The international newspaper for cardiovascular specialists May 2009 Issue 13

Image Evalve Statins centre stage at the Percutaneous ACC meeting Pages 4 and 6 mitral valve Warnholtz: The value of repair takes off the FAME trial A percutaneous approach for the treatment of clinically-significant mitral regurgitation Page 8 has demonstrated success in the first 75 patients who have undergone the procedure in Europe. In the UK, four patients have been treated so far. The SYNTAX THE FIRST THREE cases of not require opening of the for nonsurgical mitral regurgi - percutaneous mitral valve chest or a heart lung machine, tation patients, but should also new cost repair in the UK were per - it has the advantage of avoid - be considered as a therapy for formed in November 2008 in ing potential serious complica - select surgical candidates.” All analysis the Castle Hill Hospital, Hull. tions from open heart surgery, three patients treated in Hull Page 10 Recently, the minimally-inva - and typically requires only a reported relief of symptoms at sive technique has also been short hospital stay. The proce - four months. The group was performed in London. dure helps reduce symptoms also the first in the world to Bioabsorbable The technology for the pro - of mitral regurgitation, perform angioplasty simulta - cedure, the MitraClip system improves heart function while neously with mitral valve MitraClip stent results (Evalve), received CE mark preserving surgical options for repair on beating heart. last year and is the only tech - the future in most patients. In London, one patient was The procedure ture is done under transoe - published nology for percutaneous mitral “This technology is cutting treated in February with Percutaneous mitral valve sophageal echocardiogram Page 12 repair commercially available edge and may transform the MitraClip by Christopher repair is done under general control and is aimed to be very in Europe for patients with way many of our patients Baker and Mike Bellamy at the anaesthetic, via the right superior and posterior, functional or degenerative receive heart surgery,” said Imperial College Healthcare femoral vein, with a 24 French explains Baker. “It is very high mitral regurgitation. Farqad Alamgir, who led the NHS Trust. “The patient has device. The Evalve system up and towards the back of the Profile: Close to 500 patients have team in Hull. “The MitraClip done very well. The patient consists of three subsystems: a atrium, so it gives you enough been treated with the therapy reduces many of the was someone with severe steerable guide catheter, a clip room to move within it.” A Dr Christian MitraClip worldwide. In risks and trauma currently symptomatic mitral regurgita - delivery system, and the super stiff wire is used to Europe, 11 hospitals in five associated with open heart sur - tion and not thought to be fit to MitraClip device. The first guide the catheter across the Hamm countries (Germany, Italy, UK, gery. Patients now have a sec - undergo a conventional proce - part of the procedure consists septum. The clip is introduced, Pages 20 and 21 Switzerland, and The ond option which may not dure. The regurgitation was of a transeptal puncture and guided by the echocardiogram. Netherlands) have treated 75 require them to have surgery. I reduced from grade four, the the introduction of a wire “You can choose precisely patients with the device. believe the MitraClip system most severe, to grade one, across the septum into a pul - where on the valve you Cypher vs. Because the procedure does will not only play a key role which is mild,” said Baker. monary vein. The septal punc - want to place the clip. It is
2 Taxus for continue to experience life-threaten - in patients undergoing percutaneous diabetics ing recurrent events,” said Professor coronary intervention for ST-eleva - Page 22 Antiplatelet agent prasugrel Gilles Montalescot, Pitié-Salpêtrière tion myocardial infarction) study. Hospital, Paris, France. “Findings This trial showed that prasugrel sig - from the phase III study showed that nificantly reduced ischaemic events receives CE mark treatment with prasugrel significantly compared with clopidogrel, but at the PLUS THE EUROPEAN COMMISSION The FDA is evaluating whether pra - reduced the risk of cardiovascular expense of an increase in major has granted marketing approval for sugrel should be approved in the events compared with the current bleeding. Product News prasugrel (Efient, Lilly/Daiichi USA. On 3 February 2009 the standard of care, clopidogrel.” Pages 30–34 Sankyo) for the prevention of Cardiovascular and Renal Drugs By blocking the receptor P2Y12 Results atherothrombotic events in patients Advisory Committee voted unani - adenosine diphosphate on the platelet The TRITON-TIMI 38 trial, a head- with acute coronary syndrome under - mously, but not without controversy, surface, prasugrel prevents platelets to-head superiority study that evalu - Clinical News going percutaneous intervention. The to recommend approval of prasugrel. from clumping. ated the safety and efficacy of pra - Page 36 approval follows a positive opinion The first launch of Efient worldwide The European Committee for sugrel compared with clopidogrel in from the Committee for Medicinal has taken place in the UK. Medicinal Products for Human Use’s reducing atherothrombotic events in Products for Human Use of the “Despite the proven benefits of positive opinion was based largely on 13,608 patients, showed that prasug - European Medicines Agency on 18 current antiplatelet therapies, many the pivotal TRITON-TIMI 38 rel taken with aspirin was superi - Events December, 2008. acute coronary syndrome patients (Prasugrel compared with clopidogrel or to clopidogrel plus aspirin in
2 Page 38

BIBA Publishing 2 Cardiovascular News International Issue 13 May 2009

Images Evalve Percutaneous mitral valve repair takes off 1
possible to close the clip and look at the effect of that position on the degree of regurgitation using echo scans before releasing it. If it’s not optimal, you can release the valve leaflets and choose a better position. In our first case, our Severe mitral regurgitation in blue and the The MitraClip system prior to clip deployment. The MitraClip device securely attached initial position was not as good as it needed to MitraClip device grasping the mitral valve leaflets Blood flows normally on both sides of the clip to both leaflets of the mitral valve be, and we then tried several other positions before we were happy,” said Baker. patient clinical status and left ventricular func - study, a continued access registry in the USA. changes in functional capacity after successful When the leak has been reduced adequately, tion and reduces the rate of hospitalisation for The first patient was enrolled in REALISM by treatment with the MitraClip system.” the clip is deployed and the final result heart failure. The data were presented by Ted Peter Fail and his team at Terrebonne Regional assessed. About 25% of the cases use two clips. Feldman, North Shore Hospital, Evanston, Medical Center, Houma, USA. ACCESS-Europe “The interesting thing is that you see the USA, coprincipal investigator of the EVEREST “Based on my experience treating patients Evalve has announced the start of enrolment in real-time haemodynamic effect of reducing trials. “The high-risk registry data in the func - with the MitraClip system during EVEREST II, I the ACCESS-Europe study, an observational regurgitation. Our patient’s blood pressure, tional mitral regurgitation patients demonstrate am eager to participate in the REALISM study,” study of the MitraClip system. The first patients which was between 90mmHg and 100mmHg, that these patients benefit substantially from the said Fail. “I often see patients who may be candi - were enrolled by the team led by Corrado as soon as we clipped the valve, would climb to MitraClip therapy,” said Feldman. “By expand - dates for the MitraClip therapy and I am glad Tamburino, Gian Paolo Ussia, Salvatore 130mmHg and 140mmHg.” ing the options available to these patients, clini - they now have an option to participate in the con - Scandura, and Sarah Magiafico at Ferrarotto A patient without major comorbidities would cal practice will change for the better when this tinuation of this landmark trial and potentially Hospital, Catania University, Italy. be able to go home on the following day after therapy is available in the USA.” benefit from this alternative treatment.” “ACCESS-Europe will provide valuable the procedure. “Our patient is being followed The EVEREST II study consists of a ran - The REALISM study is a prospective, multi - information regarding the use of the MitraClip carefully,” Baker said. Follow-up is being under - domised arm and a high-risk registry arm: centre, continued access registry of the EVER - system with respect to health economics and taken at one, three, six and 12 months. Baker
Randomised arm – Enrolment was successful - EST II study. The REALISM study consists of clinical care,” said Tamburino. “This data will said that the disadvantage is that not every ly completed in September 2008. This study two arms: a high risk arm and a non-high risk allow us to further understand the benefits of patient or valve is suitable for the procedure. arm compares the MitraClip procedure to the arm. Up to 300 patients will be enrolled in the the MitraClip therapy for patients who are not The percutaneous repair was based on an open current standard of care, mitral valve surgery. study at clinical sites in the USA. Patients will good candidates for surgery.” heart surgical technique introduced by Dr Ottavio To ensure unbiased results, participants were undergo 30-day, six-month and 12-month clini - The study will evaluate the MitraClip thera - Alfieri, Italy, which involves fastening the leaflets randomly assigned to either the MitraClip pro - cal follow-up. REALISM will collect new py in the continuum of care of patients with together where the valve leaks using suture. cedure or to surgery, in a 2:1 ratio. information regarding functional capacity fol - mitral regurgitation. Patients will be evaluated
High-risk registry arm – Enrolment was lowing treatment with the MitraClip device. at baseline through 12 months after enrolment. Device investigations completed in January 2008. This study arm “The REALISM study will allow patients Up to 300 patients will be enrolled in 20 cen - One-year data from the high-risk registry arm of was designed to evaluate the safety and effi - suffering from the effects of mitral regurgitation tres within the European Union. In addition, EVEREST II (Endovascular valve edge-to-edge cacy of the MitraClip in patients who are to continue to have access to the MitraClip ther - up to 200 patients will be enrolled in two repair study), presented in March at the 58th considered to have a high risk of not surviv - apy under a controlled protocol while data from comparator groups, one of which includes Annual Scientific Session of the American ing surgery. the EVEREST II trial are being finalised,” said medically-managed heart failure patients with College of Cardiology Scientific Sessions, in Evalve announced in February the start of Feldman. “This will also allow us to observe the mitral regurgitation and another with patients Orlando, USA, showed that percutaneous mitral enrolment in the REALISM (Real world expand - use of the MitraClip system under real-world who have undergone mitral valve surgery for valve repair for mitral regurgitation improves ed multicenter study of the MitraClip System) conditions, and will allow us to further study the problem. Antiplatelet Gene therapy offers hope for heart failure patients agent prasugrel CARDIOLOGISTS FROM the Saint groups received rAAV6 with the Louis University, USA, are partici - bARKct peptide, two groups receives CE mark pating in a clinical trial of gene ther - received rAAV6 with green fluores - apy to treat severe heart failure. If cent protein (GFP), and the last 1
reducing the relative risk of the successful, the treatment would be group received a saline treatment. combined endpoint of cardiovascu - the first to not only treat the symp - One of the bARKct groups and one lar death, nonfatal heart attack or toms of heart failure, but also of the GFP groups also received the nonfatal stroke by 19%. Prasugrel reverse the severity of the disease. betablocker metoprolol concurrently. also reduced the risk of stent-relat - “We are testing a new treatment Twelve weeks after receiving the ed clots by 50% compared with that appears to be able to improve treatment, the rats who received the clopidogrel. the pumping function of damaged bARKct had a significantly increased The risk of noncoronary artery heart muscle,” said Arthur Labovitz, left ventricular ejection fraction. The bypass graft major bleeding, principal investigator of the research Arthur Labovitz Walter Koch treatment also reversed the left ven - including fatal bleeding, was higher at Saint Louis. tricular deterioration and normalised in the prasugrel patients (2.2%) Thirteen centres in the world are procedure performed in a cardiac that generates a peptide called the neurohormonal status. Koch said compared with the clopidogrel participating in the CUPID catheterisation lab. Data from the bARKct, which was administered to that targeting the GRK2 enzyme with group (1.7%). Compared with the (Calcium up-regulation by percuta - first phase of the clinical trial, which hearts in combination with recombi - bARKct was sufficient to reverse overall study population, a higher neous administration of gene thera - tested the safety of Mydicar, were nant-adeno-associated virus serotype heart failure even without concomi - risk of serious bleeding among pra - py in cardiac diseases) trial. positive. 6 (rAAV6). bARKct works by tant metoprolol. The rats that sugrel patients was most evident in The research study will investigate “Gene therapy allows us the inhibiting the activation of G protein- received GFP or saline alone experi - three distinct patient populations whether Mydicar, a genetically-tar - potential of offering meaningful coupled receptor kinase 2 (GRK2). enced more deterioration of cardiac that are readily identifiable: geted enzyme replacement therapy, therapy for people who do not bene - GRK2 is a kinase that is increased function during the course of the patients who weighed less than can repair heart muscle that was fit from standard medical therapy in heart failure myocardium. study. This deterioration was pre - 60kg (132lbs), patients who were damaged by either a prior heart currently available,” said Dr Enhanced GRK enzymatic activity vented, but not reversed, with the 75 years of age or older and attack or cardiomyopathy by using Michael Lim, Saint Louis contributes to the deterioration of the concomitant metoprolol. patients who have had a prior tran - gene therapy to reprogramme the University and a co-investigator in heart in heart failure, according to “Our data show that betablockers sient ischaemic attack or stroke. cardiac muscle cells to work differ - the research study. “If the CUPID Walter J Koch, Thomas Jefferson and the bARKct peptide are compat - A 5mg maintenance dose is rec - ently. study is successful, it may revolu - University. Koch’s research team ible and can be given together,” ommended for patients who weigh “The therapy is geared toward tionise the way we treat patients carried out the study, which was led Koch said. “Although betablockers less than 60kg. Prasugrel is gener - correction of a basic underlying cel - with severe heart disease.” by Giuseppe Rengo. are effective at stopping the down - ally not recommended for use in lular deficit; in particular, the replen - “The theory is that by inhibiting ward progression of the disease, patients 75 years or older; if treat - ishment of a protein involved in cal - Success in an animal model this kinase, the heart will recover they do not reverse the damage ment is deemed necessary in this cium cycling, a key event in both Long-term gene therapy resulted in partially due to reversal of the desen - already done. That is where the age group, a 5mg maintenance dose contraction and relaxation of the improved cardiac function and sitisation of the b-adrenergic recep - bARKct gene therapy comes in.” should be prescribed. Patients with heart,” explained Paul Hauptman, reversed deterioration of the heart in tors,” Koch said. “The expression of In future trials in humans, the prior transient ischaemic attack or Saint Louis University and a coin - rats with heart failure, according to bARKct leads to a negative neuro - bARKct peptide will be administered stroke should not be treated with vestigator in the research study. a study conducted by researchers at hormonal feedback that prevents the with betablockers, which are the prasugrel. “This is a truly novel approach to Thomas Jefferson University’s heart from continuing on the down - standard treatment. However, Koch An analysis assessing the risk of treating heart failure and moves ther - Center for Translational Medicine, ward slope during heart failure. This said that if a pharmaceutical inhibitor major bleeding and the reduction in apeutics to a new level.” Philadelphia, USA. The study was was one novel finding of the study.” can be developed, then a new class of heart attacks found an overall bene - Mydicar is delivered directly to published online in Circulation . Koch and his colleagues used five drugs to treat heart failure could pos - fit favouring prasugrel. the heart through a simple outpatient The rats were treated with a gene groups of rats in their study. Two sibly even replace betablockers.

