” in the welcome updated treatment of aortic stenosis CMS coverage Evolving indications for the use of transcatheter aortic valve implantation (TAVI) have led to a series of “paradigm shifts” in the treatment of severe symptomatic aortic stenosis, according to a position statement issued by PCR, which says that TAVI should now be favoured over surgical aortic valve replacement (SAVR).

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nnouncing the statement at EuroPCR 2019 (20–24 May, Paris, France), Stephan Windecker (Bern University Hospital, Bern, Switzerland) said: “The favourable outcomes of TAVI are consistent across the entire risk spectrum, suggesting that surgical risk estimation is no longer the basis to guide the choice between TAVI and surgical aortic valve replacement.”

Windecker explained: “The available evidence has been extended by two recent landmark trials in the low-risk patient population which provide us now with a comprehensive picture, ranging from extreme highrisk, intermediate-, to low-risk patients.” The aim of the PCR statement, he said, is to “synthesise the available evidence”. From this, three paradigm shifts can be identified.

The first of these relates to the decision-making process between TAVI and SAVR: “Because the benefits are so consistent, the risk stratification that we applied using the STS [Society of Thoracic Surgery] score to identify patients at increased risk for surgery is no longer useful. Rather than categorise patients in the extreme, intermediate, and low risk, we should rather look at the clinical and anatomical characteristics of individual patients to guide the decision-making between these two procedures.”

Secondly, the heart team will identify the best treatment option for individual patients, with transfemoral TAVI replacing SAVR as the default therapy for a greater number of patients: “Up to now, by default, in low-risk patients surgery was the therapy of choice, and TAVI was only to be considered in those patients where surgery would not be possible. In the nottoo-distant future, a scheme will emerge where actually the question will be reversed, with any patient being considered a priori to be a TAVI candidate and surgery being reserved to cases where that is not possible.”

The third paradigm relates to prosthetic valve choice,

Stephan Windecker

and is to be based upon life expectancy and valve durability: “That should be, if we look at very young patients [<50 years], preferentially a mechanical valve prosthesis in case of aortic stenosis. In patients that are above 65 years of age, a bioprosthetic valve. The

In the not-too-distant future ... any patient will be considered a priori to be a TAVI candidate.”

Continued on page 2

for TAVI

Stakeholders have welcomed an updated National Coverage Determination (NCD) from the US Centers for Medicare & Medicaid Services (CMS) on transcatheter aortic valve implantation (TAVI) in the treatment of symptomatic aortic valve stenosis, saying the decision will improve access to services.

THE CMS ANNOUNCED in June that it will continue to cover the procedure through coverage with evidence development (CED) when furnished according to a US Food and Drug Administration (FDA)-approved indication. In addition, changes to the procedural volume requirements for hospitals and physicians to begin or maintain a TAVI programme allow greater flexibility for hospitals and providers to meet the criteria for performing TAVI. In a press release, Edwards Lifesciences said: “We believe the modernised requirements and more streamlined patient evaluation process are meaningful enhancements that may help ensure equitable access for more patients suffering from severe aortic stenosis. We are encouraged that CMS is open to moving towards a quality measure focused on patient outcomes, not procedural volume, in evaluating hospitals eligible to provide TAVR in the USA.” Medtronic also indicated its support in a statement, saying it “believes the new coverage policy allows for appropriate patient access to TAVI—especially for patients in rural communities—while still maintaining rigorous requirements for centres and operators providing the therapy.”

Some physicians have given it a more mixed response. Satya Shreenivas (The Christ Hospital, Cincinnati, USA) pointed out: “It is vitally important Continued on page 2

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August 2019 | Issue 54

TAVI recommendations

PCR statement on TAVI signals a “paradigm shift” in the treatment of aortic stenosis Continued from page 1

discussion is not the procedure, but it is rather the valve type, and obviously there remains a grey zone of individual decision-making.”

He highlighted findings from a recent metaanalysis of seven randomised controlled trials with >8,000 patients that demonstrates a superior clinical performance for TAVI compared with SAVR. “The accumulated evidence to date shows not only noninferiority but, in fact, superiority as it relates to those endpoints that are the most important from a patient perspective, and that is mortality, stroke, and rehospitalisation. Similarly, not only is there a clinical benefit, but there is also optimisation in terms of resource utilisation as it relates to procedure time, hospital stay, and post-procedure care.”

Published in the European Heart Journal, the metaanalysis by George Siontis (Bern University Hospital, Bern, Switzerland) et al included all randomised clinical trials comparing TAVI and SAVR among highrisk and intermediate risk patients, as well as the recent PARTNER 3 and Evolut Low-Risk trials.

Siontis et al found that for all types of risk and valve type, TAVI showed a significant reduction in all-cause mortality compared with SAVR (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.78–0.99) at two years. “The important information,” said Windecker, “is that this benefit is irrespective of risk—high, intermediate, and low risk. There is a very consistent observation.”

TAVI also demonstrated better outcomes than SAVR for stroke (HR 0.81, 95% CI 0.68–0.98, p=0.028), and major vascular complications (HR 1.99, 95% CI 1.34–2.93), although the rate of permanent pacemaker implantation was higher with TAVI than SAVR (HR 2.27, 95% CI 1.47–3.64).

Windecker pointed out that the findings on stroke rates, “which from a patient perspective is an equally important endpoint [as mortality]”, have undergone a “notable evolution”.

“If you look at stroke, any stroke, there is a significant 19% relative risk reduction up to two years.

If you just look at disabling stroke, then we have a similar point estimate with a 22% relative risk reduction … but, formally, it is not statistically significant.”

In addition, the relative risk reduction for mortality at two years was 17% for TAVI when access was via the transfemoral route (HR 0.83, 95% CI 0.72–0.94, p=0.032), with a “substantial” reduction in the use of hospital resources, due to reduced procedure times,

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intensive care unit stays, and total hospital stays.

Windecker said: “If you reduce the analysis just to transfemoral access then you see that the finding is more robust, with a 17% relative risk reduction and a more narrow confidence interval. Whereas, there is no advantage or difference to be seen with an alternative access route.”

He commented upon the “remarkable consistency in the Partner 3 and Evolut Low Risk trials indicating superiority” on the endpoint of rehospitalisations, and added: “If you synthesise all these endpoints, then it is clear it is not just non-inferiority, but also superiority.”

The statement concedes that the cost of TAVI valves mean that the cost-effectiveness of the procedure needs further study.

“There are obviously areas of remaining uncertainty,” Windecker acknowledged. “Certainly we need to be better informed regarding durability for both transcatheter and surgical valves. We do not

From early outcomes and mid-term followup, overall, the results favour the minimally invasive technique.” know much about the performance of the transcatheter valves in the setting of bicuspid valve disease, and those who have concomitant relevant coronary artery disease. We still need more information as to the longterm impact of permanent pacemaker implantation; and, although the low-risk trials included younger patients—the mean age was 74—certainly we would need more information as it relates to even younger patients. Finally, there is no conclusive information as it relates to the optimal antithrombotic therapy.”

However, he concluded: “There is no doubt transcatheter aortic valve implantation constitutes a major paradigm shift in the care of patients with severe symptomatic aortic stenosis. From a procedure point of view, from a risk point of view, from early outcomes and mid-term follow-up, overall, the results favour the minimally invasive technique.”

See also: Comment & Analysis from Amar Krishnaswamy and Samir R Kapadia, page 17.

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Stakeholders welcome updated CMS coverage for TAVI Continued from page 1

we ask the right question. The entire premise of the NCD ‘how should we regulate TAVI?’ is a faulty one.

The question should be: ‘How should we improve the care of the patient with aortic stenosis?’ By asking the wrong question we continue to perpetuate arbitrary distinctions between therapies that might continue to hamper diffusion of future valve therapies.”

Scott M Lilly (Ohio State University Wexner Medical Center, Columbus, USA) said he approved of the removal of the “two-surgeon rule”, a requirement that two cardiac surgeons independently evaluate a patient face-to-face to assess their risk for open surgical valve replacement.

“Now TAVI will be reimbursed by Medicare, with evaluation by a surgeon and interventional cardiologist, comprising the heart team. This will make the evaluation of patients more efficient, and likely shorten the time from initial visit to treatment.”

But he asked: “While some health systems will publicly celebrate the ability to offer these services locally, will outcomes be as easily accessible to the public? This technology … represents an opportunity to put the patient at the centre, individualise options based on large and well-run randomised clinical trials, and deliver the care in a team-based manner, within an infrastructure where we continue to refine the technique and advance therapies.”

The CMS said the decision comes in response to the continued development of TAVI, and streamlines key elements of the original NCD that went into effect in 2012. It aims to strike an appropriate balance between ensuring that hospitals have the experience and capabilities to handle complex heart disease cases while limiting the burden and barriers that excessive requirements create for hospitals and patients.

The agency met with numerous groups to develop the decision, including medical professional societies which recommended requirements for hospitals and physicians to perform a certain volume of heart procedures. The CMS also confirmed it will continue to follow efforts by the societies to develop TAVIspecific outcome measures, and will encourage continued progress towards the establishment of potential replacements for procedural volume criteria.

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August 2019 | Issue 54

Diagnostics

Diagnosing coronary stenosis with diastolic pressure ratio measurements is equivalent to using iFR Using the diastolic pressure ratio (dPR) to identify ischaemia-producing lesions in patients with coronary artery disease provides a similar diagnostic performance to the instantaneous wave-free ratio (iFR). A pooled analysis of pre-recorded pressure tracings from the diagnostic accuracy studies VERIFY 2 and CONTRAST compared dPR (using a commercially available algorithm of the diastolic hyperaemia-free ratio [DFR]) and a linear transform of Pd/Pa (the ratio of the distal coronary pressure to proximal aortic pressure) against iFR for numerical similarity and test/retest repeatability in 893 lesions from 833 patients.

WRITING IN THE European Heart Journal, Nils P Johnson (University of Texas, Houston, USA) et al say: “Our dPR offers numerical equivalency to iFR. Despite different technical approaches for identifying the relevant period of diastole, the agreement between dPR and iFR, and the insensitivity of dPR to minor variations in its definition, further confirm numerical equivalency among resting metrics.”

VERIFY 2 was a prospective, single-centre study of 197 nearly-consecutive subjects and 257 coronary lesions in which resting pressure signals in the coronary artery were obtained, with simultaneous recordings of aortic pressure and surface electrocardiogram (ECG).

Two assessments of iFR were acquired in rapid, backto-back sequence before the administration of any hyperaemic stimulus. Tracings and their associated real-time iFR values were anonymised for the pooled analysis.

CONTRAST was a prospective, international study with 763 subjects from 12 centres with one lesion per subject. A simultaneous ECG was recorded, in addition to aortic and coronary pressure signals. Two resting assessments of iFR were performed but separated by hyperaemic stimuli of intracoronary contrast and

When two studies agree as closely as dPR and iFR, performing clinical outcomes studies becomes unnecessary.”

intracoronary and/or intravenous adenosine. Anonymous tracings from CONTRAST were used for the analysis and iFR was recalculated. The final pooled analysis consisted of 255 lesions from 195 subjects (252 with valid, duplicate measurements) from VERIFY 2 and 638 lesions from 638 subjects (629 with valid, duplicate measurements) from CONTRAST. The analysis found numerical equivalency between the metrics. The mean difference between dPR and iFR ( -0.006±0.011, r2 0.993, area under receiver operating characteristic [ROC] curve [AUC] 0.997) mirrored the difference of two iFR measurements repeated immediately ( <0.001±0.004, r2 0.998, AUC 1.00).

Minor variations in the definition of dPR changed its value by <1–2% over a broad range of the cardiac cycle.

Thus the authors point out: “dPR agrees with iFR to the same degree that iFR agrees with itself a few seconds later under stable conditions.”

A linear transform of Pd/Pa showed good diagnostic performance ( -0.012±0.031, r2 0.927, AUC 0.979).

Post-hoc iFR values were validated against real-time iFR values and matched almost exactly (average <0.001±0.004, 99.6% within ±0.01).

Johnson et al add: “When two tests agree as closely as dPR and iFR, performing clinical outcomes studies becomes both impossible and unnecessary. While a small minority of lesions demonstrated some binary discordance between dPR and iFR, <1% were consistent between both test and retest. The fact that dPR provides the same numerical value as iFR, despite a different definition of the diastolic measurement period, provides additional indirect evidence against unique properties of the so-called ‘wave-free period’, although our study did not perform wave intensity analysis directly.”

Consensus paper on intracoronary imaging focuses on acute coronary syndrome A consensus paper on the use of intracoronary imaging was released at EuroPCR 2019 (20–24 May, Paris, France) as a joint document with the European Association of Percutaneous Cardiovascular Intervention (EAPCI). It aims to provide the interventional community with guidance on when and how to use imaging technologies in clinical practice. Based on existing clinical evidence and contemporary best practice, the paper is the second on the use of imaging; the first paper was presented last year, and looked at the role of intracoronary imaging in guidance and optimisation of percutaneous coronary intervention (PCI), and its function in understanding mechanisms of stent failure.

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n behalf of the EAPCI expert consensus group, Tom Johnson (Bristol Heart Institute, Bristol, UK) explained: “This second document is focusing on acute coronary syndrome [ACS], ambiguous coronary angiographic findings, and guiding interventional strategy in decision-making by imaging.”

He said: “The imaging consensus, both Part One and Part Two, acknowledges that there is increasing complexity of both our patients and lesions. Inherently, and particularly emphasised within this second document, we understand that invasive angiography is flawed in terms of its assessment, and we should be shifting towards a more precisionbased medical strategy for our patients.

Intracoronary imaging allows lesion characterisation … and it then will facilitate for us a tailored approach to intervention—from the pre-interventional strategy to subsequent stent deployment.”

The second paper, which Johnson described as “slightly more troublesome to put together, as the data are more lacking in this environment”, consists of three themes: indications and the clinical value of intracoronary imaging in acute coronary syndrome, the role of imaging in vulnerable plaque detection and risk stratification, and the role of imaging in

assessing lesion significance.

The consensus paper acknowledges that complex patients (for example, those with acute coronary syndrome or diabetes) and patients with complex lesions (such as chronic total occlusion [CTO], long lesions, and left main stem) benefit from intravascular ultrasound (IVUS)-guided PCI, which has shown reduced major adverse clinical events, mainly driven by a reduction in target vessel revascularisation.

An equivalence of IVUS and optical coherence tomography (OCT) has been confirmed in two rigorously designed randomised controlled trials, OPINION and ILUMIEN III. However, as outlined in Part One, studies using imaging-based optimisation criteria have demonstrated a failure to achieve optimal criteria in up to half of all patients. This reflects the challenges of defining the criteria and the increasing complexity of coronary disease. Johnson reinforced that improved outcomes require the interventionist to understand the underlying lesion substrate, before stenting, and then to guide lesion preparation and stent

selection with intracoronary imaging.

The first consensus outlined the role of intracoronary imaging in the characterisation of calcification, where a calcific arc >180° with thickness >0.5mm and longitudinal length >5mm is predictive of a stent under expansion.

Beyond this, there is an expanding role for intracoronary imaging to assess and guide modification strategies for highburden calcification.

In cases where angiographic assessment is challenging—aneurysmal disease or aorto-ostial lesions—the consensus paper suggests difficulties be overcome with the use of intracoronary imaging. And where angiographic assessment is uncertain, it can be used to delineate the aetiology of ACS, which can impact future treatment if atherosclerotic disease can be ruled out. The document also states intracoronary imaging for lesions, and patient stratification can guide intensification of treatment and minimise future events, and should be mandatory in cases of lesion failure to guide repeat intervention.

Tom Johnson

Johnson summed up: “We really see imaging as central to the role of understanding the aetiology of acute coronary events, particularly in the non-obstructive or near normal coronary angiogram. Beyond that, in terms of vulnerable plaque detection and risk stratification, there appears to be evidence that a multimodality approach to understanding the underlying plaque type is probably relevant in terms of intracoronary imaging. In terms of lesion significance … we have strengthened guidance on revascularisation of left main stem disease to recommend that an MLA [minimal lumen area] of <4.5mm2 should actually push the interventionist to revascularise, either by percutaneous or surgical means. And if the MLA is exceeding 6mm2 then a conservative strategy is mandated. But if it is between 4.5 and 6mm2 then a physiological assessment should be undertaken.”

The paper has been endorsed by three societies—the Cardiac Society of Australia and New Zealand, the Chinese Society of Cardiology, and HK Stent Hong Kong Society. The consensus group was made up of 22 co-authors, the majority of whom were European, with American, Japanese, and Chinese coauthors also involved.

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August 2019 | Issue 54

Conference round-up

PCR issues statement on edge-toedge repair in the management of heart failure with secondary MR PCR and the European Association of Percutaneous Cardiovascular Intervention (EAPCI) issued a statement at EuroPCR 2019 (20–24 May, Paris, France) outlining the role of percutaneous edge-to-edge repair in the management of heart failure and secondary mitral regurgitation.

