The international newspaper for cardiovascular specialists FebruaryOctober 20132014 Issue 3132

ThomasSusheel FKodali: Lüscher: FrancescoAshok Seth: Maisano: AxelRonald Bauer: P Caputo: ProfileParavalvular leak MitralProfile valve repair RenalRobotic denervation angioplasty Page 1614 Page 1816 PagePage 2220 Major setback for renal denervation Medtronic has announced that the first sham- controlled study of renal denervation— SYMPLICITY HTN-3—has not met its primary efficacy endpoint of significantly reducing blood pressure in patients with severe resistant hypertension and systolic blood pressure of ≥160mmHg. The company has also revealed plans to suspend enrolment in three ongoing regulatory approval trials pending a review of SYMPLICITY HTN-3’s findings

n the study, 535 patients clinical trial programme. (at 87 US medical centres) Pending this panel review, Iwith treatment-resistant the company has said it plans hypertension and systolic blood to suspend enrolment in the pressures of ≥160mmHg were three countries where renal randomised to one of three denervation hypertension groups—two renal denervation trials are being conducted groups and one sham procedure for regulatory approvals group. The primary efficacy (SYMPLICITY HTN-4 in endpoint was the change in the USA, HTN-Japan and believe this course of action widely believed to be the conducted to date, and the first office blood pressure from HTN-India). However, it is the most prudent and will 2014 American College of of its kind to include a sham- baseline to six months and the reported it will continue to help us thoroughly evaluate Cardiology scientific sessions control group. We look forward primary safety endpoint was ensure patient access to the these findings and determine (29–31 March, Washington to advancing these data into the incidence of major adverse Symplicity technology (at the the appropriate next steps for DC, USA). George Bakris, peer-review process.” events. Although the safety discretion of their physicians in renal denervation therapy. We co-principal investigator endpoint was met, the efficacy markets where it is approved) would like to thank the patients of SYMPLICITY HTN-3 Wait for full results endpoint was not. and continue the Global and investigators for their and professor of Medicine The board of the upcoming Medtronic now intends SYMPLICITY post-market participation in the trial and and director of the ASH Resistant Hypertension Course to formulate a panel of surveillance registry and renal their important contribution Comprehensive Hypertension (RHC; 20–22 February, Berlin, independent advisors (made up denervation studies evaluating to the field of hypertension Center, University of Chicago Germany) has said it needs of physicians and researchers) other non-hypertension research.” Medicine, Chicago, USA, more information about the who will be asked to make indications. The final results of the study notes: “This [SYMPLICITY results before it can review recommendations about the Rick Kuntz, chief medical are due to be presented at an HTN-3] is the most rigorous them. future of its global hypertension officer at Medtronic, says: “We upcoming scientific congress— renal denervation clinical trial Continued on page 2

Long-term dual antiplatelet therapy may not always be needed According to the results of the OPTIMIZE powerful predictors of thrombotic events after primary endpoint was the rate of net adverse (Optimized duration of clopidogrel first-generation drug-eluting stents. Also, clinical and cerebral events (NACCE—death, therapy following treatment with the several other issues have been identified myocardial infarction, stroke, or major bleeding) zotarolimus-eluting stent in real-world with prolonged DAPT, including bleeding, at 12 months. clinical practice) study, three months of compliance and cost.” He added that the Overall, in the open-label study, 3,119 pa- dual antiplatelet therapy (DAPT) is non- second-generation drug-eluting stent Endeavor tients were randomised to receive three months’ inferior to 12 months’ DAPT in patients (Medtronic) is associated with long-term safety DAPT (1,563) or 12 months’ DAPT (1,556). with stable coronary artery disease or and efficacy despite short duration (three At the 12-month follow-up point, data were low-risk acute coronary syndrome months) of DAPT. The goal of the OPTIMIZE available for 97.6% of patients (1,525) in the study was to compare outcomes associated three-month arm and for 97.6% (1,518) in the austo Feres (Instituto Dante Panzzanese with three-month DAPT with those outcomes 12-month arm. The rate of the primary endpoint de Cardiologia, São Paulo, Brazil) associated with 12-month DAPT in patients was 6% in the three-month arm vs. 5.8% in the Fpresented the results of OPTIMIZE undergoing percutaneous coronary intervention 12-month—meaning that three-month DAPT at the 2013 Transcatheter Cardiovascular (PCI) with the Endeavor (zotarolimus-eluting) was non-inferior to 12-month DAPT (p=0.002 for Therapeutics conference (TCT; 27 October–1 stent in clinical practice. non-inferiority). Furthermore at a landmark 90- November, San Francisco, USA). He said Patients were included in the study if they day analysis, there was no significant difference that, based on current evidence, the impact had stable or unstable angina or recent between groups in the rate of NACCE (3.5% of a prolonged DAPT regimen was “unclear”, myocardial infarction, but were excluded if they for three-month DAPT vs. 3.3% for 12-month commenting: “Premature DAPT discontinuation required primary or rescue PCI for ST-segment DAPT; p=0.86). There were also no significant has been determined to be one of the most elevation myocardial infarction (STEMI). The Continued on page 4

Cardiovascularnews.com CN App @cn_publishing facebook.com/cardiovascularnews 2 Updates February 2014 Major setback for renal denervation

Continued from page 1 not just Medtronic. He RAPID II randomised study. body of evidence supporting In a statement, on comments: “Obviously, the Additionally, Covidien expects renal denervation with the behalf of the board, RHC final report of SYMPLICITY to record after-tax charges in Symplicity system as a therapy chairman Felix Mahfoud HTN-3 will be scrutinised the range of US$20 to US$25 option for this underserved (interventional cardiologist, carefully for patients who may million as a result of exiting population.” Klinik für Innere Medizin III have favourably responded the OneShot programme. These data, according to a Kardiologie, Angiologie und to the Symplicity system. Over the next several weeks, press release, are consistent Internistische Intensivmedizin, However, even if a subgroup the company will collaborate with SYMPLICITY HTN-2 Universitätsklinikum des of patients turn out to have with physicians and the renal data reported previously at six, Saarlandes, Homburg/Saar, been ‘responders’, another denervation community to 12 and 24-months of follow- Germany) and Costas Tsioufis trial would in theory be needed ensure existing OneShot up. (University of Athens, Chief to test the hypothesis of a patients are informed and The data show an average of Hypertension Unit, First benefit of renal denervation in the currently enrolling blood pressure reduction Cardiology Clinic, University this specific subgroup. Renal clinical trials are transitioned of -33/-14mmHg [p<0.01] of Athens, Greece) say that Axel Bauer denervation manufacturers appropriately.” from baseline and an overall they are choosing to wait for might become more reluctant Both the OneShot device response rate (systolic blood a peer-reviewed paper of the analysis of the full dataset to embark on a new trial for a and the Enlightn device are pressure drop of greater than or SYMPLICITY HTN-3 results and study design are now procedure that would be now CE marked but neither are equal to 10mmHg) of 85% for to be published (expected imperative.” However, Lobo confined to an even smaller available for commercial use patients initially randomised to around March 2014) so that notes: “I expected lesser blood proportion of hypertensive in the USA. treatment with the Symplicity they can look at the full results pressure reduction than seen patients.” At the time of going to system and available for before examining—“rather in the SYMPLICITY HTN-2 press, none of the other 36-month evaluation (n=40). than speculating”—why the trial and our own experience Further setbacks to companies (eg. Boston Despite a mean systolic blood study failed to met its primary in the Barts Hypertension renal denervation Scientific) with renal pressure of 183.5±19.5mmHg efficacy endpoint. They add: Clinic has indicated modest Both Covidien and St Jude denervation technologies have pre-denervation, 50% of these “We are committing to careful and heterogeneous responses Medical have announced plans announced plans to change or patients achieved the goal analysis, with open mind, of to renal denervation in to halt existing trials. stop their trial programmes in of systolic blood pressure this upcoming paper for further patients with true resistant St Jude Medical has stopped this area. of <140mmHg. The safety comments and sharing with the hypertension. However, its Enlightn IV study, which profile of renal denervation RHC community the potential with the Symplicity system reasons why the primary was also maintained at three efficacy endpoint was not met.” This is the most rigorous renal denerva- years, with no newly reported Mahfoud and Tsioufis tion clinical trial conducted to date, and device or procedure related also claim that they “urge serious adverse events. None investigators to pursue their the first of its kind to include a of the patients treated with the clinical endeavours, aiming to Symplicity system followed provide critical information sham-control group. We look forward to through three years required about the role of renal advancing these data into the peer-review renal artery stenting. denervation in the treatment In this trial, patients were of uncontrolled hypertension” process required to have severe, and add that there is “a uncontrolled hypertension great opportunity” to further there are design flaws with was a sham-controlled trial SYMPLICITY HTN-2 with a systolic blood pressure investigate renal denervation in SYMPLICITY HTN-3 and in of its multi-electrode system. continues to show greater than or equal to hypertension and other disease particular the use of medicines According to Heartwire, positive results for 160mmHg despite the use of states characterised by an up-titration just two weeks the company claims it renal denervation three or more antihypertensive increased sympathetic activity. prior to enrolment could have discontinued the study because Prior to its announcement medications, including a Axel Bauer (Abteilung biased the results in favour of of problems with recruitment about SYMPLICITY- diuretic. All patients were für Kardiologie und the sham-treated group.” rather than concerns about the HTN-3, Medtronic presented maintained on their usual Herzkreislauferkrankungen, While he does not believe product’s safety or efficacy. positive three-year data antihypertensive medications Eberhard-Karls-Universität, SYMPLICITY HTN-3 spells The newswire quotes St Jude from its SYMPLICITY and were randomly allocated Tübingen, Germany) recently the end of renal denervation, Medical spokeswoman Denise HTN-2 study at the 2013 in a one-to-one ratio to conducted a study (published Lobo does see it as a “major Perkins-Landry as saying: “A Transcatheter Cardiovascular undergo renal denervation in the Journal of the American setback” and predicts that US clinical trial for Enlightn Therapeutics meeting (TCT; or no additional treatment College of Cardiology) that other device manufacturers remains a very high priority 27 October–1 November, San (control group). At baseline, showed that impaired cardiac can expect a much tougher for St Jude Medical, and we Francisco,USA). the randomised treatment baroreflex sensitivity could climate in which to launch their will be working with the FDA “As the first and longest- and control patients be used to identify patients technologies. He adds: “This to develop a new protocol term experience in a had similar high blood who will respond to renal is probably a good thing given that will address anticipated randomised, controlled pressures: 178/97mmHg and denervation. He agrees with that a number of devices have enrolment challenges.” setting, these data mark a 178/98mmHg, respectively, the RHC Board that it is “much been CE marked on the basis of However while St Jude significant milestone for the despite both receiving an too early” to analyse the results weak first-in-man studies with Medical still seems to renal denervation clinical average daily regimen of five of SYMPLICITY HTN-3, but little supportive data to suggest be committed to renal community, as well as the antihypertensive medications. adds that “patient selection and true efficacy in rigorously denervation, Covidien has single-electrode Symplicity Patients in the control arm use of adequate endpoints” will screened patients with true announced that it plans to exit system,” said Robert J. of the study were offered be important in future trials of resistant hypertension and a its OneShot renal denervation Whitbourn, associate renal denervation following renal denervation. striking paucity of randomised programme completely. professor and director of the assessment of the trial’s Melvin Lobo (consultant controlled trials.” According to a press release, Cardiovascular Research primary endpoint at six months physician, NIHR Barts Similar to Lobo, Christophe the exit is “primarily in Centre at St Vincent’s following randomisation. This Cardiovascular Biomedical Mariat (Nephrology response to slower than Hospital in Melbourne, crossover treatment group Research Unit, William Harvey Department and Hypertension expected development of the Australia. “These results experienced significant and Research Institute, QMUL, Centre, Jean MONNET renal denervation market.” continue to demonstrate the sustained blood pressure London, UK) also agrees the University, Saint-Etienne, The press release notes that impact renal denervation reductions at 30 months full results of SYMPLICITY France) believes that as result of the company’s can have on patients with after renal denervation with HTN-3 are necessary to SYMPLICITY HTN-3 decision to pull out of the uncontrolled hypertension, and an average blood pressure understanding why the study will affect all companies OneShot programme, Covidien these data are an important reduction of -33/-13mmHg failed as he says: “Critical investigating renal denervation will now not proceed with its contribution to the growing [p<0.01] from baseline (n=30).

4 Coronary interventions February 2014 Transradial approach is “reasonable” in women Sunil Rao (Duke Clinical Research Institute, Durham, USA) reported—according to the results of SAFE-PCI for Women trial—that an initial strategy of transradial access is reasonable in women undergoing cardiac catheterisation because it is associated with less bleeding or vascular complications than the transfemoral approach “with the recognition that a proportion of patients will require conversion to femoral access”

resenting the study at the 2013 endpoint, at 72 hours after the the time of the substudy enrolment Transcatheter Cardiovascular procedure or hospital discharge was complete (300 patients), we had PTherapeutics meeting (TCT; 27 (whichever came sooner), was the rate randomised 1,787 women.” October–1 November, San Francisco, of bleeding or vascular complications Of these, 893 (of whom, 345 USA), Rao explained that the SAFE- and the primary feasibility endpoint underwent PCI) were randomised to PCI (Study of access enhancement of was the rate of access site crossover receive the radial approach and 894 percutaneous coronary intervention) (defined at the inability to complete the (of whom, 345 underwent PCI) were for Women trial was conducted because procedure at the assigned access site). randomised to receive the femoral the role of transradial access in women There were two pre-specified analysis approach. In the PCI cohort, the undergoing PCI was “unclear”. He cohorts: the total randomised cohort radial approach was associated with noted: “Women undergoing PCI present and a subgroup of patients within the a 60% reduction (1.2% vs. 2.9% for a unique challenge; while they are total cohort who underwent PCI (PCI the femoral approach) in the rate of at higher risk of bleeding [therefore, cohort). bleeding or vascular complications may be more suited to the transradial but this did not reach statistical approach because it is associated Initially, Rao explained, the significance (p=0.12). Rao noted that with a lower risk of bleeding than the investigators planned to enrol 3,000 there was a 70% reduction with the transfemoral approach], they have patients (of which, an estimated radial approach that did reach statistical smaller radial arteries and are more 1,800 would undergo PCI). They significance in the total randomised Sunil Rao prone to radial spasm—which has been assumed that the rate of bleeding or cohort (0.6% vs. 1.7%, respectively; implicated as a cause of transradial vascular complications with femoral p=0.03) and added: “There was no “The SAFE-PCI for Women trial procedure failure.” Rao added that access approach would be 8% and significant interaction between PCI suggests that an initial strategy of women have been significantly under- that the radial access approach and diagnostic catheterisation for the radial access is reasonable and may be represented in studies comparing would reduce this rate by 50%. primary efficacy endpoint, indicating preferred [the majority of women in the transfemoral approach with the that the benefit of radial access the study said they preferred the radial transradial approach. “Accordingly, However, he commented: “The in reducing bleeding or vascular approach] in women, with the recogni- we conducted the SAFE-PCI for rate of the primary efficacy endpoint complications was consistent across tion that a proportion of patients will Women trial to determine the efficacy was markedly lower than expected. both cohorts.” require conversion to femoral access.” and feasibility of transradial PCI in Our data safety monitoring board In both the total and PCI cohorts, the He concluded, adding that the construct women.” recommended the termination of the radial approach was associated with a of the trial—which involved enroll- In the study, women undergoing trial because it was unlikely to show a significantly increased rate of access ing patients via the National Cardio- urgent or elective PCI, or diagnostic difference in the planned sample size. site crossover and Rao said: “The vascular Data Infrastructure—was a catheterisation with the possibility As there were no safety issues, the most common reason for needing to promising approach for future clinical of PCI were randomised to the steering committee voted to continue convert from radial to femoral access investigators as it produced higher transfemoral or the transradial the study until enrolment in a quality to complete the procedure was radial quality data, reduced site workload, approach. The primary efficacy of life substudy was complete. By artery spasm.” and reduced costs.

Long-term dual antiplatelet therapy may not always be needed

Continued from page 1 after the presentation of the 2.2% for 12-month DAPT; differences between groups OPTIMIZE results at TCT, p=0.47), and that there in any of the components Dean J Kereiakes (Christ was a statistical trend of the primary endpoint at Hospital Heart and Vascular towards higher rates in the landmark analysis (90 Center, The Lindner Re- any bleeding events at days) or at 12 months; for search Center, Cincinnati, the same timeline with 12 example, the rate of stent USA) criticised the non-in- vs. three months DAPT thrombosis was 0.7% in the feriority composite endpoint (1.0 vs. 0.4%, p=0.07). three-month DAPT group used in the study. He said: He adds: “The use of vs. 0.6% for the 12-month “Although this type of end- such endpoint (NACCE) DAPT group (p=0.64) at 90 point is selected to enhance would be justified by days and 0.3% vs. 0.1%, power, it is problematic due the fact that it combines respectively, at 12 months to a lack of expected or actu- key adverse events (p=0.18). al correspondence amongst directly related to DAPT Feres concluded: “This its components. When treatment and is exactly prospective randomised discordant components what physicians want to trial showed that second are present, the individual know when considering a generation drug-eluting components lack power to treatment for their patients. stents might not always detect if clinical meaning- Fausto Feres As for the applicability require 12-month DAPT to ful differences exist. Indeed of the trial’s results, one reduce the risk of adverse in OPTIMIZE, a relative marker-positive patients with refuted Kereiakes’ should definitely take into thrombotic events.” He increase in ischaemic events acute coronary syndromes arguments, explaining consideration the population added that the results may with three-month DAPT was and these patients present- that there were no studied since the best be “especially relevant” for counterbalanced by a rela- ed “a significant proportion significant differences in available evidence suggests patients who are at high tive increase in major bleed- of patients in contemporary the rates of ischaemic that in general, patients with risk of bleeding complica- ing with 12-month DAPT.” clinical practice.” events only (death, high-risk acute coronary tions following PCI and, He added that extrapolating Feres told myocardial infarction syndrome may benefit from therefore, might need to the results of OPTIMIZE to Cardiovascular News or stroke) from 90 days prolonged DAPT regardless stop DAPT earlier. clinical practice was difficult that he and his fellow to 12 months (2.6% for of the treatment strategy However, in the discussion because it excluded bio- OPTIMIZE investigates three-month DAPT vs. and device used.”