BIBA Publishing

4 Cardiovascular News International Issue 13 May 2009 ACC: Statins take centre stage again Statin use is centre stage again in the cardiology arena, as witnessed at the American College of Cardiology (ACC) 58th Annual Scientific Session, 29–31 March, Orlando, USA. This year’s meeting attracted 25,000 attendees (15,000 cardiac specialists), down by 4,000 from last year, attesting to the weakened economy. Reviewed below are three statin-related sessions, plus an exciting first-in-man study of a hypertension treatment and a study clarifying GPIIb/IIIa use in high-risk acute coronary syndrome (ACS) patients.

JUPITER: New analysis ACC panellist Harvey D White, Green Lane Hospital, Auckland, New Zealand. Although, In patients (men ≥50 years, women ≥60 years) when asked whether this is a class effect, without prior cardiovascular disease or dia - Glynn replied: “I have no idea.” At the ACC betes, the benefits of rosuvastatin extend to press conference, Ridker said it was likely a preventing venous thromboembolism (VTE), class effect. according to analysis of the JUPITER Ridker also said: “Until JUPITER, no spe - (Justification for the use of statins in preven - cific recommendations for therapy beyond tion: an intervention trial evaluating rosuvas - advice for diet, exercise, and smoking cessa - tatin). In the initial analysis of JUPITER, the tion could be made to such individuals. We primary endpoint of myocardial infarction, now know that statin therapy is highly effec - stroke, unstable angina/revascularisation, and tive at preventing heart attacks, strokes, and cardiovascular death was reduced 44% as all-cause mortality among this previously compared to placebo (p<.00001), with an NNT ignored patient group.” (number needed to treat to prevent one adverse event) of 25. Treating to new targets JUPITER included 17,802 patients with no The TNT (Treating to new targets) trial prior cardiovascular disease or diabetes, and showed intensive lipid lowering with atorvas - with LDL <130mg/dL and hsCRP (high sensi - tatin 80mg to significantly lower the incidence tivity C-reactive protein) ≥2mg/L. According of cardiovascular disease compared with ator - to lead investigator Paul Ridker, Brigham and vastatin 10mg in stable coronary heart disease Women’s Hospital, Boston, USA, “The patients aged 65 or older. That analysis, said JUPITER trial was specifically designed to Nanette K Wenger, Emory University School address whether statin therapy might be effec - of Medicine, Atlanta, USA, assessed time to tive in preventing major cardiovascular events first events. Patients in this population, howev - L Kristin Newby (first on the left) presented results of the EARLY ACS study among a population that does not qualify for er, often have a series of cardiovascular events. statin therapy because they already have LDL- To determine potential benefits over time of factors. Among those not reaching LDL-C C levels <130mg/dL (the treatment target in the higher statin dose, Wenger conducted a DYSIS goals, two-thirds had abnormal HDL-C and/or primary prevention), yet are at high risk due to posthoc analysis looking at the trial period “Many patients in Europe and Canada, the triglyceride levels (see table below). elevated levels of the inflammatory biomarker after first cardiovascular events. majority of whom are at high-risk for cardio - Commenting on the findings in an interview, hsCRP. In prior work from more than a dozen TNT investigators randomised 3,809 subjects vascular events, do not reach their LDL-C Gitt said: “There is a lot of space for improve - cohorts worldwide – including in the aged 65 and older to atorvastatin at either 10 or goals in spite of statin therapy.” This conclu - ment, either by increasing doses, or by adding Framingham Heart Study – those with elevated 80mg daily and followed them for a median of sion, voiced by Anselm K Gitt, University of ezetimibe or other nonstatin lipid-lowering levels of hsCRP have consistently been shown 4.9 years. The time-to-event analysis estimated Heidelberg, Germany, arose from the DYSIS drugs. We now have to encourage physicians to be at increased vascular risk, even if choles - treatment hazard ratios for first through fifth (Dyslipidemia international study), a study to treat to target rather than just insuring that terol levels are low.” cardiovascular events. Included events encom - examining more than 22,000 outpatients in the right drugs are being taken.” Venous and arterial thrombosis are both passed coronary heart disease death, nonfatal Europe and Canada consecutively treated for common, serious age-related events that often myocardial infarction, resuscitated cardiac dyslipidemia. The analysis revealed that a EARLY ACS co-occur and share some risk factors, noted arrest, revascularisation procedure, procedure- majority were not reaching lipid targets. Current guidelines in North America and Robert J Glynn, biostatistician at the Brigham related infarction or documented angina, cere - DYSIS was conducted at 2,987 centres, with Europe vary in their recommendations regard - and Women’s Hospital and Harvard Medical brovascular events (fatal or nonfatal stroke, most patients (73.6%) treated by primary care ing early vs. delayed provisional treatment with School. The need for a prospective randomised transient ischaemic attack), peripheral artery physicians. All patients were ≥45 years; all eptifibatide and other GPIIb/IIIa inhibitors in trial in VTE is borne out by the fact that venous disease, or hospitalisation with primary diagno - were currently receiving a statin and had docu - high-risk acute ACS patients. Results of thromboembolism observational and case-con - sis of congestive heart failure. mented fasting lipid profiles performed after EARLY ACS, according to L Kristin Newby, trol studies with statins have not always shown First events were reported among 1,130 sta - they had been receiving statins for at least Duke University Medical Center, Durham, reduced risk. Therefore, symptomatic venous ble coronary heart disease patients aged 65 three months. Investigators examined the USA, suggest that, as a general strategy, thromboembolism was included as a prespeci - years or older. The most commonly experienced prevalence of persistent lipid abnormalities delayed, provisional use of the GPIIb/IIIa fied secondary endpoint in JUPITER. Venous endpoint as a first event was angina (171 for according to ATP III risk profile criteria (CHD inhibitor eptifibatide is preferred over early use. thromboembolism events were classified as 80mg/180 for 10mg). Overall, coronary revas - or risk equivalent/2+ risk factors/0–1 risk fac - In the double-blind, controlled EARLY ACS “provoked” (occurring in the presence of trau - cularisation was most common (300 for tors). A large majority of patients (70%) were study, patients with high-risk non-ST segment ma, hospitalisation or surgery within three 80mg/437 for 10mg). Relative risk of a first car - in the highest risk group (n=15,365), with elevation myocardial infarction were ran - months before diagnosis – with no malignancy diovascular event was reduced by 23% about 19% and 11% in the 2+/0 –1 risk factor domised 1:1 to either early, routine eptifibatide diagnosed before or up to three months after (p<.0001) in the higher-dose group as compared groups, respectively. Most patients were (n=4,722) or placebo plus provisional eptifi - the VTE) or unprovoked. with the lower-dose group. The benefit was receiving simvastatin (47.7%) or atorvastatin batide (n=4,684) prepercutaneous coronary Fewer venous thromboembolisms were found for second through fifth events, although (28%). Nonstatin lipid therapies, such as eze - intervention procedures. Patients were treated reported in the rosuvastatin group than in the the difference between treatments at the fifth timibe, fibrates, nicotinic acid, and bile acid invasively within 12–96 hours of presentation, placebo group (34 vs. 60, 43% reduction, event was no longer statistically significant, pre - sequestrants, were taken by 13.5% of patients. with about 98% of patients undergoing cardiac p=.007). The reduction with rosuvastatin was sumably because of the small number of events. Investigators used ATP III LDL-C defini - catheterisation, about 60% percutaneous inter - significant, as well, for provoked venous “Treatment with atorvastatin 80mg contin - tions for “not at LDL-C goal” for the three risk vention procedures, ~13% having coronary thromboembolisms (48% reduction, p=.03), ued to reduce the risk of any cardiovascular groups as follows: ≥100/130/160mg/dL. For artery bypass graft surgery, and ~30% treated with a strong trend for unprovoked VTE (39% event over time compared with atorvastatin all groups, low HDL-C was defined as medically only. reduction, p=.09). The rate of pulmonary 10mg among patients 65 years or older,” <40/50mg/dL, and elevated triglycerides as The primary combined outcome occurred at embolism was similar between statin and Wenger concluded. She said further that the ≥150mg/dL. Among patients with total lipid 96 hours in 9.3% of those in the early strategy placebo (17 vs. 22, 23% reduction, p=.42), and data show that the benefits of long-term inten - profiles (n=19,196) in the highest risk catego - and in 10% of the delayed/provisional strategy, a deep vein thrombosis was significantly lower sive statin therapy are maintained after multi - ry, LDL-C did not reach target level in 43.3%, nonsignificant 8% reduction (p=.23). Reductions in the statin group (17 vs. 38, 55% reduction, ple cardiovascular events in this population. and in 35.7%/16.7% of those with 2+/0-1 risk in individual components were also nonsignifi - p=.004). Bleeding was similar for both groups, cant. The difference in the primary endpoint at with 258 events in the rosuvastatin group and DYSIS: Persistent lipid abnormalities by risk categories 30 days (12.5% early, 13.8% delayed, 11% 275 in the placebo group (p=.45). When VTE in patients with total lipid profile (n=19,196) reduction, p=.065) trended favourably for eptifi - and total mortality at 4.5 years were combined batide, but was not significant. At 30 days, the with the JUPITER primary endpoint of CHD or risk equiv. 2+ risk factors 0–1 risk factor death or recurrent infarction rate for the study myocardial infarction, stroke, unstable angi - n=13,503 (70.3%) n=3,522 (18.3%) n=2,171 (11.3%) group was 11.2% compared to 12.3% for the na/revascularisation, and cardiovascular death, delayed provisional group (p=.079). there were 163 fewer events in the statin arm LDL-C not at goal (%) 43.4 35.7 16.7 The study group patients had a significant (320 rosuvastatin, 483 placebo, p<.00001). Non-HDL-C not at goal (%) 1 71.1 56.8 35.8 increase in bleeding, with 118 patients experi - The NNT was 18. Low HDL-C (%) 35.9 33.6 1.4 encing a TIMI major bleeding event, compared Glynn concluded that adding prevention of Elevated TG (%) 40.9 41.5 20.7 to 83 in the delayed provisional group VTE and death to the rosuvastatin treatment High TC (%) 2 67.4 70.2 69.5 (p=.015). Investigators reported a 7.6% vs. target “increases the estimated benefit of 5.1% rate of moderate or severe bleeding statin use.” (1) ≥130mg/dL (CHD/CHD equivalent), ≥160mg/dL (2+ RF), ≥190mg/dL (0–1 RF) (p<.001) in the early group as compared to the “I’m impressed with the NNT and with the (2) ≥155mg/dL (CHD/CHD equivalent), ≥175mg/dL (2+ RF), ≥190mg/dL (0 –1 RF) delayed provisional group. Red blood cell apparent early separation of curves,” stated transfusions were required in 8.6% of 6