BERNARD PRENDERGAST (St Thomas’ Hospital, London, UK) announced the statement, explaining: “The place of edge-to-edge repair in the armamentarium of physicians involved in the care and management of patients with heart failure requires assimilation alongside the alternatives of resynchronisation therapy, surgery, and other transcatheter techniques. Importantly, the timing of these interventions in the natural history of mitral regurgitation requires further assessment in an attempt to interrupt the progressive cycle of left ventricular dilatation and increasing degrees of mitral regurgitation.”

The prevalence of mitral regurgitation is expected to double in the next two decades as a result of the ageing population. He described it as an “ominous prognosis”, and said: “The stage is set for transcatheter treatment options.” Referencing the publication in 2018 of conflicting findings from the COAPT and MITRAFR trials, Prendergast added: “Last year, the landscape changed … with potential impact for future guidelines.”

“In essence, patients in COAPT had more mitral regurgitation but smaller left ventricles, and were receiving optimal guideline-directed medical treatment before randomisation, in contrast with MITRA-FR where therapy was adopted following clip implantation.

And, arguably, the techniques of MitraClip implantation were superior in COAPT, with better acute results, lower rates of procedural complications, and less mitral

regurgitation at oneyear echocardiographic follow-up. The results of COAPT can take their place alongside the existing evidence base supporting medical treatment and, to a lesser extent, cardiac resynchronisation. The potential impact on treatment worldwide is considerable.”

Bernard Prendergast The position statement recommends early referral for those with symptomatic heart failure and moderate to severe mitral regurgitation to a multidisciplinary heart team, which should evaluate and optimise medical therapy and consider the roles of device therapy, transcatheter mitral intervention and, where appropriate, surgery. The heart team should consist of valve intervention specialists, valve surgeons, heart failure specialists, valve imaging specialists, and electrophysiologists.

“Based on the results of COAPT, transcatheter edgeto-edge repair is appropriate in these carefully selected patients who remain symptomatic despite optimal treatment,” Prendergast declared. “And the inclusion criteria of COAPT are to be firmly adhered to, to

First-in-man study shows acute SVC occlusion can reduce cardiac filling pressure for heart failure patients Results from a first-in-man proof-of-concept study have found that occlusion of the superior vena cava (SVC) rapidly and effectively reduces pressure and volume in the heart. The findings were presented at a late-breaking trial session at the Society for Cardiovascular Angiography and Interventions Scientific Sessions 2019 (SCAI; 19–22 May, Las Vegas, USA) by Navin K Kapur (Tufts Medical Center, Boston, USA).

T

he study found that acute SVC occlusion provides a superior haemodynamic profile to inferior vena cava (IVC) occlusion, reducing cardiac filling pressures without reducing cardiac output or systemic blood pressure. This is the first study targeting the SVC as a therapeutic area for heart failure patients to reduce cardiac filling pressures.

Kapur pointed out that congestion is an important target of therapy for heart failure, and is associated with poor clinical outcomes, with rising rates of heart failure hospitalisations and/or death seen as the congestion score increases.

He outlined the limitations of current decongestive therapies, and said: “There exists a need for more rapid and effective cardiac decongestion in patients with acute heart failure.”

Among the available options are loop diuretics, but this may worsen renal function and is associated with worse clinical outcomes, with 20–30% of patients developing diuretic resistance.

Ultrafiltration has seen limited adoption due to a lack of compelling results, and vasodilators are associated with hypotension in acute heart failure, as well as with toxicity and tachyphylaxis.

Inotropes increase the cardiac workload,

allow judicious and evidence-based application of this technology.”

The statement also suggests that surgical treatment of secondary mitral regurgitation should be considered in patients with concomitant coronary artery disease who are undergoing surgical revascularisation, and that circulatory support devices and cardiac transplantation may be an alternative for patients with extreme left ventricular and/or right ventricular failure. The role of other transcatheter treatment options remains under investigation.

“We need to remember that futile expensive interventions should be avoided in patients with short life expectancy, arbitrarily defined as less than one year,” said Prendergast, “In these patients, access to appropriate support and specialist palliative care is a more appropriate treatment direction.”

Also at EuroPCR 2019, Francesco Bedogni (IRCCS Policlinica, Milan, Italy), presented one-year results from GIOTTO (GISE registry of transcatheter treatment of mitral valve regurgitation), an ongoing single-arm, observational, multicentre prospective registry with 1,348 participants in 21 Italian centres. Enrolment began in February 2016, and it aims to collect real-world epidemiological, procedural, and clinical data on early and long-term outcomes following percutaneous edgeto-edge mitral regurgitation therapy, with follow-up at 30 days and then yearly up to five years. Mean age of patients is 75±9 years, and 64.5% are male.

At 30 days, the procedural success rate was 95.1%, with 3% of deaths. Overall mortality was 17.8%, and cardiac mortality was 10.5% at one year. The hospitalisation rate was 27.1%, and hospitalisations for heart failure were 9% at one year.

The clinical features of the GIOTTO population are closer to those of the COAPT trial than MITRA-FR, and reported similar outcomes. “It is very interesting that [this] real-world population with similar baseline characteristics to the COAPT trial has similar results,” Bedogni said.

with no improvement in clinical outcomes, and are associated with arrhythmias.

The prospective, single-arm study investigated SVC occlusion as a therapeutic approach to improve heart function in human subjects with advanced heart failure. Its primary objective was to confirm the safety of transient SVC occlusion. The secondary objective of the study was to measure acute haemodynamic changes associated with transient SVC occlusion.

The study population consisted of patients aged 18–75 years who were admitted with acutely decompensated heart failure with reduced ejection fraction, and who had been referred for cardiac catheterisation.

Eight patients admitted with systolic heart failure and volume overload were included in the study. An endovascular balloon was used to occlude the SVC for five to 10 minutes. Patients underwent neurological testing before, during, and after SVC occlusion, with repeat testing within 10 minutes of balloon release, and again after one, three, and 24 hours.

Successful SVC occlusion was performed on all patients within the study.

After five minutes of SVC occlusion cardiac filling pressures normalised, systemic blood pressure remained stable, and heart function was stable.

In the final three patients, a second SVC occlusion was performed for 10 minutes, with similar haemodynamic findings. After seven days of follow up for all eight patients, and 30 days of follow up for five patients, no neurological safety issues or vascular consequences were reported.

Kapur concluded: “Intermittent SVC occlusion with a novel catheter-mounted SVC balloon system is well tolerated and reduces cardiac filling pressures without anatomic evidence of neurological or vascular injury.”

He described SVC occlusion as a “potentially novel therapeutic approach to rapidly and significantly reduce cardiac filling pressures in acutely decompensated systolic heart failure”.

Kapur added: “The VENUS-HF study will test the feasibility and safety, and provide early insight into the clinical utility of SVC therapy as an approach to reduce congestion and improve outcomes for patients with acute congestive heart failure.”

Acute superior vena cava occlusion provides a superior haemodynamic profile to inferior vena cava occlusion.”

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August 2019 | Issue 54

Conference round-up

DAPT followed by ticagrelor monotherapy may be better than standard DAPT in complex PCI

Ticagrelor monotherapy following onemonth dual antiplatelet therapy (DAPT) may be a better treatment than standard DAPT for patients undergoing complex percutaneous coronary intervention (PCI), with greater benefit shown as the number of high-risk features increases. Presenting the findings on behalf of the GLOBAL LEADERS investigators at EuroPCR 2019 (20–24 May, Paris, France), Patrick W Serruys conceded that the findings should be “interpreted as hypothesis generating” and that they need further confirmation in randomised trials.

GLOBAL LEADERS WAS an all-comers, open label study, conducted in 130 centres worldwide, in which patients were randomised 1:1 to either a reference or an experimental strategy. It analysed the effect of ticagrelor monotherapy for 23 months following one-month DAPT versus standard DAPT for 12 months followed by 12 months of aspirin monotherapy in patients undergoing complex PCI. “No previous study has evaluated the efficacy and safety of ticagrelor monotherapy following one-month DAPT in comparison to the standard 12-month DAPT in patients with complex PCI. Any type of lesion— left main, saphenous vein graft [SVG], chronic total occlusion [CTO] bifurcation, in-stent restenosis [ISR]— was allowed in this trial, and the use of drug-eluting stents was unrestricted in numbers and length.”

Complex PCI patients were divided into experimental CI 0.31–0.91], but without a p-value for interaction. The and reference strategy arms. In the experimental group, composite endpoint of all death, all stroke, all MI, and all patients with acute coronary syndrome (ACS) and stable revascularisation [POCE] with complex PCI has a risk coronary artery disease (CAD) received a low dose of reduction of 20% [HR 0.80, 95% CI 0.69–0.93], with aspirin (75–100mg per day) for 30 days, followed by a p-value for interaction which is significant at 0.017.

90mg ticagrelor twice daily for two years. The reference The same is true for NACE—complex PCI has a [risk] strategy arm was further subdivided—patients with acute reduction of 20% [HR 0.80, 95% CI 0.69–0.92] with a coronary syndrome received a low dose of aspirin for p-value for interaction of 0.011.” two years and ticagrelor (90mg twice daily) for one year; For BARC 3 and 5 bleeding there was no difference stable CAD patients received low dose between the ticagrelor monotherapy and aspirin for two years and clopidogrel 75mg the standard DAPT at two years (HR 0.97, per day for one year.

95% CI 0.67–1.4).

The primary endpoint of the study In non-complex PCI patients, standard was a composite of all-cause death and therapy and ticagrelor monotherapy Core Lab adjudicated non-fatal new Q demonstrated “almost identical” results, wave myocardial infarction (MI) at two with an event rate of 12.5% and 12.4%, years. The secondary safety endpoint was respectively, for POCE, and 1.9% in both a composite of BARC 3 or 5 bleeding groups for BARC 3 or 5 bleeding; the up to two years post-randomisation. event rate for NACE in non-complex PCI Additional secondary endpoints consisted patients was 13.6% with both standard of investigator-reported endpoints up DAPT and ticagrelor monotherapy.

Patrick Serruys to two years, which was a composite of For patients undergoing complex PCI, all-cause mortality, stroke, and nonthe event rate for POCE was 17.2% with fatal new Q-wave MI, and patient-oriented composite standard therapy vs. 14% for ticagrelor monotherapy, endpoints (POCE: all-cause death, any stroke, any MI, “a 21% reduction of risk”. There was no difference any revascularisation) and net adverse clinical events between the therapies for BARC 3 or 5 bleeding (2.5%), (NACE: POCE and BARC type 3 or 5 bleeding). and NACE events in complex PCI patients was 18.8% Of the 15,991 patients with high-risk features with standard DAPT, compared with 15.39% for who were randomised to the study, 15,450 were ticagrelor monotherapy “a reduction of 20%”. included; 4,570 underwent complex PCI—2,283 in A sub-analysis that stratified for the number of highthe experimental arm and 2,287 in the reference arm. risk features found no difference between the therapies Baseline characteristics were “extremely well balanced” in cases of non-complex PCI as risk factors increase. between the two groups, said Serruys, with 74.2 % of However, in complex PCI Serruys described a “gradient” the reference group undergoing multivessel PCI, and effect, where the difference between the event rate for 73.2% among the experimental group (p=0.461). Almost ticagrelor monotherapy and standard DAPT increased as 30% of patients in both groups had three or more lesions the number of risk factors increased from zero to ≥four, treated, and 60% had three or more stents implanted. an effect observed for the primary endpoint and for POCE Serruys told the conference: “Complex PCI with and NACE, but not BARC 3 or 5 bleeding. ticagrelor has a risk reduction of 36% [hazard ratio (HR) Summing up, he said: “Ticagrelor monotherapy 0.64, 95% confidence interval (CI) 0.48–0.85, p-value for following one-month ticagrelor and aspirin may be interaction 0.015]. All-cause mortality and new Q wave a better alternative to the standard DAPT in patients goes in the same direction, with risk reductions of 33% who underwent complex PCI, but it remains to be and 47% [HR 0.67, 95% CI 0.48–0.93; and HR 0.53, 95% demonstrated in randomised trials.”

LDL-apheresis plus statins reduces LDL more than statin therapy alone after PCI Low density lipoprotein (LDL)-apheresis reduced LDL more than medical treatment with statins in patients who underwent percutaneous coronary intervention (PCI) for acute heart failure, a randomised controlled study has found. Data from PREMIER (Plaque Regression and Endothelial Progenitor Cell Mobilisation With Intensive Lipid Elimination Regimen) were presented on behalf of the investigators at a late-breaking clinical trial session at the Society for Cardiovascular Angiography and Interventions 2019 Scientific Sessions (SCAI; 19–22 May, Las Vegas, USA) by Subhash Banerjee (VA North Texas Health Care System, and UT Southwestern Medical Center, Dallas, USA).

H

e said: “This is the first randomised controlled study to demonstrate the safety of LDL-apheresis in non-FH [familial hypercholesterolaemia] ACS [acute coronary syndrome] patients treated with PCI. LDL-apheresis reduced LDL more than medical treatment, with a strong trend for early coronary plaque regression.”

The multicentre study was funded by the Department of Veterans Affairs

(VA), and included patients from four VA centres in the USA. Investigators randomised 160 acute coronary syndrome (ACS) patients within 72 hours after PCI. LDL was removed by extracorporeal filtration during LDL-apheresis. The study compared single LDL-apheresis plus statin therapy (n=84) to statin therapy alone (n=76).

The primary safety endpoint was the total number and percentage of patients

with major periprocedural adverse events.

These included hypotension, angina, myocardial ischaemia, myocardial infarction (MI), a cerebrovascular event, vermicular tachycardia, bleeding (at PCI access and/or apheresis cannulation sites), and all-cause death.

The primary effectiveness endpoint was the percentage change in total plaque volume within a ≥20mm target coronary artery at 90 days on intravascular ultrasound with virtual histology (IVUSVH) follow-up.

Secondary safety endpoints were the total number and percentage of patients with statin-related abnormal liver function tests and muscle injury events.

Secondary effectiveness endpoints were the change in endothelial progenitor

A single LDLapheresis treatment lasting approximately three hours reduced low density lipoprotein by an average of 53%.”

cells colony forming unit (EPC-CFU) per ml of peripheral blood from baseline to 30 days and 90 days post-PCI, the percentage change in the necrotic core component of coronary plaque at 90 days, and major adverse cardiovascular events (MACE) at 90 days and six-month follow-up.

On the primary safety endpoint of major peri-PCI events the investigators noted three hypotensive events in two patients in the single-LDL apheresis arm who were treated with intravenous fluids.

They also found that a single LDLapheresis treatment lasting approximately three hours reduced LDL by an average of 53%. Both treatment groups were comparable at baseline. The mean LDL reduction at discharge decreased by 17% in the no LDL-apheresis cohort. The primary efficacy endpoint—percentage change in atheroma or plaque volume at 90 days by IVUS—reduced by 4.81% (95% confidence interval [CI] -8.91 to -0.71) in the LDL-apheresis group, and increased by 2.31% (95% CI -3.98–8.61) in the no LDL-apheresis group (p=0.06).

Banerjee told the conference: “The use of LDL-apheresis in ACS patients needs further study to verify the findings.” He suggested that the next step is to examine the outcome of LDL-apheresis treatment on a broader range of patients, with greater representation of women.

Issue 54 | August 2019

Conference round-up

Ultrathin strut thickness demonstrates benefits in small vessels Late-breaking trial data presented at EuroPCR 2019 (20–24 May, Paris, France) on three-year outcomes of a substudy of the BIO-RESORT randomised controlled trial in patients who were treated in small vessels demonstrate significantly lower target lesion revascularisation (TLR) rates for the Orsiro drug-eluting stent (Biotronik) than for the Resolute Integrity Stent (Medtronic).

Presenting on behalf of the investigators, Clemens von Birgelen (Thoraxcentrum Twente, Enschede, the Netherlands) said: “We feel that strut thickness is the most important parameter in this context.”

VON BIRGELEN POINTED out that percutaneous coronary interventions (PCI) in small coronary vessels have an increased adverse event risk but nevertheless have to be performed in many patients. Newer drug-eluting stents (DES), such as Orsiro and Synergy, have substantially thinner struts than earlier DES. He said: “In routine clinical practice, up to 50% of the patients have small vessel lesions, depending on the definition used. Thin struts may be particularly advantageous in small vessels due to the greater relative impact of strut size on lumen obstruction.”