6 Coronary interventions February 2014 Resolute Integrity has similar efficacy to Promus Element

The first randomised study to investigate the third-generation zotarolimus-eluting Resolute Integrity stent (Medtronic) has found that it is non-inferior to the third- generation everolimus-eluting Promus Element stent (Boston Scientific), indicating that both stents are similarly efficacious and safe

tudy authors Clemens von Birgelen (Department failure (cardiac death, target vessel related myocardial of the Cardiology, Thoraxcentrum Twente, infarction, and clinically indicated target-vessel SEnschede, The Netherlands) and others report revascularisation). Secondary endpoints included the in The Lancet that, compared with earlier generation individual components of the primary endpoint, all- drug-eluting stents, the design and/or material of the cause mortality, any myocardial infarction, clinically bare metal stent platforms of third-generation stents indicated target-lesion revascularisation, and stent (such as Resolute Integrity and Promus Element) thrombosis. Von Birgelen et al also note: “Operators have been “changed substantially” to provide more were requested to report any evident or suspected flexibility and higher deliverability. However, they add: longitudinal stent deformation, which was defined as “Such changes might have the trade-off of reducing distortion or shortening of an implanted stent in the longitudinal stent stability, which would account for longitudinal axis.” the occurrence of longitudinal stent deformation that At one year, there were no significant differences has been reported after contact between deployed in the rate of the primary endpoint between stents and guiding catheters, balloon catheters, or other groups—6.1% for Resolute Integrity and 5.2% for catheter-based devices.” Promus Element (non-inferiority p=0.006). There were Furthermore, according to von Birgelen et al, the data also no significant differences in any of the secondary reported for the incidence and clinical significance of outcomes. Longitudinal stent deformation was only longitudinal stent deformation with third-generation reported in patients who received the Promus Element stents has been conflicting. stent (nine overall, which is 1%). However, the authors comment: “None of the patients with longitudinal As the safety and efficacy of Resolute Integrity has stent deformation had any adverse clinical events as not been evaluated in a randomised trial, the aim of a result.” the DUTCH PETERS (Durable polymer-based stent “Both stents were similarly efficacious and safe, and challenge of Promus Element vs. Resolute Integrity) provided excellent clinical outcomes especially in view was to compare the clinical outcomes—including of the large number of patients who presented with Clemens von Birgelen longitudinal stent deformation—of these two third- acute myocardial infarction,” they conclude. generation stents in an all-comers population. Von Birgelen told Cardiovascular News: “While in DUTCH PEERS, the proportion of patients with represent a challenging touchstone for future stents Of the 1,810 patients in the study, 905 (1,205 acute coronary syndrome (and in particular, ST- and scaffolds.” lesions) received the Resolute Integrity stent and 905 segment elevation myocardial infarction) was among The DUTCH PETERS (TWENTE II) study (1,166 lesions) received the Promus Element stent. the highest of all randomised multicentre all-comers was presented as a late-breaking trial at the TCT The composite primary endpoint was target-vessel stent trials, clinical outcome was excellent and may conference. Pre-hospital bivalirudin reduces death or major bleeding

Data from the EUROMAX (European ambulance acute coronary syndrome angiography) study indicate that pre-hospital administration of bivalirudin (Angiox, The Medicines Company), in the ambulance or during transfer to a hospital capable of primary percutaneous coronary intervention (PCI), is associated with a reduced rate of death or major bleeding at 30 days compared with standard treatment

resenting the results PCI, and what is the impact patients scheduled for primary risk reduction in major or aim. They inform pre-hospital at the Transcatheter of contemporary practice on PCI were randomised—in the minor bleeding (p<0.001). The management of STEMI and PCardiovascular the efficacy and safety of ambulance or at a non-PCI results were consistent across support a role of bivalirudin in Therapeutics (TCT) conference bivalirudin?” hospital—to bivalirudin (1,089) all subgroups. However, Steg this setting.” (27 October–1 November, San Therefore, the aim of the or heparin (1,109). The rate of noted: Steg told Cardiovascular Francisco), Philippe Gabriel open-label EUROMAX study the primary endpoint was 5.1% News: “The risk of stent Steg (Cardiologie, Département was to determine if bivalirudin in patients receiving bivalirudin “I won’t sweep it under thrombosis is increased with Hospitalo-Universitaire was superior to heparin (with or and 8.5% in those receiving the carpet, the rate of bivalirudin but the increase FIRE, Hôpital Bichat, Paris, without glycoprotein inhibitors) heparin, resulting in a highly stent thrombosis was is minimal in absolute terms. France) commented that the when initiated during significant 60% reduction in significantly higher Also, I am not sure that it is “landmark” HORIZON-AMI transportation to a primary the relative risk of death or in patients receiving easy to identify patients at high study showed that bivalirudin PCI facility in contemporary major bleeding with bivalirudin bivalirudin (1.6% vs. 0.5% risk of stent thrombosis in the reduced the risk of mortality practice (ie. frequent use of (p<0.001). for heparin; p=0.02). This context of STEMI; therefore, or major bleeding compared radial access and novel P2Y12 Bivalirudin was also was largely driven by an I am not sure that the risk of with unfractionated heparin inhibitors) in patients with ST- associated with a significant increase in definite stent stent thrombosis associated and glycoprotein inhibitors segment elevation myocardial 72% reduction in the relative thrombosis in the first 24 with bivalirudin will or in patients undergoing infarction (STEMI). The risk of the key secondary hours; in reality, it was the should play a role in patient primary PCI but added that composite primary endpoint endpoint (p<0.02) compared first four hours.” selection. Furthermore, I it prompted new questions. was the rate of death or with heparin. Steg reported believe that the increase He said: “What is the role of (non-coronary artery bypass that with both the primary He concluded: “These results is relative to the use of bivalirudin in the ambulance grafting) major bleeding at 30 and secondary endpoints, were achieved on a background glycoprotein inhibitors in for patients triaged to primary days and the key secondary the benefits observed with of contemporary care, with the control arm (ie. it is not PCI? Is it possible to reduce endpoint was the rate of death, bivalirudin stemmed from a high rate of radial access, bivalirudin that increases stent the risk of stent thrombosis re-infarction or major bleeding substantial reductions in use of novel PY12 inhibitors thrombosis; it is the use of by using a prolonged infusion at 30 says. major bleeding—the drug was and optional glycoprotein glycoprotein inhibitors that of bivalirudin at the end of Overall, 2,218 STEMI associated with a 58% relative inhibitors use on the control reduces it in the control arm). February 2014 Research 7 Increased use of left ventricular assist devices could improve heart failure survival for a heart transplant but are expected to It should be noted that left ventricular die within a year5. assistant devices are not without risk or Why more patients with heart failure drawbacks. Patients can face complica- are not referred for further evaluation in tions, such as clots and infections, have GUY MACGOWAN the UK is not always clear. One reason to be on medication for life, and have may be that physicians believe that medi- to be willing and able to endure ongo- cal management is the only option avail- ing maintenance. But, the benefits of COMMENT & ANALYSIS able given the limited number of hearts implanting such a device (ie. prevent- available for transplant. Another reason ing premature death) could be said to might be that they believe left ventricular outweigh these risks. Guy MacGowan reviews the benefits of using left ventricular assist devices are untested or that the Therefore, physicians need greater assist devices to improve survival in patients with heart failure, NHS will not fund surgical procedures to awareness of the benefits of left ventricu- and examines why there seems to be a reluctance to use the the implant the devices. lar assist devices so that they can refer devices in the UK However these devices have now been advanced heart failure patients for further used for several decades and have been evaluation to transplant centres and, ach year, fewer than 1,000 hearts heart failure who receive such a device steadily improving—particularly with potentially, enable their patient to receive are available across Europe for in the USA (which has about the same more recent developments. a life-saving treatment. Etransplant1. This does not bode percentage of population in heart failure well for the estimated 750,000 patients and outpaces the number of UK heart The latest innovations in device 4 References with heart failure (or the 27,000 who are transplants by almost 20-to-1) , the UK technology have made them simpler, 1. Stehlik J, et al. Heart Lung Transplant 2010; 29: diagnosed each year)2 in the UK alone. would need to increase its implantation smarter and more versatile. Recent 1089–103 2. Heart Research Institute. www.hriuk.org/about-heart- There are alternative (potentially life- rate of left ventricular devices by 300%. data show that survival with a next disease/heart-facts generation device is 93% at 180 3. Emin et al, European Journal of Heart Failure (2013) saving) options to heart transplantation, This low use of left ventricular assist 15, 1185–1193 such as left ventricular assist devices, device in the UK occurs despite the fact days and 90% at one year6. 4. Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov/latestData/rptData.asp but patients are rarely referred to the that the European Society of Cardiology 5. European Society of Cardiology. http://www.escardio. centres that can evaluate them to see if (ESC) recommends these devices for By comparison, survival in patients org/guidelines-surveys/esc-guidelines/GuidelinesDocu- ments/acute-chronic-heart-failure-2012.aspx. they would be suitable for one of these patients who have end-stage heart failure with severe heart failure on medical man- 6. Aaronson et al. Circulation 2012; 125: 3191–200 options. For example, the UK’s six who are receiving optimal treatment, and agement alone with Seattle Heart Failure 7. Strueber et al. J Am Coll Cardiol 2011; 57(12): 1375–82 transplant hospitals implant fewer than who are suitable for heart transplanta- Model has been estimated to be 73% at Guy MacGowan is a cardiologist at 100 left ventricular assistant devices tion5. The ESC also recommends left 180 days and 58% at one year7. Further- Freeman Hospital in Newcastle upon per year3. ventricular assist devices for end-stage more, the NHS does fund implantation of Tyne, UK. He has no conflicts of interests To match the proportion of people with heart failure patients who are not suitable left ventricular assist devices. relating to left ventricular assist devices Conservation revascularisation is non-inferior to aggressive revascularisation According to the SMART-CASE study, which was presented during a first report investigation at the Transcatheter Cardiovascular Therapeutics conference (27 October–1 November, San Francisco, USA), a conservative strategy of only performing percutaneous coronary intervention (PCI) in lesions with a diameter stenosis of >70% does not increase the risk of all-cause death, myocardial infarction, or any revascularisation at 12 months compared with an aggressive strategy of performing PCI in lesions with a diameter stenosis of >50%

rincipal investigator Hyeon-Cheol Gwon The primary endpoint was a composite of all-cause (Department of Internal Medicine, death, myocardial infraction, or any revascularisation PCardiovascular Center, Seoul National at 12 months. Clinical follow-up was planned at one University Hospital, Seoul, Korea) noted that there month, six months, one year, two years, and three is discrepancy between guidelines about when PCI is years. Colbalt chromium everolimus-eluting stents indicated in an intermediate lesion (diameter stenosis were used for all lesions. of >50%–70%)—American guidelines recommend At one year, the rate of the primary endpoint that it is indicated where there is a diameter stenosis was 7.3% in the conservative group vs. 6.8% in the of >50% but European guidelines recommend it is aggressive group (p=0.0055 for non-inferiority). indicated when there is a diameter stenosis of >70%. There were no significant differences between the He added: “Surprisingly, the clinical outcome of PCI groups in any of the secondary endpoints apart from based on the criteria of diameter stenosis of >50% vs. target lesion revascularisation—4.1% for the conserva- >70% has never been studied.” tive strategy compared with 1.7% for the aggressive Therefore, the objective of the SMART-CASE study strategy (p=0.045). The findings were consistent in was to find the optimal strategy of PCI for the angio- most of the subgroups, but there was trend towards graphically intermediate lesion with the hypothesis favouring aggressive therapy (p=0.07) in patients aged that conservative revascularisation using a criterion <65 years and a trend towards favouring conservative of >70% diameter stenosis would be non-inferior to therapy in patients aged ≥65 years (p=0.13). aggressive revascularisation using a criterion of >50% Also in patients aged <65 years, the rate of any diameter stenosis. revascularisation was significantly higher (p=0.03 for In the study, 899 patients with an intermediate the comparison) in the conservative group. stenosis, as identified by quantitative coronary Gwon concluded: “Conservative revascularisation angiography, of >50–70% were randomised to using a criterion of diameter stenosis of >70% conservative (449) or aggressive (450) PCI. Exclusion was found to be non-inferior to aggressive criteria included cardiogenic shock, a left main lesion, revascularisation. The revascularisation of prior drug-eluting stent in target vessel, and myocardial angiographically intermediate lesions can be deferred infarction with the past 48 hours. Hyeon-Cheol Gwon safely.” 8 Revascularisation strategies February 2014 Meta-analysis raises questions about ischaemia-driven revascularisation

A meta-analysis published in JAMA Internal Medicine indicates that percutaneous coronary intervention (PCI) does not reduce the risk of death or non-fatal myocardial infarction in patients with stable coronary artery disease with myocardial ischaemia that has been identified through stress testing or fractional flow reserve (FFR). These results raise questions about the effectiveness of ischaemia-driven revascularisation

athleen Stergiopoulous (Division of Cardiovas- analysis, via randomisation, 2,106 received PCI and cular Medicine, Department of Medicine, State 2,048 received medical management alone. The rate of KUniversity Of New York–Stony Brook School all-cause death was not significantly different between of Medicine, Stony Brook, USA) and others report that treatment groups—6.5% for patients receiving PCI they performed a systematic review and collaborative vs. 7.3% for patients receiving medical management meta-analysis of PCI vs. medical management alone in alone (p=0.42). There were also no differences in the stable coronary artery disease and myocardial ischaemia rates of non-fatal myocardial infarction (9.2% for PCI because of the “equipoise” surrounding the issue. They vs. 7.6% for medical management; p=0.06), unplanned explain that a large observation study showed that revas- revascularisation (18.3% vs. 28.4%; p=0.14), and cularisation in patients with at least moderate ischaemia recurrent or persistent angina (20.3% vs. 23.3%; p=0.67). was associated with fewer cardiac deaths than medical According to the authors, the results “strongly management alone but add: “Two post-hoc studies of suggested” that the relationship between ischaemia patients enrolled in the COURAGE (Clinical outcomes and mortality is not altered or ameliorated by catheter- using revascularisation and aggressive drug evaluation) based revascularisation of obstructive flow-limiting trial with either mild or moderate-to-severe ischaemia coronary stenosis and that the genesis of late clinical at baseline failed to demonstrate a reduction in death or events is not necessarily a consequence of the ischaemic myocardial infarction in patients treated with PCI com- vascular territory subtending a stenotic coronary pared with those who received medical therapy.” segment “but rather due to the development of new Stergiopoulous et al examined five studies in the meta- plaque ruptures in distant coronary segments without David Brown analysis, which included COURAGE, MASS (Medicine, flow-limiting stenoses.” They add the findings also “call angioplasty, or surgery) II, and FAME (Fractional flow into question the common practice of ischaemia-driven News: “This meta-analysis suggests that the cardiology reserve vs. angiography for multivessel disease) 2. revascularisation where the presence of myocardial community should reconsider the strategy of ischemia- They reviewed data for patients who were identified as ischaemia routinely determines patient selection for guided revascularisation. Many of the over 10 million having myocardial ischaemia (through stress testing or coronary angiography and revascularisation.” stress tests performed annually in the USA are to identify FFR) and looked at the incidence (after a maximum of Study authors David Brown (Division of ischemia as a prelude to referral for revascularisation. If five years of follow-up) of all-cause death, non-fatal Cardiovascular Medicine, Department of Medicine, our findings are confirmed in the ongoing ISCHEMIA myocardial infarction, unplanned revascularisation, or State University Of New York–Stony Brook School trial, many of these stress tests and subsequent angina in these patients. Of 4,064 patients in the meta- of Medicine, Stony Brook, USA) told Cardiovascular revascularisations may be unnecessary.” Reclassification with FFR of ambiguous lesions is safe Results from the Registre Français de la FFR, published in Circulation and presented at the American Heart Association annual meeting (16–20 November, Dallas, USA), indicate that a fractional flow reserve (FFR)- guided revascularisation strategy that diverges from the strategy suggested by angiography does not increase the risk of major adverse cardiovascular events (MACE) at one year

tudy authors Eric Van and its impact on one-year clini- patient level—use of FFR led to patients in the rate of freedom Belle (Heart Catheterisa- cal outcomes.” Patients were reclassification of revascularisa- from angina at one year (>94% Stion Laboratory, Hôpital included in the registry if they tion strategy in 43% of patients. vs. >91%, respectively; p=0.75). Eric Van Belle Cardiologique, Lille, France) had at least one angiographi- They add: “Such reclassification Van Belle note that in three and others write that prior to cally ambiguous lesion in a was observed in 33% of a priori subgroups—diabetic patients angiography alone, but guided the registry, there have been major coronary vessel evaluated [ie. angiography alone] medical requiring insulin, patients with by FFR measurement.” no reports on the use of FFR by FFR. Based on angiography patients, 56% of a priori PCI decreased left ventricular ejec- Van Belle told Cardiovascular in patients referred for diag- alone, of the 1,000 patients in patients, and 51% of a priori tion fraction, and those with News: “The results of the nostic angiography (previous the registry overall, 55% of pa- CABG patients.” three-vessel coronary artery present study further support studies have concentrated on tients would have been assigned According to the results of disease—reclassification with the concept of a ‘coronary patients selected for percuta- to medical therapy and 45% the registry, at one year, the rate FFR continued to be safe. physiology-guided treatment’ neous coronary intervention) would have been assigned to re- of MACE in the 464 patients The authors conclude that the of patients with coronary artery or how reclassification of the vascularisation (38% to PCI and whose revascularisation strategy study demonstrates that: “In this disease. It suggests in particular revascularisation strategy fol- 7% to coronary artery bypass has been reclassified following population, the use of FFR is that in the near future a coronary lowing FFR affects outcomes. grafting [CABG]). With ad- FFR did not differ significantly associated with reclassification angiography will no longer They note that the registry was ditional diagnostic information from the MACE rate of patients of the revascularisation be interpreted without the designed to: “Evaluate the rate from FFR, 58% were assigned whose strategy remained decision in about half of FFR results and that FFR will of reclassification of the patient to medical therapy and 42% the same—11.2% vs. 11.9% patients. It further demonstrates become a mandatory and fully- coronary revascularisation strat- were assigned to revascularisa- (p=0.78). There was also no dif- that it is safe to pursue a integrated part of any diagnostic egy by performing FFR at the tion. However, Van Belle et al ference between the reclassified revascularisation strategy coronary angiography time of diagnostic angiography, report that—on an individual patients and the non-reclassified divergent from that suggest by investigation.”