BIBA Publishing

6 Cardiovascular News International Issue 13 May 2009

nerves, which lie mostly within in the adventi - angiograms (in 18 patients 14–30 days) or in ACC: Statins take tia of the renal artery wall, Krum said, have magnetic resonance angiography (in 14 Five-in-one polypill been recognised as seminal in the initiation patients at six months). centre stage again and maintenance of systemic hypertension. At six-month follow-up, data available in 25 Explaining his approach as one similar to that patients showed eGFR to be improved ≥20% may halve risk 4
patients in the study group vs. 6.7% of patients used in coronary artery catheterisation, Krum in six patients, and reduced ≥20% in one in the delayed provisional group (p=.001). stated: “In renal artery denervation, the patient (associated with substantial blood pres - of heart disease “EARLY ACS results do not support a strate - catheter is inserted via the femoral artery, and sure decrease and reduced use of ARB and HEALTHY INDIVIDUALS may be able to gy of early, routine eptifibatide use in this pop - when within the renal artery, the operator diuretic). cut their risk of cardiovascular disease by ulation,” Newby said. She pointed out, howev - sends out radio waves which denervate the Systolic blood pressure reductions of ≥10 50 –60% by taking a single pill that com - er, that “It may be possible, looking at this sympathetic nerves without damaging the lin - mmHg were reported in 87% of patients (see bines three blood pressure lowering drugs at balance of bleeding and risk, to identify groups ing of the vessel. In all, five or six radiofre - table below). low doses, a statin, and aspirin with no addi - with higher risk for ischaemic events and low quency signals are applied.” Analysis showed also, among 12 patients tional side effects, according to research bleeding risk who are potentially highly likely Inclusion in the trial required that patients undergoing ambulatory blood pressure moni - presented at the American College of to benefit from early routine eptifibatide use. had office-seated systolic blood pressure of toring (ABPM) at baseline and >30 days post Cardiology’s 58th annual scientific session, We have some hints that high-risk patients who ≥160mmHg despite 3+ antihypertensive med - treatment, that changes in systolic office-seated in March, Orlando, USA. are troponin positive might be a target group.” ications (including one diuretic) or confirmed blood pressure correlated with systolic ABPM The TIPS (Indian Polycap Study) Ongoing analyses, she added, may identify intolerance to medications, with estimated changes. The number of non or reverse-dippers enrolled 2,053 participants. During the such subgroups. glomerular filtration rate (eGFR) of was reduced from 67% to 33% from baseline to three-month study, researchers compared ≥45mL/min/1.73m 2. Among 50 patients select - post intervention. While the mean number of the impact of the polypill and eight other Catheter-based renal ed at five centres in Australia and Europe, five antihypertensive medications remained pharmacologic therapies on blood pressure, sympathetic denervation were excluded for inappropriate anatomy and unchanged from baseline to latest follow-up, blood cholesterol levels and heart rate, A first-in-man trial of therapeutic renal sympa - 45 were treated with catheter-based renal den - three patients required reduction of medications among other measures. The combination thetic denervation appears to confirm the role ervation. Mean age was 58 years (44% female). after normalisation of their blood pressure. pill (Polycap), which includes low doses of of renal sympathetic nerves in resistant hyper - The mean number of antihypertensive medica - Among the five untreated patients, mean thiazide (12.5mg/day), atenolol (50mg/day), tension and to support it as a potential thera - tions was 4.7 (±1.5) (ACE/ARB 96%; rises in systolic blood pressure were 1 and ramipril (5mg/day), simvastatin peutic strategy. The trial of catheter-based renal betablocker 76%; calcium channel blocker 10mmHg at one and three months, respectively. (20mg/day), and aspirin (100mg/day), sig - sympathetic denervation, said Henry Krum, 69%; vasodilator 18%; diuretic 96%). “The critical thing was that, at least after 12 nificantly reduces LDL cholesterol, blood Alfred Heart Centre, The Alfred Hospital, Mean procedure time was 38 minutes. Krum months, the benefits persisted,” Krum said. pressure and platelet aggregability. Melbourne, Australia, evaluated the strategy’s noted that pain associated with ablation was “One of the questions asked about the proce - “Before this study, there were no data vascular safety, renal safety, evidence of renal managed via intravenous narcotics and/or dure is, will the nerves regrow and as a result, about whether it was even possible to put denervation and effects on blood pressure. sedative, and that pain did not persist beyond the benefit starts to disappear over time? We five active ingredients into a single pill, in An estimated 30–40% of the adult popula - the radiofrequency energy application. can’t answer that question beyond 12 months, terms of feasibility, the bioavailability of dif - tion in the developed world has hypertension. Complications occurred in two patients: one but at least at 12 months, the benefits persisted ferent agents and possible interactions, and Despite numerous safe and effective pharma - renal artery dissection and one femoral and indeed, if anything, seemed greater.” we found that it works. And side effects with cologic therapies, only about 50% of these pseudoaneurysm. Both were treated without Krum concluded, “Therapeutic renal sympa - the polypill were no different than when tak - patients achieve blood pressure guideline tar - further sequelae. No long-term vascular com - thetic denervation produced predictable, sig - ing one or two medications,” said Salim gets. Renal sympathetic efferent and afferent plications were observed in follow-up nificant, and sustained reductions in blood Yusuf, McMaster University and Hamilton pressure in patients with resistant hyperten - Health Sciences, Hamilton, Canada, cochair Catheter-based renal sympathetic denervation sion.” He said further that the results appear and principal investigator of the study. both to confirm the important role of renal Participants were randomised to the Mean blood pressure reduction (mmHg) sympathetic nerves in resistant hypertension Polycap (n=400) group or to one of eight and to suggest that renal sympathetic denerva - other study arms, each with about 200 indi - Follow-up 1 month 3 months 6 months 9 months 12 months tion could be of therapeutic benefit in this viduals, which included aspirin alone, sim - Systolic -14* -21* -22* -24* -27* patient population. vastatin alone, hydrochlorthiazide alone, Diastolic -10* -10* -11* -11* -17** Prospective randomised clinical trials are three combinations of the two blood pres - *p<.001/**p=.02 beginning in 2009. Additional trials in heart fail - sure lowering drugs, three blood pressure ure and chronic kidney disease are anticipated. lowering drugs alone, and an arm with three blood pressure lowering drugs plus aspirin. Patients were recruited from 50 centres in 80% of the older adult population may now India between March 2007 and August qualify for statin therapy. 2008. The mean age of the participants was From here to JUPITER A second aim of our study was to determine 54 years, one-third had diabetes, mean base - whether the JUPITER-indicated group could be line blood pressure was 134/85mmHg, distinguished from those with low hsCRP and mean cholesterol was 180mg/dL, HDL no indication for statin therapy and from those 44mg/dL, and LDL 117mg/dL. The polycap who qualify for statin therapy based on current was well tolerated and there was no evi - ERICA SPATZ NCEP/ATPIII criteria. We found that compared dence of problems with increasing number to those who would continue to have no indica - of active components in the pill. tion for statin therapy, the JUPITER-indicated group was more likely to be older, female, Promising results COMMENT & ANALYSIS obese, have hypertension, and the metabolic Compared to groups not receiving blood syndrome. In contrast, JUPITER-indicated sub - pressure lowering agents, the polycap PRIMARY PREVENTION STRATEGIES for JUPITER study population, limiting our analysis jects shared several characteristics with the reduced systolic pressure by 7.4mmHg and cardiovascular disease have the potential to to men 50 years and older and women 60 years NCEP/ATPIII-indicated group, including diastolic pressure by 5.6mmHg; this was impact a sizeable portion of the population. and older. We then determined who among this sociodemographic characteristics, smoking, similar to when three blood pressure lower - Thus, when findings from the JUPITER group already qualified for statin therapy based abdominal obesity, and hypertension. These ing drugs were used, with or without aspirin. (Justification for the use of statins in primary upon the National Cholesterol Education findings may help us in guiding future screen - Blood pressure reductions increased with the prevention: an intervention trial evaluating Panel/Adult Treatment Panel (NCEP/ATP) III ing efforts that target populations more likely number of pressure lowering drugs used rosuvastatin) revealed that older adults without criteria. In the remaining group, we used LDL-C to have elevated hsCRP levels, and thus an (2.2/1.3mmHg with one drug, 4.7/3.6mmHg known cardiovascular disease, at-goal low-den - and hsCRP levels to determine eligibility for increased risk for cardiovascular disease. with two drugs, and 6.3/4.5mmHg with three sity lipoprotein cholesterol (LDL-C), and ele - statin therapy based on JUPITER’s findings, In summary, targeting elevated hsCRP levels drugs). While the effects of the polypill were vated levels of high sensitivity C-reactive pro - specifically LDL-C <130mg/dL and hsCRP for risk-reduction therapy has the potential to lower than projected by previous investiga - tein (hsCRP) had decreased cardiovascular >2mg/L. We then compared the demographic impact approximately 20% of the adult popula - tors (20/11mmHg reduction), this is likely events when treated with rosuvastatin, as com - and clinical characteristics of individuals in the tion of men aged >50 years and women aged because most participants were not hyper - pared to placebo, many questions arose about three groups stratified by statin eligibility: >60 years who would otherwise not be recom - tensive. Still, blood pressure reductions its adoption into clinical practice. Current NCEP/ATPIII-indicated group, JUPITER-indi - mended for a statin medication. Expanding rec - among this group could theoretically lead to guidelines for statin use focus on patients with cated group, and those who remained without ommendations for statin therapy will undoubt - about a 24% risk reduction in coronary heart elevated LDL-C levels. However, if recom - any indication for statin therapy. edly widen the evidence-practice gap, posing disease and 33% risk reduction in strokes in mendations for statin therapy are to be expand - The results were striking. Approximately increasing challenges for health providers and those with average blood pressure levels, ed beyond those with high cholesterol levels, a 58% of the middle-aged to older adult popula - systems already struggling to reach individuals according to Yusuf. Polycap reduced LDL critical next step is to understand the size and tion had an indication for statin therapy based with an NCEP/ATPIII recommendation for by .70 mmol/L, which was slightly less than clinical characteristics of the population poten - upon NCEP/ATPIII criteria, though less than statin therapy. Additionally, it is unclear what is that with simvastatin alone (.83 mmol/L; tially impacted. half of this group was actually receiving treat - the most cost-effective strategy for identifying p<.04); both of which were greater than Our group sought to estimate the size of and ment. An additional 19.2% of the population asymptomatic patients with elevated hsCRP groups without simvastatin (p<.001). The describe this new population for whom statin would qualify for statins based on JUPITER’s levels. However, the JUPITER trial offers the reductions in heart rate with polycap (7 therapy may now be recommended, based on findings, including 8.1 million with an LDL-C opportunity to advance therapeutic strategies to beats/min) and other arms using atenolol (7 JUPITER’s findings. Using data from the <130mg/dL and hsCRP >2mg/L, and an addi - prevent adverse cardiovascular outcomes. beats/min) were similar; and both were National Health and Nutrition Examination tional 3.1 million individuals with LDL-C greater than that in arms without atenolol Survey (NHANES), a nationally representative between 130–160mg/dL and hsCRP >2mg/L, a Dr Erica Spatz, internist, is a fellow at (p<.001). probability sample of the community-residing group for whom JUPITER’s recommendations Robert Wood Johnson Clinical Scholar pro - The study was sponsored by Cadila population in the USA, we replicated the might reasonably be extended. Thus, almost gramme, Yale School of Medicine, USA. Pharmaceuticals, India.