The sub-analysis of the all-comers BIO-RESORT trial performed two comparisons—one looked at the ultrathin sirolimus eluting stent Orsiro

and Resolute Integrity, a thin strut zotarolimus eluting stent; and the second comparison was between Synergy (Boston Scientific), a very thin strut everolimus eluting stent (EES), and Resolute Integrity. Participants were 1,506 all-comer patients with small target vessels; 525 were treated with Orsiro, 485 with Resolute Integrity, and 496 with the Synergy DES. The main endpoint was target lesion failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or TLR. Mean age of participants was 64 years—around 30% were female, and about 20% had diabetes, which von Birgelen described as “normal rates for the Netherlands”.

Simultaneously published in JAMA Cardiology, the findings showed that

Clemens von Birgelen

We feel that strut thickness is the most important parameter in this context.” the rate of target lesion failure (TLF) for Orsiro was 7% (Orsiro vs. Resolute Integrity p=0.08), for Resolute Integrity it was 10%, and for Synergy 9.5% (Synergy vs. Resolute Integrity p=0.72).

The three stents showed similar results for cardiac death and myocardial infarction, and patients treated with the ultrathin strut Orsiro experienced

9

significantly fewer repeat target lesion revascularisations (TLR) than those treated with the thin strut Resolute Integrity (Orsiro 2.1% vs. Resolute Integrity 5.3%, p=0.009; Synergy 4.0%).

Divergence between the timeto-event curves of the Orsiro and Resolute Integrity groups seemed more pronounced after the first year post-index procedure, when dual antiplatelet therapy (DAPT) was stopped in most patients.

This is supported in a landmark analysis between one and three years, where the TLR rate with Orsiro was 1%, with Resolute Integrity it was 3.7% (p=0.006), and with Synergy 2.7%. von Birgelen said: “The results may be clinically relevant, as they suggest a relationship between the use of ultrathin strut sirolimus-eluting stents and a lower repeat revascularisation risk in all-comers patients with small target vessels. Due to a greater relative impact of stent strut size on lumen obstruction, the substantially thinner struts of these new-generation drug-eluting stents may be particularly advantageous in small vessels.”

Additionally, Orsiro showed a numerically lower three-year rate of definite or probable stent thrombosis at 0.6%, compared to 1.5% for Resolute Integrity (p=0.16) and 1.5% for Synergy.

Moreover, there was no statistically significant between-DES difference in other safety endpoints.

In the large scale, multicentre BIORESORT trial, 42.9% of the full cohort of 3,514 patients undergoing PCI presented the need for small vessel treatment.

Issue 54 | August 2019

11

Structural Heart Interventions Scoring system TASKed with predicting acute stroke following TAVI

rates of acute stroke. There was no difference in balloon pre-dilatation or post-dilatation in terms of acute stroke.”

The TASK score was designed using preprocedural parameters, “parameters that are known to the physician prior to the procedure”, explained Barbash, derived from uni- and multivariable analysis, “and, for simplicity, we elected to assign equivalent power to each TASK score parameter”.

The five parameters identified that were independently associated with a risk of acute stroke and used to develop the TASK score were: a history of previous stroke (odds Researchers have developed a risk stratification system for clinical predictors of ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.5); procedural stroke during transcatheter aortic valve implantation (TAVI) that they hope will chronic kidney disease, defined as a glomerular filtration also have implications for the use of embolic protection devices during the procedure. The rate <60mL/min/1.73m2 (OR 2, 95% CI 1.2–3.3); use of TASK score was developed from an international multicentre retrospective analysis, and a non-balloon expandable valve (OR 2, 95% CI 1.2–3.3), outlined in a late-breaking clinical trial session at EuroPCR 2019 (20–24 May, Paris, France). low body weight, with body mass index <25 (OR 1.3, 95% CI 0.9–2); and peripheral vascular resenting, Israel Barbash (Chaim Sheba Medical Europe and the Middle East. It was an alldisease (OR 1.9, 95% CI 1.3–2.9). From Center, Ramat Gan, Israel) said that it could be comers study—“all procedures that were these, four risk groups were defined, and used to facilitate patient selection for embolic done in these centres were included”—and each was assigned a TASK score: low-risk protection, as well as in the enrolment of high-risk included all valve types and any procedure (OR 1) zero points, intermediate-risk (OR patients for future studies of the devices. He added: that used a transfemoral approach, 2.19) one–two points, high-risk (OR 3.83) “The TASK score may stratify patients for risk of yielding 8,779 patients for analysis. The three points, and very high-risk (OR 9.43) acute stroke. We designed the score to use only simple primary endpoint was stroke or transient ≥four points. preprocedural components, which will be useful for the ischaemic attack (TIA) within 24 hours “Each one point increase in the TASK physician in selecting patients.” after TAVI; there were 127 acute stroke score … resulted in a significant increase Embolic protection devices decrease the incidence events, a rate of 1.4% of all cases. of acute stroke—from 0.6% with zero of procedural cerebrovascular emboli, but their current “Low body weight and chronic kidney points to 16% in patients who had five utilisation rates are relatively low. Barbash attributed disease and peripheral vascular disease Israel Barbash points. Patients who were in the high-risk this to multiple factors—“a lack of unequivocal data for were higher among the acute stroke group had a nearly four-fold increase in efficacy in reducing clinical stroke events, the added group,” Barbash said, although atrial fibrillation, a the risk of stroke as compared to the low-risk group. procedural complexity of additional arterial access to known risk factor for stroke post-TAVI, did not differ And the patients in the very high-risk group had a nearly deliver the device, and cost”. between the two groups.

10-fold increase in the risk of stroke as compared to the “The majority of strokes occur during the procedure or Additionally: “The majority of patients underwent low-risk group.” very early after the procedure, up to 24 hours.” However, a TAVI procedure under general anaesthesia, and the Barbash stressed the study’s “several significant Barbash pointed out, previous studies “assessed utilisation of … a balloon expandable valve had lower limitations” should be taken into account: “We predictors for strokes occurring either early or late after intentionally used preprocedural parameters, but the procedure; thus, these predictors may not necessarily procedural factors, which may have significant impact be applicable for prediction of acute stroke during on the risk of acute stroke, were intentionally not the procedure, or for utilisation of embolic protection included in this study. There was no standardisation in devices during TAVI.” the evaluation of the patients who sustained a stroke The objectives of the TASK study were to identify between the 12 sites that submitted cases, although all predictors for acute stroke, and to attempt to design sites reported according to the VARC 2 definition. The a simple, clinically relevant tool to identify high-risk proposed TASK score was not evaluated in a validation patients for acute stroke after TAVI. The investigators cohort due to the low event rate—this is something we performed a retrospective study on data from 12 sites in definitely should do in the future.”

P

Each one point increase in the TASK score led to a significant increase in the risk of acute stroke.”

Annuloplasty shows better improvement than leaflet edgeto-edge treatment A comparison between Cardioband (Edwards Lifesciences) and MitraClip (Abbott) for the treatment of functional mitral regurgitation (FMR) has concluded that, although both effectively reduce symptoms of MR and heart failure, Cardioband showed a more pronounced improvement in functional New York Heart Association (NYHA) class and rehospitalisation and mortality rates.

THE FINDINGS WERE presented

by Marcel Weber (University Hospital Bonn, Bonn, Germany) at EuroPCR 2019 (20–24 May, Paris, France), and also published in EuroIntervention.

Weber said: “Both [procedures] have been proven to be effective with regard to MR reduction and improvement of clinical symptoms. However, a

comparison of the two types of devices with regard to their effectiveness on reducing MR and improving patients’ outcomes and symptoms has not yet been performed.”

Weber et al collected 123 consecutive patients that were treated with the Cardioband device and 455 consecutive patients treated with the MitraClip

in five experienced European centres between 2013 and 2018; each centre contributed at least 19 Cardioband patients. Investigators performed propensity score matching, which resulted in two groups of 93 patients with no significant differences in baseline demographic parameters. Each group underwent a standardised 2D transthoracic echocardiography (TTE) assessment at baseline, and clinical follow-up at 12 months.

The success rate, defined as a reduction of MR to ≤grade 2, was high in both groups (MitraClip 86% vs. Cardioband 77%, p=0.18). The Cardioband procedure was better at reducing heart failure symptoms (NYHA ≤2 88%) than the MitraClip (75%) procedure (p=0.046) at 12-months follow-up. Within 12 months, Cardioband patients had lower rates of mortality (odds ratio [OR] 0.30, 95%

confidence interval [CI] 0.09–0.98, p=0.032) and all-cause rehospitalisation (OR 0.57, 95% CI 0.28–0.97, p=0.03).

And a subanalysis of 50 patients with severely reduced left ventricular ejection fraction (LVEF) found a greater difference in the benefit from annuloplasty with the Cardioband system compared to the MitraClip edgeto-edge treatment.

Summing up, Weber said: “The MitraClip and the Cardioband procedures are effective alternatives for the treatment of patients with symptomatic FMR at high surgical risk.

Both procedures reduced symptoms and improved functional capacities.

Patients with severely depressed LVEF might benefit from annuloplasty with the Cardioband system, but long-term and randomised studies are required to confirm the preliminary findings of these registry data.”

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Structural Heart Interventions

Transseptal puncture techniques must be mastered if physicians wish to perform leftsided interventions Francesco Maisano Comment & Analysis Interest in transseptal puncture has surged with the development of structural interventions for the left side of the heart. Francesco Maisano provides an update on its changing role in modern interventional cardiology.

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he transseptal puncture technique was developed in the 1950s by Ross et al as a diagnostic tool to investigate patient haemodynamics before cardiac surgery. However, as Doppler echocardiography became established as the main method of interpreting haemodynamics, diagnostic applications were rapidly abandoned, and transseptal puncture was no longer used much by most interventional cardiologists, although electrophysiologists continued to routinely perform it for atrial fibrillation ablation.

The advent of left-sided catheterbased therapies, and the introduction into clinical practice of several left heart structural interventions, has reawakened an interest in learning and retraining in transseptal puncture. Transseptal puncture has become a necessary step for approaching the left atrium.

Mitral valve balloon commissurotomy was the first structural procedure that required transseptal puncture and, later, the first cases of transcatheter aortic valve implantation (TAVI) were performed via an antegrade transvenous–transseptal approach, before smaller delivery systems became available. Mitral valve interventions and left atrial appendage (LAA) occlusions have also become available, and are being progressively adopted in many centres.

echocardiographic guidance, in addition to fluoroscopy and continuous pressure measurement.

Depending on the type of intervention, the patient anatomy, and the type of device, different locations can be preferable: for example, inferior punctures for LAA occlusion, posterior punctures for leaflet repair, inferior– posterior punctures for mitral valvein-valve, and so on. Under 2D and 3D echo guidance, the exact location of the puncture can usually be well identified.

Three standard echo views are used to determine the coordinates of the puncture: the bi-caval view is used to determine the position of the puncture on the superior–inferior axis, the short axis view at the base is used to check the position on the anterior–posterior axis,

August 2019 | Issue 54 and the four-chamber view to measure the height (distance) from the mitral valve annulus. In addition, 3D images can provide further information about the relative position of the puncture in relation to the target of therapy.

Precise and safe

With echo guidance, the puncture is not only more precise, but it is also safer.

When punctures are confined within the membranous portion of the fossa ovalis, the risk of tamponade is very low, and further manipulation of the catheters is safe and fast. Intracardiac echocardiograpy has been also used to guide transseptal punctures, and the availability of 3D probes for intracardiac echocardiography may expand its application further.

Pre-procedural planning tools are available to simulate the position of the transseptal puncture from a computed tomography (CT) scan, and fusion imaging can be used to guide the procedure by integrating live fluoroscopy and echocardiography, as well as the prerecorded overlays of the CT scan, eventually incorporating markers from the planning tools.

Novel TSP catheters

Mirroring the field of structural interventions, which has rapidly developed with the introduction of new devices and techniques, there has

There has recently been a drive to develop novel transseptal catheters to better fulfill the requirements of modern interventions.”

recently been a drive to develop novel transseptal catheters to better fulfill the requirements of modern interventions.

Although the original transseptal system still in use in most labs does not differ much from the original Mullin’s sheath and Brockenbrough needle, several innovations are now available. These include different catheter shapes and structures, safer needles, steerable needles and catheters, and radiofrequency catheters to address complex anatomies (for example, post-cardiotomy and floppy septum). The most recent new technologies include the TSP crosser (Transseptal Solution), a steerable transseptal catheter with a localisation/ stabilisation tool to identify and then navigate on the fossa; the FlexPoint (Indian Wells Medical), a steerable needle to simplify the procedure; and the Kapsus catheter (Bavaria Medizin Technologien GmBH), to assist and control the site of puncture within the fossa (Figure 1).

Embrace the new

The modern structural interventionalist should embrace most of the new technologies and techniques to tackle the vast variability of patient anatomies and procedural requirements. Learning transseptal techniques is once again becoming a “must-do”, and there are plenty of opportunities to receive training. At our institution, we run several transseptal courses, including hands-on training with high fidelity physical and computer simulators, and similar short versions of these courses are available at major conferences, such as Transcatheter Valve Therapies (TVT), Transcatheter Cardiovascular Therapeutics (TCT), PCR, and PCR London Valves.

Now is the time to learn the basics as well as the advanced skills necessary to perform transseptal puncture in left heart structural interventions.

Francesco Maisano is at the Department of Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland.

Reaching a critical puncture

These novel procedures have introduced a new requirement for transseptal puncture—particularly in mitral interventions, as the location of the puncture within the fossa ovalis plays a critical role in the efficiency of the procedures and their probability of success. For this reason, transseptal puncture for mitral interventions is routinely performed using

Figure 1: A) Kapsus catheter (Bavaria Medizin Technologien GmBH); B) FlexPoint (Indian Wells Medical); C) TSP crosser (Transseptal Solution).

Structural Heart Interventions

Issue 54 | August 2019

PASCAL poised to rival MitraClip for safety and efficacy PASCAL’s (Edwards Lifesciences) safety and efficacy may rival that of MitraClip (Abbott) for the treatment of mitral regurgitation (MR), according to data published in JACC: Cardiovascular Interventions.

F

abien Praz, Stephan Windecker (University Hospital Bern, Bern, Switzerland), and Samir Kapadia (Cleveland Clinic, Cleveland, USA) write that the PASCAL repair system “is a welcome addition to the armamentarium of transcatheter mitral valve devices”, although they concede it would be “undue to draw definitive conclusions” from their initial findings.

They analysed 30-day outcome data from their early feasibility study (EFS) on 62 patients from 14 centres, along with previously published findings from a compassionate use (CU) experience in 23 patients published in the Lancet in 2017 (also Praz et al). Participants included symptomatic patients with primary (26% from CU, 36% EFS) and secondary (52% CU, 55% EFS) mitral regurgitation. Mean age and left ventricular ejection fraction was similar in both groups.

Procedural success was high in the early feasibility study, with MR ≤grade 2+ in 98% of patients. A reduction of MR to ≤grade 1+ was obtained in 86% of the treated patients in the early feasibility study and 77% of those in the compassionate use cohort, a finding, say Praz and colleagues, “that may be explained by the more liberal implantation of two devices in 49% of cases (26% during the CU experience)”.

They continue: “Although the placement of two implants occurred more frequently than one would have expected considering the wider implant device, postprocedural mitral stenosis with mean gradient >5mmHg was uncommon.”

The mortality rate was 1.6% in the early feasibility study, and 13% in the compassionate use group, with no strokes in either cohort. Major bleeding occurred in

Head-to-head trials are necessary, and registries of patients with unique anatomies.”

6.5% of cases in the early feasibility group, compared to 0% among those treated for compassionate use.

Praz et al say that two important questions remain: how PASCAL fits into the treatment options with MitraClip, and how different percutaneous mitral repair and replacement therapies can be integrated in future clinical trials and clinical practice.

The authors point to some of the possible advantages

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of PASCAL over MitraClip, including wider paddles, the ability to independently grasp leaflets, and the presence of a central spacer. But they caution: “It remains to be seen if more complex anatomies (for example, larger flail segments, large prolapse, cleft, short posterior leaflet) or smaller mitral valve areas (for example, patients with mitral annular calcification) can be preferentially treated with PASCAL.” Due to differences in the shape and size, and the tension exerted on the leaflets, head-to-head comparison trials of the devices are necessary, they say, as well as registries of patients with unique anatomies.

These must also incorporate sequential or combined treatments,“even if they are challenging to design”, because they are likely to be used in clinical practice when more than one device becomes available. “Early experience attests to the feasibility of the procedure, and further studies will be instrumental to define the appropriate use and indication for this novel device.”

The researchers add: “This is probably the most strategic era for the evolution of percutaneous mitral valve therapies. Interestingly, the … technical characteristics of the PASCAL devices may also be advantageous for the treatment of the regurgitant tricuspid valve that is characterised by thin leaflets and larger coaptation defects.”