10 Research February 2014 Coronary revascularisation in diabetic patients: Where do we stand? minimised with newer drug-eluting stent in diabetic patients remains paramount. technology. In addition to aspirin and statin therapy EHRIN post-PCI, strong consideration should PCI in diabetic patients be given to more intensive antiplatelet ARMSTRONG A number of factors should be considered therapy. In both the TRITON-TIMI 38 among diabetic patients selected for PCI, (prasugrel) and PLATO (ticagrelor) including medical management, stent trials, diabetic patients derived greater type, and secondary risk factor modifica- benefit from more intensive antiplatelet COMMENT & ANALYSIS tion post-PCI. therapy relative to clopidogrel5,6. In Diabetic patients are at increased TRITON-TIMI 38, this benefit included Diabetes is a worldwide epidemic that affects more than 170 risk of restenosis and stent thrombosis a significantly lower risk of stent million people1 and is expected to double in the coming decades. relative to non-diabetic patients. thrombosis among diabetic patients Because it is associated with a 2–4 fold increased risk of heart However, recent studies with newer assigned to prasugrel. disease, the proportion of patients with diabetes and coronary generation drug-eluting stent suggest artery disease will also increase. In this commentary, Ehrin that most of this excess risk is among Conclusion Armstrong reviews the revascularisation options and medical patients who require insulin therapy Diabetes and coronary artery disease therapy for patients with diabetes and coronary artery disease for their diabetes3. It is unclear whether remains a challenging clinical problem. this increased risk of recurrent events is Recent trials focused on diabetic patients he recently published FREEDOM trial also had a normal left ventricular due to insulin, or whether insulin use is have helped emphasize the high-risk trial randomised 1,900 diabetic ejection fraction. Consistent with a marker for more significant disease. nature of this patient population. Future Tpatients with multivessel coro- these limitations, only 10% of patients Regardless, the status of current medical revascularisation strategies may hold nary artery disease and stable angina to screened for FREEDOM met the study therapy for diabetic patients should promise for treatment of this challenging coronary artery bypass grafting (CABG) inclusion criteria, and almost half of be assessed prior to PCI to better risk patient population. or percutaneous coronary interven- those did not provide consent2. stratify patients. tion (PCI)2. At five years of follow-up, Based on these results, patients with Drug-eluting stents significantly reduce Ehrin Armstrong is an interventional patients randomised to CABG had sig- diabetes and symptomatic multivessel the rates of restenosis and need for repeat cardiologist from University of Colorado, nificantly lower mortality and myocardial coronary artery disease who are interventions among both diabetic and Denver, USA infarction. These results were clinically candidates for surgery should undergo non-diabetic patients relative to bare meaningful, with an absolute event rate CABG as the preferred revascularisation metal stents. Comparisons of different This commentary was written to support of the primary endpoint at five years of option. PCI remains the preferred drug-eluting stents types have suggested the American Diabetes Association’s 18.7% in the CABG group and 26.6% in approach for diabetic patients with possible differences in outcomes among Make the Link! Diabetes, Heart Disease the PCI group. single vessel coronary artery disease, diabetic patients. In general, these and Stroke initiative. For more informa- Although FREEDOM was a well- surgical contraindications, or high-risk results favour use of second-generation tion, see: http://professional.diabetes. designed multicentre international trial, acute coronary syndromes. Because drug-eluting stents as compared to first org/makethelink 4 the results are not generalisable to all FREEDOM included primarily first- generation drug-eluting stents . In the References patients with diabetes and coronary generation drug-eluting stents, it is USA, the zotarolimus-eluting Resolute 1. Wild et al. Diabetes Care 2004; 27: 1047–53 2. Farkouh et al. The New England Journal of Medicine artery disease. Many diabetic patients possible that the risk-benefit ratio may stent (Medtronic) remains the only 2012; 367: 2375–84 have additional comorbidities, placing also favour PCI in certain diabetic drug-eluting stents with a specific FDA 3. Silber et al. JACC Cardiovasc Interv 2013; 6: 357–68 4. Stone et al. Circulation 2011; 124: 893–-900 them at prohibitive risk of surgery. The patients where the risk of restenosis indication for diabetic patients. 5. Wiviott et al. Circulation 2008; 118: 1626–36 majority of patients in the FREEDOM and target lesion failure could be Optimal medical therapy after PCI 6. James et al. Eur Heart J 2010; 31: 3006–16 Bioresorbable scaffold is safe and feasible for STEMI patients According to a study published ahead of print in the European Heart Journal, the early results from the ongoing Prague 19 study indicate that implantation of a bioresorbable scaffold (Absorb, Abbott Vascular) in patients with ST-segment elevation myocardial infarction (STEMI) is safe and feasible as the device is associated with good procedural results in these patients

iktor Kočka (Cardiocenter, Third Faculty This study [the one published in the European Heart with recommendation to consider the treatment of edge of Medicine, Charles University in Prague, Journal] presents the procedural angiographic plus dissections large than 30% of the lumen circumference VUniversity Hosptial Kralovske Vinohrady, results and early (up to six months) clinical outcomes.” and to consider post-dilation in the case of malapposi- Prague, Czech Republic) and others write that a Of the 142 consecutive STEMI patients who tion detectable in multiple frames; no such cases were, bioresorbable scaffold has potential advantages underwent primary PCI during the study’s eight-month however, encountered.” for STEMI patients—stating: “STEMI patients are enrolment period (between December 2012 and August There were two clinical events in the scaffold group: frequently younger, have less extensive coronary 2013), 41 received a bioresorbable scaffold (overall, 49 the first patient suffered stent thrombosis 13 days post artery disease (compared with non-STE acute scaffolds were used). The reasons for not implanting a implantation after he stopped using all prescribed coronary syndromes) and may live many years after scaffold included a high likelihood of dying within the medication; the second underwent planned staged primary percutaneous coronary intervention (PCI) reabsorption timeframe (Killip III–IV class), infarct primary of his left circumflex artery coronary artery and thus derive the benefit of not having a permanent artery reference diameter <2.3 or >3.7mm (ie. not with a drug-eluting metallic stent five weeks after rigid metallic structure in their coronary arteries.” suitable for currently available scaffold sizes), and primary PCI and had a small myocardial infarction due However, they add that the device has not yet “been lesion length >24mm (ie. precluding single scaffold to a side branch occlusion. According to the authors, systematically investigated” in STEMI patients. implantation). this event was “completely unrelated to the previously Therefore, the multicentre, open-label Prague 19 The authors report that implantation of the bioresorb- implanted bioresorbable vascular scaffold.” study was set up to analyse the feasibility and safety able scaffold was associated with a 98% (40 of 41) suc- Kočka et al conclude: “This study’s results showed of using a bioresorbable scaffold during primary PCI. cess rate without any technical difficulties and comment: that bioresorbable vascular scaffold implantation Kočka et al note: “The study is planned for three years, “Twenty-one patients had OCT intracoronary imaging in acute STEMI is feasible and safe, and could be with a clinical follow-up plus CT coronary angiography performed at the end of the primary PCI without any potentially used in a larger proportion of patients.” after one year and invasive coronary angiography with complication. A visual estimate of scaffold apposition They add while the short-term outcomes were optical coherence tomography (OCT) after three years. and edge dissection was performed by the operator, “encouraging”, longer follow-up was needed.

12 Structural heart disease February 2014 Transcatheter Valve News Negligible aortic regurgitation with new TAVI valve

The 30-day data from the REPRISE II study indicate that patients creased (from 0.7±0.2mmHg at baseline who receive the Lotus transcatheter aortic valve implantation to 1.6±0.4mmHg; p<0.001). (TAVI) device (Boston Scientific) have about a one in 100 chance However, Meredith noted that “one of of developing paravalvular leak the most interesting observations” in the trial was the low rate of aortic regurgita- peaking at the 2013 Transcatheter positioning, and has an adaptive seal tion at 30 days—about 80% of patients Cardiovascular Therapeutics (TCT; that has been designed to minimise had no or trace aortic regurgitation and of S27 October–1 November, San paravalvular leak. “The objective of the the 16.5% of the patients with paravalvu- Francisco, USA), REPRISE II investiga- REPRISE II study was to evaluate the lar leak, 15.5% had mild, 1% had moder- tor Ian Meredith (MonashHeart, Clayton, safety and performance of the Lotus ate, and there were no cases of severe Australia) said that although early TAVI valve in patients at high risk for surgery,” paravalvular leak. He said: “The chance devices provide significant benefit for -in Meredith added. of developing paravalvular leak after suc- operable or high-risk patients, they have The study had a prospective single-arm cessful deployment of a Lotus valve was limitations—for example, studies have design and its primary endpoints were approximately one in 100.” indicated that they are associated with mean aortic valve pressure gradient at 30 The rate of all-cause mortality was paravalvular leak, valve malposition, and days compared with a performance goal Ian Meredith 4.2% and was all due to cardiac death, stroke. He noted: “Second-generation of 18mmHG (performance) and all-cause and the rate of stroke was 5.2% (largely devices should therefore reduce aortic mortality at 30 days (safety). Follow-up implanted with the valve. Meredith said: due to non-disabling stroke). Other regurgitation, have simple, precise and was scheduled at discharge, 30 days, “We easily met the primary performance results showed that the valve was suc- atraumatic aortic or ventricular reposi- three months, six months, and yearly up endpoint. The mean aortic valve pressure cessfully implanted and positioned in all tioning, and allow for full atraumatic to five years. Patient inclusion criteria gradient was 11.5±5.2mmHg, which 120 patients. retrieval.” was age ≥70 years, New York Heart was significantly less than the perfor- Concluding, Meredith said: “There According to Meredith, the Lotus Association (NYHA) class II or above, mance goal of 18mmHg (p<0.001)”. was negligible aortic regurgitation and valve has been designed with these aortic valve area <1cm2 plus mean pres- He added that the mean aortic gradient the clinical event rates are consistent requirements in mind. He explained sure gradient >40mmgHg, and high risk pressure at 30 days was also significant with those reported for other valves. that the valve is deployed via controlled for surgery. reduced compared with baseline levels These results suggested that differenti- mechanical expansion (rather than be- At the 30-day follow-up point, tran- (12.1±4.4mmHg vs. 46.4±15mmHg, ated second-generation Lotus TAVI ing balloon- or self-expandable), has a sthoracic echogram data was available respectively; p<0.001) and that the mean device will be a valuable addition for the central radiopaque marker to aid precise for 111 of the original 120 patients effective orifice area was significantly -in treatment of severe aortic stenosis.” Safety and efficacy of CoreValve confirmed for extreme risk patients Results from the CoreValve US pivotal trial extreme risk iliofemoral study show that the CoreValve transcatheter aortic valve implantation (TAVI) device (Medtronic) is safe and effective for extreme risk patients with severe aortic stenosis, as they indicated that the device is associated with a low rate of stroke at one year

resenting the data at TCT, improvement in outcome with rate of all-cause mortality was He concluded: “The results co-principal investigator TAVI that it was no longer 24% at one year (mostly due from the US CoreValve extreme PJeffrey Popma (director ethical to randomise patients to cardiovascular deaths), and risk iliofemoral study support of interventional cardiology, to medical therapy alone. The that 90% of patients improved the safety and efficacy of Beth Israel Deaconess Medical hypothesis was that TAVI with by at least one NYHA class this therapy in those who are Center, Boston, USA) reported the CoreValve system would and 60% of patients improved deemed unsuitable for aortic that the CoreValve US pivotal be superior to standard therapy, by at least two NYHA classes valve replacement.” trials were investigating two with the investigators estimating by one year. Furthermore, The results of the alternative groups of patients—surgically that the rate of all-cause according to Popma, the access analysis were also inoperable (extreme risk) and mortality/stroke at one year haemodynamics were “profound announced at TCT. These high risk for surgery. The aim of with standard therapy would be and sustained”—the effective showed that patients who the present study, he said, was to ≥43% and would be <36.5% orifice area increased from received the CoreValve system “evaluate the safety and efficacy with TAVI. 0.73 to 1.89cm2 and the mean via the subclavian or direct of the CoreValve transcatheter The primary analysis was Jeffrey Popma gradient decreased from 47.4 to aortic approach had significant heart valve for the treatment performed with an “as-treated” 8.8mmHg at one year. and sustained functional and of patients with symptomatic population—enrolled patients and 91% for echocardiographic The rates of paravalvular quality-of-life improvements. severe aortic stenosis in whom (all with severe aortic stenosis assessments. leak (both moderate and severe) However, the one-month major the predicted risk of operative and New York Heart Association Popma reported that the were low and improved over stroke rate in these patients mortality or serious, irreversible [NYHA] functional class II rate of all-cause mortality time—for example, 11% trended higher than those morbidity was 50% or greater at or greater) with a documented or major stroke (the primary of patients had moderate who received the CoreValve 30 days.” attempt for an iliofemoral endpoint) was 25.5% at one paravalvular leak at one transfemorally (6.3% vs. 2.4%, The primary endpoint was implant. Enrolled patients year with the CoreValve month but this was reduced respectively). all-cause mortality or stroke who were deemed unsuitable system, which he said was a to 4.1% by one year. Popma On the basis of the CoreValve at one year. Popma and his for iliofemoral implantation “highly statistically significant explained that while there was a extreme results, without an fellow investigators used an were reviewed in a separate reduction compared with significant association between independent device advisory objective performance goal to analysis. Of the 455 patients the performance goal (43%; severe paravalvular leak and panel review, the FDA has assess the benefit of TAVI on in the as-treated population, p<0.0001).” He added that late mortality, there was no approved the CoreValve device the primary endpoint in these 355 were alive at one year with there was a low rate of major association between other types for use in patients who are patients because prior studies 98.9% of them available for stroke both at one month (2.4%) of paravalvular leak (including too ill or too frail to undergo demonstrated such a marked clinical assessment follow-up and at one year (4.1%), the moderate) and late mortality. surgery. February 2014 Structural heart disease 13 Transcatheter Valve News The challenges of validating TAVI devices in the laboratory suitable for testing bioprosthetic heart lenges of testing new devices by adopting valves. At our laboratories (IMMR), we new strategies. For example, through the have seen bioprosthetic heart valves that use of new spectacular imaging—2D and NICOLAS have calcified within a few weeks after 3D, and a hybrid operating room with a implantation! rotational C-arm and 3D echocardiogra- BORENSTEIN The development of transcatheter de- phy. With these imaging techniques, we vices for the mitral valve is also associated are able to understand in real time with with challenges in the laboratory. Sizing is perfect vision where the chordae and the COMMENT & ANALYSIS paramount, and knowing the differences leaflets are with respect to the delivery between human and bovine, porcine, catheter and the stented valve. bovine or canine anatomy as well as the Therefore, we are proud to be one of the Transcatheter aortic valve implantation (TAVI) has revolutionised relevant physiologic/haemodynamic spe- highly specialised centres that worked to the management of patients with severe aortic stenosis, particu- cifics is crucial to finding the most suitable develop TAVI and transcatheter therapies larly surgically inoperable patients whose only option prior to animal models for testing each design of a for the mitral valve and to be involved in TAVI was medical management. However, several hurdles in the transcatheter device. the subsequent fine tuning of these de- research laboratory have to be overcome before such devices can vices. However, we always acknowledge be used in clinical practice To overcome these hurdles in that research intrinsically bears a certain research, a collaborative effort is amount of uncertainty. ne hurdle of pre-clinical research humans, but to an even greater extent) to warranted between the veterinar- Alternate approaches have therefore is the limitation of using animal have a coronary obstruction, aortic para- ians who work (every day) with the been proposed with using a heterotopic Omodels. While we know that valvular leak and mitral insufficiency due animal models and the research position—ie in the descending aorta (the animal models are absolutely paramount to anterior leaflet impediment. Further, teams who test the devices. There Hufnagel procedure), the mitral valve (ie. as the “last filter” before a device is used as the native valves are healthy, free of has to be a good understanding valve in valve procedure), and pulmonary in humans, there can be difficulties. calcium and non-stenotic, with very elastic between the engineers who develop valve—rather than an orthotopic position. The greatest hurdle in testing TAVI tissue in animal models, the seating of the the devices and the physicians who These difficulties were mostly overcome devices is the limitations of using animal valve is made even more difficult. use them in the clinics. For example, with second and third generation devices models to mimic human anatomy. It was However, some species are useful in the specialists of the animal models can as they are anatomically more prone to particularly difficult in the early days of field of transcatheter structural heart dis- help with insightful suggestions as seating adequately and are more refined TAVI to implant a valve in an orthotopic ease devices. For instance, an adult sheep to what model is best for the specific but anatomic and physiologic limitations position in a four-legged animal. The main can have a heart that is within the realm devices that warrant testing still hold true. reason being that in a four-legged animal of human sizes and, therefore, mostly model, the coronary ostia are very close used for chronic implantations (ie. tested After 1,500 implantations over more Nicolas Borenstein, scientific and techni- to the aortic annulus and the aorto-mitral over a long period of time). Also, sheep than 80 different studies in the field of cal manager, preclinical research, surgical continuity is much more intricate than in hearts are associated with a very intense TAVI and transcatheter mitral valve repair, training, GLP studies, IMMR, Institut humans. Therefore, it is possible (as in calcification process and this makes them our centre has learnt to adapt to the chal- Mutualiste Montsouris, Paris, France Pacemaker implantation after TAVI does not increase risk of all-cause mortality Although previous studies have shown that pacemaker implantation is associated with increased mortality and heart failure hospitalisation, a new study in Circulation has not found an association between permanent pacemaker implantation after transcatheter aortic valve implantation (TAVI) and an increased risk of all-cause mortality or heart failure hospitalisation

tudy authors Marina Urena (Quebec Heart balloon-expandable valve or a self-expandable valve. sation due to heart failure, with no difference between & Lung Institute, Laval University, Quebec The primary endpoint was a composite of all-cause permanent pacemaker implantation and no permanent SCity, Canada) and others state that pacemaker mortality and heart failure hospitalisation. Secondary pacemaker implantation groups (34.1% vs. 31.8%; implantation after TAVI is a common complication endpoints included: all-cause mortality, cardiovascular p=0.980). “ “with an overall incidence of about 15%”. They add: mortality, sudden cardiac death, a composite of sud- Speculating as to why these results were not consistent “Strong evidence supports the potential negative den cardiac death and unexpected death resulted from with the studies that showed the need for a paced rhythm impact of right ventricular apical pacing, which has unknown cause, and left ventricular ejection fraction increases the risk of late mortality and heart failure, been associated with an increased rate of the com- changes. Urena et al state that several TAVI studies have shown bined endpoint of mortality and rehospitalisation due Urena et al reviewed 1,811 consecutive patients who that new conduction disturbances following TAVI “may to heart failure.” underwent TAVI at eight centres between January 2005 resolve over time in about 50% of patients, especially However, little evidence exists for the impact of and February 2013. Of these, 239 patients received a with the use of balloon expandable valves.” They add that pacemaker implantation after TAVI and the data that are permanent pacemaker implantation within 30 days of one third of the patients with a pacemaker in their study available are from small studies. The authors comment: undergoing TAVI—with significantly more patients in did not exhibit any pacing activity on the ECG performed “While these studies did not find any impact of perma- the self-expandable group requiring a pacemaker than in at the six- or 12-month follow-up point. nent pacemaker implantation on mortality, concerns the balloon expandable group (25.5% vs. 7.1%, respec- The authors also note that while an association between that they may have been underpowered as a result of an tively; p<0.001). The authors report that there were no poorer mortality and permanent pacemaker implantation inadequate sample size have been raised.” significant differences between the patients who received has been observed in younger patients, “some studies The aims of the new study were, therefore, to review a pacemaker and those who did not in the rate of 30-day have shown that permanent pacemaker implantation has the impact of permanent pacemaker implantation on late mortality or major complications after TAVI (p>0.20), no impact on mortality in octogenarians and nonagenar- outcomes, left ventricular function and functional status adding: “After a mean follow-up of 22±17 months, a total ians, who in fact represent the vast majority of patients changes in a cohort of patients who received either a of 525 patients had either died or required a rehospitali- undergoing TAVI nowadays.” 14 Structural heart disease February 2014 Transcatheter Valve News Managing mild paravalvular leak after TAVI Paravalvular leak after transcatheter aortic valve implantation (TAVI) continues to be a concern, and the question of whether mild paravalvular leak is important remains unanswered. Susheel Kodali (director, Interventional Cardiology Fellowship Program, co-director, NYP Columbia Heart Valve Center, Columbia University Medical Center, New York, USA) speaks to Cardiovascular News about the identification and management of mild paravalvular leak