BIBA Publishing

8 Cardiovascular News International Issue 13 May 2009

revascularisation. Patients in the angiogra - nary artery disease. The results of the FAME phy-guided group underwent stenting of all trial emphasise the superiority of “functional The value of FAME lesions of at least 50% diameter stenosis that complete revascularisation” to “angiographi - were indicated prior to randomisation to cally complete revascularisation”. Of note, require PCI based on angiographic appear - the angiography guided complete revasculari - ance and clinical data. Patients assigned to sation of patients with symptomatic multives - the fractional flow reserve group underwent sel coronary artery disease recently failed to ASCAN WARNHOLTZ FFR measurement of all indicated lesions be noninferior to surgical treatment by aorto - based on the same criteria as in the angiogra - coronary bypass grafting in the SYNTAX 4 phy group but received PCI only in lesions trial. Interestingly, analysing major adverse COMMENT & ANALYSIS with fractional flow reserve of .8 or less. cardiac and cerebrovascular events of a com - Percutaneous coronary intervention was per - parable subset of patients of the FFR guided THE RECENTLY PUBLISHED results of the the applied cut-off value of .75 or .8 for formed exclusively with drug-eluting stents. treatment arm of the FAME trial with the sur - COURAGE 1 trial have questioned the proven ischaemia. The controlled pressure Approximately one-third of the patients pre - gical arm of the SYNTAX trial has revealed advances and benefits of percutaneous coro - wire pullback allows a clear discrimination sented an acute coronary syndrome. Patients almost identical major adverse cardiac and nary intervention (PCI). Since the publication of ischaemia-inducing lesions from nonis - with ST-segment elevation within the last five cerebrovascular events rates. Therefore, frac - of this trial, the interventional community has chaemic lesions in a multiple stenosed coro - days were excluded. A mean of close to three tional flow reserve guidance of interventional responded globally with more defensive nary artery. Furthermore, the gradual lesions per patient were a priori indicated in treatment may abrogate the disequilibrium of strategies and a slight reduction of the num - increase in the ratio of distal to aortal pres - each group. Fractional flow reserve measure - PCI compared to bypass surgery in patients ber of performed PCI. However, subanalyses sure after pullback of the pressure wire in a ments identified close to two lesions as being with multivessel disease. My recommenda - have revealed that patients with a significant diffusely diseased coronary artery provides haemodynamically significant. Accordingly, a tion is to conduct a prospective clinical trial extent of stress-induced myocardial evidence that this vessel will not benefit mean of 1.9 stents were implanted in the FFR to compare “functional complete revasculari - ischaemia still benefit from the percutaneous from revascularisation despite proven group, while 2.7 stents were used in the sation” by FFR guided treatment with “com - coronary intervention of an ischaemia-induc - ischaemia. Despite the advantages of the angiography group. Procedure time did not plete revascularisation” by bypass surgery in ing coronary stenosis. Therefore, the results FFR test, its invasive character still precludes differ between groups. The volume of con - patients with multivessel coronary disease to of the COURAGE trial do not argue against its use as a standard test for myocardial trast agent used was lower in the fractional retest the comparability of the interventional the value of percutaneous coronary interven - ischaemia in all patients with suspected coro - flow reserve group. After one year of follow- vs. surgical approach in these patients. tion but emphasise the importance of obtain - nary artery disease. Currently, fractional flow up, the composite endpoint of death, myocar - ing evidence of myocardial ischaemia prior to reserve should be considered in patients with dial infarction, and the need for revascularisa - Ascan Warnholtz is Assistant Professor of PCI. Among the noninvasive stress tests a clinical indication for a coronary angiogra - tion was significantly reduced in the FFR cardiology and Head of the Emergency available, electrocardiographic or nuclear phy and intermediate coronary artery group compared to the angiography group. Department and Chest Pain Unit at the stress tests lack sufficient specificity and/or stenoses of unknown significance. It pro - The reduction of major adverse cardiac University of Mainz, Germany. sensitivity, as well as spatial resolution. This vides also valuable information if discrepan - events was predominantly caused by a reduc - is especially true for multivessel coronary cies between the angiographical and nonin - tion of early myocardial infarction and late References 1. Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron disease. Stress echocardiography is mostly vasive pretest findings and/or the clinical reduction of required revascularisation proce - DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris applied to enhance specificity, sensitivity, and picture occur during the coronary angiogra - dures. The frequency of anginal attacks and CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, spatial resolution. The accuracy of stress phy. Instead of taking the patient off the cath the concomitant use of antianginal medication Berman DS, Mancini GB, Weintraub WS; COURAGE Trial echocardiography is highly dependent on the lab table for noninvasive stress tests, FFR were comparable in both groups. Based on Research Group. Optimal medical therapy with or with - out PCI for stable coronary disease. N Engl J Med . skills of the sonographer, it is time consum - can answer questions right away. the American market, material costs were 2007;356(15):1503-16. ing, and, in some settings, not cost effective; The prognostic value of fractional flow reduced in the FFR group compared to the 2. Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van't Veer M, Bär F, Hoorntje J, Koolen J, Wijns a major drawback. reserve measurement was ascertained in sin - angiography group. W, de Bruyne B. Percutaneous coronary intervention of The determination of myocardial fractional gle-vessel coronary disease by the DEFER 2 Taken together, the FAME trial adds valu - functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol .;49(21):2105-11. flow reserve (FFR) by using a coronary pres - trial. The recently published FAME 3 trial has able prognostic information for patients with 3. Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, sure guidewire is an invasive test to detect evaluated the prognostic significance of FFR multivessel disease. At least, for the selected Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study inducible myocardial ischaemia. This method in patients with coronary multivessel disease. patient population investigated in the FAME Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J is validated, and increasingly applied for In a multicentre trial with 20 participating trial, the FFR guided approach is preferable Med . 2009;360(3):213-24. more than a decade. The spatial resolution of sites throughout the USA and Europe, 1,005 to the angiography guided approach. It may 4. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. Serruys FFR, its reproducibility and independence of patients with multivessel coronary artery dis - not only save patients’ lives by reducing PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den Brand M, Bass EJ, the patient’s haemodynamics are unrivalled ease were randomised to either angiographi - major adverse cardiac events rates, but also Van Dyck N, Leadley K, Dawkins KD, Mohr FW; SYNTAX by other stress tests. It is characterised by cally driven percutaneous coronary interven - alleviate the healthcare-related economic bur - Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery high specificity and sensitivity depending on tion or fractional flow reserve guided den of the interventional treatment of coro - disease. N Engl J Med . 2009;360(10):961-72.