Data presented at Transcatheter Valve Therapies 2019 (TVT; 12–15 June, Chicago, USA) also suggest a possible role for the PASCAL system in the management of tricuspid regurgitation. Neil P Fam (St Michael’s Hospital, University of Toronto, Toronto, Canada) outlined a multicentre experience of compassionate use of the PASCAL system for patients with severe tricuspid regurgitation.

He concluded that this first-in-human experience of PASCAL for tricuspid regurgitation indicated that the system was associated with “high procedural success, acceptable safety, and significant clinical improvement in patients with challenging tricuspid anatomy and severe tricuspid regurgitation”.

TRILUMINATE suggests edge-to-edge repair is safe and effective in the treatment of tricuspid regurgitation Use of edge-to-edge repair in patients with tricuspid regurgitation appears to be a safe procedure, according to 30-day data from the TRILUMINATE clinical trial, which were presented at EuroPCR 2019 (20–24 May, Paris, France). In addition, it effectively reduced tricuspid regurgitation by at least one grade at 30 days, and had a low complication rate.

GEORG NICKENIG (University of Bonn, Bonn, Germany) outlined findings from the study to evaluate the safety and performance of the TriClip (Abbott) in symptomatic moderate-to-severe tricuspid regurgitation on behalf of his co-investigators: “Tricuspid regurgitation is a very prevalent disease and it is associated with a poor outcome, and we have only limited treatment options available, such as diuretics, and very high surgical risk procedures.” He pointed out that minimally invasive catheterbased procedures had the potential to reduce tricuspid regurgitation and had low procedural risk, and that previous retrospective studies have indicated that percutaneous edge-to-edge repair of the tricuspid valve could be a promising option for treatment of clinicallysignificant tricuspid regurgitation.

The prospective single-arm multicentre trial was conducted at 21 sites in the USA and Europe, with 85 participants in the initial feasibility study. The trial was powered for a primary effectiveness endpoint of a reduction in tricuspid regurgitation of at least one grade at

30-days postprocedure; the primary safety endpoint was a composite of major adverse events at six months. Inclusion criteria were moderate to severe symptomatic tricuspid regurgitation, and no indication for left-sided pulmonary valve correction. Among the exclusion criteria were severe hypertension or pulmonary artery pressure and a left ventricular ejection fraction ≤20%.

Average age of participants was 78 years, and 34% were male; 86% had hypertension and 17.6% had had a previous myocardial infarction. Additionally, 33% had had a previous mitral intervention. Immediately after the procedure, both implant success and acute device success rates were 100%—“meaning that we were able to place a clip where we want to place a clip within the leaflets in every patient,” said Nickenig; 91.6% Georg Nickenig

acute procedural success was achieved, “meaning that we reduced tricuspid regurgitation by at least one grade”.

He continued: “In 86% of the patients we were able to reduce tricuspid regurgitation with the TriClip … by more than one grade, in many patients by two grades or even more grades.”

At baseline, 94% of patients had severe, massive or torrential disease. After the procedure, said Nickening, “more than 50% of patients left the hospital or were assessed at 30 days with moderate or even less tricuspid

regurgitation”.

“The consequences of the improvement of tricuspid regurgitation were significant; 80% of the patients were in New York [Heart Association] class III and IV at the beginning of the trial, and after the trial, conversely, more than 80% of the patients were in New York [Heart Association] class I and II, as judged by the study.”

Patient self-assessment of quality of life also improved by 30 points between baseline and 30 days. Nickenig explained: “An increase of five points is considered to be a significant finding.”

In terms of safety data, there were no cardiovascular deaths and all-cause mortality was zero, there were no strokes or myocardial infarctions, and there was no need for conversion to open surgery.

Nickenig concluded: “Subjects experienced a significant improvement.

The TriClip effectively reduced tricuspid regurgitation in that early experience in this feasibility trial. TRILUMINATE … found this to be a promising treatment option, of course to be tested in randomised clinical trials.”

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Structural Heart Interventions

August 2019 | Issue 54

Use of drugs that affect serotonergic pathways leads to an increased risk of valvular heart disease The risk of valvular heart disease is increased by drugs that affect serotonergic pathways, according to a meta-analysis published in Heart.

JACQUELINE H FORTIER (University of Ottawa Heart Institute, Ottawa, Canada), Giovanni Ferrari, (Columbia University, New York, USA) et al found a consistent, significant association between many medications that affect serotonergic pathways and valvular heart disease.

Serotonergic appetite suppressants and ergot-derived dopamine agonists have previously been associated with drug-induced valvular heart disease. The meta-analysis aimed to evaluate current evidence of a link between several medications that affect serotonergic pathways and valvular heart disease.

The authors searched PubMed to

identify any studies evaluating an association between medications with serotonergic activity and cardiac valvular pathology. They excluded case reports, and uncontrolled and in vitro studies.

Relevant studies were assessed for quality and potential bias. Those that were considered to be of adequate quality were included in a quantitative synthesis, and a sensitivity analyses was conducted.

Potential publication bias was also examined.

Fortier, Ferrari et al found a consistent significant relationship between certain medications and heart valve disease, including serotonergic medications (odds ratio [OR] 3.3, 95% confidence interval

[CI] 1.99–5.49) and dopaminergic medications (OR 2.56, 95% CI 1.68– 3.91). They also found a consistently significant relationship in subanalyses that limited exposure to a single medication or effects to a single heart valve.

In addition, two small studies found an association between drug-induced valvular heart disease and selective serotonin reuptake inhibitors, as well as 3,4-methylenedioxymethamphetamine (MDMA), commonly known as ecstasy.

The investigators note that most of the studies included in the meta-analysis were retrospective or observational in

The researchers found a consistent significant relationship between certain medications and heart valve disease.”

SAVR has lower rates of mortality and MACCE than TAVI using firstgeneration devices in low- and intermediate-risk patients after five years Five-year results suggest that surgical aortic valve replacement (SAVR) is associated with lower mortality and major adverse cardiac and cerebrovascular event (MACCE) rates than transfemoral transcatheter aortic valve replacement (TAVI) performed using first-generation devices in low- and intermediate-risk patients with severe aortic stenosis.

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he findings from the OBSERVANT study (Observational Study of Effectiveness of SAVR–TAVI Procedures for Severe Aortic Stenosis Treatment) were published in Circulation: Cardiovascular Interventions. Marco Barbanti (University of Catania, Catania, Italy) et al say that the data need to be confirmed in further randomised trials using new-generation TAVI devices.

Between December 2010 and June 2012, investigators enrolled an unadjusted population of 7,618—of these, 5,707 patients had SAVR and 1,911 patients underwent TAVI. Two groups with similar baseline characteristics were selected by propensity score matching, and all outcomes were adjudicated through linkage with administrative databases.

Primary endpoints were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at five years. There were 1,300 patients in the matched population—650 in each group. The propensity score method generated a low- and intermediate-risk population (mean logistic EuroSCORE 2: 5.1±6.2% vs.

4.9±5.1%, SAVR versus transfemoral TAVI, p=0.485).

Barbanti et al found that, at five years, the rate of death from any cause was 35.8% in the surgical group and 48.3% in the transcatheter group (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.12–1.69,

p=0.002). TAVI was also associated with an increased risk of major adverse cardiac and cerebrovascular events compared to SAVR (42.5% vs. 54%, HR 1.35, 95% CI 1.11–1.63, p=0.003). The cumulative incidence of cerebrovascular events, myocardial infarction, and coronary revascularisation were similar in the study groups at five years.

Barbanti told Cardiovascular News that there were several reasons that could account for the “provocative results” obtained. He explained: “The

nature, with a higher risk of selection and presentation biases. There was also significant heterogeneity and variability between studies, particularly when it came to dose and duration of exposure.

Fortier, Ferrari and colleagues point out: “Although many of these medications have been withdrawn from the market, some small studies suggest that recreational drug 3,4-methylenedioxymethamphetamine and widely prescribed selective serotonin reuptake inhibitors may affect similar pathways.”

Giovanni Ferrari

above all, incomplete coronary revascularisation and untreated degenerative mitral and functional tricuspid regurgitation—that could have had a significant impact on the long-term prognosis of the TAVI patients. And, lower haemoglobin and albumin values, and a higher rate of oxygen dependency among TAVI patients compared with SAVR patients, which persisted despite the propensity adjustment, imply a sicker TAVI group at baseline. In addition, the study enrolled patients during the early months of TAVI adoption in many centres. A learning curve was likely present, which might have affected TAVI outcomes early in the study.”

One-year data from OBSERVANT showed that mortality is similar for transfemoral TAVI and SAVR in a real-world propensity matched population with aortic stenosis and at low and intermediate risk. The authors advise that the latest findings need further validation in randomised controlled trials that use new-generation TAVI devices in a real-world population.

At five years, the rate of death from any cause was 35.8% in the surgical group vs. 48.3% in the transcatheter group.” inclusion of an unselected population, including patients with unfavourable anatomical and clinical features for TAVI, likely led to a higher incidence of postprocedural sequalae (paravalvular leak, pacemaker implantation) and unsolved cardiac pathologies—

Marco Barbanti

Structural Heart Interventions

Issue 54 | August 2019

The findings on transcatheter aortic valve implantation in patients who are at low risk for cardiac surgery will usher in a new era for patients

Sapien 3 (top); CoreValve Evolut (bottom)

Amar Krishnaswamy Samir R Kapadia Recent low-risk trials for transcatheter aortic valve implantation (TAVI) look set to expand its indications for use. Amar Krishnaswamy and Samir R Kapadia assess the impact of the findings on everyday practice, and look at areas where uncertainties remain.

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Recent low surgical-risk trials

Among 1,000 low surgical-risk patients who were randomised to the balloonexpandable Sapien 3 valve (Edwards Lifesciences) or to SAVR in the PARTNER 3 trial, those undergoing TAVI demonstrated superiority at two years with respect to stroke rate at 30 days (0.6% vs. 2.4%, p=0.02) and mortality at one year (1% vs. 2.5%, p=0.001), with a similar permanent pacemaker implantation (PPI) rate and lower hospital length-of-stay (three vs. seven days).1 The CoreValve low surgical-risk trial randomised 1,468 patients to receive either the Medtronic Evolut-R/EvolutPro self-expanding TAVI platform or

routine surgery. Similar outcomes were noted to those found in the Partner 3 trial, including for stroke (0.5% vs. 1.7%) and mortality (4.5% vs. 4.5%). However, there was a higher rate of PPI among the TAVI group (17.4% vs. 6.1%), consistent with previous trials of the self-expanding valve platform. Given these robust data, patients and physicians eagerly anticipate US Food and Drug Administration (FDA) approval of TAVI for this low-risk group of patients. But there are still some issues that remain to be cleared up.

Stroke risk in TAVI vs. SAVR

Unfortunately, all patients undergoing cardiac procedures have an inherent risk of embolic stroke. Though initial trials of TAVI compared to SAVR questioned whether there was a higher risk of stroke with TAVI among high surgical-risk patients, longer-term follow-up proved that this was not the case; the more recent trials among medium and low surgical-risk patients have shown that stroke risk is in fact lower with TAVI. Nevertheless—and despite improvements in devices and operator experience and a changing patient risk profile—stroke rates have not really declined for TAVI or SAVR, and therefore remain clinically relevant.

In SAVR, the stroke risk is directly related to cross-clamping the aorta,

further complicating our understanding.

Although available data suggest that leaflet thrombosis may be higher with TAVI valves than with surgical valves, well-conducted head-to-head comparisons are not available.

What is known is that among randomised trials of TAVI vs. SAVR there is no clinical signal of early valve degeneration of TAVI prosthetics and, in fact, some reports have even suggested an earlier deterioration of SAVR valves.5,6 The computed tomography (CT) substudies of the low surgical-risk trials will provide important data about the true incidence of leaflet thrombus in transcatheter and surgical valves, as well as the clinical consequences. Long-term follow-up is also needed for thorough risk–benefit assessment of TAVI versus SAVR.

Cautious optimism

Comment & Analysis

ranscatheter aortic valve implantation (TAVI) is a mature procedure for the treatment of patients with severe and symptomatic aortic valve stenosis (AS). From the time of its inception in 2002 until it received US Food and Drug Administration (FDA) approval—initially for inoperable patients in 2012, then for high surgicalrisk patients in 2013, followed by medium-risk patients in 2016—TAVI has ushered in a revolution in the treatment of AS. Importantly, this shift in care has been the result of consistent improvements in TAVI device technology and operator experience, with robust and randomised clinical trial data demonstrating either non-inferiority or superiority to surgical aortic valve replacement (SAVR). Given the favourable results from the recently published low surgical-risk trials, TAVI is set to again change the paradigm of AS treatment.1,2

17

and therefore it cannot be further reduced beyond that brought about through careful aorta manipulation and haemodynamic management. In TAVI, it can be mitigated by the use of cerebral embolic protection (CEP) filters. Though many CEPs are currently under clinical trial, the Sentinel device (Boston Scientific) is the only one that is approved by the FDA for use during TAVI. Various clinical trials, singlecentre experiences, and meta-analyses have demonstrated a consistent 60–80% relative risk reduction in stroke when using this device, in comparison to “unprotected” TAVI.3 Meta-analyses have also shown a reduction in magnetic resonance imaging (MRI) detected brain lesions without clinically apparent stroke. Whether this may exert a long-term influence on “silent-infarct” related cognitive decline has yet to be determined.

Valve durability and leaflet thrombus

Though recent reports of valve leaflet thrombus of TAVI prosthetics have appropriately raised concerns, it is important to realise that the clinical ramifications of this are, as yet, unclear.4 In fact, these papers have led to an increased recognition of leaflet thrombus among surgical valves,

A detailed imaging analysis to understand anatomic feasibility and valve choice is imperative if these exemplary results are to be maintained.”

It is important to understand that the excellent results achieved for TAVI in the low surgical-risk trials have been achieved at centres that have high TAVI volume and experienced operators, and they were obtained following a thorough evaluation of patients’ anatomic and clinical suitability. If patients are to receive the ideal treatment all of these factors must remain consistent.

Patients with other cardiovascular pathologies, such as mitral regurgitation, severe coronary artery disease, and aortic aneurysm, should be considered for complete surgical correction. Simply offering TAVI at every opportunity will not provide optimal results.7 Furthermore, a detailed imaging analysis (preferably by the operators and performing sites) to understand anatomic feasibility and valve choice, and facility with techniques for “bailout” when necessary (that is, in the case of threatened coronary compromise, vascular complication, or annular trauma), is imperative if these exemplary results are to be maintained. This is important not only in the performance of TAVI, but also to identify those patients—low-risk or otherwise—who would be better suited to traditional SAVR. References 1. Mack MJ, et al. Transcatheter aortic valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019; 380(18): 1695–1705.

2. Popma JJ, et al. Transcatheter aortic valve replacement with a self-expanding valve in low risk patients. N Engl J Med 2019; 380(18): 1706–15.

3. Seeger J, et al. Rate of peri-procedural stroke observed with cerebral embolic protection during transcatheter aortic valve replacement: a patient-level propensitymatched analysis. Eur Heart J 2019; 40(17): 1334–40.

4. Makkar RR, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2015; 373(21): 2015–24.

5. Daubert MA, et al. Long-term valve performance of TAVR and SAVR: a report from the PARTNER I trial.

JACC: Cardiovasc Imaging 2016.

6. Sondergaard L, et al. Durability of transcatheter and surgical bioprosthetic aortic valves in patients at lower surgical risk. J Am Coll Cardiol 2019; 73(5): 546–53.

7. Vemulapalli S, et al. Procedural volume and outcomes for transcatheter aortic valve replacement. N Engl J Med 2019.

Amar Krishnaswamy and Samir R Kapadia are at the Cleveland Clinic, Cleveland, USA. ■ In the next issue, Pavel Overtchouk and Thomas Modine give their views on the impact of the findings in low-risk TAVI trials.

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August 2019 | Issue 54

Interview

Profile

Josep Rodés-Cabau Josep Rodés-Cabau has been at the forefront of advances in structural heart disease interventions, relishing the immediate outcomes provided by transcatheter treatments. He tells Cardiovascular News about his contributions to progress in techniques, and outlines his predictions for the development of interarterial shunting in the treatment of heart failure.

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

I found the combination of science and humanism in the medical field fascinating. Also, my uncle, Dr Jacint Cabau—a general cardiologist who is passionate about his profession and highly dedicated to his patients— influenced my decision to become a doctor and cardiologist. Then, during my cardiology residency, I very much enjoyed my time in the cath lab. Being able to apply a treatment and see immediate results (I was particularly impressed by primary coronary angioplasty) had a major impact on my decision to become an interventional cardiologist.

Who were the biggest influences on your early career?