Overall, what percentage none and trace aortic regurgitation. The paravalvular leak. These differences in of patients experience challenges are in the grey zone between baseline characteristics may confound paravalvular leak after TAVI? mild and moderate. Efforts should be the analysis. Nevertheless, the fact that Having some degree of paravalvular made by all operators to integrate all despite accounting for these differences leak is very common after TAVI. of the information available in making on multivariable analysis, both mild Different studies have shown that mild the assessment of aortic regurgitation. and moderate/severe paravalvular leak paravalvular leak is present in 40–60% of In addition to echo, this may include is associated with increased one-year patients, and moderate or severe leak is haemodynamic and angiographic data in mortality is concerning. present in 10–20% of patients. A recent limited cases. meta-analysis of 45 studies, by Athappan How should a patient with et al, demonstrated that moderate or What do data indicate for the mild paravalvular leak be severe aortic regurgitation was present effects of mild paravalvular managed? in 11.7% of patients. In the PARTNER leak (ie. does it affect The goal is to minimise paravalvular trial, in which all the echos were analysed mortality/morbidity)? leak to start. We have learnt a lot about by a core lab, moderate or severe aortic Multiple studies have shown that how to size TAVI devices over the last Susheel Kodali regurgitation was present in about 12% moderate or severe paravalvular leak decade. Careful pre-procedural planning and mild in about 40% of patients. is clearly associated with higher one- and appropriate valve size selection have be managed as any other patient with year mortality. In the meta-analysis reduced paravalvular leak rates. Also, the optimal medical therapy of their heart In your view, what is by Athappan et al, the hazard ratio for devices and procedural techniques have failure. the definition of mild moderate or severe paravalvular and improved allowing for a more predictable paravalvular leak (as one year mortality was 2.27 with a valve deployment in the correct intra- Do you think, with opposed to moderate/ highly significant p value. In the same annular position that has also helped improvement and severe)? meta-analysis, mild paravalvular was reduce paravalvular leak rates. However, development of TAVI The grading of paravalvular leak can be also associated with higher one year due to anatomic issues and limitations of devices (eg. Sapien 3 or the a challenge. The studies to date have had mortality. However, the hazard ratio was the current devices, some patients will Lotus valve), paravalvular variable methods for grading it—some 1.83 with a p value of 0.048. We recently have mild paravalvular leak post implant. leak will be less of a have used angiography while others have presented an analysis from the PARTNER Our strategy is to immediately post- concern in the future? used echocardiography. The gold standard trial with over 2,200 patients. In this dilate the valve after implantation if we The hope is that these newer devices, method is echocardiography. Even with analysis, there was a stepwise increase think the risks are low and doing so will which have various mechanisms to seal the use of echo, there is variability from in mortality with both mild (hazard improve the paravalvular leak. We have the gap between the prosthesis and an- reader to reader. There have been efforts ratio 1.47, p value 0.003) and moderate/ shown in our analysis that post-dilatation nulus, will reduce paravalvular leak in to standardise the grading through the severe paravalvular leak (hazard ratio results in improved stent expansion the future. At recent meetings, there has Valve Academic Research Consortium 2.38, p value <0.001) on multivariable and reduced regurgitant volume. There been significant excitement regarding (VARC 2) document, which advocates analysis. It is important to note that there are risks with post-dilatation so careful them as initial feasibility studies have for a semi-quantitative grading of aortic are significant differences in the baseline thought to the risk-benefit ratio should demonstrated much less paravalvular regurgitation based on echo. In reality, characteristics of the patients that had be given before proceeding with post- leak. However, these are early stage it is fairly easy to define moderate and none-trace paravalvular leak vs. mild dilatation. Otherwise, if patients are left investigations and we need to continue to severe aortic regurgitation as well as paravalvular leak vs. moderate/severe with mild paravalvular leak, they should study them carefully. Six-month results confirm no aortic regurgitation with Direct Flow Medical’s TAVI device Results from the DISCOVER trial, which were presented at the Transcatheter Cardiovascular Therapeutics conference (TCT; 27 October –1 November, San Francisco, USA), show that no patients who received Direct Flow Medical’s transcatheter aortic valve implantation (TAVI) system had moderate or severe post-procedural aortic regurgitation at the six-month point. They also showed that the rate of freedom from all-cause mortality was 96% at six months

ccording to a press with no patient experiencing infarction in the evaluable cohort. able to virtually eliminate aortic DISCOVER, Direct Flow release, the Direct moderate or severe aortic The system avoids rapid pacing of regurgitation with outstanding Medical has announced that it AFlow Medical regurgitation at six months. the heart during deployment and patient safety. These results has completed enrolment in the TAVI device is designed to Additionally, the mean gradient does not require post-dilatation continue to be unprecedented for US SALUS trial of its TAVI minimise the risk of aortic of 13.0mmHg demonstrated following placement, minimising a TAVI device.” system. The aim of the trial regurgitation by enabling in-situ that the Direct Flow Medical the risk of haemodynamic The DISCOVER trial is a is to assess the safety of the haemodynamic assessment valve can significantly reduce, instability for patients. prospective, multicentre study Direct Flow Medical system to during the procedure, as well and maintain, low transvalvular Principal investigator Joachim conducted at nine European treat patients with severe aortic as unlimited repositioning gradients over time. Schofer, from the Medical Care sites in 100 patients with severe stenosis who are at extreme until optimal valve placement The safety profile of the system Center, Hamburg, Germany, aortic valve stenosis who require risk for surgical aortic valve is achieved. The press release was confirmed with a 97% VARC presented the results at TCT and replacement of their native aortic replacement. The company reports that the results from defined combined safety rate at says: “These data show that the valve but are at extreme risk for reports that it is working closely the DISCOVER trial confirm six months with no additional excellent results obtained with open surgical repair. with the FDA and plans to the system’s ability to virtually strokes (major or minor) and no the Direct Flow Medical system Further to the announcement initiate an US pivotal trial in this eliminate aortic regurgitation, patient experiencing a myocardial are sustainable over time. It is of the six-month results from year. February 2014 Surgery 15 Women at greater risk of events after left ventricular assist device implantation A study published in the Journal of the American College of Cardiology indicates that following implantation of a left ventricular assist device, women have a greater risk of post-discharge bleeding, haemorrhagic stroke, ischaemic stroke, or pump thrombosis than men

ndrew Boyle (chief of cardiology, Cleveland isolated event or due to the management response to the Clinic, Florida, USA) and others note that left haemorrhagic event. Aventricular assist devices are becoming “the The authors found that, in separate multivariate analy- standard of care” for the management of patients with ses, that female sex was a risk factor for post-discharge refractory heart failure, but add that “bleeding continues bleeding, ischaemic stroke, haemorrhagic stroke, and to be the most frequently reported complication, while pump thrombosis. They add: “We found a significant stroke and pump thrombosis [although the rates of the increased incidence of thrombotic [stroke or pump are low] are among the most serious”. They report that thrombosis] and haemorrhagic events [haemorrhagic the purpose of their study was to determine, using data stroke or post-discharge bleeding] in females compared from multicentre trials of HeartMate II (Thoratec), the with males.” pre-operative risks factors for these complications in Regarding the potential reasons for the higher inci- patients receiving a left ventricular assist device as a dence of these events in women, Boyle et al explain that bridge-to-transplantation or as destination therapy. There oral contraceptives and hormone replacement therapy were 956 patients in the retrospective review, with 405 are both associated with an increased risk of venous patients receiving a device for a bridge to transplanta- thromboembolism while women who undergo a natural tion indication. menopause before age of 42 years have double the risk Overall, the rate of bleeding was 38%, the rate of of ischaemic stroke compared with women who undergo Andrew Boyle haemorrhagic stroke was 8%, the rate of ischaemic a natural menopause after the age of 42. “The state of stroke was 6%, and the rate of pump thrombosis was menopause and details regarding the use of oral contra- neurologic event rate in women, even if confirmed in 4%. Boyle et al comment that 36 patients experienced ceptives or hormone replacement therapy were unavail- future studies, should not dissuade us from considering an ischaemic stroke at an average of 316 days after able, but these underlying risk factors could be having mechanical circulatory support in women.” experiencing a haemorrhagic stroke, stating: “It is an impact on the higher incidence of ischaemic stroke Boyle told Cardiovascular News: “We do not know of certainly possible that a patient with a haemorrhagic in older women and a higher incidence of haemorrhagic any way to mitigate the risks in women as reducing the event could be at higher risk for an ischaemic event stroke in younger women.” anticoagulation is likely to lead to more thrombosis and later on if anticoagulation is withheld.” However, they In an accompanying editorial, Samer S Najjar (medi- increasing the anticoagulation is likely to lead to more state that as details regarding how the haemorrhagic cal director, Heart Failure and Heart Transplantation, bleeding. Older men, however, appear to have a reduced events were managed (ie. if anticoagulation was MedStar Heart Institute, Washington DC, USA) com- risk of thrombosis, making them a potentially suitable withdrawn) were not captured in the study, it was ments that women in left ventricular assist device stud- target to reduce anticoagulation if they demonstrate a difficult to determine if the ischaemic event was an ies have a similar rate of survival to men, “thus, a higher propensity to bleed.” 16 Interview February 2014 Profile Ashok Seth

Ashok Seth (chairman, Fortis Escorts Heart Institute, New Delhi, India) is the immediate past president of Cardiological Society of India and is the principal investigator of the Absorb First registry. He has been awarded the “Padma Shri” by the president of India, one of the highest civilian honours of the Government of India, and talks to Cardiovascular News about performing his father’s angioplasty, his mission to make Delhi state a safer place to live, and the importance of planning ahead to avoid complications

Why did you decide to become a Of all the research you have been sanitation, hygiene and infection control). One way to doctor and, in particular, why did you involved with, which piece are you improve access to technologies is for India to develop its decide to specialise in interventional proudest of and why? own devices, which are also manufactured in cardiology? I am most proud of the work that I am currently doing India. We now have good Indian-made I come from a family of doctors and I was interested in with the bioresorbable vascular scaffold (Absorb, Abbott drug-eluting stents, in the future medicine since my childhood—my father once caught Vascular). I believe that this technology may be the we will have Indian bioresorba- me, aged four, attempting to operate on a friend! Also, I biggest breakthrough because it does not leave metal ble scaffolds and transcatheter was fascinated to see how grateful my father’s patients behind—it is many steps beyond the existing technolo- aortic valve implantation were when they became well after he had treated them. gies. Compared with the first-generation of metal drug- (TAVI) devices—mak- Therefore, I always wanted to be a doctor. eluting stents, the latest generation have now achieved ing it more affordable However, becoming a cardiologist was more some- a high level of safety and efficacy. Therefore, we need for the common man thing that happened by chance when I went for my to show that the bioresorbable scaffold is as good as the in India to receive postgraduate training to England. Initially in early 80s, best metallic drug-eluting stent in the short term and these treatments. I was determined to become a gastroenterologist but superior in the longer term. I am actually switched to cardiology when I did not get a job that I As principal investigator of the Absorb First registry, working with some wanted as a gastroenterology registrar. At the time, I did I am using this stent in many complex patients in real Indian companies not realise the potential of interventional cardiology but life to evaluate its advantages and limitations. I am very to develop these I soon realised that the field was going to expand and hopeful that we will show that the bioresorbable scaffold indigenous devices held tremendous potential. is as good as the gold standard drug-eluting stent in the in India and am short- and mid-term, and better in the long term. already in process Who have been your career mentors? of putting them into I have had two mentors. The first one was Dr Man- As someone who has pioneered clinical trials. Fai Shiu at the Birmingham University Teaching several angioplasty techniques, what Hospital (where I worked in England), who taught do you think are the most important me to plan every procedure and think ahead as to factors to performing successful how to avoid complications in the balloon era when angioplasty? angioplasty was in its infancy. By following his The hardest thing to do as a doctor is to inform a pa- meticulous approach to planning and assessment, I tient’s loved ones and relatives that the patient has not am not surprised by problems encountered during survived a complex or lifesaving procedure. Therefore, a procedure. The second mentor was Dr Geoffrey you want to do your best to achieve the best result with Hartzler. I attended one of his courses in Kansas safety. Firstly, as previously mentioned, you have to City (USA) in mid 80s and I was amazed at his skills plan every aspect of the procedure and consider the and results with what he could achieve with the problems or complications that may occur and the pos- crudest technology of those times. He demonstrated sible solutions in hand—that way, your hand and your to me that complex angioplasty could be performed mind work in tandem, avoiding complications where safely with good results and that one needed to have possible. You also need to be aware of the limits of your creativity, clarity, confidence and conviction. expertise; you need to know when a procedure is beyond your competency and you need to know when to stop What do you think has been the a procedure because it is not working. There should be most important development in no “ego battles” between the “complex lesion” and the interventional cardiology during your “interventional cardiologist”. career? The improvement in the safety of angioplasty has been What are the challenges of providing dramatic. The procedures we performed at the beginning an interventional cardiology service of my career were primitive compared with what we are in India given that while the country able to do today. Thirty years ago, we were concerned is one of the world’s fast growing about patients having acute occlusions, myocardial economies, poverty and poor infarctions or requiring emergency bypass surgery healthcare are still major issues? during the procedure. Death was a reality. These days, At the moment, our goal is to ensure that people in India angioplasty has become so safe that we no longer need have access to quality medicine and the latest technolo- to rely on bailout devices or to have an operating theatre gies in interventional cardiology at an “affordable cost”. on standby. In fact, many centres these days do not even We are focusing on the middle class of this country (eg. have cardiac surgery on site. It is a day procedure and teachers, shop workers, or factory workers) because the improved safety and efficacy is due to not one but the wealthier class can already afford these technolo- numerous developments in the art, science and technol- gies and those living in our rural areas or are poor have ogy of angioplasty. more basic priorities (eg. access to clean water and good February 2014 Interview 17

Fact File

Appointments „„Chairman, Fortis Escorts Heart Institute, New Delhi, India „„Chairman, Cardiology Council, Fortis Group of Hospitals „„Honorary professor of Cardiology, Gandhi Medical College, Bhopal; Medical College, Raipur; Medical College, Bilaspur; Padmashree Dr D Y Patil University, Mumbai; Bangladesh Medical College, Dhaka, Bangladesh