The landmark FAME (Fractional flow reserve vs. angiography in mul - Fractional flow Wireless integrated FFR solution is launched tivessel evaluation) trial, published ST JUDE MEDICAL and GE cathlab workflow and ease of use. severity of coronary lesions, as in the 15 January issue of the New Healthcare have announced the “The PressureWire Aeris system measured by FFR, is documented England Journal of Medicine , reserve on all worldwide commercial launch of the represents a true paradigm shift in together with other procedural data demonstrated a statistically signifi - first fully integrated wireless solu - our thinking about the accessibility and angiographic imagery, creating cant 30% difference in major major systems tion for the measurement of fraction - of FFR,” said Dr Augusto Pichard, a more complete patient record. adverse cardiac events such as al flow reserve (FFR). The new FFR Washington Hospital death, myocardial infarction and VOLCANO ANNOUNCED in solution, seamlessly integrated into Center, Washington, repeat revascularisation. The March, at the American College of existing cathlab infrastructure, will DC, USA. “The randomised, prospective, multi - Cardiology meeting, Orlando, USA, enable physicians and cathlab staff integration with our centre trial looked at 1,005 the availability of its integrated frac - immediate access to FFR measure - existing GE haemo - patients with multivessel coro - tional flow reserve (FFR) technolo - ment without time-consuming setup. dynamic recording nary artery disease 12 months gy on all major cardiovascular X-ray The solution is based on the system means that after receiving a stent and systems. PressureWire Aeris technology and traditional limita - compared outcomes for Volcano’s integrated fractional FFR upgrade package available for tions of FFR meas - patients whose treatment was flow reserve technology can be pur - the XT and XTi system configura - urements, including guided by FFR to those whose chased as part of its s5i system, tions of GE’s Mac-Lab haemody - utilising a stand - treatment was guided only by offering clinicians access to namic recording system, a system alone machine for angiography. intravascular ultrasound and FFR at used to record and display physio - calculation, are The FAME study, in which the patient bedside. Volcano has logical parameters in the coronary removed.” pressure guidewires from Radi relationships with each of the major cathlab. PressureWire Aeris was With all FFR Medical Systems were cardiovascular X-ray companies to developed and marketed by Radi results integrated exclusively used, also showed facilitate the installation of the s5i Medical Systems, which was into the existing physiological infor - that FFR measurement is cost- with integrated fractional flow acquired in December 2008 by St mation archive, this new solution is saving and does not add time to reserve in any cath lab. Jude Medical, and is now part of the also the only system on the market the procedure. Volcano said it experienced an company’s Cardiovascular Division. where the haemody - FFR growth of 36% in the fourth The Mac-Lab FFR upgrade utilises namic quarter 2008 vs. fourth quarter 2007 existing cath lab infrastructure, and that physicians are increasingly including screens, input mod - relying on FFR to help guide percu - ules and controls, and taneous coronary intervention together with the procedures. PressureWire Volcano’s integrated s5i Aeris technology was on display at the 2009 forms a seamless - ACC meeting in Orlando at ly integrated FFR the company’s booth, as well measurement sys - as in the booths of GE, Philips, tem for greatly improved Siemens, and Toshiba. PressureWire Certus and RadiAnalize Xpress BIBA Publishing

10 Cardiovascular News International Issue 13 May 2009

Erasmus University Medical Center, Rotterdam, The Netherlands, and Fred Mohr, SYNTAX analysis: Stents are cheaper University of Leipzig, Germany, set out to compare bypass grafting and percutaneous intervention using Taxus Express2 paclitaxel- eluting stent (Boston Scientific) to investigate than bypass in low-risk patients whether the situation has changed. The find - ings of the SYNTAX were first presented at For patients with severe coronary artery disease, bypass surgery may hold an edge over stenting in clinical outcomes. But when the European Society of Cardiology 2008 quality of life and economics are considered, percutaneous coronary intervention (PCI) gains the upper hand in straightforward and meeting in Munich, Germany. intermediate cases, while bypass surgery is the best choice for those with the most complex coronary anatomy, according to The trial results at 12 months demonstrated no research presented during the i2 Summit at the American College of Cardiology’s 58th Annual Scientific Sessions, Orlando, USA. overall statistically significant differences between PCI and bypass graft in rates of death A NEW REPORT from the SYNTAX vessel or left main coronary disease, percuta - or infarction, although percutaneous intervention (Synergy between PCI with Taxus and cardiac neous coronary intervention led to better quali - patients were more likely to require a repeat surgery) trial shows that the advantages of ty-adjusted life expectancy than coronary artery revascularisation than were surgery patients. bypass surgery are less obvious once quality bypass graft and lower healthcare costs. “SYNTAX has provided the medical com - of life and economic data are included in the Findings were similar for patients with disease munity with critical information on the man - analysis. Instead, the complexity of coronary of intermediate complexity. However, for agement of patients with advanced and com - artery disease becomes a major factor in deter - patients with complex three-vessel disease, plex coronary artery disease,” said Ted mining whether stenting or surgery is the pre - quality-adjusted life expectancy was better with Feldman, NorthShore University ferred treatment. bypass graft, while overall costs at one year HealthSystem in Evanston, USA, a lead inves - “Clinicians, patients, guideline issuers and were nearly identical for the two procedures. tigator on the trial. “While CABG may still be payers will find this information helpful in “The most important message is that there is the preferred treatment in many patients with making clinical decisions, as well as in setting no single answer. The relative cost-effective - complicated disease, some patients may now treatment priorities,” said David J Cohen, ness of PCI and coronary artery bypass graft be candidates for the less-invasive alternative Saint-Luke’s Mid America Heart Institute and for left main and three-vessel disease depends offered by stents. These data will assist cardi - University of Missouri, USA. “From a patient’s strongly on the complexity of underlying coro - ologists in making treatment therapy decisions perspective, quality of life differences are very nary disease,” Cohen said. “It is also important for these patients.” important to consider. Similarly, given current to note that our analysis applies only to the The final one-year results published showed constraints within the healthcare system, evi - USA healthcare system. Given differences in similar safety for the two randomised groups, dence that one approach is less costly could treatment patterns and resource costs, the spe - with a combined rate of all-cause death, also be incorporated into treatment guidelines.” cific balance of costs and effectiveness may be stroke, and myocardial infarction of 7.6% for The main SYNTAX trial enrolled 1,800 very different in other countries.” percutaneous coronary intervention and 7.7% patients with a build-up of cholesterol plaque in Five-year follow-up is planned for all for bypass surgery (p=.98). The rate of stroke either three coronary arteries or the critically Patrick Serruys patients in the SYNTAX trial. itself was significantly lower for percutaneous important left main coronary artery, randomly intervention (.6% for PCI as compared to assigning 897 to coronary artery bypass graft - one year of follow-up, although chest pain relief Bypass surgery for sickest patients 2.2% for bypass surgery, p=.003). Overall 12- ing and 903 to percutaneous coronary interven - was slightly better with bypass graft. In the The SYNTAX study, published in the 5 March month all-cause death, stroke, infarction and tion with drug-eluting stents. At the one-year USA, surgery initially cost about US$6,000 (or 2009 edition of the New England Journal of repeat revascularisation, however, were signif - mark, rates of death, heart attack or stroke were about 25%) more than angioplasty, reflecting Medicine , concluded that coronary artery icantly higher for percutaneous intervention similar for the angioplasty and bypass graft higher hospital costs and much higher physician bypass grafting should remain the standard of (17.8% vs. 12.4%, p=.002), due to more repeat groups, while the number of repeat heart proce - fees. However, angioplasty added approximate - care for patients with three-vessel or left main revascularisation in the PCI arm (13.5% vs. dures was significantly higher in the percuta - ly US$2,500 in follow-up costs over the next coronary artery disease, since the use of bypass 5.9%, p=.001). Most repeat revascularisations neous coronary intervention group. year, mostly because of additional heart proce - graft, as compared with PCI, resulted in lower in the percutaneous coronary intervention arm, The new study set out to determine whether dures and the need for long-term anticlotting rates of the combined endpoint of major adverse however, were performed by additional angio - there were differences in the quality of life with medication. cardiac or cerebrovascular events at one year. plasty, with only 2.8% of PCI patients ulti - the two procedures. Researchers measured not A formal cost-effectiveness analysis found The study, led jointly by Patrick Serruys, mately requiring bypass surgery. only overall quality of life but also the impact that, for the population as a whole, the clinical of a patient’s heart disease on symptoms, phys - benefits of bypass graft did not justify its high - ical limitations, pain, vitality and other factors. er cost at one year. However, the complexity of “The most important message is that there is no In addition, they collected economic data coronary disease – determined by such factors single answer. The relative cost-effectiveness of throughout the study on cardiovascular proce - as where the plaque was located, the number of dures, hospitalisations, outpatient testing, lesions to treat, the length of lesions and PCI and coronary artery bypass graft depends physician visits, and medications. whether they were calcified or layered with They found that both stenting and bypass fragile blood clots – had a substantial influence strongly on the complexity of underlying coronary graft improved the overall quality of life over on cost-effectiveness. In straightforward three- disease.” David J Cohen, USA

opment and new clinical trial out - and bare metal stent prices were stable comes have been the three major over the fourth quarter 2008 – BIBA Research’s fourth quarter 2008 report drivers of the drug-eluting stent pene - although the exchange rate US tration recovery across Western Dollar/Euro and US Dollar/Pound confirms recovery of drug-eluting stent use Europe in the past 14 months, the Sterling had a considerable impact on report says. pricing. Spain and the UK were THE NUMBER of percutaneous percutaneous coronary intervention since the previous quarter, pushing Germany and France the countries with the high - coronary transluminal angioplasty trends in Western Europe from BIBA the stent-per-procedure ratio in recorded the highest 195,611 est and the lowest aver - (PTCA) procedures performed in Research. The report collected and Western Europe up to the 1:1.29 level over-the-quarter percutaneous age bare metal stent Western Europe in the time frame elaborated data from a sample of in the fourth quarter. The stent-per- drug-eluting stent coronary transluminal price, respectively, 1 October to 31 December 2008 was approximately 250 hospitals across procedure ratio had been measured at penetration rate angioplasties were with a brand price measured at 195,611 – a 1.4% Western Europe. 1:1.26 in the same time frame one increase (+1.1%), performed in Western measured within the decrease since the third quarter and According to the report, procedures year earlier. The overall stent market followed by The Europe between October 1,200 range. UK 2.8% lower than the fourth quarter with a stent accounted for 88.8% of size has decreased by .6% compared Netherlands (+1%) and December 2008 – and Germany were one year earlier. This is one of the the total number of PCTAs. The stent to the same period in 2007. and the UK (+.9%). 1.4% less than in the the countries with the main findings of the latest report on market size has increased by .7% The report says that Germany All the other European third quarter. lowest prices in the drug- remained the Western European mar - countries remained stable eluting€stent segment, ket with the highest procedure-per- or grew at a conservative rate. whereas Spain, France, and Italy capita ratio, followed by Italy, The drug-eluting stent market size have recorded some of the highest Sweden, Switzerland, and France. At was measured at approximately prices. The maximum price variation the opposite end, Spain and the UK 130,400 units in the fourth quarter within brands across Western Europe recorded two of the lowest rates. 2008, meaning a >US$202 million in the fourth quarter was measured at turnover. The annual turnover figure approximately 1,800. Drug-eluting stent penetration rate for the drug-eluting stent market was The overall market size for The drug-eluting stent penetration measured at 516,000 units or coronary balloons was measured at rate was measured at 51.6% in US$803 million. the 254,000-unit level in the fourth Western Europe: this represents the Germany, Italy, and France were quarter, meanin€g just a .9% drop over fifth consecutive increase since the the three largest European markets the previous quarter. Guiding third quarter 2007. Cardiologists have for the number of procedures, stent catheters usage was at approximately regained confidence in drug-eluting usage and turnover. 343,000 units in the fourth quarter stent-based therapies since the late- 2008. Guide wires usage was stable thrombosis episodes two years ago. A Device pricing over the previous quarter at drop in average price, product devel - The report highlights that drug-eluting approximately 366,000 units.