I did my cardiology residency at the Vall d’Hebron University Hospital in Barcelona, Spain—one of the best centres in Europe. The cardiology department had a group of highly talented cardiologists in terms of clinical skills and academic profile, all of whom had a major positive influence on me, as did the strong spirit of global excellence there. I did my fellowship training in coronary interventions at the Montreal Heart Institute in Canada, and in congenital interventions at the Institut Cardiovasculaire Paris Sud (Paris, France) and the Sainte-Justine Hospital (Montreal, Canada) under the mentorship of Jean François Piéchaud and Joaquim Miro, respectively—two of the most skilled interventionalists I have ever met. I am very thankful to all of these centres and the people working in them.

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

Transcatheter valve replacement, which started with pulmonary valves, then aortic, mitral, and, more recently, tricuspid valves. All heart valves can be replaced through transcatheter techniques, a dream come true.

What has been the greatest disappointment—an advance that you hoped would change practice, but which failed to do so?

I would probably say coronary thrombectomy in the context of primary percutaneous coronary interventions (PCI). It is still difficult to understand why such an elegant and effective manoeuvre for reducing thrombus burden failed to show clinical benefits. This is a good example of the importance of properly designed trials to generate evidence-based data.

What are your current research interests?

My current research interests in the field of structural heart disease interventions range from innovation (new devices, device iterations, and disruptive therapies) to technique refinements and improvements in patient evaluation, periprocedural aspects, and mid- to longterm clinical outcomes. This includes the field of transcatheter valve replacement and repair (particularly aortic, mitral, and tricuspid valves), interventional

therapies for preventing thromboembolic events (left atrial appendage [LAA] closure, patent foramen ovale [PFO] closure), and new therapies for the treatment of heart failure, such as interatrial shunting. I currently hold the research chair “Fondation Famille Jacques Larivière” for the development of structural heart disease interventions (Laval University), which is the basis for most of my projects in this area.

What do you consider to be your biggest contribution to the field of interventional cardiology?

It is difficult to choose a single piece of work. Instead, I would select, in the transcatheter aortic valve implantation (TAVI) field, several series of original studies on the evaluation of valve haemodynamics (these include the very first publication, 10 years ago, showing better valve haemodynamics following TAVI versus surgical aortic valve replacement [SAVR]), identification of factors of increased risk in order to

In the near future, we will see transcatheter mitral treatments as complementary, with some patients better suited for repair and others for replacement—as in the surgical field.” implement preventive and/or therapeutic measures (for example, coronary obstruction, prediction of treatment futility, infective endocarditis), antithrombotic treatment (including the ARTE [Aspirin Versus Aspirin plus Clopidogrel Following Transcatheter Aortic Valve Implantation] trial) and, last but not least, the evaluation and management of conduction disturbances (including determining the predictors of sudden death and the MARE trial [Ambulatory Electrocardiographic Monitoring for the Detection of High-Degree AtrioVentricular Block in Patients With New Onset Persistent Left Bundle Branch Block After Transcatheter Aortic Valve Implantation]).

I would also highlight my contribution to the technical and academic training of dozens of interventional fellows from around the world (particularly Europe, South America, and Australia). I am really proud of our fellowship programme at the Quebec Heart and Lung Institute/Laval University, which makes a very relevant contribution to the field of interventional cardiology.

What is the most important paper that was published in the past year?

I would select the PARTNER 3 and Evolut Low Risk trials. These studies represent the consolidation of TAVI as the treatment of aortic stenosis in elderly patients.

From our research group, I would choose the TOPASTAVI registry (Ribeiro, Rodés-Cabau et al, JACC 2018),

which provided very important insights into the treatment of low-flow, low-gradient aortic stenosis, one of the most challenging groups of patients with aortic stenosis.

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

I would select four priorities—research dedicated to better understanding, prevention, and management of conduction disturbances post-TAVI; studies on valve durability; research evaluating the most appropriate antithrombotic treatment following structural interventions (including valve replacement and interventional therapies for embolic prevention, such as LAA and PFO closure); and research dedicated to improving transcatheter devices and delivery systems, as well as periprocedural aspects in the mitral and tricuspid space.

What do you think the next breakthrough innovation will be?

I think the next breakthrough innovation will be interatrial shunting as a new treatment for heart failure in patients with preserved and reduced ejection fraction.

I had the opportunity to lead the initial experience

Issue 54 | August 2019

Interview

19

Fact File

replacement—as in the surgical field. No doubt there are very exciting times to come in the mitral space.

What do the high rates of pacemaker implantation rates seen with TAVI signal for its long-term viability as a therapy, particularly as it moves into treatment of low-risk populations?

I agree that this remains one of the most important drawbacks of the procedure, which could partially hamper enthusiasm regarding the expansion of TAVI. The long-term negative effects of conduction disturbances and pacemaker implantation are well known, and this becomes even more important in younger patients with a long life expectancy. However, I am optimistic. In the near future, I anticipate that we are going to see refinements in valve positioning (implantation depth) translating into much lower rates of pacemaker implantation for some valve types. Also, there will be improvements in the management of conduction disturbances post-TAVI (particularly left bundle branch block), likely contributing to lowering the rates of permanent pacemaker implantation.

Additionally, we have just finalised an expert panel document (to be published in JACC) providing some guidance, based on current evidence and consensus opinion of a group of experts in the field, that may help to reduce practice variability among centres and operators. The end objective should be no (or extremely infrequent) arrhythmic deaths while keeping the pacemaker rate as low as possible after TAVI. I think that this will be achievable in the near future.

Is there any value of attending conferences in this online age?

with one interatrial shunting device (the V-Wave device, V-Wave Ltd), showing the safety of this therapy, along with clinical improvements in a significant proportion of patients.

Multiple devices have recently been developed, with very promising preliminary results, and there are two ongoing randomised trials trying to provide definitive data on the efficacy of this therapy for the treatment of heart failure. My guess is that these trials will be positive, and that this therapy will become a new treatment for such patients in the coming years.

How do you see treatment options evolving in mitral valve repair over the next few years? Of the developing technologies, will one emerge as the gold standard or will it remain dependant on patient factors, such as anatomy?

Transcatheter mitral repair, particularly clipping and some annuloplasty devices, is at the stage of treatment refinement and results improvement, with the potential for a combination of the therapies in some patients (for example, clip plus annuloplasty). At the same time, transcatheter mitral valve replacement is emerging, with some very promising preliminary results but also some difficulties. I think that, in the near future, we will see these two treatments as complementary, with some patients better suited for repair and others for

In my opinion, the main value of attending conferences is in the multiple face-to-face meetings. I think that interest in lectures, case demonstrations, and so on is clearly reduced in an era where all the information can be accessed online in a much more cost- and timeeffective manner. Additionally, I think that there is an excessive number of meetings; I am not sure that this is sustainable in the longer term.

Do you use social media and, if so, what is its added value?

I do not use social media. Firstly, because of a lack of time. And, while I assume that there are advantages regarding knowledge dissemination, I have concerns about superficial and misleading messages, along with the potential for extreme (and potentially harmful) opinions to be expressed.

What advice would you give to someone who was starting out in cardiovascular medicine?

Be passionate and focus on a specific topic. I recognise the importance of general cardiology, but nowadays the field of cardiovascular medicine is too extensive to allow for proficiency in all areas. That being said, there is no doubt that developing a good knowledge of cardiovascular imaging is already—and will continue to be—a must for all cardiovascular subspecialities, including interventional cardiology.

What are your hobbies and interests outside of medicine?

I like sport, both practising and watching it (I was a semi-professional soccer player, and now I enjoy cycling and jogging, frequently with my kids). I also very much enjoy watching a good film or reading a book, although this happens less frequently than I would like.

Current appointments

Director, Catheterization and Cardiovascular Interventions, Quebec Heart and Lung Institute, Quebec City, Canada Associate professor of medicine, Laval University, Quebec City, Canada Research chair “Fondation Famille Jacques Larivière” for the development of structural heart disease interventions, Laval University, Quebec City, Canada Associate editor of the Journal of the American College of Cardiology

Selected publications (from >450)

Clavel MA, Rodés-Cabau J, et al. Comparison of the haemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis. J Am Coll Cardiol 2009; 53: 1883–91.

Ribeiro HB, Rodés-Cabau J, et al. Predictive factors, management, and clinical outcomes of coronary obstruction following transcatheter aortic valve implantation: insights from a large multicenter registry. J Am Coll Cardiol 2013; 62: 1552–62.

Campelo-Parada F, Rodés-Cabau J, et al.

First-in-man experience of a novel transcatheter repair system for treating severe tricuspid regurgitation. J Am Coll Cardiol 2015; 66: 2475–83.

Regueiro A, Rodés-Cabau J, et al.

Association between transcatheter aortic valve replacement and subsequent infective endocarditis and in-hospital death. JAMA 2016; 316: 1083–92.

Del Trigo M, Rodés-Cabau J, et al.

Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proofof-principle cohort study. Lancet 2016; 387: 1290–7.

Rodés-Cabau J, et al. Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: the ARTE randomized clinical trial. JACC: Cardiovasc Interv 2017; 10: 1357–65.

Selected professional honours and awards

Best clinical investigator Quebec Heart and Lung Institutue, December 2017 List of World’s Most Influential Scientific Minds 2017 (Clarivate Analytics) List of World’s Most Influential Scientific Minds 2018 (Clarivate Analytics)

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August 2019 | Issue 54

MedTech Insights

Source: BIBA MedTech TAVI Monitor.

Source: BIBA MedTech TAVI Monitor.

Edwards Lifesciences drops Centera TAVI valve in favour of focusing on Sapien range Edwards Lifesciences—in a press statement announcing its global second quarter (Q2) financial results—has revealed that it is taking the self-expanding transcatheter aortic valve implantation (TAVI) device Centera off the market. The company says resources will instead be focused on the balloon-expanding Sapien range of TAVI devices, adding that it expects the US Food and Drug Administration (FDA) to approve Sapien 3/Sapien 3 Ultra for lowrisk patients this quarter (Q3).

THE CENTERA VALVE has been on the European market for just over a year, and has never been approved for the US market. According to Michael A Mussallem, chairman and CEO of Edwards Lifesciences, Centera has “demonstrated excellent clinical outcomes and is performing well for patients”, but the company took the “difficult decision” to take it off the market because “the time and resources required to optimise deliverability, as well as expanding the indications [of Centera] to match [those of] the Sapien 3 valve, are significant”. Sapien 3 is indicated for intermediate-risk, high-risk, and inoperable patients (in Europe and the USA), and may soon be indicated for low-risk patients. “We now estimate that in the third quarter [of this year], the FDA will approve the Sapien 3 and the Sapien 3 Ultra valve for patients with low surgical risk,” Mussallem comments. In contrast, Centera is only indicated for high-risk/inoperable patients.

Prior to reporting its Q2 results, Edwards Lifesciences issued an urgent field safety notice for Centera.

In the notice, the company says it has received reports “of difficulty tracking and manipulating the Centera system around the aortic arch that resulted in vascular injury, including aortic dissection and death during early cases”. It adds that a “thorough

investigation” of these reports shows that the tracking difficulty is “more likely to occur when the device is used in specific tortuous aortic anatomies. The observed incidence of serious events related to this issue is approximately 1.5% based on the limited global experience with this device to date,” Edwards Lifesciences reports. It goes on to specify anatomies for which alternative treatment options to Centera should be considered and recommends preand intraprocedural steps to reduce the risk of encountering problems with tracking the device. In the notice, the company also provides advice on what operators should do if they encounter such problems.

Usage of Centera and Sapien 3 Ultra in Western Europe

The BIBA MedTech TAVI monitor first began tracking the use of the Centera valve in Western Europe in Q2 2018 (the device received the CE mark in February 2018). In that quarter, 2.3% of all Edwards’ TAVI valves implanted (6,541 overall) were a Centera valve.

However, Centera accounted for less than 2% of all Edwards TAVI valves implanted in each subsequent quarter (Q3 2018–Q1 2019, see Figure 1).

Of note, in November 2018, Edwards Lifesciences received the CE mark for its Sapien 3 Ultra device,

and the TAVI Monitor began tracking the use of this device in Q1 2019.

In this quarter, 2.8% of all Edwards’ TAVI devices implanted in Q1 2019 were a Sapien 3 Ultra (see Figure 1). Mussallem says that, over time, Edwards expects that “the Sapien 3 Ultra valve system will replace the Sapien 3 valve globally”.

However, Sapien 3 Ultra’s potential to replace Sapien 3 may be hampered by the fact that it was the subject of an urgent safety notice recently issued by Edwards Lifesciences. The company issued the safety notice for Sapien 3 Ultra shortly after it had issued one for Centera (within the same calendar month); in the notice, it states that there have been reports of “burst balloons” with the device, and these have “resulted in significant difficulty retrieving the Sapien 3 Ultra delivery system into the sheath and withdrawing the system from the patient. The overall observed complaint rate for balloon burst is approximately 1%, based on the limited experience with the device, of which approximately 0.5% had clinical implications for the patient, such as difficulty removing the delivery system, vascular injury, bleeding and/or need for surgical intervention,” Edwards Lifesciences comments. Similar to its advice in the Centera safety notice, it outlines recommendations for avoiding burst balloons and what to do should the operator suspect that a balloon has burst.

Edwards Lifesciences’ market share

It is not yet known what effect that Centera being taken off the market and the recent safety notice for Sapien 3 Ultra will have on Edwards Lifesciences' market share. Also unknown is the potential impact of Sapien 3/Sapien 3 Ultra being approved for low-risk patients; although it is presumed that if they are approved for this indication, the number of implanted Edwards’ devices may increase.

At present, Edwards Lifesciences is the market leader in the Western European TAVI market, and has been for some time (including before either Centera or Sapien 3 Ultra were on the market). In Q1 2019, for example, 43.2% of all TAVI devices implanted (15,603) were an Edwards valve vs. 39.9% for Medtronic devices (CoreValve range) and 11.2% for Boston Scientific devices (Acurate neo). See Figure 2.

According to the press statement announcing the Q2 2019 financial results, Edwards Lifesciences reported TAVI sales of US$678 million globally—an increase of 16% compared to the second quarter of 2018, and an 18% increase on an underlying basis.

Speaking about the overall financial results for Edwards Lifesciences, Mussallem comments: “We are very pleased with our strong performance in the first half of 2019.

As patients and clinicians increasingly understand, the significant benefits of transcatheter-based technologies, supported by the substantial body of compelling evidence, we remain as optimistic as ever about the longterm growth opportunity."

BIBA Briefings

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

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

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August 2019 | Issue 54

US perspectives

International medical graduates in US cardiovascular care are vital to healthcare in the USA and beyond William W Pinsky Mandeep R Mehra Comment & Analysis William W Pinsky and Mandeep R Mehra explain to Cardiovascular News how international medical graduates contribute to both their adopted country and their country of origin, providing benefits for all.

I

t should come as no surprise that international medical graduates (IMGs) are vital to US healthcare, with 25% of our active physician workforce having received their medical education outside of the USA and Canada, according to data from the American Medical Association.

In the cardiovascular specialties, the proportion of IMGs—one-third of active physicians—is even more significant. In interventional cardiology, 44% of active physicians in the USA are IMGs. Of these IMGs in cardiovascular specialties, 15% are US citizens who travelled abroad for their medical

education. The IMGs in the USA who are cardiovascular physicians come from more than 130 other countries. They are drawn to the USA as a premier location for advanced training in cardiovascular care, where they not only have access to traditional training but also to a host of programmes that represent emerging knowledge, research, and techniques shaping the future of cardiovascular care.

The training opportunities afforded to IMGs in US graduate medical education (GME) programmes are the foundation for the extraordinary contributions they make to care, not only in the USA, but around the world. The Educational

SCAI document gives advice to cath labs on financial viability The Society for Coronary Angiography (SCAI) has issued a statement, endorsed by the Alliance of Cardiovascular Professionals (ACVP), providing advice on the economics of cardiovascular cath labs and how they can be financially viable.

THE AIM OF the document is to “illuminate general economic principles of CCL [cardiovascular catheterisation laboratory] operations and provide details that can be used immediately”.

James C Blankenship (Geisinger Medical Center, Danville, USA) and colleagues say: “Understanding the economics of cath labs is essential for physicians, administrators, and other cardiac cath lab personnel as they strive to balance the best possible patient care with fiscal constraints and competing demands for resources.”

Published in Catheterization and Cardiovascular Interventions, the recommendations include details on how to align strategy, personnel, and culture with leadership, organisation, and processes, and how to optimise profitability, as well as on the relationship between efficiency and reducing expenses.

Commission for Foreign Medical Graduates (ECFMG) is the sole sponsor of foreign national physicians for the J-1 visa to participate in US clinical training programmes. The J-1 is the most common visa classification employed for this purpose, and therefore the ECFMG’s data provide a representative snapshot of the pipeline of foreign national IMGs who pursue US training to enter cardiovascular care. This indicates that IMGs from outside the USA are pursuing advanced US training in several fields. In 2018, the ECFMG sponsored 651 foreign national IMGs as fellows to train in nearly 40 cardiovascular specialisations within anaesthesiology, general surgery, internal medicine, paediatrics, radiology, and thoracic surgery. They engaged in training programmes located in 43 US states, with numbers growing by 23% over the past five years.