Fellowships You are the immediate past president basic cardiopulmonary resuscitation (CPR). By working „„Fellow of Royal College of Physicians of of the Cardiological Society of India. with the Government of Delhi and device companies, London (FRCP, Lond) What do you believe were your our goal is that, through widespread education, 75% of „„Fellow of Royal College of Physicians of key achievements during your the population (approximately, 17 million people live in Edinburgh (FRCP, Edin) presidency? Delhi) will know basic life support within three years. „„Fellow of Royal College of Physicians of One achievement was to develop three Ireland (FRCP, Irel) guidelines specific to India and this region What has been your most memorable „„Fellow of Cardiological Society of India (FCSI) including one for rheumatic heart disease case and why? „„Fellow of American College of Cardiology (a condition that is highly prevalent in One memorable case was doing my father’s (FACC) India) and for permanent pacemaker angioplasty. I believe I am one of the most experienced „„Fellow of European Society of Cardiology implantation. Previously, the only interventional cardiologists in the region, so I thought (FESC) guidelines that were available were I was the best person to do the procedure. During the „„Fellow of Society for Cardiovascular ones that had been developed with procedure, I was able to forget that the patient was Angiography and Interventions (FSCAI) Western populations in mind. my Dad and did everything very meticulously and „„Fellow of Asian Pacific Society of Therefore, we need national professionally. But when I finished the procedure, I Interventional Cardiology (FAPSIC) database, registries, guidelines that suddenly became aware of what I was doing and started were more applicable to South to think of all things that could have gone wrong—it Honours and awards Asian populations. I also helped felt like the blood drained out of me! As a result of this 2003 Padma Shri award’ (fourth highest to formulate national policies to sudden realisation, I missed a simple step in the sealing civilian award by the Govt. of control coronary artery disease—for of the arterial puncture site (a procedure that I routinely India) do several times) and ended up having to press my 2010 Mason Sones Award (Society of father’s groin for the next three hours to try and stop in Cardiovascular Angiography & bleeding! Eight years on, my now 90-year-old father is Interventions) still doing well but I still shudder to think about what Officer’s Cross Order of Isabella could have gone wrong! As a religious person, I am the Catholic’ (national award of thankful to God. Spain) Another patient was a 44-year old civil servant who 2011 Lifetime achievement award for was in cardiogenic shock and we air lifted himfrom vocational excellence in the field a north-eastern state of India and had to put him on of medicine (Rotary Club of Delhi) extracorporeal membrane oxygenation (ECMO) during Special award for outstanding the procedure to keep him alive. I had to perform one contributions in cardiology of the most complicated and difficult techniques to treat (American Association of his severe disease process. I was not sure that he would Cardiologists of Indian Origin) survive, but his family were convinced that the procedure 2012 Global Pioneer of Interventional would work and insisted that I do it. Afterwards, it was a Cardiology Award’ by the Asian week before he was off the ventilator and three before he Intervention Cardiovascular was able to leave hospital. A year later, he walked into my Therapeutics (AICT) office with his young wife and his lovely teenage children and I could not believe it—I had to ask him if he was Societies the same person! He is now working as a high-ranking 2004– Founding board of governors, civil servant and regularly goes jogging. I admire the Asian Interventional Cardiovascu- family for having the faith—whether it was in me, God, lar Therapeutics (AICT) or whoever—that the procedure would work. Because of 2010– Founder course director, India their faith in the procedure, the young man and his lovely Live family can be together and that gives me joy. 2011 Co-chair, SCAI international committee Outside of medicine, what are your 2008–2011 Board of Governors, SCAI hobbies and interests? 2011 Nominating Board Member, SCAI I love to go scuba diving and have dived at many places, 2011–2012 President, Cardiological Society including the Great Barrier Reef and Sharm el-Sheikh. of India I also enjoy performing traditional Indian songs that 2012–2015 Member, American College of are a form of romantic poetry transferred into music. Cardiology India advisory board example, policies to raise awareness of the health They are slow songs that contain a lot of emotion. (representing Cardiological risks associated with smoking and other risk factors. My I actually performed for an audience of 400, which Society of India) biggest contribution may be making the state of Delhi a included the chief minister of the state and many other 2013–2015 Vice president, Asian Pacific safer place live to by teaching the public how to perform dignitaries. Society of Cardiology 1996– Founder member & board of Trustees, Asia Pacific Society of Interventional Cardiology 18 Surgery February 2014 Sutureless aortic valve replacement could be first-line therapy for “grey area” patients

A study in the Journal of Thoracic and Cardiovascular Surgery shows that minimally invasive surgical aortic valve replacement with a sutureless aortic valve is associated with less paravalvular leak and reduced mortality compared with transcatheter aortic valve implantation (TAVI)—indicating that minimally invasive sutureless surgical aortic valve replacement could become the first-line therapy for patients in the grey area between TAVI and open surgical valve replacement

uthors Giuseppe Santarpino undergone TAVI with the Sapien or Sapien XT group than in the sutureless group (13.5% vs. 0%; (Klinik für Hezchirugie, (Edwards Lifesciences) with those who had p=0.027).” The TAVI group also has a significantly AKlinikum Nürnberg, Nürnberg, undergone minimally invasive surgery with lower rate of survival at the median follow-up Germany) and others report that the the Perceval S valve. point of 18.9±10.1 months—86.5% vs. 97.3% for use of a sutureless device in surgical Santarpino et al reviewed data from all the sutureless group (p=0.015). However when the aortic valve replacement have enabled patients with diagnosed with severe aortic authors looked the survival rate of TAVI patients shorter procedural times, adding that it valve stenosis with an indication of surgery who did not have paravalvular leak (17) vs. that of also allows “easy implantation of the aortic at their centre from 2010. Of 244 patients, patients in the sutureless group, they did not find valve prosthesis when using a minimally 122 underwent TAVI (all aged ≥65 years and a significant difference between groups (100% vs. invasive surgical approach”. They explain with at high risk for surgery) and 122 underwent 97.3%, respectively). Additionally, minimally invasive the Perceval S sutureless valve (Sorin), the the minimally invasive approach sutureless aortic valve replacement was associated with native diseased valve is removed and (all aged ≥65 years and at a higher rate of freedom from rehospitalisation (86.5% the bioprosthetic valve is mounted low risk for surgery). From vs. 54.1% for the TAVI group; p=0.054) and TAVI was on expandable stent fixed to the this group of patients, associated with a non-significant trend towards a higher aortic valve annulus without the authors identified 37 rate of neurologic events. sutures; therefore, it allows matching pairs. They The authors concluded: “Removal of the diseased for a hybrid solution that noted: “At discharge, native valve may enhance procedural quality by is “somewhere between the incidence of aortic avoiding paravalvular leak. In combination with conventional aortic valve regurgitation caused minimally invasive sutureless aortic valve replacement, replacement and the by postprocedural this may become first-line treatment for high-risk transcatheter approach”. paravalvular leakage patients considered in the grey zone between TAVI The aim of the study was was higher in the TAVI and conventional surgery. Further, larger, prospective, to compare outcomes randomised studies are warranted to confirm our of patients who had Giuseppe Santarpino results.” No difference in mortality between surgical mitral valve repair and mitral valve replacement A study, published in The New England Journal of Medicine, did not find any significant differences in the rate of 12-month mortality between patients who underwent surgical mitral valve repair and those who underwent surgical mitral valve replacement. There were also no differences between groups in the rate of left ventricular reverse remodelling

ichael Acker (Department of vs. replacement. The primary endpoint Surgery, Division of Cardio- was the degree of left ventricular reverse Mthoracic Surgery, University remodelling (assessed with the left ven- of Pennsylvania School of Medicine, tricular end systolic volume index). Of the Philadelphia, USA) and others write that 251 patients in the study, 126 were ran- in patients with ischaemic functional domised to receive repair and 125 were mitral valve regurgitation, clinical studies randomised to replacement. At 12 months, suggest that surgical mitral valve repair is the mean left ventricular end systolic associated with lower perioperative mor- volume index was 54.6±25ml per square Annetine Gelijns tality than surgical mitral valve replace- metre in the repair group and 60.7±31.5ml ment. However, they add that the latter is per square metre in the replacement group contradict much of the published litera- Study author Annetine Gelijns (Icahn associated with better long-term correc- (mean change from baseline -6.6ml and ture on this topic, which reports several School of Medicine at Mount Sinai, New tion with a lower risk of recurrence—not- -6.8ml per square metre, respectively)— advantages to mitral repair over replace- York, USA) told Cardiovascular News: ing: “This perceived tradeoff between meaning that there were no significant ment, including lower operative mortality, “The increased level of recurrent regurgi- reduced operative morbidity and mortality differences between groups (p=0.18). improved left ventricular function, and tation falls in line with valve replacement with repair and better long-term correc- There were also no significant differences higher rates of long-term survival.” They offering more durable long-term protec- tion of ischaemic mitral regurgitation with in the rate of 12-month mortality between add that, because of perceived benefits of tion. However, such regurgitation did replacement has generated substantial groups: 14.3% for repair vs. 17.6% for repair, the field of cardiothoracic surgery not lead to increases of health problems variation in surgical practice for this high replacement (p=0.45). However, signifi- has “embraced mitral valve repair over among patients in the repair group.” She prevalence condition.” cantly more patients in the repair group replacement, without a strong evidence adds: “further patient follow-up is neces- As evidence in this area is lacking, had a recurrence of moderate or severe base. According to 2008–12 data from sary to confirm our findings and may Acker et al report, the Cardiothoracic regurgitation than patients in the replace- the Society of Thoracic Surgeons, 66% of lead to the identification of predictors Surgical Trials Network conducted a ment group (32.6% vs. 2.3%, respec- mitral valve surgeries in patients undergo- of recurrence of mitral regurgitation to multicentre randomised trial to assess tively; p<0.001). ing coronary artery bypass grafting used a allow for more appropriate selection of the relative risks and benefits of repair Acker et al comment: “Our findings repair approach.” patients.” February 2014 Research 19 Pre-hospital therapeutic hypothermia may not be beneficial A recent study—presented at the American Heart Association annual meeting (16–20 November, Dallas, USA) and published ahead of print in the Journal of the American Medical Association—found that early therapeutic hypothermia (prior to hospital; immediately after return of spontaneous circulation) does not improve survival or neurological function in patients who have survived a cardiac arrest. The principal investigator of the study, Francis Kim (Department of Medicine, School of Medicine, University of Washington, Seattle, USA) talks to Cardiovascular News about the role of pre-hospital therapeutic hypothermia for the management of patients who have survived a cardiac arrest

What data are available for Animal studies have indicated that the therapeutic hypothermia? benefits of therapeutic hypothermia may The rationale for therapeutic decrease after reperfusion and, therefore, hypothermia comes from two studies earlier cooling may be more beneficial. that were published in The New England Furthermore, intravenous cooling has Journal of Medicine in 2002. They been proposed as a safe and effective both found that in patients who had portable method that can be potentially survived cardiac arrest due to ventricular used by the emergency services. fibrillation, mild hypothermia (either through ice packs or cooling blankets) What method of cooling did improved survival. you use in your study? However, the recent targeted As soon as possible after the return temperature management (TTM) study of the pulse [in patients randomised (also published in The New England to receive pre-hospital cooling], Journal of Medicine) has generated a paramedics rapidly infused patients with lot of controversy. This study found that up to two litres of normal saline that had hypothermia at a targeted temperature of been stored at four degrees. 33 degrees did not significantly improve outcomes compared with hypothermia at You did not find that pre- a targeted temperature of 36 degrees in hospital cooling improved patients who had survived an out-of- survival or neurological hospital cardiac arrest. status. Why did you think that was? What was the rationale for There are several potential reasons why conducting your study? early cooling does not appear to be The aim of our study was to assess beneficial: the benefits of cooling as early as „„After their pulse has returned, most possible after the return of the pulse. patients have a temperature of 36 degrees and the TTM study found equivalence between 36 and 33 degrees; therefore, perhaps early cooling is not necessary „„Using two litres of cold fluid may have caused harm and negated any po- tential benefits of early cooling. Infusion of fluid was associated with increased rates of re-arrest during transport. „„We may need longer to see a benefit with early cooling in terms of neurologi- cal outcome [the study assessed patients at discharge].At the moment, we are assessing outcomes at the three-month follow-up point and would like to assess later time points as well.

Do you think pre-hospital cooling still has potential to be an effective therapy? Possibly if a different cooling method was used (ie. not fluid) or starting cooling even earlier than in our study (at the time of cardiopulmonary Francis Kim resuscitation) may be more beneficial. 20 Research February 2014 The use of vascular robotic systems for PCI physician to manipulate the movement allow us to remove the threat of radiation of interventional devices such as the during every procedure. guidewire and balloon/stent catheters via I have found that patients are com- RONALD P the bedside-mounted robotic arm. In my fortable with the increasing amount of experience, I have found that perform- technology that is used in care delivery, CAPUTO ing PCI procedures from the cockpit also and are open to the use of vascular reduces physical fatigue from standing robotic systems provided they are in- and leaning over the patient during the formed about how they are used as well COMMENT & ANALYSIS procedure. as the benefits they will receive from Additionally, the cockpit’s radiation it. Because of the benefits brought by shielding eliminates the need for robotic assistance, I envision that the use he aim of a vascular robotic visual estimates. Potentially, these subtle physicians to wear the heavy and of vascular robotic systems will expand system is to help interventional movements could mean the difference cumbersome lead aprons used in into other cardiac procedures (eg. chronic Tcardiologists perform percutane- between a successful cardiac catheteri- traditional PCI procedures to protect total coronary occlusion, peripheral ous coronary intervention (PCI) proce- sation procedure and one that requires against radiation exposure. Furthermore, vascular disease and structural heart dures with greater precision. The systems secondary stent placement or a second the location of the cockpit in the cath lab conditions) due to the increased level of are designed to provide greater accuracy procedure at a later date due to resteno- provides radiation protection because it precision that is offered. However, the of lesion measurement, aid in better sis. Greater precision in stent placement is positioned several feet away from the key to increased industry acceptance advancement of guidewires, and help en- is certainly warranted—using traditional patient and the fluoroscopy unit (but is and expansion of use lies with the level sure correct placement of stents—which, PCI methods, up to 47% of stents longi- close enough to enable verbal contact of commitment from the full cardiac all together, can lead to less instances tudinal geographic miss using traditional between the patient and staff). The catheterisation team: a commitment must of additional stent placement per lesion. methods1. These procedure variations PRECISE study (sponsored by Corindus be made to learning a new skill, training For example, robotic systems allow for can have a big impact on the incidence of Vascular Robotics), released in April of effectively and consistently using the sub-millimetre movements to place stents target vessel revascularisation. 2013, showed that radiation exposure technology. and balloons, and can advance or retract With a robotic system, the interven- for the physician was reduced by 95.3% guide wires with movements as small as tional cardiologist performs the PCI from traditional manual procedures; Ronald P Caputo, interventional car- a millimetre. procedure from a “cockpit” rather than for patients, a reduction in radiation is diologist, St. Joseph’s Hospital Health The precision afforded by these being next to the patient. The cock- afforded by the robot by a shortened Center, Syracuse, USA capabilities is greater than what can pit contains displays to visualise the procedure length. Personally, I welcome Reference be achieved manually or using only procedure, and provides controls for the the introduction of a technology that will 1. Costa, MA. Am J Cardiol 2008; 101: 1704–11 iFR/FFR approach More efficient way to grow heart muscle from stem cells could avoids use of adenosine yield new regenerative therapies Generating new cardiac muscle from human embryonic stem in majority of patients cells (hESCs) and/or induced pluripotent stem cells (iPSC) could fulfil the demand for therapeutic applications and drug The final results of the ADVISE (Adenosine vasodilator testing. The production of a similar population of these cells independent stenosis evaluation) II registry, which were presented remains a major limitation, but in a study published in Stem at Transcatheter Cardiovascular Therapeutics (TCT) annual Cells Translational Medicine, researchers now believe they meeting (27 October–1 November, San Francisco, USA), confirm have found a way to do this earlier findings that a hybrid approach of instant wave-free ratio (iFR) and fractional flow reserve (FFR) would reduce the use of y combining In addition, using adenosine in 65.1% of patients small molecules an integrated approach Band growth fac- involving computa- DVISE II was a prospective, availability of iFR as an adenosine- tors, the international tional and experimental double-blind, global, multicentre free partner to FFR can be a significant research team led by systems, the researchers Aregistry that was designed to development in the field of coronary investigators at the demonstrated that using investigate the diagnostic utility of iFR physiology.” Cardiovascular Research molecules to modulate (Volcano) in assessing the severity of cor- The press release reports that the hybrid Center at Icahn School the Wnt pathway, which onary stenosis. According to a company iFR/FFR approach is possible because of Medicine at Mount passes signals from cell press release, the final results replicate both measurements take place on the Sinai, USA, developed to cell, plays a key role earlier findings and show that the hybrid same pressure guidewire. In the hybrid a two-step system that in whether a cell evolves iFR/FFR approach correctly matched an workflow, iFR measurement is generally caused stem cells to dif- into an atrial or ventricu- FFR-only approach in 94.2% of coronary made in seconds after positioning the ferentiate into ventricular lar muscle cell. stenoses as well as successfully avoiding standard Volcano pressure guide wire. heart muscle cells from “The further clarifica- the use of adenosine in 65.1% of patients. Joe Burnett, executive vice president and hESCs and iPSCs. tion of the molecular Amir Lerman, co-principal investigator general manager of Volcano’s functional The process resulted heart rate responses,” mechanism(s) that of ADVISE II and professor of medicine management business, says: “ADVISE in high efficiency and said lead investigator underlie this kind of at the Mayo Clinic in Rochester, USA, II is important because it shows that reproducibility, in a Ioannis Karakikes, Stan- subtype specification is says: “I believe that the more physiology the retrospective performance of the manner that mimicked ford University School essential to improving we can use to guide our patient therapy, iFR algorithm has now been confirmed the developmental steps Of Medicine, Cardiovas- our understanding of the better. Study data has suggested that in a controlled, prospective manner at of normal cardiovascular cular Institute, Stanford, cardiovascular develop- FFR is associated with improved patient 40 global centres with many different development. USA. Other members ment. We may be able outcomes when used to help decide users. This represents the final stage in “These chemically of the team included to regulate the commit- whether coronary vessels with stenosis our validation of iFR compared with induced, ventricular-like scientists from the Icahn ment, proliferation and require revascularisation with stents or other physiologic indices and gives us cardiomyocytes (termed School of Medicine at differentiation of pluri- other treatment strategies. However, its the confidence to move forward with a ciVCMs) exhibited the Mount Sinai, New York, potent stem cells into use in clinical practice remains low, partly series of outcome studies where iFR will expected cardiac elec- and the Stem Cell & heart muscle cells and due to the requirement for adenosine contribute to clinical decision making live trophysiological and cal- Regenerative Medicine then harness them for administration. For this reason, I believe in the cath lab , including the SYNTAX II cium handling properties Consortium at the Uni- therapeutic purposes,” that the development and potential trial and the DEFINE family of studies.” as well as the appropriate versity of Hong Kong. Karakikes says. February 2014 Research 21 Drug-eluting stents reduce target vessel revascularisation in older patients According to the XIMA (Xience or Vision stents for the management of angina in the elderly) study, the use of drug-eluting stents in patients aged ≥80 years is associated with less myocardial infarction and target vessel revascularisation than is the use of bare metal stents. Also, the longer use of dual antiplatelet therapy (DAPT) with drug-eluting stents is not associated with an increased risk of bleeding