BIBA Publishing

12 Cardiovascular News International Issue 13 May 2009

News in brief Two-year results of bioabsorbable Taxus and Cypher safe A study published in the Journal of the American College of Cardiology concluded that the implantation of either paclitaxel- or drug-eluting stent published sirolimus-eluting stents in unprotected left main coronary artery lesions is safe and A n analysis published on 12 March, 2009 in The Lancet , from the ABSORB clinical trial, demonstrated that Abbott’s effective, and these stents provide compara - bioabsorbable drug-eluting stent, currently in development, successfully treated coronary artery disease and was absorbed ble outcomes. Results of the ISAR-LEFT MAIN trial were reported at the into the walls of treated arteries within two years. Transcatheter Cardiovascular Therapeutics meeting last year by Julinda Mehilli, THE FOLLOW-UP DATA were originally Deutsches Herzzentrum, Munich, Germany. reported in October 2008 at the Transcatheter In this randomised study, 607 patients Cardiovascular Therapeutics meeting. Abbott were enrolled: 302 to Taxus (Boston has announced the initiation of the next phase Scientific) and 305 to Cypher (Cordis). At one year the incidence of death, infarction, of the ABSORB trial to evaluate the safety or target lesion revascularisation was 13.6% and performance of the device. with Taxus and 15.8% with Cypher (p=.44). The two-year data also demonstrated that One patient in the Taxus group and two after the bioabsorbable device was absorbed, patients in the Cypher group experienced the treated blood vessels appeared to move definite stent thrombosis (p=.57). Mortality and function similar to unstented arteries. at two years was 10.7% in the Taxus and “Abbott’s bioabsorbable drug-eluting stent 8.7% in the Cypher group (p=.64). leaves behind a vessel that expands and con - Angiographic restenosis was 16% for Taxus tracts in a manner similar to a vessel that has and 19.4% for Cypher (p=.30). never been stented, which could be an advan - “Excellent” haemodynamic support tage over permanent metal-based stent Results from the PROTECT I trial evaluating implants,” said Patrick W Serruys, Erasmus the feasibility and effectiveness of the University Hospital, Rotterdam, The Abiomed’s Impella 2.5 circulatory assist Netherlands, lead author in The Lancet and device in high-risk percutaneous coronary coprincipal investigator of the first phase of intervention procedures were published in the ABSORB trial. “This bioabsorbable device the February issue of the JACC has the potential to provide optimal vessel Cardiovascular Interventions . scaffolding and drug delivery capability over The PROTECT I study concluded that “The the crucial first several months after a stenting Impella 2.5 system is safe, easy to use, and procedure while avoiding the long-term provides excellent haemodynamic support during high-risk percutaneous coronary restrictions of metallic stents.” intervention.” Results The trial enrolled 20 patients at seven centres between July 2006 and April 2007. The ABSORB trial is the world’s first clinical Eligible patients had left ventricular ejection trial evaluating a fully bioabsorbable drug- fraction of less than 35% and were required eluting coronary stent, and advanced imaging to undergo percutaneous intervention on methods were used to assess patient out - either an unprotected left main coronary comes. As published in The Lancet , the first artery or the last patent coronary conduit. phase of the ABSORB trial demonstrated the Abiomed is conducting two pivotal stud - following results: ies in the USA comparing the Impella 2.5 to John Ormiston the intra-aortic balloon pump.
A zero per cent rate of stent thrombosis for all patients out to two years of follow-up; Ormiston, Mercy Hospital, Auckland, New Switzerland. Key endpoints of the study
No new major adverse cardiac events (any Zealand, principal investigator in the first include assessments of safety – major adverse event that resulted in retreatment of the phase of the ABSORB trial. “With no rigid cardiac events and stent thrombosis rates – at treated artery lesion, heart attack, or cardiac stent remaining, vasomotion was restored, 30 days, six, nine, and 18 months, and one death) between six months and two years. and the artery appeared to behave like a nor - and two years, with additional annual clinical At two years, the bioabsorbable device mal artery. Who would want a permanent follow-up for up to five years, as well as an demonstrated a major adverse cardiac device if a temporary one may do the job and assessment of the acute performance of the events rate of 3.6% (one patient); then disappear?” stent, including successful deployment of the
Bioabsorption of the stent at two years after Abbott’s bioabsorbable everolimus-eluting device. Other key endpoints of the study implantation, as confirmed by an assess - coronary device is made of polylactic acid, a include imaging assessments by angiography, ment of the stent struts using optical coher - proven biocompatible material that is com - intravascular ultrasound, optical coherence Abiomed’s Impella 2.5 ence tomography; monly used in medical implants such as dis - tomography, and other state-of-the-art inva -
Restoration of vasomotion was observed at solvable sutures. As with a metallic stent, sive and noninvasive imaging modalities at “Stent 4 Life” is launched two years, with the drug acetylcholine used Abbott’s bioabsorbable stent is designed to six and 18 months, and at one or two years. A campaign aiming to reduce mortality in in nine patients showing vasodilation in the restore blood flow by propping a clogged ves - patients with acute coronary syndromes has previously stented area, and the drug mether - sel open, and to provide support until the Next phase been launched in March by a coalition gin used in seven patients showing vasocon - blood vessel heals. Unlike a metallic stent, The second phase of the ABSORB will enroll which includes the European Society of striction in the previously stented area; however, a bioabsorbable device is designed approximately 80 patients at 10 centres in Cardiology Working Group on Acute Cardiac Care and the European Association of
Reduction in plaque area in treated arteries, to be slowly metabolised by the body and Europe, Australia, and New Zealand, and will Percutaneous Cardiovascular Interventions. corresponding to an increase in blood flow completely absorbed over time. incorporate device enhancements designed to “Stent 4 Life” is a project designed to between six months and two years, as con - Abbott will begin enrolling patients in the improve deliverability and vessel support. encourage the wider use of reperfusion firmed by intravascular ultrasound and vir - second phase of its international ABSORB The first patient was enrolled into the second therapy with percutaneous coronary inter - tual histology. clinical trial in the first half of 2009. stage of the ABSORB clinical trial at Onze ventions (PCI) in Europe. “Abbott’s bioabsorbable stent may be a Lieve Vrouw Ziekenhuis Hospital, Aalst, New European guidelines on the manage - major breakthrough in the treatment of nar - The trial Belgium, by Bernard De Bruyne. ment of heart attack emphasise not only rowed coronary arteries. The two-year The ABSORB trial is a prospective, non-ran - “Interventional cardiology has come a long speed of action but also the importance of ABSORB trial results show that the bioab - domised (open label), two-phase study way. It started with balloon angioplasty, reperfusion to restore blood flow to the sorbable device did its job of relieving coro - designed to enrol approximately 110 patients which evolved into bare metal stents, and heart and improve survival rates. The cam - nary obstructions and preventing renarrowing, in Australia, Belgium, Denmark, France, The then drug-eluting metal stents were created,” paign particularly addresses treatment of STEMI (ST-segment elevation acute myocar - and that it did this safely,” said John Netherlands, New Zealand, Poland, and said Serruys. “Now we have the fourth dial infarction) patients. “Stent 4 Life” aims revolution in interventional cardiology to identify those countries where the use of Abbott’s bioabsorbable stent technology, and patient outcomes from the primary PCI can be encouraged, and thereby first stage of ABSORB clearly show that the quality of care improved. The basis for bioabsorbable devices are the future of the campaign is a questionnaire study with coronary artery disease treatment.” local cardiac societies in Europe and an “Based on the strong clinical outcomes from assessment of individual requirements for a the first stage of Abbott’s bioabsorbable device national programme. trial, interventional cardiologists have been The recently announced National Infarct eager to enrol their patients into the second Angioplasty Project in the UK is one such action plan. Current registry data suggest stage of the trial,” said Ormiston. “If the bioab - that around 20-30% of all STEMI patients in sorbable stent continues to perform well in this Europe still receive no reperfusion therapy. trial and subsequent larger trials with more However, the report suggests that adher - complex narrowings, bioabsorbable device ence to the guidelines and a greater use of technology may become the new standard of primary PCI could dramatically improve care for patients with coronary artery disease.” STEMI patient survival.