The purpose of the J-1 visa is educational and cultural exchange. In keeping with this, ECFMG-sponsored J-1 physicians are required to return home for at least two years after completion of training before they are eligible to change visa status. Although legal options have evolved that allow some of these physicians to remain in the USA, many return to their home countries, where they apply the knowledge and skills acquired in the USA. These skills are highly transferrable, ensuring a positive impact on local healthcare. It is common for IMGs who return home to become leaders in clinical and academic settings, influencing the practice and education of new generations of physicians. And, physicians who return to countries where technological resources are lacking are well positioned to advocate for the

Revenue optimisation, the authors suggest, “requires accurate documentation and coding of procedures, comorbidities, and complications. In fee-for-service and bundled payment reimbursement systems, higher volumes of procedures yield higher revenues.”

Additionally, they say, a “halo effect” from collateral services, combined with negotiating lower prices with vendors, can be used to aid the introduction of expensive new procedures that improve patient care.

The document offers strategies for “surviving and thriving” in an era of health reform, with tips on how to maximise revenue in fee-for-service reimbursement systems, and on how to minimise both cath lab and non-cath lab expenses. It explains the economics of new procedures, and offers instructions on “how to make them at least break even”.

And the statement advises that “fiscal considerations should never eclipse quality concerns. High quality CCL care that prevents complications, increases efficiency, reduces waste, and eliminates unnecessary procedures represents a win for patients, physicians, and CCL administrators.”

According to the authors, service expansion is crucial.

They point out that, as the volume of interventional

Understanding the economics of cath labs is essential for physicians, administrators, and other cath lab staff.”

adoption of such resources.

Some IMGs remain in the USA to practice, providing vital healthcare services. But many retain strong ties to their home countries and make significant contributions to local medical education and healthcare systems. These contributions include service to home country medical schools, foundations established by US-based ethnic physician organisations, and travel to their home country to conduct medical and surgical clinics.

The role of IMGs in cardiovascular specialties in the USA mirrors their role in other medical specialties―they serve in large numbers, enrich the clinical learning environment with an international perspective, and add much needed diversity to the physician workforce. As cardiovascular physicians, we are gratified the USA continues to welcome highly qualified physicians who become leaders in cardiovascular care regardless of where they originate and where, ultimately, they practice.

William W Pinsky is president and CEO of the Educational Commission for Foreign Medical Graduates (ECFMG), board chair of the Foundation for Advancement of International Medical Education and Research (FAIMER), and an honorary professor of the University of Queensland, Brisbane, Australia.

Mandeep R Mehra is the William Harvey distinguished chair in advanced cardiovascular medicine, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, and a professor of medicine at Harvard Medical School, Boston, USA.

coronary procedures has declined, structural procedures have stabilised CCL volumes and revenues. “When clinically appropriate, increase a CCL’s scope of practice to include peripheral procedures, implantable rhythm recorders, pulmonary artery pressure monitoring devices, and other new procedures.”

But the statement cautions against adopting new technology before it has proved its worth, and proposes that the cost-per-case can be reduced by maximising the number of procedures performed per piece of equipment per day, given that capital equipment is a fixed expense.

This can be achieved by “minimising CCL down time, and operating the CCL during evenings and weekends”.

A change in the focus of reimbursement models from fee-for-service to patient-centred quality measures and value has created opportunities and challenges for outpatient facilities, say Blankenship et al. They predict an expanding role for outpatient centres as procedures become less invasive and there is less conversion to open surgery: “In the future, outpatient facilities will likely offer lower cost, higher quality, and higher patient satisfaction compared to inpatient facilities for elective cardiovascular procedures.”

To maximise quality, the statement proposes that three measures should be addressed—structure, process, and outcomes—both at cath lab level and by individual physicians. However, it cautions: “Physicians and administrative leaders must ensure that strategies to control costs … do not compromise quality or safety.”

Blankenship et al conclude: “An efficient CCL can provide superb cutting-edge patient care, excellent patient experience, extreme employee workplace satisfaction, and financial support for other less profitable hospital programmes.”

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August 2019 | Issue 54

Innovative therapies

Renal denervation still holds strong potential as a therapy for hypertension Partha Sardar Herb Aronow Comment & Analysis Although renal denervation may not hit the heights originally envisaged for it in the management of hypertension, and areas of uncertainty remain, Partha Sardar and Herb Aronow explain why they believe that second-generation trials demonstrate that it has the potential to become a mainstream therapy.

R

enal sympathetic denervation (RSD) is being actively investigated as a novel treatment modality for patients with hypertension (HTN). Earlier prospective cohort and first-generation randomised controlled studies demonstrated that RSD was safe, but associated with variable impact on blood pressure.1–3 Most notable among these was the randomised sham controlled SYMPLICITY HTN-3 trial, which failed to meet its primary efficacy endpoint and caught many experts in the field off guard.3

Explaining the findings

A number of potential explanations for the lack of observed benefit were proposed, including inexperienced operators, suboptimal patient selection, incomplete denervation with early catheter designs and ablation techniques, inappropriate endpoint selection and variation in concomitant antihypertensive agent use.2,4

As a result, second-generation trials were designed to address many of these earlier trial limitations. Design changes included selection of operators who had participated in prior RSD trials, inclusion of patients with less severe HTN who were on or off antihypertensive medications—most of whom had combined systolic/diastolic HTN—use of ablation catheters constructed to provide more comprehensive, four-quadrant renal nerve ablation, ablation of both main and accessory renal arteries, including larger secondary branches, and selection of ambulatory rather than office blood pressure as the primary efficacy endpoint.

Reasons for optimism

These second-generation RSD trials have yielded more modest, yet consistently significant, blood pressure lowering, with single- as opposed to doubledigit blood pressure reduction.2,4 The second-generation RADIANCE-HTN and SPYRAL trials injected new

optimism into the field when they demonstrated significant blood pressure reduction following RSD with either radiofrequency or ultrasound energy and in patients who were both on and off of antihypertensive medications.1,2 In our recent meta-analysis,2 which included six first- and second-generation randomised trials and 977 patients, the reduction in 24-hour ambulatory systolic blood pressure (ASBP) was 3.7mmHg greater with RSD than with sham procedure. Likewise, daytime ambulatory systolic blood pressure (ASBP), office systolic BP, and office and ambulatory measures of diastolic BP were also lowered significantly more with RSD. Notably, the reduction in daytime ASBP was significantly greater in the three second-generation trials included in the analysis (6.1mmHg more than

Secondgeneration renal sympathetic denervation trials have yielded more modest, yet consistently significant, blood pressure lowering, and have injected optimism into the field.” sham) than in first-generation studies (2.1mmHg).

These second-generation trials required that procedures be performed by experienced operators only, excluded patients with isolated systolic HTN, used advanced catheters and ablation techniques, modified medical therapy to better assess for treatment effect, and used 24-hour ambulatory blood pressure as the primary endpoint.

Virtue sirolimus-eluting balloon set for commercial release, as Terumo and Orchestra BioMed enter global strategic partnership BioMed and Terumo have formed a global strategic partnership for the development and commercialisation of the Virtue sirolimus-eluting balloon (SEB) in the percutaneous coronary and peripheral interventions field.

VIRTUE SEB IS the first and only non-coated drugeluting angioplasty balloon that delivers a proprietary bioabsorbable, sustained-release formulation of sirolimus, according to a press release, which also states that sirolimus is the gold standard drug for preventing restenosis following a percutaneous interventional procedure. In April, the US Food and Drug Administration (FDA) granted Virtue SEB breakthrough

device designation for treatment of coronary in-stent restenosis (ISR), a condition that represents more than 10% of total interventional coronary procedures.

In a prospective study of very challenging ISR patients, Virtue SEB demonstrated excellent angiographic results at six months, and positive clinical outcomes to three years. Orchestra BioMed plans to conduct a near-term US registrational trial for ISR.

Every little helps

Recent data, including those from our meta-analysis, suggest that the blood pressure lowering effect of RSD, even if smaller than initially anticipated, is similar to that observed with many currently approved antihypertensive drugs, and of a magnitude that should translate into a significantly lower cardiovascular event risk. Furthermore, a single intervention with lasting impact on a condition as ubiquitous as HTN would be a tremendous advance.

Nevertheless, many questions remain about RSD, including its long-term safety and effectiveness, and how it might be integrated into the treatment armamentarium for HTN. Whether it will replace or augment medication regimens, and whether it will become an elective procedure for those who are less adherent or prefer not to take medications, remains to be seen.5 There will also be a need to carefully define which patients are most likely to respond to RSD, and for tests to establish the success of RSD, including real-time operator feedback during the procedure.2,5 Despite these many uncertainties, we believe that RSD is poised to become a mainstream therapy, offering hope for many of today’s hypertensive patients.

References 1. Kjeldsen SE, Narkiewicz K, Burnier M, Oparil S. Take a blood pressure pill or benefit from renal denervation?

Eur Heart J 2018; 39(33): 3010–2. doi: 10.1093/ eurheartj/ehy440 2. Sardar P, Bhatt DL, Kirtane AJ, et al. Sham-controlled randomized trials of catheter-based renal denervation in patients with hypertension. J Am Coll Cardiol 2019; 73(13): 1633–42.

3. Bhatt DL, Kandzari DE, O’Neill WW, et al; SYMPLICITY HTN-3 investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014; 370: 1393–1401. doi: 10.1056/NEJMoa1402670.

4. Ram CVS. Status of renal denervation therapy for hypertension. Circulation 2019; 139(5): 601–3.

5. Papademetriou V, Stavropoulos K, Doumas M, Tsioufis K. Now that renal denervation works, how do we proceed? Circ Res 2019; 124(5): 693–5.

Herbert D Aronow is an associate professor of medicine at Brown University and Director of the Cardiac Catheterization Laboratories at Rhode Island & The Miriam Hospitals, Providence, Rhode Island, USA. Partha Sardar is an interventional cardiology fellow at Brown University, Providence, USA.

Under the terms of the agreement, Terumo will make a one-time, upfront payment of US$30 million and an equity commitment of US$5 million to Orchestra BioMed, as well as substantial future clinical and regulatory milestone payments to Orchestra BioMed. It will also make a strong commitment to finance and execute a global clinical programme in collaboration with Orchestra BioMed to gain regulatory approval for the commercial sale of Virtue SEB in multiple markets and indications. Orchestra BioMed will share meaningfully in future commercial revenues of Virtue SEB through royalties and per-unit-payments as the exclusive supplier of the proprietary sustained-release sirolimus formulation used in Virtue SEB. Orchestra BioMed retains the rights to develop and licence technology used in Virtue SEB for clinical applications outside of coronary and peripheral vascular interventions.

Virtue SEB is currently not approved in any market, but Terumo and Orchestra BioMed plan to conduct trials to support global regulatory approvals in indications including ISR, small coronary vessels, and peripheral artery disease below-the-knee.

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August 2019 | Issue 54

Patient care

USA needs to put greater emphasis on homebased cardiac rehabilitation A scientific statement from the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology has called for greater use of home-based cardiac rehabilitation as a secondary prevention tool in the USA, to bring it into line with common practice in other countries.

PUBLISHED IN CIRCULATION, the statement from Randal J Thomas (Mayo Clinic, Rochester, USA) et al says that although cardiac rehabilitation programmes have been shown to reduce morbidity and mortality in adults with ischaemic heart disease, heart failure, or cardiac surgery, they are significantly underused in the USA, and that “new delivery strategies are urgently needed to improve participation”. It adds: “Homebased cardiac rehabilitation has been incorporated into the healthcare systems of several countries, including Australia, Canada, and the UK. The British Heart Foundation recently reported that in the UK >50% of eligible patients are now participating in cardiac rehabilitation after a cardiac event or procedure.

Unfortunately, home-based cardiac rehabilitation faces substantial challenges to implementation in the USA, most notably a lack of reimbursement by the Centers for Medicare & Medicaid Services and other third party payers. Of interest, in a recent study of cardiac rehabilitation-eligible patients, when given the option to receive cardiac rehabilitation through a home-based or a centre-based approach, nearly half preferred a home-based approach.”

Thomas et al carried out a systematic review of published studies that compared home-based cardiac rehabilitation with centre-based cardiac rehabilitation to assess the comparative effectiveness

and potential benefits of home-based programmes and to explore implementation strategies for their development. A literature search identified 23 studies that used randomised, experimental designs that directly compared outcomes, and the authors used these as the primary scientific basis of the statement. They excluded meta-analyses, systematic reviews, qualitative studies, published letters, editorials, and case reports, as well as studies that compared home-based cardiac rehabilitation with usual care. Patient populations included adults with myocardial infarction, stable angina, or heart failure, and those who had undergone coronary revascularisation.

The included studies assessed at least one of the following health outcomes: mortality, morbidity (defined as reinfarction, revascularisation, or cardiac-related hospitalisation), exercise capacity, modifiable cardiovascular risk factors (for example, smoking, lipids, blood pressure, blood glucose, exercise capacity), health related quality of life (HRQOL), adverse events, health services use, cost, or intervention adherence.

The statement recommends: “Although home-based cardiac rehabilitation appears to hold promise in expanding the use of cardiac rehabilitation to eligible patients,

Unfilled prescriptions for PCSK9 inhibitors lead to higher rates of cardiovascular events

Patients whose prescription for PCSK9 inhibitors (proprotein convertase subtilisin kexin type 9 inhibitors) are either unfilled or rejected by insurance companies have a higher rate of cardiovascular events than those whose prescriptions are paid for. Kelly D Myers (The FH Foundation, Pasadena, USA) et al also found that high co-payments may make patients less likely to fill prescriptions, even when insurers approve them, and that prescriptions written for women, blacks, and Hispanics were more likely to be rejected by companies. The study was published in Circulation: Cardiovascular Quality and Outcomes.

T

he authors write: “Individuals in the rejected and abandoned cohorts had significantly increased risk of cardiovascular events compared with those in the paid cohort. Rejection, abandonment, and disparities related to PCSK9 inhibitor prescriptions are related to higher cardiovascular outcome rates.”

PCSK9 inhibitors reduce lowdensity lipoprotein cholesterol levels and cardiovascular event rates. But the drugs were initially expensive, with prescriptions rejected at high rates by payers, and their use is often delayed or abandoned. Myers et al tested the hypothesis that acute coronary

syndromes, coronary interventions, stroke, and cardiac arrest are more prevalent in patients with rejected or abandoned PCSK9 inhibitor prescriptions than in those with paid prescriptions.

Anonymised data from a healthcare claims dataset identified 139,036 patients aged ≥18 years who had been prescribed PCSK9 inhibitors between August 2015 and December 2017, had a claims history, and had an established date of exposure for paid, rejected, or abandoned status.

Investigators performed propensity score matching and compared the effects of rejected versus paid and abandoned versus paid status. Patients who received

Randal J Thomas

additional research and demonstration projects are needed to clarify, strengthen, and extend the home-based cardiac rehabilitation evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups.”

Thomas told Cardiovascular News: “We present evidence and limitations of home-based cardiac rehabilitation, and suggest that the evidence supports its use in patients who are at low-to-moderate risk who cannot attend a centre-based programme. There are a number of unanswered questions about it, including its longer-term impact on cardiovascular disease outcomes, its impact in the elderly and underserved populations, and so on. But current evidence is sufficient to suggest it can be considered for lower-risk patients who cannot attend a centre-based programme.”

The statement was co-published in the Journal of Cardiopulmonary Rehabilitation and Prevention and the Journal of the American College of Cardiology.

Evidence supports its use in patients at low-to-moderate risk who cannot attend a centrebased programme.”

≥168 days of paid PCSK9 inhibitor medication within a 12-month period were defined as paid.

Hazard ratios (HR) for composite cardiovascular events outcomes in propensity score matched analyses were 1.1 (95% confidence interval [CI] 1.01–1.19, p =0.02) for rejected versus paid prescriptions, and 1.12 (95% CI 1.01–1.24, p=0.03) for abandoned versus paid. In a further analysis in which paid patients were defined as receiving ≥338 days of treatment within a 12-month period, HR was 1.16 (95% CI 1.02–1.30, p=0.04) for rejected versus paid prescriptions, and 1.21 (95% CI 1.04–1.38, p=0.03) for abandoned versus paid. In addition, researchers found higher rejection rates for PCSK9 inhibitor prescriptions with women, racial minorities, and lower-income groups.