riting in the Journal of the American College of Cardi- Wology, study authors Adam de Belder (Department of Cardiology, Brighton and Sussex University Hospi- tals NHS Trust, Brighton, UK) and others state that use of drug-eluting stents may be warranted in elderly patients because they often have complex coronary artery disease, but add: “Prolonged use of DAPT puts them at higher risk of major bleeding complications. Non-compliance with DAPT may also be likely in el- Xience V derly patients and this would put them at higher risk of stent thrombosis.” Abbott Vascular) or a everolimus-eluting unpredictable nature of mortality in this ing stents (4.3% vs. 8.7%; respectively Therefore, the XIMA study was de- stent (399; Xience, Abbott Vascular). age group. Indeed, the drug-eluting stent p=0.014). The rate of major haemorrhage signed to review the hypothesis that the They were followed up at six months and group had a significantly higher rate of or cerebrovascular accident did not differ use of drug-eluting stents in patients aged at 12 months. The rate of the cumulative non-cardiac mortality than the bare metal between groups. ≥80 years would be superior to the use of primary endpoint did not significantly stent group; a finding that might have In an accompanying editorial, George bare metal stents. The primary endpoint differ between groups—18.7% for bare had an important bearing on the primary Dangas (Cardiovascular Institute, Mount was a composite of mortality, myocardial metal stents vs. 14.3% for drug-eluting endpoint.” Sinai Medical Center, New York, USA) infarction, target vessel revascularisa- stents (p=0.092). However, the authors At one year, the rate of target vessel comments: “One may suggest a clinical tion, cerebrovascular accident, or severe report that in two predefined subgroup revascularisation was significantly lower strategy of everolimus-eluting stent- haemorrhage. analyses (radial access and multivessel in the drug-eluting stent group compared ing via radial access in elderly patients In the study, 800 octogenarian patients disease), the use of drug-eluting stents with the bare metal stent group (2% vs. appears attractive, as it reduces vascular aged ≥80 with stable angina or acute was found to reduce the rate of the pri- 7%, respectively; p=0.0009). The rate of complications while improving rates of coronary syndromes were randomised to mary endpoint. De Belder et al note: “A myocardial infarction was also signifi- myocardial infarction and target vessel receive a bare metal stent (401; Vision, potential confounder in this trial was the cantly lower at one year with drug-elut- revascularisation.” 22 Guidance February 2014 “Be very afraid of radiation unawareness” Eugenio Picano (Institute of Clinical Physiology, CNR, Pisa, Italy) and others write in the European Heart Journal that cardiologists need to be more aware of the radiation risks associated with imaging, percutaneous cardiovascular interventions, and electrophysiology—claiming that they should not be afraid to use appropriate tests, but should be afraid of not knowing about the radiation risks associated with them

icano et al report that the increas- in practitioners’ knowledge pertaining to ing use and complexity of imaging radiation safety.” Pand interventional techniques have They also review radiation exposure not been matched “by increasing aware- during interventional [and electrophysi- ness and knowledge by prescribers and ology] procedures as a whole, claiming practitioners.” They add: “The majority of that fluoroscopic-guided diagnosis and doctors—including cardiologists—grossly intervention account for 12% of all radio- underestimate the radiation doses for most logical examinations performed and for commonly requested tests. The significant 48% of their collective dose. Picano et al increase in the cumulative exposure of pa- note: “The introduction of non-radiology- tients and population to ionising radiation based methods of cardiac mapping and is likely to cause an increased incidence the use of co-registration of CT or cardiac of cancer in years down the line, with an MRI images of the targeted structures (for Luigi P Badano important yet potentially avoidable public instance, the left atrium) have the potential health threat.” to drastically reduce these doses.” home messages of the article are that gists make every effort to reduce unnec- Furthermore, they state that recent The authors are not just concerned tests involving ionising radiation should essary radiation exposure from medical reports indicated that “one third of cardiac about reducing the risks of radiation only be performed if the information imaging. This is best obtained through examinations are partially or totally inap- exposure to patients as they comment: required cannot be obtained through tests a systematic implementation of the 3As propriate—ie. the risks and costs outweigh “The protection of doctors is just as that do not involve ionising radiation and strategy proposed by the International benefits.” important as the protection of patients.” also: “If you perform a test that utilises Atomic Energy Agency in 2011: i—audit In their article in the European Heart They write that most experienced ionising radiation, choose the one with (of true delivered dose); ii—appropri- Journal, they outline the radiation expo- and interventional cardiologists and the lowest radiation dose and be aware of ateness (since 30% of prescribed tests sure associated with different imaging electrophysiologists have an exposure per the many factors modulating dose.” They are inappropriate); and iii—awareness techniques and review different methods annum of (about): “5mSV, two to three conclude: “A smart cardiologist cannot (since the knowledge of doses and risks of reducing that radiation exposure. For litres higher than diagnostic radiologists, be afraid of the essential and often life- is still largely suboptimal in doctors and example, with cardiac nuclear imag- with a typical cumulative lifetime saving use of medical radiation, but must patients). In addition, currently available ing, they say: “Radiation exposure can attributable risk on the order of magnitude be very afraid of radiation unawareness.” dose-reduction techniques for heart scan be decreased by 75% using a protocol of one cancer (fatal and non-fatal) per 100 Study author Luigi P Badano, and invasive cardiology issued by FDA, whereby stress imaging is performed first exposed subjects.” However, they add that European cardiologist, Department of the European Union and the American (‘stress first’), with rest images eliminated “adequate radiation protection and diligent Cardiac, Thoracic and Vascular Sciences, College of Radiology, should be strongly in patients with normal stress images protection can reduce the radiation University of Padua, Padua, Italy, told applied in daily practice to allow a reduc- (‘stress only’)—but in current practice in exposure by 90%.” Cardiovascular News: “It is mandatory tion of patients’ dose while maintaining the USA, it is seldom used due to gaps According to Picano et al, the take- that clinical and interventional cardiolo- the image quality.” ACC launches criteria for evaluating News in brief stable ischaemic heart disease tests On-X Life Technologies receives The American College of Cardiology (ACC), along with nine key specialty and subspe- approval for expanded labelling cialty societies, has published a document assessing 80 potential clinical scenarios claim with the goal of assisting physician and patient decision-making. The criteria identify On-X Life Technologies has announced that its common scenarios in clinical practice and provide a level of appropriateness for the previously CE-marked On-X prosthetic heart technology’s use based on a risk-benefit analysis valve has received European regulatory ap- proval for an expanded labelling claim, which ccording to a press release, the criteria are spe- the document were the American Heart Association, now permits the company to market its valve cifically designed to provide actionable stand- American Society of Echocardiography, American with a reduced requirement for the use of blood- Aards that can be easily implemented in clinical Society of Nuclear Cardiology, Heart Failure Society thinning drugs such as warfarin. settings. The press release reports that the release of of America, Heart Rhythm Society, Society for A press release reports that the branded On-X the 2013 multimodality appropriate use criteria for the Cardiovascular Angiography and Interventions, Society Plus 1.5 aortic heart valve is now the only heart detection and risk assessment of stable ischaemic heart of Cardiovascular Computed Tomography, Society for valve that allows patients to be managed at INR disease marks the first time that multiple tests for stable Cardiovascular Magnetic Resonance, and The Society levels as low as 1.5 ischaemic heart disease have been rated side by side for of Thoracic Surgeons. According to the press release, the expanded the same clinical indication. “The goal of the document is not to rank order labelling claim was supported by interim data diagnostic tests but to help guide physicians and from a recently completed arm of an FDA IDE According to the document’s writing committee, patients when it comes to making reasonable testing clinical trial—Prospective randomized On-X the inclusion of multiple testing modalities lever- choices amongst the available testing modalities,” said anticoagulation clinical trial (PROACT)—pre- ages a greater knowledge base across the tests, Michael J Wolk, professor of Clinical Medicine at Weill sented by principal investigator John D Puskas promoting optimised decision making. Consoli- Cornell Medical College and the chair of the writing (Cardiothoracic Surgery, Emory University, dation is also meant to eliminate minor differ- committee. “These ratings help ensure that tests with Atlanta, USA) at the annual scientific meeting of ences among the prior single-test criteria. the highest potential to benefit are being used, while the American Association for Thoracic Surgery tests are avoided that can cause unnecessary concern (AATS). As well as the ACC, the partners in development of and complicated follow-up.”

24 Cardiac rhythm management February 2014 Meta-analysis shows four novel oral anticoagulants perform better than warfarin A first-of-its-kind meta-analysis comparing four tant feature is that we were able warfarin in patients who have new oral anticoagulants with warfarin has found to assess the relative benefit of difficulty maintaining a thera- they perform better than warfarin reducing stroke, the new oral anticoagulants in peutic INR. intracranial haemorrhage and mortality in atrial important, clinically relevant fibrillation patients. The study was published subgroups. We know that the Is warfarin still an ahead-of-print in The Lancet risk of stroke and bleeding vary option for stroke considerably in atrial fibrilla- prevention in atrial hristian T Ruff (Brigham warfarin group],” the authors tion patients. Our data demon- fibrillation? If so, and Women’s Hospital write. They also reduced all- strate that the relative benefit which patients may Cand Harvard Medi- cause mortality and intracrani- and safety is consistent across a benefit best? cal School, Boston, USA) and al haemorrhage; however, the wide range of subjects, includ- Warfarin will remain a legiti- others undertook a prespecified authors note, gastrointestinal ing vulnerable populations mate option for stroke preven- meta-analysis of all patients bleeding was increased with such as the elderly, patients tion in patients with atrial (n=71,683) included in the four the new oral anticoagulants. with a prior stroke, and those fibrillation. There are many landmark randomised trials with renal dysfunction. We also patients in whom warfarin RE-LY (study of dabigatran/ The authors conclude: “The observed an interesting finding remains the only option, such Pradaxa, Boehringer Ingelheim), relative efficacy and safety when we investigated whether as those with a mechanical ROCKET AF (study of rivar- of new oral anticoagulants Christian T Ruff the benefit of the new oral heart valve or end-stage renal oxaban/Xarelto, Bayer Health- was consistent across a anticoagulants was dependent disease. Warfarin performed care), ARISTOTLE (study wide range of patients. Our trials are homogenous, on how well warfarin was man- very well in all of these trials of apixaban/Eliquis, Bristol- findings offer clinicians a which again they are not. aged during the trials, as as- and remains an effective and Myers Squibb and Pfizer) and more comprehensive picture Indeed, Ruff and colleagues’ sessed by the centre-based time affordable anticoagulant. ENGAGE AF-TIMI 48 (study of the new oral antico- meta-analysis does not really in therapeutic range (above of edoxaban/Lixiana, Daiichi agulants as a therapeutic answer the question of which and below 66%). We showed Does this meta- Sankyo). option to reduce the risk of novel oral anticoagulant is that the reduction in stroke and analysis show us any In the meta-analysis 42,411 stroke in this patient popula- best, whether from an efficacy systemic embolism seen with differences between participants received a new tion.” or safety perspective.” the novel oral anticoagulants the four novel oral oral anticoagulant and 29,272 Cardiovascular News spoke was not dependent on how well anticoagulants received warfarin. Ruff et al In an accompanying to Ruff about the study. warfarin was managed. These studied? found that the new oral antico- editorial, Torben Bjerregaard agents are more effective than This meta-analysis combined agulants significantly reduced Larsen (Aalborg University What is the novelty of warfarin even in patients who data from all the trials and did stroke or systemic embolic Hospital, Aalborg, Denmark) this meta-analysis? have well controlled interna- not specifically look to see if events by 19% compared with and Gregory Lip (University It is the first study to include tional normalised ratios (INRs). one agent was better than an- warfarin, “The benefit was of Birmingham, Birmingham, data from all four landmark tri- However, the success in man- other. The data suggest, how- mainly driven by a large re- UK) write: “Such a meta-anal- als in stroke prevention in atrial aging warfarin was important ever, that all the novel oral duction in haemorrhagic stroke ysis assumes that all the novel fibrillation comparing novel with respect to bleeding. There anticoagulants have similar [130 events were reported in oral anticoagulant drugs are oral anticoagulants to warfarin, was even greater reduction relative benefits in reducing the novel oral anticoagulants the same (which they are not) and we reviewed data from in bleeding with the new oral stroke, intracerebral haemor- group and 263 events in the [...] and that the randomised 71,683 patients. Another impor- anticoagulants compared with rage and mortality.

Rivaroxaban prevents prothrombogenic remodelling of human atrial myocardium in a potentiated response involving the action of factor X and simulated increase of inflammatory and oxida- atrial tachyarrhythmia results in a tive stress molecules, which create an potentiated response involving the ANDREAS GOETTE inflammatory, prothrombotic status in increase of inflammatory and oxidative atrial tissue. stress molecules, which create an In detail, we could show that factor X inflammatory, prothrombotic status in application to human atrial myocardium atrial tissue. Importantly, the factor X COMMENT & ANALYSIS resulted in the 1.7 fold upregulation induced inflammatory signalling can of PAR2-mRNA, activation of be substantially attenuated by factor X troke is one of the major prob- ed coagulation factor X plays a central MAP kinases (ERK1/2) and NF-κB antagonist, rivaroxaban. Thus, factor X lems in patients with atrial role in the coagulation cascade linking signalling. Furthermore, factor X and protease-activated receptors appear Sfibrillation (AF). Recent studies the extrinsic and intrinsic coagula- increased the expression of adhesion as novel therapeutic targets to reduce have clearly elucidated the pathophysi- tion pathway. In addition, evidence molecule ICAM-1, chemokine IL-8, as prothrombogenic atrial remodelling. ology of atrial thrombus formation in shows that factor X acts as a signalling well as prothrombotic molecule PAI-1. References AF. Endocardial changes in the left molecule mediating cellular responses The combination of rapid pacing and 1. Schotten U, Verheule S, Kirchhof P, Goette A. Patho- physiological mechanisms of atrial fibrillation: a transla- atrium appear of particular importance by activating protease-activated recep- factor X caused significant upregulation tional appraisal. Physiol Rev. 2011;91(1):265-325. in the process of clot formation.1 Novel tors (PARs) inducing inflammatory and of PAR1, PAR2, ICAM-1, IL-8, 2. Bukowska et al. Coagulation factor Xa induces an inflammatory signalling by activation of protease-acti- oral anticoagulants like rivaroxaban thrombogenic activity. LOX-1, and PAI-1 at the mRNA level. vated receptors in human atrial tissue. Eur J Pharmacol. (Xarelto, Bayer Healthcare) have been A recent study by our group in Rivaroxaban prevented upregulation 2013;718:114–123 shown to reduce atrial thrombogenesis Germany provides evidence that factor of PARs, ICAM-1, LOX-1, IL-8, and Andreas Goette is director of in AF. In addition, low dose of rivar- X acts as mediator of inflammatory activation of MAP kinases. Cardiology and Intensive Care oxaban proved to reduce cardiovascular signalling via activation of protease- Thus, our study provides evidence Medicine, St Vincenz Hospital, events in patients with acute coronary activated receptors 1 and 2 in human that in human atrial tissue, factor Paderborn, Germany, and head syndromes. Thus, inhibition of clotting atrial tissue.2 Most importantly, the X acts a mediator of inflammatory of Working Group Molecular factor X might have beneficial effects synergistic action of factor X and signalling via specific receptors. Electrophysiology, University Hospital in the vascular circulation. The activat- simulated atrial tachyarrhythmia results Most importantly, the synergistic Magdeburg, Germany February 2014 Cardiac rhythm management 25 The challenge of optimal ICD programming

The incidence of ATP induced VT appropriate ATP occurred less often, acceleration is less than 5%. demonstrates that many VT episodes We still discuss the most appropriate terminated spontaneously and did not HELMUT U KLEIN shock energy for the first shock. Lower need ICD intervention. Therefore, shock energy has the advantage of non-treatment of slower VT rates and shorter charge time, prolonged battery delayed ICD intervention will help life and less myocardial damage. In reducing inappropriate and unnecessary times of less defibrillation testing, ICD therapy. COMMENT & ANALYSIS programming high shock energy Another step forward to less already for the first shock seems to be appropriate and inappropriate ICD Despite the constant development of new algorithms for preferable. intervention was presented recently by better discrimination of supraventricular from ventricular Discriminator algorithms are difficult the ADVANCE III trial. Programming tachyarrhythmias, the problem of inappropriate implantable to improve, ATP is highly effective a longer detection interval (30 out of cardioverter defibrillator (ICD) therapy remains unsolved, writes (85%) and high energy shock delivery 40 intervals to detect) and providing Helmut U Klein reliably terminates VT/ventricular the possibility of ATP during charging fibrillation (VF) episodes. However, reduced the number of total ICD ven with sophisticated algo- Besides general rules of programming, inappropriate ICD intervention remains a interventions and of inappropriate rithms, we still face 5–10% inap- individualised, ie. patient adapted drawback of ICD therapy; therefore, we ICD shock therapy, in both primary- Epropriate ICD therapy delivery programming is mandatory. 5) Primary- have to ask if the detection algorithms and secondary prevention ICD with both, antitachycardia pacing (ATP) or secondary prevention ICD indication need to be improved or do we have a indication. Further progress of better and shocks. What is the reason for this may require different programming. wrong understanding of necessary ICD ICD programming was reported with dilemma? With our enthusiasm of being Discriminating algorithms such as intervention? Results of the PREPARE the PAINFREE-SST study, using an able to deliver ramp or burst pacing to sudden onset, stability, the relationship study have demonstrated already that improved detection algorithm with terminate stable ventricular tachycar- between atrial- and ventricular programming a monitor zone without additional wavelet morphology analysis, dia, we neglected the fact that many electrograms as well as morphology ICD intervention for slower VT episodes T-wave discrimination, improved non- tachycardia episodes do not need to be comparisons are valid discriminators is important to avoid unnecessary sustained VT termination recognition terminated within seconds after onset in almost all devices. We learnt that ATP or shock delivery, and our fear of and the possibility of lead integrity or of the arrhythmia because they may “time-out settings” and rate smoothing haemodynamic instability of a VT with noise assessment. terminate spontaneously. We forget that might not be advantageous in specific non-treatment is not justified. In summary, ICD programming needs besides inappropriately detected ar- tachyarrhythmic events. Discriminators A complete change of ICD reliable arrhythmia detection algorithms rhythmias, unnecessary ICD intervention should remain “active” during programming has been introduced with and prediction of a potentially occurs as well. redetection of an arrhythmic event. the results of MADIT-RIT. Monitoring dangerous arrhythmia event. With the Today, all ICD manufacturers provide The benefit of having “near field”, “far only of VT rates up to 200bpm results of MADIT-RIT and ADVANCE highly sophisticated ICD programming field” and atrial electrograms is obvious, without ICD intervention is favourable III, we have to realise that there is a features, consisting of a complex although the overall benefit of using dual compared to early intervention at paradigm shift of ICD programming to detection hierarchy and arrhythmia chamber devices for better arrhythmia rates between 170–200bpm. Delaying less fast and less aggressive arrhythmia adjusted ATP or shock delivery. discrimination is still a matter of debate. ICD intervention for slower VT rates termination using prolonged detection, The goals of ICD programming are Dual zone programming for ICD (≤200bpm) for one minute, and for VT delayed intervention and no therapy simple to define. 1) Therapy delivery has intervention seems to be superior to rates between 200–250bpm for 12sec, delivery for slower and stable VT to be lifesaving but must not be harmful. single zone programming. At least, significantly reduced inappropriate ICD events, allowing them to terminate 2) Inappropriate ICD intervention as one attempt of ATP should precede interventions when compared with the spontaneously. well as unnecessary therapy needs to be shock delivery, even with higher “conventional” programming arm of avoided. 3) Device specific algorithms ventricular tachycardia (VT) rates up to the study. Both, inappropriate ATP- and Helmut U Klein is adjunct professor have to be appropriately applied; not 250bpm; burst pacing seems to be more shock delivery were significantly less of Medicine, University of Rochester rarely, there is a tradeoff between successful than ramp pacing, at least frequent with these two new modalities Medical Center, Heart Research Follow- various discriminator algorithms. 4) for primary prevention ICD indication. of programming. The fact that also up Program, Rochester, USA