BIBA Publishing

14 Cardiovascular News International Issue 13 May 2009

(SKS) technique is simple and quick, but pro - duces a metallic septum upstream from the Why we prefer the minicrush bifurcation that may predispose to stent throm - bosis, despite of being more successful in 11 1 medium-to-large coronary arteries . Both “V” as a two-stent strategy stenting 12 – a variation of simultaneous kissing stent technique – and “Y” stenting 13 have the potential to cover the bifurcation, but they are limited in true bifurcation lesions. Secondly, as previously described the mini - ALFREDO R GALASSI crush technique has the advantage, as com - pared to the standard crush, of avoiding manipulation or positioning of two bulky stent COMMENT & ANALYSIS 2 simultaneously, and, as compared to the “step crush technique” it is less cumbersome; fur - Treatment of bifurcation lesions remains a technical challenge for the interventional - thermore, in the minicrush technique recross - ist, as it is still hampered by an increased rate of restenosis as compared with nonbi - ing, balloon inflations and kissing inflations occur only once and not twice such as in the furcated lesions. Part of this treatment complexity is related to the different anatomic two-step procedure 9 –10 . patterns of the stenosis, considering that all anatomical bifurcation characteristics Thirdly, as shown in the silicone phantom may influence the treatment strategy. by Ormiston 7, gaps in stent coverage some - times occur with kissing balloon postdilatation THE BEST TREATMENT for bifurcation be overall heterogeneous 5 and still a remark - after standard crush deployment, but are sig - lesions has not been established yet. In the able subgroup of patients with bifurcation nificantly less common with minicrush. They absence of proven efficacy of dedicated lesions (with larger side branches and/or large occur in the-side branch stent, usually on the devices, drug-eluting stents and various tech - myocardium at risk supplied by the side side opposite to the crushed portion of the niques – generally divided into two basic branch and/or more diseased vessels and/or stent; they are due to the postdilatation side- strategies, with or without side-branch stent - with suboptimal result of the side branch), and 3 branch balloon, which pushes struts aside. ing – are commonly used to treat patients may be treated with double stenting even if the When comparing standard crush with mini - with bifurcation lesions. Because some recent intention is to try to avoid it. crush side-branch, ostial coverage by metal randomised studies of stenting of both For these reasons, although randomised con - struts was reduced in the original work by branches failed to demonstrate superiority trolled trials remain a gold standard in clinical Ormiston from 47% (39 –53) to 36% (31 –40), over main-vessel stenting and balloon dilata - investigation, large single-centre series provide p<.002 (Figure 1) 7. Also, separate stent infla - tion with provisional stenting of the side important information and help calibrate tions rather than simultaneous stent inflation, branch 1–4 , the routine usage of two stents is results from randomised studies evaluating as in the standard crush, may favour more not generally recommended as a default pro - treatments for bifurcation lesions and con - homogenous and complete stent coverage; cedure, and is only used in case of long and tribute to our knowledge as we try to select the with this “ballooning crushing” there is less diffuse side-branch disease. best therapy for each patient. risk that the main-vessel stent will be The Colombo trial utilising sirolimus-eluting In a pilot study, we described a further deformed and potentially unapposed to the stents showed that a simple strategy with a one- refinement of the crush technique, which con - vessel wall and thus predisposed to restenosis. stent technique is not inferior to a complex strat - sists of crushing the 1–2mm proximal side Figures Fourthly, following standard crush deploy - egy with two stents; however, the study might be branch stent with a balloon (minicrush) instead 1. Minicrush with minimal strut overlap in a sili - ment, the two layers of crushed side-branch difficult to interpret, as the number of patients is of crushing the 3–4mm proximal side branch con phantom. The side-branch ostial percentage stent, in addition to a layer of main branch limited and there was a very high crossover rate stent with another stent, as in the standard area stenosis following different deployment struts, form three layers of struts. The limited from simple to complex strategies 1. crush 6. Following this approach, it seems that stategies showed that mean side branch ostial length of 1–2mm of stent that is crushed with The CORPAL (Drug-eluting stents for com - there is less risk that the main-vessel stent will area stenosis of 36% after the minicrush deploy - minicrush – instead of the 3–4mm of the stan - plex lesions: randomised rapamycin vs. pacli - be deformed and potentially unopposed to the ment strategy was significantly less, than the dard crush – determines minimal overlap of taxel) trial showed that elective side-branch vessel wall and thus predisposed to restenosis mean side branch ostial stenosis of 47% after the struts; indeed, this may be associated with stenting did not provide an advantage over the or stent thrombosis of the side branch, as is classical crush strategy (p=.002). more complete endothelialisation and reduced simple T-provisional stent; however, the trial suggested by Ormiston and colleagues 7 (Figure 2. Minicrush vs. T-provisional one stent clinical risk of thrombosis. was dealing with a limited number of cases 1). This study showed excellent in-hospital and angiographic outcome after adjustment for and the complex strategy was performed with outcomes for the minicrush technique with low propensity score. Alfredo R Galassi, Davide Tomasello, a technique that did not have much success major advance cardiac events and restenosis 3. Minicrush vs. T-provisional (entire cohort = T- Davide Capodanno et al from the 6 when it employed T-provisional but not as rates, especially at the side branch (2%) . provisional one-stent and T-provisional two-stent); Ferrarotto Hospital, University of 2 double-stent intention-to-treat technique . In our recently published retrospective clinical and angiographic outcome after adjust - Catania, Italy, are the authors of the study. The Nordic trial considered a two-stent tech - study 8, the largest single-centre experience so ment for propensity score. References nique to perform worse than an one-stent tech - far, we looked at 457 consecutive patients who 1. Colombo A, Moses JW, Morice MC, et al. Randomized nique, in patients with a stenosis diameter, as were treated with either two-stent minicrush al group who received a single stent (HR .52, study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 2004;109:1244 –9. determined by angiography, of >50% of the technique (n=199) or the T-provisional 95% CI, .27–.99; p=.047, and HR .41, 95% CI, 2. Pan M, de Lezo JS, Medina A, et al. Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: a main vessel or an occlusion of the side branch. approach (n=258), in which a second stent was .20–.85, p=.016, respectively) (Figure 2). randomized comparison of a simple versus complex strat - Indeed, in this series, restenosis rate in the side used only if deemed necessary at the opera - Comparing minicrush with entire T-provisional egy. Am Heart J 2004;148:857– 64. 3. Steigen TK, Maeng M, Wiseth R, et al., on behalf the branch was significantly higher in the group tor’s discretion (T-provisional one-stent=170 group after propensity score adjustment for NORDIC PCI Study Group. Randomized study on simple using a simple strategy (19.2%) as compared and two-stent n=88). Clinical follow-up was baseline differences restenosis was significant - versus complex stenting of coronary artery bifurcation 3 lesions: the Nordic bifurcation study. Circulation with those using a complex strategy (10.9%) . available for all patients at 25±15 months and ly reduced in minicrush arm only for the side 2006;114:1955– 61. The recent CACTUS (Coronary bifurca - cumulative major adverse cardiac events were branch (HR .55, 95% CI, .37–.82, p=.004) 4. Colombo A, Bramucci E, Sacca’ A et al. Randomized study of the crush technique versus provisional side-branch tions: application of the crushing technique similar between minicrush and both T-provi - (Figure 3). stenting in true coronary bifurcations: The CACTUS (Coronary Bifurcations: Application of the Crushing using sirolimus-eluting stents) trial, comparing sional patient groups (20.6% vs. 25.9% vs. Both techniques of bifurcation treatment met Technique Using Sirolimus-Eluting Stents) Study. two different techniques – the crush and the 26.1%, p=NS across all three groups). high procedural success with low complication Circulation 2009; 119:71-78 5. Medina A, Surez de Lezo J, Pan M. A new classification of provisional side-branch T-stenting – showed in However, it is interesting to note that target rates and similar major adverse cardiac event coronary bifurcation lesion. 350 patients in 12 European centres a similar bifurcation revascularisation (defined as a long-term outcome. However, the minicrush Rev Esp Cardiol 2006;59:183– 4. 6. Galassi AR, Colombo A, Buchbinder M, et al. Long-term major adverse cardiac event rate for both treat - repeat revascularisation with a stenosis of 50% technique yields a lower restenosis rate at both outcomes of bifurcation lesions after implantation of drug- ments (15.8% in the crush group vs. 15% in within 5mm proximal or distal to the carina of main and side branches. These results may eluting stents with the “mini-crush technique.” Catheter Cardiovasc Interv 2007;69:976–83 the provisional stenting group, p=NS). Also in bifurcation, both onto the main branch and/or confirm the advantage of using prescheduled 7. Ormiston JA, Webster MWI, Webber B, Stewart JT, Ruygrok PN, Hatrick RI. The “crush” technique for coro - this study, there was a high crossover rate from side branch) was significantly lower in mini - two-stent technique to give a complete cover - nary artery bifurcation stenting: insight from micro-com - a one-stent technique to two (31%), determin - crush patients as compared with T-provisional age of the side branches’ ostium, when the side puted tomographic imaging of bench deployments. J A m Coll Cardiol Intv 2008; 1: 351-7. ing a difficult interpretation of its findings. two-stent patients (8.5% vs. 17.4%, p=.05) branch is suitable for stenting and has disease 8. Galassi AR, Tomasello SD, Capodanno D, Barrano G, Ussia In conclusion, a one-stent technique does (See table below). extending beyond the ostium. GP, Tamburino C. Mini-crush versus t-provisional tech - niques in bifurcation lesions: clinical and angiographic not seem to perform worse than two-stent tech - At nine month angiographic follow-up, after long-term outcome after implantation of drug-eluting nique, although, as recently stated, it could be propensity score adjustment for baseline dif - Four good reasons why we prefer the stents. JACC Intv 2009; 2:185-194 minicrush technique as a two-stent strategy 9. Kaplan S, Barlis P, Dimopoulos K et al. Culotte versus T- impossible to do randomised trials in bifurca - ferences, there was significantly less restenosis stenting in bifurcation lesions: immediate clinical and tion lesions as each patient’s anatomy may in both the main and side branch in the mini - Firstly, as shown by Ormiston 7 in a phantom angiographic results and midterm clinical follow-up. Am Heart J 2007; 154: 336-343. favour a particular technique; trial patients will crush compared with patients in the provision - model among two-stent techniques, crush stent - 10. Adriaenssens T, Byrne RA, Dibra A et al Culottes tenting technique in coronary bifurcation disease: angiographic ing and his modifications (minicrush and two- follow-up using dedicated quantitative coronary angio - Minicrush T-provisional T-provisional p value step crush technique) are performing better graphic analysis and 12-month clinical outcomes. Eur Heart J 2008; 29: 2868-76. (n=199) 1-stent (n=170) 2-stent (n=88) than other two-stent techniques. Indeed, these 11. Sharma SK, Choudhurry A Lee J et al. Simultaneous kiss - Cumulative major adv. events % 20.6 25.9 26.1 NS a latter have strengths, but many weaknesses as ing stents technique for treating bifurcation lesions in a medium-to-large size coronary arteries. Am J Cardiol 2004; Target lesion revascularisation % 16 20.3 26.1 NS compared to crush: With “T” stenting there are 94: 913-7 b 12. Schampaert E, Fort S, Adelman AG et al. The V-stent: a Target bifurcation revasc. % 8.5 14.5 17.4 <.05 gaps in metal coverage and drug application at novel technique for coronary bifurcation stenting. a Cathet Late stent thrombosis % 1 2.3 0 NS the side branch ostium especially in shallow Cardiovasc Diagn 1996; 39: 320-6. 1 9–10 13. Helqvist S, Jorgensen E, Kelbaek H et al. Percutaneous a=For comparison among all three groups angles . Culotte stenting is technically more treatment of coronary bifurcations: a novel “extended Y” b=For mini-crush vs. T-provisional two-stent groups difficult and is associated with double layering technique with complete lesion stent coverage. Heart 2006; 92: 981-2. of stent struts. The simultaneous kissing stent