The authors also note that those with both familial hypercholesterolaemia (FH) and previous atherosclerotic cardiovascular disease (ASCVD) had the highest risk of events—with a markedly increased risk compared to those without

Hazard ratio for composite cardiovascular events was 1.1 for rejected vs. paid.”

the conditions—but were denied access to the drugs to a similar extent. HR was 2.8 (95% CI 1.78–4.42, p<0.001) for the FH cohort versus individuals who did not have a documented diagnosis of FH or pre-final adjudication status (FAS) ASCVD; 2.12 (95% CI 1.86–2.43, p<0.001) for ASCVD versus non-FH and non-ASCVD; 1.75 (95% CI 1.48–2.08, p<0.001) for FH plus ASCVD versus ASCVD alone; and 5.4 (95% CI 4.28– 6.9, p<0.001) for FH plus ASCVD versus non-FH and non-ASCVD. In addition, there was no statistical difference in risk between primary prevention FH and secondary prevention ASCVD. “Individuals with FH and ASCVD face an extremely high risk of cardiovascular events and are more likely to have heart attacks and serious cardiovascular events if they are rejected or abandon their prescription. Alarmingly two-thirds of their prescriptions were rejected in this study,” Myers told Cardiovascular News.

“It is critical that individuals with FH are identified, and comprehensive therapy is initiated early in life.”

The authors recommend the collection of prospective data specific to patients who would benefit from the therapy, such as in the current CASCADE FH registry, to understand the long-term effects of the drugs, as well as any potential challenges.

They also suggest the health disparities for sex, race, education, and income noted in their study should be examined and addressed.

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August 2019 | Issue 54

PCR's pearl anniversary

The evolution of PCR: Milestones and achievements in its 30-year journey 2019 saw the 30th anniversary of EuroPCR, with 11,206 participants gathering in Paris. William Wijns, PCR chair, shares his perspective on how it has evolved since 1989 and the reasons for its success, and explains why healthcare professionals should sign up to the newly drafted PCR Charter.

What have been the key milestones for the PCR Courses over the past 30 years?

The first key milestone for PCR was the creation of the Course in Toulouse in 1989 by Professor Jean Marco and his colleague Jean Fajadet. It was intended to be one of the first international courses on interventional cardiology, entirely in the English language. That fact may not seem remarkable nowadays, but at the time the discipline was considered by many to be unworthy of development, so in some ways it was revolutionary.

By 1997, the number of participants had increased so significantly that the Course had to move to Paris.

A number of milestones were reached in the 2000s, among them the launch of PCRonline.com. In addition, EuroIntervention became the official journal, and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) was created, and named the Course as its official congress.

During the same decade, there was a rapid expansion to support the specific needs of patients worldwide, and six PCR Courses were created—AsiaPCRSingLIVE (now AICT-AsiaPCR), PCR London Valves, GulfPCR-GIM, AfricaPCR, PCR-CIT China Chengdu Valves, and PCR Tokyo Valves.

educational technique for sharing the skills of seasoned operators. Many other session formats have evolved over the years, adapted as required by the subject matter to meet expectations in teaching methods and learning outcomes.

Also, although it is difficult to quantify, I feel that the positive and enthusiastic spirit of PCR has also contributed. Freedom of speech has been at the core of what we do since the beginning, and participants often say how much they enjoy and benefit from the encouragement they are given to raise their hands and share their own experience.

How can PCR ensure it continues to remain relevant?

The world has changed tremendously over the last 30 years, and at PCR we work ceaselessly to adapt accordingly.

Young healthcare practitioners help us to keep our ears to the ground, and are actively involved in building programmes that ensure their needs are met. Keeping participants up-to-date with innovation continues to be a priority, and will ensure our continued relevance.

The digital shift has already enabled us to provide additional opportunities that

What are the main factors that have contributed to the success of PCR Courses?

Firstly, their relevance to daily practice and the fact they are built by, and for, all community members—that is, not just interventional cardiologists, but all the heart team: physicians, cardiac surgeons, imaging specialists, nurses, and allied professionals.

PCR is complementary to national societies: we provide a structure and open platform through which physicians can reach out and interact on an international scale. Our practical approach to clinical problem solving has also contributed, as proved by the increasing numbers participating in our workshops.

PCR has always attached great importance to knowledge transmission.

Our wide range of learning tools are inspired by Jean Marco's vision of improving education. LIVE demonstrations were implemented from the outset, and remain a highly

EuroPCR 2019

EuroPCR 2019

are complementary to the Courses. As well as Course resources and scientific content available on PCRonline.com, the PCR-EAPCI Textbook today includes 110 online chapters, and is continuously updated by its editors, authors, and community members. And, for the past few years, tailor-made two-day PCR seminars have been also offered, as well as much appreciated webinars on essential practical topics. The range of solutions PCR provides will continue to adapt to evolving needs worldwide.

The positive and enthusiastic spirit of PCR has helped to contribute to its success.”

What can you tell us about the PCR Charter?

The charter was drafted to formulate our essence and inspire future generations, and was announced at EuroPCR 2019.

It collected nearly 300 signatures in the first four days. After a 30-year journey, it seemed the right time to give voice to what we are—to express what our community stands for, and what our values are.

The PCR Charter will be used to encourage reflection and inspire healthcare professionals so that it reinforces the sharing of knowledge, experience, and practice, not only during Courses or within the framework of an established mentor–fellow relationship, but also on a regular basis between all peers. Those wishing to find out more are invited to do so on www.pcr-charter.com.

William Wijns is at the National University of Ireland, Galway, Ireland.

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August 2019 | Issue 54

Device news

Product News premarket approval (PMA) for use in the percutaneous closure of ostium secundum atrial septal defects (ASDs).

A press release from the company says that the FDA approval was supported by data collected from the pivotal stage of the Gore ASSURED clinical study, which demonstrated 100% closure success at six months in patients with a successful implant.

The press release also outlines the properties of the Cardioform ASD Occluder, which has an anatomically adaptable waist that conforms to the Medtronic launches defect to close ASDs from 8–35mm Telescope guide extension in diameter, including those without a catheter retro-aortic rim, by facilitating optimal Medtronic has announced the global tissue ingrowth while maintaining launch of the Telescope guide extension thromboresistance. Gore Medical says catheter, a newly designed catheter that, as the company’s latest extension to used to provide additional backup the Gore Cardioform Occluder family, it support and access to distal lesions. builds on a legacy of safety outcomes.

Guide extension catheters help to The Gore ASSURED clinical study, deliver coronary stents, balloons, and says the company, met its safety, other interventional devices during closure, and technical success primary angioplasty procedures that attempt to endpoints. It evaluated the safety and restore blood flow through the coronary efficacy of ASD closure using the and peripheral arteries.

Gore Cardioform ASD Occluder in Developed alongside interventional 125 patients with evidence of right cardiologists, many of whom are heart volume overload demonstrating increasingly challenged with complex the need for defect closure. Patients cases, the Telescope guide extension were aged between two and 84 years catheter is designed to enable smooth in 22 investigation sites, including 15 delivery of interventional devices in children’s hospitals. more challenging cases.

In the press release, Matthew J “It is not an exaggeration to say Gillespie (Children’s Hospital of that guide extension technologies Philadelphia, Pennsylvania, USA), cohave greatly impacted the ability to principal investigator of the ASSURED deliver devices to the distal coronary study, says: “The FDA approval of the vasculature, especially for cases where Gore Cardioform ASD Occluder is a traditional guide support may be significant milestone for innovation in limited,” says Ajay Kirtane, director the minimally invasive treatment of of the New York Presbyterian ASDs. This soft, conformable Hospital/Columbia University device was not previously Cardiac Catheterization available for this range Laboratories (USA). “In of defects, but is now an this light, the Telescope, a option for larger defects that guide extension catheter with typically have a greater risk specific design optimisations for complications, including aiming to stably deliver devices right heart enlargement, atrial through tortuous anatomy, is fibrillation, and pulmonary a welcome addition to the hypertension. The ability to Cardioform interventional toolbox.” retrieve and reposition the The Telescope guide extension Gore Cardioform ASD Occluder helps catheter combines a solid, round me ensure proper positioning and offers pushwire with a coil-reinforced me confident closure.” hydrophilic-coated distal segment to help reach challenging lesions, with Philips announces new improved pushability and deliverability. advanced automation Telescope also features a flexible capabilities for its EPIQ TruFlex soft polymer tip, designed to CVx and EPIQ CVxi cardiac responsively bend and deflect during ultrasound systems use, and SmoothPass technology to A Philips press release reports that both channel stents, balloons, and other the EPIQ CVx and EPIQ CVxi now interventional devices into place. include automated applications for 2D assessment of the heart, as well as robust FDA approves Cardioform 3D right ventricle volume and ejection ASD Occluder for the fraction measurements—with the aim of treatment of atrial septal making accurate exams faster and easier defects to conduct.

The Cardioform ASD Occluder (Gore Together, the new applications Medical) has received US Food provide clinicians with the means to and Drug Administration (FDA) confidently evaluate the heart’s function,

increasing diagnostic confidence for patients with pulmonary hypertension, congenital heart disease, coronary disease, and heart failure.

The AutoStrain LV application, according to the press release, uses “Automatic View Recognition” technology to identify the different views of the heart, designed to provide exceptional visualisation and analysis of left ventricular function. Also available are “AutoStrain LA” and “AutoStrain RV”, which are applications that automate the measurement of left atrial (LA) and right ventricular (RV) longitudinal strain respectively. By creating reliable and reproducible strain measurements for the left ventricle (LV), left atrium, and right ventricle, the AutoStrain LV, LA, and RV applications support clinicians treating patients with atrial fibrillation, arrhythmia, and other complex heart conditions.

The 3D Auto RV application segments, identifies the borders, and aligns the views of the right ventricle, enabling clinicians to carry out quantification and check measurements in as little as 15 seconds. These new applications expand on the advanced automation applications already available on the EPIQ CVx platform, including the Dynamic HeartModel, which provides a clear vision of the heart’s chambers and how well they are pumping blood—specifically on the left side, where heart failure often begins.

David Handler, general manager of Cardiac Ultrasound at Philips, says: “The complexity of cardiac exams can be a barrier to accessing high quality care. Philips is addressing this by leveraging artificial intelligence to make echo exams easier, faster, and more reproducible. By incorporating advanced automation, there is less variability between scans, leading to accurate treatment decisions which benefits patients. The new release of EPIQ CVx is a major step forward.”

be based on platform technologies developed by SAT in recent years.

At their core, a press release reports, the valves will use DSM’s advanced and proven CarboSil Thermoplastic Silicone-Polycarbonate-urethane (TSPCU) biomedical polymers, negating the need for invasive open heart surgery or the lifelong burden of anticoagulant drugs. In a second phase, these polymeric leaflet valves will be offered to patients in developed economies suffering heart valve failure associated with age, diet, and other factors.

Tim Shannon, vice president of Sales & Marketing at DSM Biomedical, comments: “There is a global trend towards more cost-effective safe treatments with comparable outcomes versus the existing standard of care.

SAT’s strong technical and clinical

DSM and SAT enter partnership to develop the first next-generation heart valve

Valfix Medical has received a US patent—10,278,820 (percutaneous valve repair and replacement)—for its heart valve repair and replacement technology. A press release reports that the company is developing transcatheter solutions for patients suffering from valvular heart disease and heart failure.

It adds that Valfix Medical technology is distinguished in its approach to offer both repair and replacement treatment in one procedure, noting that “this unique toolbox approach” gives more options for interventional cardiologists to deliver the most effective therapy for this complex condition.

Eli Bar, CEO and founder of Valfix Medical, says: “It is exciting to receive this patent as it confirms our technology patentability; our technology is unique and distinct in the market. This patent granted confirms and protects our core technology, and adds significant value to our stakeholders.”

Concurrently with the issuance of this patent, Valfix Medical continues to develop its patent portfolio, with other patents in preparation and pending.

Royal DSM is to collaborate with Strait Access Technologies (SAT) to develop the world’s first durable and cost-effective transcatheter replacement heart valves with polymeric leaflets.

This collaboration is initially focused on developing valves to treat rheumatic heart disease.

A press release reports that existing mechanical or animal tissue replacement valves are unsuited for the challenging pathologies of typically younger rheumatic heart disease patients.

Additionally, a lack of suitable medical facilities and high valve costs effectively mean that the majority of patients living with rheumatic heart disease have a risk of a premature death.

SAT and DSM are collaborating to produce breakthrough products that address the unique biological, cost, and access challenges posed.

The replacement heart valves being developed by SAT and DSM will

Valfix

expertise, combined with DSM’s CarboSil TSPCU and regulatory expertise in the cardiovascular therapeutic area, will improve access to advanced healthcare in the regions that need it most.”

Patent granted to Valfix Medical for its percutaneous valve and replacement technology

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August 2019 | Issue 54

Studies

Clinical News

India-designed Myval associated with no devicerelated mortality at one year

One-year data for the Myval transcatheter aortic valve implantation (TAVI) system indicate it is associated with 100% freedom from device-related mortality at one year. These data, which were presented at EuroPCR 2019 (20–24 May, Paris, France) also showed that the valve was associated with 100% acute procedural success. The Myval device is a product indigenously designed and manufactured in India by Meril Life Sciences.

The MyVal-1 study is a first-inhuman, prospective, multicentre, singlearm, open label study of the Myval TAVI valve for the treatment of severe symptomatic native aortic valve stenosis which enrolled 30 patients and will follow-up to five years. At 12 months, the study met its primary endpoint for safety and effectiveness: 100% procedural success, no major adverse events, and marked improvement from baseline to 12 months in quality of life scores (as measured by the six-minute walk test and the Kansas City Cardiomyopathy Questionnaire).

Furthermore, 80.77% of patients were New York Heart Association (NYHA) class I, and the remainder were NYHA class II at 12 months, compared to 23.33% who were class I postprocedure.

According to a press release, the Myval system is a balloon expandable transcatheter heart valve, made of a nickel cobalt alloy frame. It has a hybrid honeycomb cell design, with open cells on the upper half to ensure unjailing of the coronary ostia, and closed cells on the lower half for high radial strength.

Additionally, Myval is equipped with an internal polyethylene terephthalate (PET) sealing cuff for lower profile and puncture resistance and an external PET buffing to minimise paravalvular leaks.

Ashok Seth (Fortis Escorts Heart Institute, New Delhi, India), who presented the findings at EuroPCR, and was the principal investigator in the study, comments that, in addition to the procedural success and zero device-related mortality rate, there were also no new pacemaker implantations, no strokes, and no paravalvular leaks observed in patients. Furthermore, echo

parameters were maintained at 12 month follow-up.

“Based on these encouraging firstin-human results, further studies are being planned in a larger population and differing geographies for longer durations of time,” Seth says.

Imrankhan Lohani, Head of MyvalTHV Clinical Research at Meril Life Sciences, comments: “We are excited by these results. Our Myval transcatheter heart valve was granted the CE mark in April of this year. As we get set to launch it across Europe, we believe this valve from the emerging world is going to positively impact care substantially.”

Admedus’ announces favourable five-year outcomes for its CardioCel bioscaffold

Admedus has announced positive data from an independent study into the performance of its tissue engineered bovine pericardial implant CardioCel, which is used in the repair of congenital heart defects in children.

Published in the Annals of Thoracic Surgery, the retrospective multicentre study of 501 implants in 377 patients demonstrated that the CardioCel bioscaffold showed no calcification after five years, and that 96% of patients would not require reintervention.

Investigators also found that CardioCel has good durability when used for the repair of congenital heart defects, and performs comparably in the systemic and pulmonary circulations in neonates, infants, and older children.

A press release from the company also pointed out that CardioCel increased quality of life and offered cost savings to alternative implants. The primary endpoint of the trial was CardioCelrelated surgical or catheter intervention.

Secondary endpoints included implant related thromboembolism, residual shunt, infection, calcification leading to loss of function, and haemodynamic compromise. Mortality or reintervention was considered early if the event occurred within 30 days of implantation.

Cardiocel is a bioscaffold that uses Admedus’ Adapt technology, and is described by the company as a specially treated bovine tissue with zero DNA.

NICE issues recommendations on insertion of cerebral protection devices during TAVI

The National Institute for Health and Care Excellence (NICE) has released evidence-based recommendations on the percutaneous insertion of a cerebral protection device to prevent cerebral embolism during transcatheter aortic valve implantation (TAVI).

It says that the evidence raises no major safety concerns, other than those associated with the TAVI procedure.

However, the evidence on efficacy for preventing TAVI-related stroke is inconclusive, and the procedure should therefore only be used with “special arrangements” for clinical governance, consent, and audit or research.

Clinicians wishing to percutaneously insert a cerebral protection device during TAVI should inform the clinical governance leads in their NHS trusts.

They must ensure patients and their care providers understand the procedure’s safety and efficacy, as well as any uncertainties, and that they provide clear written information to support shared decision-making. Details of all patients should be entered into the UK TAVI registry.