Lambiase highlighted that the effective conversion of Subcutaneous ICD continues to show induced ventricular tachycardia/ventricular fibrillation (VT/ VF) with the S-ICD is 98.2% and that 93% of events are positive results in a real-world scenario effectively treated in less than 21 seconds of induced VF. Overall, he said, only 33 patients (7%) received inappropri- Updated results of the EFFORTLESS S-ICD registry have shown the Subcutaneous ate shocks. Implantable Cardioverter Defibrillator (S-ICD, Boston Scientific) continues to perform With regards to clinical events, 129 events were classi- appropriately in a real-world scenario with a conversion rate of 98.2% for induced and fied as device or procedural related, of these 35 (27%) were ambulatory ventricular tachycardia or fibrillation (VT/VF), which is comparable with classified as complications and there is nothing documented standard ICD performance regarding lead fractures or breakages. The perioperative complication-free rate was 97% and the 360-day complica- ier Lambiase, The Heart Hospital, London, UK, has already been entered from UK, The Netherlands, Italy, tion-free rate was 94%. presented data at the Heart Rhythm Congress (HRC, Germany, Denmark, New Zealand and Czech Republic. Seventeen patients (3.6%) were explanted, over half of P20–23 October, Birmingham, UK). Sweden, France, Austria and Switzerland are opening the those due to infection, Lambiase reported. The EFFORTLESS (Evaluation of factors affecting the process, he noted. A total of 20 infections were reported, 18 of those were clinical outcome and cost effectiveness of the S-ICD) regis- Results presented by Lambiase at HRC are based on data S-ICD related. “Most of these infections happened most try is an international, standard of care study aimed to collect collected as of April 2013 with 472 (49±18 average age, probably because of technique and inexperience implanting short, mid and long-term operational and clinical real-world 72% male) patients enrolled (231 retrospective patients and this type of device,” he noted. data (five years post implant) on the S-ICD system. The reg- 241 prospective patients). According to Lambiase, 63% of Lambiase concluded that up to now “There is a high level istry, according to Lambiase, is aiming to recruit up to 1,000 patients have been enrolled for primary prevention. Patients of data compliance indicating integrity of registry design and patients implanted since CE mark approval in 2009. from a broad range of indications have received the S-ICD. execution. The effective conversion of induced and ambula- Lambiase reported that 538 patients have been enrolled Among those 37% related to ischaemic cardiomyopaty, 13% tory VT/VF with the S-ICD is comparable with standard ICD (as of 16 July 2013) from those 255 are being studied due to channelopathies, 8% due to idiophathic ventricular performance and the system continues showing low complica- retrospectively and 283 prospectively. Data of 504 patients fibrillation and 7% due to congenital heart disease. tions and clinical event rates in a real-world scenario.” 26 Market watch February 2014

ment, which facilitates Symplicity system by valve is precise and fully more favourable patient helping significantly re- controllable,” said Chris- outcomes, it says in the duce ablation time,” said toph Naber, from the Con- Product News release. Michael Böhm, chairman, tilia Heart and Vascular Department of Internal Center, Essen, Germany. CE mark for new Medicine, University of “With this new valve size, FDA approves ranging in diameter from evaluating the safety and Symplicity system Saarland, Homburg/Saar, a broader patient popula- Boston 2.25mm to 4mm and effectiveness of the com- Medtronic has announced Germany. “Further, the tion will be able to benefit Scientific’s lengths of 8mm to 38mm pany’s orbital atherecto- that it has received both ease of use and excep- from the unique advan- Promus Premier on both monorail and my technology in treating CE-mark approval and tional deliverability help tages of the Direct Flow coronary stent over-the-wire catheter the problematic subset Australian therapeutic simplify the procedure.” Medical system.” Boston Scientific has platforms. This provides of patients with severely goods administration received FDA approval physicians and their pa- calcified coronary le- (TGA) listing for a new First fully CE mark for for its Promus Premier tients with a broad range sions. It is the first study, Symplicity renal denerva- repositionable XL version of everolimus-eluting, of options designed to best it states in a company tion system, consisting 29mm TAVI device Perceval surgical platinum chromium suit their needs, it says in press release, in history of a flexible 4 French gets CE mark aortic valve coronary stent system. the press release that sought approval for multielectrode catheter Direct Flow Medical has Sorin has announced that The first implantation of treating these lesions. (Symplicity Spyral) and a announced that it has it has received the CE the system is scheduled to Cardiovascular Led by principal radio frequency genera- received the CE mark for mark for the XL version be performed by Martin Systems receives investigator, Jeffrey tor (Symplicity G3). The the first fully reposition- of its Perceval biopros- Leon, director, Center for FDA approval for Chambers, of Metropoli- company reports that the able 29mm transcatheter thetic aortic valve, which Interventional Vascular coronary device tan Heart and Vascular new system is designed aortic heart valve, deliv- is designed to replace Therapy at Columbia Uni- Cardiovascular Systems Institute, Minneapolis, to significantly reduce ered through its flexible, a diseased native or versity Medical Center/ announced that it has ORBIT II demonstrated ablation time and provide 18 French transfemoral malfunctioning prosthetic New York-Presbyterian received approval from that Cardiovascular ease of deliverability delivery system. The tran- aortic valve using either Hospital, New York, USA. the FDA to market its Systems’ technology during renal denervation scatheter aortic valve im- traditional or minimally According to a press Diamondback 360 Coro- produced clinical out- procedures for patients plantation (TAVI) device invasive heart surgery. release, the Promus Pre- nary Orbital Atherectomy comes that exceeded the with uncontrolled hyper- is designed to virtually This approval expands the mier stent system offers System (OAS) as a treat- trial’s two primary safety tension. eliminate aortic regurgita- Perceval portfolio, permit- physicians improved drug- ment for severely calci- and efficacy endpoints According to a press re- tion in all sizes of annulus ting cardiac surgeons to eluting stent performance fied coronary arteries. by a significant mar- lease, the Spyral catheter by allowing complete treat patients with annulus in treating patients with “Coronary calcium gin—within one of the features four electrodes assessment of haemody- sizes ranging from 19mm coronary artery disease. is undertreated in the most challenging patient that are able to deliver namic performance and to 27mm The stent features custom- cardiac cath lab. Having populations. simultaneous or selective unlimited repositioning of According to a press ised platinum chromium a user-friendly device At 30 days, ORBIT II radiofrequency energy the valve after full deploy- release, a recent pub- alloy stent architecture, available to effectively results showed patient into the renal artery wall ment in the native valve lished retrospective an everolimus drug with treat severe coronary freedom from MACE to disrupt the output of annulus. observational study of a biocompatible, fluori- calcium may increase was 89.8% and proce- overactive sympathetic A press release reports the Perceval valve in 137 nated co-polymer, and an the safety of coronary dural success was 89.1%. nerves. It is that the approval expands patients shows operat- enhanced stent-delivery artery disease interven- Excluding in-hospital compatible the population of ing time reduction, no system. tions for this difficult-to- MACE, procedural with a 6 patients who can intra-operative mortality, Leon says: “It is very treat population, while success was 98.6% with French be treated using shorter Intensive Care rewarding, professionally, improving long-term 97.7% of stents success- guide the Direct Flow Unit (ICU) and hospital to be the first to provide patient prognoses,” says fully delivered. Moreo- Medical valve stay (a median of one and this new drug-eluting stent Gregg Stone, professor ver, 92.8% of patients to patients with seven days respectively). therapy to my patients. of Medicine, Columbia were free from severe annulus sizes The authors conclude that Perhaps the most impres- University, Director of angiographic compli- ranging from Perceval used in minimal- sive benefit of the Promus Cardiovascular Research cations, and core lab 21mm to 28mm. It ly invasive aortic valve Premier stent system is and Education Center for assessed final procedure adds that the double- replacement is a feasible, its unparalleled visibility, Interventional Vascular residual stenosis was Spyral ring design of the Direct effective and safe device. which combined with Therapy New York Pres- 4.7%. Flow Medical valve “We are consistently its enhanced customised byterian Hospital/Colum- According to Cham- catheter and is delivered conforms to the anatomy achieving key milestones stent architecture, leads bia University Medical bers, “Patients who suffer over a 0.014 inch guide- and creates a tight and regarding the Perceval to an advance in currently Center and Co-Director from severely calcified wire via a rapid exchange durable seal around the platform. Patients with XL available durable polymer of The Cardiovascular coronary lesions are one system. annulus. The system is sizes represent a consid- drug-eluting stents.” Research Foundation of the toughest to treat The press release designed to improve long- erable percentage of the The Promus Premier New York, USA. populations—and previ- adds that the catheter is term survival of patients eligible population for Stent System is offered ORBIT II is Cardio- ous studies have shown powered by the new G3 by resolving the clinical aortic valve replacement, in a matrix of 94 sizes, vascular Systems’ study these patients have worse radiofrequency generator, issues associated with cur- therefore, our additional outcomes. Thirty-day which it says leverages rent commercial valves. size is a great opportu- ORBIT II results demon- the benefits of Medtron- The system avoids rapid nity to treat patients with strate that Cardiovascular ic’s proprietary Symplic- pacing of the heart during the latest therapies,” Systems’ orbital atherec- ity treatment algorithm deployment, and does not said Michel Darnaud, tomy technology is safe with its built-in safety require post-dilatation president, Cardiac Surgery and effective. With FDA features. The system following placement, Business Unit, Sorin approval, physicians now uniquely offers physicians minimising the risk of Group. have new technology to control and flexibility haemodynamic instability treat patients with se- with the ability to turn for patients. The Direct CE mark approval verely calcified coronary specific electrodes on and Flow Medical transcathe- expands patient lesions.” off to accommodate dif- ter system is indicated for group for Portico The Diamondback ferent anatomies. The G3 the treatment of patients TAVI system 360 Coronary OAS uses generator includes a new with severe aortic stenosis St Jude Medical has an- an electrically driven touch screen user inter- who are at extreme risk nounced that its 25mm 1.25mm diamond-coated face compatible with the for surgical aortic valve transcatheter aortic valve crown to safely reduce single-electrode Symplic- replacement. implantation (TAVI) Porti- calcified lesions in coro- ity catheter. “As with the smaller co device has received the nary blood vessels. This “The multielectrode sizes of the Direct Flow CE mark. The company ultimately helps enable Symplicity system builds Medical valve, the im- states that the approval Diamondback 360 successful stent deploy- upon the single-electrode plantation of the 29mm means that Portico system February 2014 Market watch 27

gitation, improvement in symptoms and reduction in hospitalisations for heart failure. More than 11,000 patients in more than 30 countries have been treated with the MitraClip device. “MitraClip is a break- through in the treatment of severe mitral regurgita- can now be used in more continue to be evaluated tion, a condition that is patients. in a non-randomised, mul- progressive and causes A company press ticentre study (the Portico extreme fatigue and short- release reports that, made TF CE Trial). Data from ness of breath, eventually of bovine pericardial this study was recently making even simple tasks tissue attached to a self- presented at the Tran- virtually impossible, and expanding stent frame, scatheter Cardiovascular increasing the risk of the Portico valve is the Therapeutics (TCT) scien- stroke, heart failure and first transcatheter aortic tific symposium. Results death,” says Ted Feldman, heart valve that can be highlighted the 23mm director, Cardiac Cath- completely resheathed, and 25mm Portico valves’ eterization Laboratory and repositioned at the haemodynamic perfor- The Mr and Mrs Charles implant site, or retrieved mance and improvement R Walgreen Chair in PK Papyrus before being released in the severity of patients’ Interventional Cardiology, from the delivery system. heart failure symptoms NorthShore University may support development tion lesions will ben- a stent that is straight- It adds that the 25mm as measured by the New HealthSystem, Evanston, of treatment guidelines, efit from our specialized forward to introduce into valve supports a patient’s York Heart Associa- USA. He adds: “Clini- expanded indications and technology. The Axxess the artery with a flexibil- native annulus with tion (NYHA) functional cal data and real-world reimbursement. Both stud- line offers the unique ity that means simplified diameters ranging from classification system. international experience, ies are currently enrolling benefits of a dedicated placement.” 21mm to 23mm, and The 23mm Portico TAVI dating back to 2003, have patients. self-expanding bifurcation the CE mark approval device received the CE consistently shown that stent,” commented Jeffrey Medtronic to means that the Portico mark last year. the MitraClip is a safe Larger version of B Jump, president of Bio- resume sales platform can now treat and effective therapy for Axxess stent now sensors’ Cardiovascular of CoreValve in patients with an annulus MitraClip patients unable to undergo available Division Germany ranging from 19mm to approved for use mitral valve surgery, Biosensors has announced Medtronic announced on 23mm. In 2014, St Jude in the USA providing meaningful im- that it has launched a New device for 14 November 2013 that Medical expects to add Abbott Vascular has provements in quality of larger version of its acute coronary a German court ordered two additional valve sizes announced that it will life that are sustained over Axxess bifurcation drug- artery perforation the discontinuation, in its to the Portico line, which immediately launch the time. It has allowed many eluting stent. The new Biotronik has announced entirety, of a prior court will expand the eligible MitraClip, which is a of my patients to go from 4.0x9mm size received that it has received the CE ruling that prohibited range of patients to those minimally invasive device bed rest to a more active the CE mark in September mark for its PK Papyrus Medtronic from commer- with annulus sizes ranging for the management of lifestyle shortly following and has been specifically covered coronary stent for cially marketing or selling from 19mm to 27mm. significant symptomatic treatment.” designed for the safe and the management of acute the CoreValve system in “The addition of the degenerative mitral regur- The press release effective treatment of coronary artery perfo- Germany since 26 August 25mm Portico valve gitation in patients who reports that Abbott contin- bifurcation lesions involv- ration. According to a 2013. broadens the patient are at prohibitive risk for ues to conduct clinical tri- ing large main branch company press release, the “Medtronic is very population that can now mitral valve surgery, on to als of the MitraClip thera- vessels and wide bifurca- PK Papyrus provides 58% pleased with this deci- be treated with this family the USA market now that py through two landmark, tion angulation. The stent greater flexibility and a sion as it will ensure of valves,” says Gerhard it has received FDA ap- prospective, randomised was launched at the 2013 24% reduced crossing pro- that patients in Germany Schuler, head of the proval for the device. trials—COAPT in the Transcatheter Cardiovas- file than Abbott Vascular’s who need aortic valve department of Internal According to a press USA and RESHAPE- cular Therapeutics (TCT) Jostent Graftmaster. replacement will have Medicine/Cardiology at release, multiple trials, HF in Europe—that will scientific symposium (27 The press release re- access to this life-saving the University of Leipzig published reports and reg- evaluate the impact of October–1 November, San ports that the PK Papyrus therapy,” said John in Leipzig Germany. istries of patients treated MitraClip treatment on the Francisco, USA). is able to provide greater Liddicoat, senior vice According to the press with the MitraClip device progression of heart fail- According to a press flexibility than Abbott’s president, Medtronic, and release, the Portico 23mm consistently demonstrate ure. The studies also will release, Axxess 4.0x9 Jostent Graftmaster due president of the Medtronic and 25mm transcath- a positive safety profile, generate important clini- features a self-expanding to its innovative “elec- Structural Heart Busi- eter aortic heart valves reduction in mitral regur- cal and economic data that nitinol (nickel/titanium) trospun” membrane. It ness. “As a result of the stent platform, to accom- adds that the enhanced ruling, Medtronic will modate the anatomical di- “electrospinning” technol- resume distribution of ameter mismatch between ogy allows for a propri- the CoreValve system in the proximal large main etary single-layer covered Germany.” branch vessel and bifurca- stent design, rather than The Higher Regional tion. Its distal flared end the traditional “sand- Court Karlsruhe explained has been specifically de- wich technique” used on that, due to the Euro- signed to protect a higher comparable stents on the pean Patent Office (EPO) vessel angulation. As with market. preliminary opinion that the existing stents in the Georg Nickenig, the Edwards’ EP2055266 Axxess range, Axxess University Hospital Bonn, Spenser patent claims are 4.0x9 is abluminally coat- Germany, commented: not valid, it could not as- ed with a biodegradable “In acute situations when sume “with sufficient like- poly-lactic acid polymer there is a vessel perfora- lihood” that the Spenser that releases Biolimus A9 tion, I need a stent that is patent is valid. (BA9). highly effective and has Medtronic will post the “With the addition of optimum deliverability. €5 million bond required Axxess 4.0x9 to our cur- With PK Papyrus, I am by the order as soon as rent Axxess portfolio, a confident that, if such a possible and then resume MitraClip broader range of bifurca- situation arises, I have sales in Germany. 28 Studies February 2014

(PVL ≤1), procedural suc- Society (CCS) angina bypass grafting (CABG). cess rate 98% and stroke grading scale. Only pa- These data were presented rate below 2%. Since its tients with severe angina, 60th Annual Meeting of Clinical News first use, ACURATE TA CCS Class three or four the Southern Thoracic has now been implanted were enrolled in the study. Surgical Association (30 to date in over 1,000 The topline analysis October–2 November, Barostim trial, as well as patient group of drug resistant patients in Europe, Argen- showed that the study Scottsdale, USA). therapy may be data from a large German patients, clinically as well tina and Japan. met the primary endpoint, A press release reports cost-effective epidemiological study. as from a health economic The press release also with patients receiving that the 1,380-person for resistant The health economic standpoint,” said Joachim reports that during the the Reducer achieving a study evaluated the inci- hypertension model in this study uses Beige, study co-author, recent EACTS 2013 in statistically significant dence of post-operative CVRx has announced risk equations and cost Head KfH Renal Unit / Vienna (Austria), the ver- improvement in CCS stroke in people undergo- that findings from a data from the published Department of Nephrol- satility of the ACURATE scores (two classes or bet- ing CABG while using health-economic analysis, literature to project the ogy, Hospital St. Georg, TA system was further ter) compared to patients the Heartstring device published in the Journal economic and clini- Leipzig, Germany. demonstrated by Michael receiving a sham control to maintain haemostasis of Hypertension, indicate cal impact of Barostim “Moreover the estimated Hilker (Universitätsklini- (p-value = 0.024). The during the attachment Barostim therapy is a therapy for patients with reductions in end-stage kum Regensburg) as an analysis also showed that of grafts to the aorta cost-effective treatment drug-resistant hyperten- events such as stroke and effective solution to failed patients treated with the (proximal anastomosis). option for patients with sion. The model in the end stage renal disease are biological valves (valve- Reducer showed a statisti- Across all aortic disease drug-resistant hyperten- study is a combination substantial. This illustrates in-valve). cally significant improve- levels, the Heartstring sion. The Barostim system of a decision tree and a the impact which the ment of one or more CCS device was associated with is a programmable, mini- Markov model, and it uses blood pressure reduction Reducer classes compared to the a 45% reduction in stroke mally invasive device that established multivariate of Barostim therapy can significantly sham control patients (p- risk compared with what consists of an implantable risk equations from the have.” improves value = 0.003). would have been expected pulse generator (IPG), a Framingham heart study functional Tim Henry, director of given patient risk factors. 2mm electrode, and an and the SCORE project to 1000th patient capabilities in Cardiology, Cedars-Sinai The objective of the external programmer. enable a robust projection implanted with angina patients Heart Institute in Los study was to examine the A press release reports of the impact of Barostim ACURATE TA Neovasc has announced Angeles, USA, noted, incidence of post-opera- that, based on blood pres- therapy on cardiovascular Symetis has announced that the topline results “Patients with refrac- tive stroke in CABG using sure reductions attained events and mortality. that the 1000th implanta- from its COSIRA trial (a tory angina are a growing the Heartstring device in with Barostim therapy, the The model shows that tion of its ACCURATE multicentre, prospective, subset of patients and varying diseased aortas. analysis projected that the Barostim therapy may TA transcatheter aortic randomised, sham-con- have limited treatment op- These data were derived therapy is associated with substantially reduce valve implantation device trolled study) indicate that tions. Although we await from a retrospective analy- an anticipated incremental debilitating and costly has taken place. The the company’s percuta- the final results, these sis of patients who under- cost-effectiveness ratio cardiovascular events company reports that the neous device (Reducer) preliminary results from went CABG with one or (ICER) of €7,797 per such as stroke, end stage ACURATE TA valve significantly improves the the COSIRA study suggest more proximal anastomo- quality adjusted life year renal disease, myocardial was first implanted in symptoms and functioning that the Neovasc Reducer ses constructed using the (QALY) gained from a infarction, coronary heart November 2009 at the of patients with refractory may provide an exciting Heartstring technology at payer perspective in a Eu- disease and heart failure. Leipzig Herzzentrum by T angina. new option for these chal- Emory University Hospital ropean setting. It adds that Over a lifetime, Barostim Walther and J Kempfert. According to a press lenging patients.” in Atlanta from April 2003 this is significantly below is estimated to reduce the According to a press release, the COSIRA The Reducer provides to December 2012. the recognised European rate of stroke by 35%, release, the ACURATE (Coronary sinus reducer relief of angina symptoms Lead author on the cost-effectiveness thresh- end stage renal disease by TA was granted the CE for treatment of refractory by altering blood flow in study, Vinod Thourani old of €35,000. 23%, myocardial infarc- mark in September 2011 angina) trial assessed the the heart’s venous system, (associate professor of Barostim therapy is tion by 19%, and heart and the first commercial safety and efficacy of the thereby increasing the Cardiothoracic Surgery, designed to trigger the failure by 12%. Barostim implant was performed in Reducer in 104 patients perfusion of oxygen- Emory University, USA) natural blood pressure was estimated to pro- November 2011. In April in the European Union ated blood to ischaemic states: “Surgeons constant- regulation system by vide 1.66 additional life 2012, Symetis reported and Canada. Patients areas of the heart muscle. ly strive to prevent stroke electrically activating the years and 2.17 additional the clinical outcome of its were randomised 1:1 Placement of the Re- during CABG surgery, and carotid baroreceptors. Ba- quality-adjusted life years SAVI Registry (n=250) between treatment and ducer is performed using these data provide addi- rostim neo is the second- when compared with opti- showing superior results sham control arms. Its a minimally invasive tional evidence to support generation system that is mal medical management. in the patient population primary endpoint was a transvenous procedure that the use of an off-pump commercially available “This study provides treated in everyday clini- two-class improvement six is similar to implanting a technique and Heartstring in Europe. The therapy is an important perspective cal settings: more than months after implantation coronary stent and takes when performing this life included in the joint Euro- on the value of lowering 97% of patients with no in patients’ ratings on the approximately 20 minutes. saving procedure.” pean Society of Hyperten- the blood pressure for this relevant paravalvular leak Canadian Cardiovascular The complete results sion and European Society of the COSIRA trial are Edwards of Cardiology guidelines being submitted as a Lifesciences for the treatment of resist- late-breaking clinical trial launch US trial ant hypertension. presentation at the annual of Sapien 3 The reduction in blood meeting of the American TAVI device in pressure with Barostim College of Cardiology intermediate risk therapy was based on (29–31 March, Washing- patients the double-blinded, ton DC, USA) Edwards Lifesciences randomised clinical trial has announced that it has published in the Journal of Campless received investigational the American College of technique may device exemption (IDE) Cardiology and long-term minimise strokes approval from the FDA to follow-up data. The study during CABG initiate a single-arm, non- analysed the impact of According to Maquet, a randomised clinical trial of Barostim therapy on a new study suggests that a its Sapien 3 transcatheter cohort of drug-resistant campless technique, con- aortic valve implantation hypertension patients with sisting of off-pump coro- (TAVI) device for the a systolic blood pressure nary artery bypass in com- treatment of intermediate >170mmHg. Patient char- bination with Maquet’s risk patients with severe acteristics were based on Heartstring proximal seal symptomatic aortic ste- the actual patients treated system, reduces the risk nosis. The company also with Barostim therapy in of perioperative strokes completed enrolment in its the randomised Barostim Heartstring during coronary artery US clinical trial of Sapien February 2014 Studies 29

in complete ST-segment II (Direct implantation of resolution at 60-90 rapamycin-eluting stents minutes post-procedure. with bioabsorbable drug Secondary endpoint clini- carrier technology) study cal outcomes continued has been completed. DI- to show a lower mortality RECT II is a prospective, rate with the MGuard randomised study that EPS compared to the compared the safety and control (1.0% vs. 3.3%, efficacy of Svelte’s drug- p=0.092) at 12 months. eluting coronary stent These findings are in integrated delivery system line with the previously (IDS) with the Resolute announced six-month Integrity drug-eluting follow-up results showing stent (Medtronic) in 159 that all-cause mortality patients at 19 investigative with MGuard EPS was sites. lower than bare metal and According to a com- drug eluting stents used pany press release, the as a control (0.5% vs. study builds on the posi- 2.8%, p=0.056). tive results of the DIRECT “It is very reassuring I first-in-man study, which to see that the 12-month evaluated the Svelte drug- follow up data is consist- eluting coronary stent IDS ent with the acute results in 30 patients in New Zea- presented at TCT last land. The Svelte system year, especially the data met the study endpoints in that shows the mortal- DIRECT I while demon- ity benefit trend of using strating in-stent neointimal 3 valve in the treatment vice president, transcath- 4.5% decrease in neoin- The clinical event this unique technology,” volume obstruction of of high-risk or inoperable eter heart valves. timinal thickness, from adjudications, quantita- states Dariusz Dudek, 2.7% at six months, a one- patients. 0.156mm [0.143-0.168] tive coronary angiogra- physician-in-Chief, 2nd third to one-half reduction According to a press Combo dual to 0.149 [0.136-0.161] phy and OCT analyses Department of Clinical in volumetric obstruction release, the Sapien 3 valve therapy stent (p=0.19); and a 9.7% de- were performed by the Cardiology and Cardio- observed in similar stud- is the only transcatheter demonstrates crease in in-stent percent- Cardiovascular Research vascular Interventions at ies with market-leading heart valve available to excellent early- age neointimal volume, Foundation Core Lab in the University Hospital in drug-eluting stents. Clini- US patients that can healing and from 17.5% [16.0-19.0] New York, USA Krakow, Poland. “These cal outcomes reflected be delivered through a durable outcomes to 15.8% [14.5-17.1] positive results should the strong angiographic low-profile 14-French at 24 months (p=0.002), for the Combo Lower mortality give clinicians the con- findings, with 0% clini- expandable sheath (eS- OrbusNeich has an- stent. No further stent in STEMI patients fidence to use MGuard cally driven major adverse heath). It also has an outer nounced that new clinical thrombosis, neoatheroscle- with MGuard technology as a first line cardiovascular events skirt to provide a seal to data presented at the 2013 rosis or clinically driven stent of defense against distal (MACE) reported through address paravalvular leak. Transcatheter Cardiovas- target lesion revascularisa- InspireMD has announced embolization for their 18-months. The Sapien 3 valve can cular Therapeutics (TCT) tion were observed. new 12-month results STEMI patients.” Primary endpoints of be implanted with the scientific symposium “We previously re- from the MASTER The MASTER trial the DIRECT II study transfemoral approach show durable outcomes ported nine-month results (MGuard for acute ST el- enrolled a total of 433 were target vessel failure through an incision in the as well as excellent early from EGO-COMBO that evation reperfu- patients with STEMI and in-stent late loss. All leg, as well as alternative healing and optimal ne- established the impres- present- patients are scheduled to access approaches. It is an ointimal suppression out sive early healing profile receive six-month clinical investigational device that to 24 months following of the Combo stent,” Lee and angiographic follow- is not available commer- placement of the Combo says. “These 24-month up, with clinical cially in any country; CE dual therapy stent. results now demonstrate follow-up contin- Mark approval in Europe These results from the the Combo stent’s excel- sion) ued through five is anticipated in the near EGO-COMBO study were lent durability over the trial, demonstrating that years. A subset future. presented by Stephen WL long-term with a trend the MGuard outperformed of patients The press release Lee of the Queen Mary of neointima regression bare metal and drug Mguard will receive reports that the new US Hospital, University of observed by OCT. This eluting stents in all-cause optical coher- trial of the Sapien 3 valve Hong Kong, China. is the first time ever for a mortality in ST segment ing within ence tomogra- will enrol up to 1,000 In a press release the drug-eluting stent reported elevation myocardial 12 hours of phy (OCT) imag- patients with a Society of company states that the in the market.” infarction (STEMI) pa- symptom onset ing at six-months. Thoracic Surgeons score study was the first of its In the study, 61 patients tients. Results from the undergoing percutaneous “We are pleased to of 4–8%, which indicates kind to assess the healing received 88 Combo stents trial were presented at the coronary intervention have completed this the average predicted risk profile of a drug-eluting with a mean diameter of TCT conference. were randomised at 50 rigorous evaluation of the of operative mortality stent by longitudinal 3.06±0.39mm and a mean According to a press sites in nine countries Svelte drug-eluting stent at 30 days. All enrolled pa- sequential optical coher- length of 23.9±7.62mm. release, the MGuard to the MGuard EPS (n IDS following the strong tients can receive a Sapien ence tomography (OCT) OCT was performed at stent uses the company’s =217) or commercially and sustained outcomes 3 valve. and uniquely showed an baseline, at early follow- proprietary MicroNet available bare metal of the DIRECT I study,” “The Sapien 3 valve improvement in outcomes up (before five months) technology, which is a or drug-eluting stents said Stefan Verheye, co- is a significant advance- (neointimal regression) be- and at nine months in circular knitted mesh that (n=216). director of the Antwerp ment, and we’re excited tween nine and 24 months all patients. The clinical wraps around the stent Cardiovascular Institute at to make progress toward in terms of neointimal vol- follow-up was carried to protect patients from Enrolment the Middelheim Hospital bringing this sought-after ume, neointimal thickness out to 12 months. Per the plaque debris flowing completed in in Antwerp. “As continued transcatheter therapy to and plaque volume. extension study protocol, downstream upon de- DIRECT II study emphasis is placed on US patients. It represents Between nine and 24 59 patients were evaluated ployment. The aim of this of rapamycin- downsizing access sites a big step toward fulfilling month OCT follow-up, pa- clinically at 24 months, technology is to specifi- eluting stents with and improving procedural the promise of a simpler tients exhibited an 11.3% and, of those, 41 agreed cally address the unmet biodegradable efficiencies as well as clin- procedure with fewer decrease in neointimal to have a restudy by OCT. need for STEMI patients. polymer ical outcomes, this system complications and faster volume, from 35.5mm3 All patients received The MASTER trial Svelte Medical Systems presents an important patient recovery,” said [30.7-40.3] to 31.5mm3 dual antiplatelet therapy achieved its primary end- has announced that the fi- option to interventional Larry L Wood, corporate [26.9-36.2] (p<0.001); a (DAPT) for nine months. point (p value = 0.008) nal patient in the DIRECT cardiologists.” 30 Industries February 2014

Tryton Medical of Medical Sciences, launches new Poznan, Poland) will hold Cardiovascular Bifurcation the inaugural Bifurcation News team Clinical News Institute Institute workshop, which Tryton Medical has will focus on the clinical announced the launch of outcomes and treatment Editor-in-chief: Alvimedica and Boston Scientific and as associate professor its “Bifurcation Institute”, of bifurcation lesions Dr Kevin Fox CID join forces appoints new of medicine, Yale which it says is a with the Tryton Side Publisher: University School of Branch Stent. Alvimedica has chief medical comprehensive education Stephen Greenhalgh announced a merger officer for Medicine, USA. He has resource that has been Lesiak said: “There is with CID (Carbostent & interventional also served as an advisor established to advance a significant unmet need Head of Publishing: Implantable Devices). cardiology for many cardiovascular the standard of care for for education and training Marcio Brito Under the brand Boston Scientific device companies and bifurcated coronary artery regarding bifurcations. In name Alvimedica, has appointed Craig he participated in the disease. Membership patients undergoing PCI Editor: the companies aim to Thompson as its new early development of for the institute is stenting, approximately Dawn Powell be a new European senior vice president technologies for the free and provides one third has a bifurcation [email protected] alternative in the global chief medical officer of treatment of coronary physicians with access lesion. Left main disease market for medical interventional cardiology. total occlusions, to e-newsletters that is a persistent challenge Design: David Reekie devices. The company reports including the BridgePoint summarise recent clinical in interventional According to an Alvi- that Thompson will play coronary chronic total data and news. cardiology, as more than Layout: medica press release, a key role in driving occlusion system A press release reports 75% of left main lesions Matt Hadfield Alvimedica now owns the development of acquired by Boston that the Institute also are bifurcation lesions. three centres of excel- innovative medical Scientific in 2012. provides links to timely The Bifurcation Institute Advertising: lence in research and solutions within the “Craig is a webcasts and a case aims to evolve treatment Sanna Eronen develpment across three Boston Scientific very experienced library that highlights the patterns and current [email protected] different European sites: interventional cardiology interventional latest techniques and tips procedural guidance Catalca, Turkey; Salug- business and states that cardiologist who is an for treating bifurcation to incorporate safe and Subscriptions: gia, Italy; and Assen, the he is a global leader important addition to our disease. Additionally, effective treatment of Sue Couch [email protected] Netherlands. in complex cardiac clinical team, increasing clinical symposia and bifurcations in daily The press release also interventions. our ability to innovate educational workshops practice.” Please contact the reports that the CID According to a press medical solutions that will available through the The Bifurcation Cardiovascular News product portfolio is release, Thompson provide unique value to institute. Institute features the team with news or “fully complementary” previously served physicians and patients,” The press release results of the landmark advertising queries to the cardiovascular as director, invasive said Keith Dawkins, adds that on 5–6 March Tryton IDE trial Tel: +44 (0)20 7736 8788 product line currently cardiology and vascular executive vice president 2014, Maciej Lesiak and presented in a Late- marketed by Alvimedica. medicine, Yale New and global chief medical his institution (Karol breaking clinical trial Published by: Haven Hospital, USA, officer, Boston Scientific. Marcinkowski, University session at TCT 2013. BIBA Medical, 526 Fulham Road London, SW6 5NR, UK 5–8 April 30 August–3 Tel: +44 (0) 20 7736 8788 36th Charing September Fax: +44 (0) 20 7736 8283 Cross International ESC—European Society Calendar of events Symposium of Cardiology Printed by: London, UK Barcelona, Spain Buxton Press T +44 (0)20 7736 8788 E [email protected] 20–22 February 9–14 March Cape Town, South Africa E [email protected] W www.escardio.org/ Reprint requests and all correspondence regarding Resistant Hypertension Interventional W www.africapcr.com W www.cxsymposium.com congresses/esc-2014 the newspaper should be Course Cardiology 2014 E africapcr@europa- addressed to the editor at Berlin, Germany Snowmass Village, USA organisation.com 28–31 May 13–17 September the above address. W www. E [email protected] ISMICS TCT 2014— resistanthypertensioncourse. W www.promedicacme. 29–31 March Boston, Massachusetts Transcatheter © BIBA Medical Ltd, 2014 com com/meeting/Interventional- ACC.14—American W www.ismics.org Cardiovascular All rights reserved. Cardiology-2014-29th- College of Cardiology Therapeutics 22–25 February Annual-98.html annual scientific meeting 20–23 May Washington DC, USA Write to us! CRT 2014 Washington, DC, USA EuroPCR E [email protected] If you have comments on Washington, DC, USA 13–15 March W www.accscientificsession. Paris, France W www.tctconference.com this issue or suggestions for upcoming editions write to W www.crtmeeting.org Africa PCR org W www.europcr.com [email protected]

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