NICE also suggests that patient selection should be performed by the multidisciplinary team, and that the procedure should only be done in specialised centres, by clinicians and teams with specific training and experience. Centres doing this procedure should have both cardiac and vascular surgical support for the emergency treatment of complications and subsequent patient care.

NICE also encourages further research on percutaneous insertion of a cerebral protection device to prevent cerebral embolism during TAVI, to include details of patient selection and risk stratification for TAVI-related stroke, and says it may update its guidance on publication of further evidence.

According to the NICE guidance, the evidence review identified three types of cerebral protection devices. One is a deflector system that covers all three main branches of the aortic arch. The other two cover the brachiocephalic trunk and the left common carotid artery; one of these is a filter system and the other a deflector system.

The guidance will be reviewed again in June 2022, and a full outline of the recommendations is available on the NICE website.

Nearly 50% of treatment strategies would change with use of investigational HeartFlow planner

angiogram for each patient and provided a treatment recommendation. The same three interventional cardiologists then reviewed each patients’ HeartFlow Analysis and used the HeartFlow Planner to virtually explore different treatment scenarios and provide a treatment recommendation. The study compared the differences in recommended treatment plans.

For example, in one case, the interventionalists initially recommended that a lesion be treated with a 38mm stent based on the diagnostic angiogram.

After reviewing different treatment options with the HeartFlow Planner, the interventionalists changed the recommendation to treat the lesion with a 15mm stent, as the reduced stent length demonstrated a similar physiologic effect.

A press release reports that the HeartFlow Planner is an interactive tool that enables interventional cardiologists and heart teams to modify vessels virtually, and thereby determine the optimal treatment strategy prior to an invasive procedure.

Every HeartFlow analysis case is accompanied by enough data to allow the HeartFlow Planner to modify vessel narrowings and arrive at a personalised ideal anatomical model, and to allow additional computations based on altered flow rates resulting from modified vessels.

With the HeartFlow Planner, an interventional cardiologist or heart team can explore the treatment area and view the modified vessel and resulting FFRCT changes in real time. This tool allows non-invasive study of treatment scenarios to identify which intervention is optimal. The HeartFlow Planner is currently not available for commercial use and is under review with the US Food and Drug Administration (FDA).

Campbell Rogers, chief medical officer, HeartFlow, says: “The BOWIE results highlight the potential benefit of using a real-time interactive tool prior to a revascularisation procedure as it can help inform the treatment plan, optimise completeness of revascularisation, and streamline resource utilisation in the cath lab.”

New data show that the use of Watchman FLX the investigational HeartFlow Trial initiated to Planner—a real-time, non-invasive compare Watchman FLX to interactive planning tool—led to a direct oral anticoagulants change in treatment strategy in 45% of The OPTION trial is to compare the patients with coronary artery disease safety and effectiveness of the nextand reduced the need for invasive generation Watchman FLX (Boston physiology. The data from the BOWIE Scientific) left atrial appendage (Benefits of obtaining information for closure platform with first-line oral planning with non-invasive fractional anticoagulants—including direct oral flow reserve coronary CT-angiography anticoagulants and warfarin—for stroke [FFRCT] prior to invasive evaluation) risk reduction in patients with nonstudy were presented by Eric Van Belle valvular atrial fibrillation who undergo a (Lille Heart & Lung Institute, Lille, cardiac ablation procedure.

France) at EuroPCR 2019 (20–24 The randomised, controlled OPTION May, Paris, France); Van Belle was the trial will enrol 1,600 patients with principal investigator for BOWIE. non-valvular atrial fibrillation who are BOWIE is a retrospective suitable for oral anticoagulation therapy study that included 101 patients. and have recently had or will have an Three interventional cardiologists ablation. Patients at up to 130 global independently reviewed the diagnostic sites will be randomised to receive

Issue 54 | August 2019 the newest-generation Watchman FLX device or an oral anticoagulant, inclusive of commonly prescribed direct oral anticoagulant or warfarin.

The primary effectiveness endpoint is all-cause death, stroke, and systemic embolism through 36 months, and the primary safety endpoint is nonprocedural bleeding through 36 months.

Oussama Wazni (Ventricular Arrhythmia Center, Center for Atrial Fibrillation and the Atrial Fibrillation Stroke Prevention Center, Cleveland Clinic, Cleveland, USA), the principal investigator for the OPTION trial, says: “Cardiac ablation is an effective way to treat an abnormal heart rhythm for many patients, though symptomatic relief can lead these patients to stop taking their blood thinners and unknowingly put themselves at an elevated risk for a stroke.

“This first-of-its-kind trial will explore whether the one-time Watchman FLX device could replace commonly used anticoagulants for long-term stroke risk reduction in this growing patient population.”

Ian Meredith (executive vice president and global chief medical officer, Boston Scientific), says: “Beyond advancing the robust clinical literature supporting the Watchman therapy, findings from the OPTION trial have the potential to expand the number of patients with atrial fibrillation who can receive an alternative to lifelong anticoagulants, and thus avoid their potential sideeffects. The unique study design encompasses patients who will receive a Watchman FLX device either after or concurrent to an ablation procedure.”

Purpose-designed temporary pacing guidewire has potential to make implantation of transcatheter heart valves “safer and more efficient” Speaking during an innovation session at TVT 2019 (12–15 June, Chicago, USA), Mark Hensey (Centre for Heart Valve Innovation, St Paul’s Hospital, University of British Columbia, Vancouver, Canada) outlined the early experience with a purpose-designed temporary pacing guidewire (Wattson, Teleflex). He said the wire delivered “safe and effective pacing” for both aortic and tricuspid positions.

Hensey reported that a temporary transvenous pacemaker (TVP) is “commonly utilised to allow burst and back-up pacing” during transcatheter heart valve procedures. However, he said that TVP placement is “not without risks”—commenting that it can lead to vascular injury, bleeding, and thrombosis, among other complications.

“Tricuspid valve-in-valve procedures, in particular, offer challenges because traditional placement of the wire in the right ventricle is not possible and you have to look at other options, such as the left ventricle or the coronary sinus,” Hensey commented.

He added that studies have demonstrated that a guidewire placed in the left ventricle could be used

Studies to provide unipolar pacing during transcatheter heart valve procedures but that this was also not without problems.

Hensey explained that it “requires modification of the wire and technical expertise” and unipolar pacing “results in high thresholds and, potentially, loss of capture”.

“If there is a need for back-up pacing, you cannot pace without the delivery system in place,” he added.

Therefore, the Wattson temporary pacing guidewire was developed. The wire is 0.035 inches in diameter and 280cm in length, with Hensey noting it was slightly than longer than standard guidewires to allow removal of the transcatheter heart valve system if pacing was required post deployment.

The guidewire also has multiple exposed electrodes to allow consistent capture, connects to a standard external pacemaker, and provides bipolar pacing.

At present, the guidewire has been used in five patients–of whom, two underwent transcatheter tricuspid valve-in-valve interventions. All patients received a Sapien 3 valve (Edwards Lifesciences), the mean threshold was 2.2±0.45mA with no loss of capture in any case, and no patients required pacing after implantation. There were no complications. Overall, according to Hensey, the advantages of the Wattson guidewire is that it avoids the need for a transvenous pacemaker, which reduces the risk of complications, reduces procedural time, and reduces radiation exposure. Also, it provides “reliable bipolar pacing”.

“In our early experience, the Wattson wire delivered safe and effective pacing along with excellent rail support in both aortic and tricuspid positions. It does have the potential to make transcatheter heart valve implantation safer and more efficient,” Hensey concluded. However, he added that further clinical experience was required and that an “early feasibility study was underway”.

Hensey and colleagues recently published their early experiences with the guidewire in EuroIntervention.

Biotronik announces positive data for Magmaris

A press release from Biotronik highlights data from the BIOSOLVE-IV registry outlining procedural success and a positive safety profile at one year for its Magmaris Resorbable Magnesium Scaffold (RMS) device.

The target lesion failure (TLF) rate at 12 months was 4.7%. The press release also reports on Magmaris' safety profile, with cardiac death occurring in 0.1% of the patients, and scaffold thrombosis in 0.6%. The device success rate was 97.1% and the procedural success rate was 98.8%.

Stefan Verheye (Antwerp Cardiovascular Institute, Antwerp, Belgium) presented results on the first 800 patients from the BIOSOLVE-IV registry cohort at EuroPCR 2019 (20–24 May, Paris, France). In the company’s press release he comments: “Overall, BIOSOLVE-IV confirmed low TLF rates from previous trials in a real world

setting, including 17.8% NSTEMI [non-ST segment elevation myocardial infarction] patients, and 5.6% of patients with bifurcation lesions. When looking closer at the five scaffold thrombosis cases, we noticed that in four of them antiplatelet or anticoagulant therapy was interrupted early after scaffold

33

NYHA class of >one class over control at six months (2.55±0.1 vs. 1.33±0.1, p=0.0078), which was greater than both the NOGA-treated and control groups.

“Results suggest that intramyocardial cell therapy possibly improves left ventricular function and symptoms by attenuating myocardial remodeling on top of successful PCI [percutaneous coronary intervention] and optimal standard care after AMI. Results [for the Helix system] are similar to the NOGA-treated patients, as previously observed in the Alster stem cell trial,” said Paitazoglou in her presentation.

Carillon Mitral Contour System reaches 1,000 implants for functional mitral regurgitation Helix

implantation.”

The Magmaris Resorbable Magnesium Scaffold is not currently commercially available in the USA.

Early treatment with Helix system improves ejection fraction and symptoms

The Helix biotherapeutic delivery system (Biocardia), which delivers cell therapy to patients within four weeks of a heart attack, led to improved ejection fraction and fewer symptoms (improved by >one New York Heart Association [NYHA] class), according to data presented at EuroPCR 2019 (20–24 May, Paris, France).

A press release from the company highlights the findings, and explains that the system uses a corkscrew shaped needle to anchor into damaged heart tissue, treating patients early following acute myocardial infarction (AMI) to prevent long-term heart failure.

Findings from Early transendocardial injection of autologous bone marrowderived mononuclear cells following ischaemic myocardial events: the Alster-Helix registry were presented by Christina Paitazoglou (Cardiologicum, Hamburg, Germany) during a latebreaking trial session of first-in-man trials and early phase studies.

The study aimed to determine if intramyocardial injection of autologous bone marrow-derived mononuclear cells using the Helix system two to four weeks after acute myocardial infarction is feasible, and whether it might block ventricular adverse remodeling and improve symptoms of heart failure.

Nine patients were treated with cell therapy delivered intramyocardially with the Helix system, and the results were reviewed relative to 11 patients previously treated with the NOGA XP delivery system (Biosense Webster) and a control group of 11 patients treated with optimal standard care.

At 12 months, patients with Helixdelivered cell therapy experienced a 7.33% improvement in ejection fraction (p=0.017) compared to the control group (there were no 12-month data available for the NOGA system). Helix patients also showed an improvement in

Cardiac Dimensions has announced in a press release that its Carillon Mitral Contour System has now been implanted in 1,000 patients in the USA, Europe, Australia, Turkey, and the Middle East.

The Carillon System is a right-heart transcatheter mitral valve repair (TMVr) device designed to treat the primary cause of functional mitral regurgitation

Carillon

(FMR) in patients with MR grades 2+, 3+ and 4+. The 1,000th system was implanted during a live case at CSI Frankfurt 2019.

President and CEO of Cardiac Dimensions, Gregory D Casciaro, states in the press release: “This is a highly anticipated milestone for our company as we witness the 1,000th implantation of the Carillon System. It was not long ago that surgical intervention was the final solution to treating FMR. We are now part of a new paradigm of minimally invasive care that can safely and effectively treat FMR in a wide range of patients.

“Because the Carillon System preserves mitral valve leaflet integrity, patients can be treated earlier in the highly progressive disease cycle.”

The company also says that early data presented at a late-breaking trial session at last year’s Transcatheter Cardiovascular Therapeutics (TCT) conference complements the growing body of evidence demonstrating the consistent and durable effectiveness and safety of the Carillon System.

It adds that the Carillon System is the first and only device to demonstrate a reduction in regurgitant volume and favourable left ventricular remodelling in a blinded, randomised, shamcontrolled trial of percutaneous valve therapy. It is CE-marked and approved for investigational use in the USA.

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August 2019 | Issue 54

Companies

treatment option to more patients sooner.”

Industry News American College of Cardiology names its first director of diversity and inclusion

The American College of Cardiology (ACC) has appointed Ranna Parekh as its first director of diversity and inclusion. Parekh will work with the ACC Task Force on Diversity and Inclusion and other societies and organisations to lead and expand initiatives to create a more diverse and inclusive environment within the field of cardiovascular disease.

In a press release, Parekh says: “Given the rapidly changing demographics in the United States, ensuring health equity will be even more critical in the upcoming years. I am deeply committed to principles of inclusion, cross cultural understanding and community involvement, and am honoured to be able to work with the ACC’s members in using the College’s diversity and inclusion principles to realise ACC’s vision of ‘a world where innovation and knowledge optimise cardiovascular care and outcomes’ for all.”

The Task Force on Diversity and Inclusion was established in 2016 to address the low percentage of women entering the cardiovascular workforce.

The initiative aims to harness the

diversity of ACC’s members to advance patient care, spur innovation, and improve health equity among individual patients and populations through a fiveyear diversity and inclusion strategic plan.

Parekh took up her position at the end of July. She will use her expertise and experiences to identify and explore barriers to entry into cardiology, develop diversity and inclusion-related educational services and projects, and lead and coordinate the diversity and inclusion efforts of staff and members across the College. She was deputy medical director, director of diversity and health equity, and director of minority fellowship programmes at the American Psychiatric Association from January 2015.

Zoll Medical acquires TherOx

Zoll Medical, an Asahi Kasei Group company that manufactures medical devices and related software solutions, has acquired TherOx—a company that markets systems to deliver super saturated oxygen (SSO2) therapy.

A press release reports that SSO2 therapy, recently approved by the US Food and Drug Administration (FDA), has been demonstrated to reduce infarct

Robotic PCI company adds interventional cardiology experts to its medical advisory board

Ranna Parekh

size after primary coronary intervention (PCI) with stenting in patients with left anterior descending ST-elevation myocardial infarction (STEMI).

Neil Johnston, president of ZOLL Circulation, comments: “Zoll and TherOx are both focused on emergency cardiac care. This acquisition expands the Zoll product portfolio in support of excellence for patients and caregivers.”

Kevin T Larkin, president and CEO of TherOx, says: “SSO2 therapy can help reduce infarct size among patients who suffer from large anterior acute myocardial infarction, which are the most serious heart attacks. Adjunctive to PCI, SSO2 Therapy is intended to salvage heart muscle and reduce infarct size. We are looking forward to becoming part of Zoll, so that together we can bring this breakthrough

Robocath has announced that the wellknown interventional cardiologists Michael Haude (Städtische Kliniken Neuss, Neuss, Germany), Faziel Lorgat (Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa), and Holger Nef (Giessen University Hospital, Giessen, Germany) have joined its medical advisory board. Founded in 2009, Robocath designs, develops, and commercialises robotic solutions to treat cardiovascular diseases, including R-One, designed to optimise the safety of robotic-assisted coronary angioplasty.

A press release reports that the board plays a key role in defining the company's clinical strategy. Their work will contribute to the worldwide growth of robotics in interventional cardiology.

The three experts join existing board members: Alberto Cremonesi (Humanitas Gavazzeni Hospital, Bergamo BG, Italy), Alain Cribier (Emeritus Professor and TAVI founder, Rouen University Hospital, Rouen, France), Jean Fajadet (Pasteur Clinic, Toulouse, France), Eric Durand (Rouen University Hospital, Rouen, France), Rémi Sabatier (Caen University Hospital, Caen, France), and Gregg Stone (Columbia University Hospital, New York, USA).

Calendar of events 25–29 September TCT 2019 San Francisco, USA www.crf.org/tct

26–27 September British Atherosclerosis Society Annual meeting Oxford, UK

www.britathsoc.org/meetings/ bas-annual-meeting-2019keble-college-oxford/

3–5 October EACTS 2019 Lisbon, Portugal

www.eacts.org/annualmeeting-2/

4 October 2019 14th Annual Scientific Meeting of the Cardiorenal Forum London, UK

http://cardiorenalforum.com/

29 October– 01 November 30th Annual Cardiovascular Interventions La Jolla, USA

www.cvinterventions.com

14–15 November Controversies & Advances in the Treatment of Cardiovascular Disease, the Nineteenth in the Series Beverly Hills, USA www. controversiesincardiology. com

17–18 November PCR London Valves London, UK

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

22–25 February 2020 CRT 2020 National Harbor, USA www.crtmeeting.org

17–20 June 2020 TVT 2020 Chicago, USA crf.org/tvt

23–27 September 2020 TCT 2020 Miami, USA tctconference.com

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