BIBA Publishing

16 Cardiovascular News International Issue 13 May 2009 New appropriateness criteria guide treatment of patients with coronary artery blockage Physicians and patients now have a practical tool for weighing of the factors to decide whether it is appropriate to treat chest pain with medical therapy alone or prescribe medical therapy and also perform revascularisation. THE DOCUMENT “Appropriateness Criteria for Coronary Revascularization” is the first to focus on cardiac treatment, rather than on diagnostic testing. It was jointly developed by the American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, Peter Smith Gregory J Dehmer American Heart Association, and American Society of Nuclear Cardiology. The guide -
How much cholesterol plaque has built up ate if the expected improvements in survival, patterns of care, and in helping to reduce the lines have been endorsed by the American and in which arteries; symptoms, functional status and/or quality of large variation in rates of revascularisation that Society of Echocardiography, Heart Failure
How much of the heart muscle, according to life outweighed the possible risks. In most has been observed throughout the USA. Society of America, and Society of stress testing, is being starved for blood and cases, the panel considered revascularisation “For physicians who look at the appropriate - Cardiovascular Computed Tomography. oxygen; and as either bypass surgery or a catheter proce - ness criteria and conclude that 95–100% of the “One of the strengths of this document is
Whether the patient is already taking the dure. Because evidence is available to support revascularisation procedures they perform that it provides a framework for thinking about right heart medications in the right dosages. either procedure for patients with advanced would be graded as appropriate – terrific,” said clinical scenarios and having a discussion In developing the appropriateness criteria, a coronary disease, each method of revasculari - Gregory J Dehmer, Texas A&M University about coronary revascularisation,” said 17-member technical panel made up of gener - sation was independently rated. College of Medicine, Scott & White Clinic, Manesh R Patel, Duke University Medical al cardiologists, interventional cardiologists, The panel determined that revascularisation Temple, USA, writing committee member. Center, Durham, USA, and chair of the appro - cardiac surgeons, internal medicine special - would be inappropriate in a patient who had “But for those who find that only 60 or 70% of priateness criteria writing group. “These rec - ists, health services researchers, and others plaque build-up in one or two arteries, experi - their procedures are appropriate and the rest ommendations describe when coronary revas - sifted through approximately 180 clinical sce - enced symptoms only during heavy exercise, are inappropriate, this document provides a cularisation would be expected to improve a narios, scoring each according to whether had a small amount of heart muscle at risk, and very powerful message and gives them a patient’s health status.” revascularisation was appropriate, inappropri - was not taking medication to help control benchmark for improving their practice.” While guidelines provide a comprehensive ate, or uncertain. symptoms. However, they deemed revasculari - “In the arena of cardiovascular science, we summary of evidence from clinical trials, “This was quite a serious undertaking,” said sation appropriate if a similar patient had have a fair amount of data on revascularisation appropriateness criteria focus on the types of Peter K Smith, Duke University, and member severe symptoms despite already taking the and its ability to improve how patients feel or patients cardiologists see in the clinic and hos - of the writing committee on behalf of The best available heart medication. long they live,” Patel said. “As a group that pital every day. Appropriateness criteria pres - Society of Thoracic Surgeons. “The process Appropriateness criteria are not intended to includes general cardiologists, interventional - ent information in easily understood clinical involved extensive review and debate of the diminish the importance of clinical judgment ists and surgeons, we are saying: For these scenarios that characterise patients according available body of evidence, and resulted in in evaluating individual patients, nor to include common clinical scenarios, here is when it is to four critical features: remarkable consensus between specialties.” every possible type of patient. Instead, one of appropriate – in most patients – to perform
The severity and type of symptoms; Revascularisation was considered appropri - their most important uses will be in evaluating revascularisation.” SPIRIT II: Xience V shows Trial will compare Nevo to Xience CORDIS ANNOUNCED in March plans to The six-month trial results from NEVO RES advantages over Taxus launch a global, head-to-head, randomised I will be presented at the EuroPCR confer - clinical trial called NEVO II which will com - ence in Barcelona. This randomised trial pare the Nevo sirolimus-eluting coronary compares Nevo to the Taxus stent (Boston between two and three years stent to the Xience V everolimus-eluting stent Scientific) and involves 394 patients. Results (Abbott). Cordis and Conor Medsystems, LCC from this trial will support a design dossier LONG-TERM DATA from Abbott’s SPIRIT II at three years, including an 88% reduction in are sponsors of the study. submission for CE mark. clinical trial demonstrated that the clinical the risk of cardiac death and a 57% reduction Nevo is the first and only drug-eluting The previously announced NEVO RES II advantages of the Xience V everolimus-eluting in the risk of major adverse cardiac events. stent utilising a unique reservoir technology, clinical trial, a nonrandomised, single-arm stent continued to increase between two and “In the clinical outcomes that matter most, which Cordis acquired from Conor registry of approximately 1,000 patients, has three years compared to the Taxus such as heart attack, repeat procedure at the Medsystems, LLC in 2007, and incorporates been canceled. The company will complete Express2/Taxus Liberte paclitaxel-eluting target lesion or death, Xience V demonstrat - hundreds of small reservoirs, each acting as the protocol-defined follow-up for patients stents. Both Taxus Express2 (73% of lesions) ed a consistent reduction compared to Taxus a depot into which drug-polymer composi - enrolled in this trial to date. and Taxus Liberte (27% of lesions) out to three years,” said Patrick W tions are loaded. This design allows drug In other drug-eluting stent news from were used as controls in the trial. Serruys, Erasmus University delivery from a stent with a surface that is Cordis, the company announced plans to ini - The data also showed that Data from the Hospital, Rotterdam, The 75% bare metal upon insertion and becomes tiate a trial in the USA of approximately patients treated with Xience SPIRIT II trial Netherlands, and principal fully bare metal following drug delivery and 2,000 patients that will compare clinical out - V continue to experience showed that, between investigator of the SPIRIT II polymer bioresorption in approximately comes in a broad range of patients receiving fewer heart attacks, deaths two and three years, trial. “What's even more three months. dual antiplatelet therapy for 12 months ver - Xience maintained cardiac or repeat procedures at the impressive is that the clinical Nevo contains the same drug, sirolimus, sus 30 months after receiving a Cypher death rate of .5%, while target lesion compared to death rate for Taxus was differences between Xience V as the Cypher, also from Cordis. The data Stent. This trial will contribute to the compa - patients treated with Taxus 1.3% at two years and and Taxus continue to widen supporting the safety and efficacy of ny’s involvement in a broader dual out to three years. The 4.2% at three years. between two and three years, sirolimus in coronary applications is now antiplatelet therapy clinical program that is results from the SPIRIT II trial confirming the long-term safety available out to six years, and this body of being led by the FDA. were presented during the and efficacy of Xience V." clinical evidence is unmatched by any other In order to focus on realising the full American College of Cardiology’s 58th SPIRIT II is a prospective, multicentre, antirestenotic stent coating. potential of Nevo, Cordis noted that it will annual scientific session in Orlando, USA. randomised, single-blind, controlled clinical NEVO II will be a global trial of approxi - cease development of the Cypher Elite Between two and three years, Xience V trial comparing Xience V to Taxus in 300 mately 2,000 patients with coronary artery sirolimus-eluting program. maintained cardiac death rate of .5%, while patients (223 Xience V patients, 77 Taxus) with disease. Results from this trial will provide Approximately 700 patients in the USA the observed cardiac death rate for Taxus was either one or two de novo native coronary long-term data in support of a premarket have been enrolled in the clinical trial for 1.3% at two years vs. 4.2% at three years). artery lesions. Patients from Europe, India and application with the FDA. The company this product and they will continue to be fol - Xience V maintained a low rate of major New Zealand were enrolled in the trial plans to meet with regulatory authorities lowed for five years, the duration of the fol - adverse cardiac events between two and between 5 July 2005, and 15 November 2005. soon to finalise the design for this trial. low-up period in the protocol. three years (6.4% at two years vs. 6.4% at The primary endpoint of the SPIRIT II trial In the USA, NEVO III will serve as the piv - three years), while Taxus increased approxi - was in-stent late loss at six months, wherein otal trial for a premarket application sub - mately 40% between two and three years Xience V demonstrated superiority to Taxus mission to the FDA. NEVO III is designed as See the six-month results from (10.5% at two years vs. 14.9% at three years). with a statistically significant 69% reduction a nonrandomised, single-arm trial evaluat - NEVO RES at the EuroPCR in Barcelona, In addition, the SPIRIT II results demon - in late loss (mean, .11mm for Xience V vs. ing clinical outcomes in approximately 19–22 May. strated Xience V’s continued clinical benefits .36mm for Taxus). 1,000 patients.

BIBA Publishing

18 Cardiovascular News International Issue 13 May 2009

vs. 8% in the RRISC trial) might have also played a role. In contrast to Taxus reduces restenosis in the RRISC study, where most restenoses were nonocclusive, nearly one-half of the restenotic lesions in the SOS trial were occlusive, in saphenous vein graft lesions which repeat PCI is often not attempted, explaining in part why the Results of the SOS (Stenting of saphenous vein grafts) study published in the Journal of the American difference in target vessel revascular - College of Cardiology showed that Taxus reduced angiographic restenosis, target lesion revascularisa - isation did not reach statistical signif - tion, and target vessel failure compared to bare metal stents in saphenous vein graft lesions. icance in the SOS trial.” The paclitaxel-eluting stent group THE TRIAL RANDOMISED 80 ment and in-stent restenosis, retrospective observational series in the SOS trial had less target lesion patients with 112 lesions to either p<.0001). During a median follow- comparing drug-eluting with bare revascularisation without attenuation bare metal stents (n=39, 43 grafts, 55 up of 1.5 years, the Taxus (Boston metal stents in saphenous vein grafts of benefit during follow-up, as was lesions) or Taxus stents (n=41, 45 Scientific) patients had less target have been conflicting: six studies seen in the RRISC trial. “Both the grafts, 57 lesions) in five centres lesion revascularisation (28% vs. showed better results with drug-elut - Emmanouil S Brilakis Express2 bare metal stent used in (four in the USA, one in Greece) 5%, p =.003) and target vessel fail - ing stents and nine suggested no dif - SOS and the BxVelocity used in between 2005 and 2007. The inclu - ure (46% vs. 22%, p=.03), a trend ference between bare metal and As in the RRISC trial, the authors RRISC are thick strut stents (strut sion criteria was age >18 years, one toward less target vessel revasculari - drug-eluting stents.” affirmed, a significant reduction in thickness 132 and 140µm, respec - or more 50 –99% de novo or restenot - sation (31% vs. 15%, p=.08) and The RRISC (Reduction of resteno - late loss was observed in the drug- tively); therefore, bare metal stent ic lesions in a saphenous vein graft myocardial infarction (31% vs. 15%, sis in saphenous vein grafts with eluting stent arm of SOS. The in- design is unlikely to explain the high - that were 2.5 –4mm in diameter, need p =.10), and similar mortality (5% Cypher sirolimus-eluting stents) trial, stent late loss in the drug-eluting er in-stent restenosis rates in the bare for percutaneous coronary interven - vs. 12%, p=.27). the only other published, prospective, stent group was similar in the two metal stent arm of the SOS trial.” tion (PCI) in the opinion of the “The most important finding of randomised trial investigating drug- studies (.38 ± .51mm in RRISC, and The researchers of the SOS study attending cardiologist, and willing - this trial is that paclitaxel-eluting eluting stents vs. bare metal stents in .42 ± .57mm in SOS) but was less in concluded that the use of paclitaxel- ness to return for repeat graft angiog - stents reduce angiographic restenosis saphenous vein graft lesions, showed the bare metal group in the RRISC eluting stent in saphenous vein graft raphy at 12 months and be contacted rates and target vessel failure in restenosis and target vessel revascu - study (.79 ± .66mm) than in the SOS lesions is associated with lower rates after one, six, 12, and 24 months for saphenous vein graft lesions com - larisation were lower with Cypher trial (1.29 ± 1.03mm). Accordingly, of angiographic restenosis and target clinical follow-up. The study was led pared with bare metal stents,” the (Cordis) vs. bare metal stent angiographic restenosis occurred vessel failure than bare metal stents. by Emmanouil S Brilakis, VA North authors wrote. “Drug-eluting stents BxVelocity (Cordis) at six months, more frequently in the bare metal “Large, prospective, multicentre, ran - Texas Healthcare System and have been shown to reduce resteno - but after 36 months, mortality was stent arm of the SOS trial (51% vs. domised-controlled clinical trials that University of Texas Southwestern sis in many lesion types and clinical higher with Cypher (29% vs. 0%, p= 33% in the RRISC trial). “This was use a clinical rather than angiograph - Medical Center, Dallas, USA. syndromes. However, there is a .001). In addition, any early benefits likely in part due to the performance ic endpoint are needed to confirm the The results showed that the pri - paucity of prospective data on drug- with the sirolimus-eluting stent had of follow-up coronary angiography at beneficial role of drug-eluting stents mary endpoint – binary angiographic eluting stents in saphenous vein graft disappeared, as evidenced by equiva - 12 months in the SOS trial vs. at six in saphenous vein graft lesions.” restenosis at 12 months – was signif - interventions, although bare metal lent rates of infarction (18% Cypher months in the RRISC trial. The high - Such a study (VA Cooperative Study icantly lower in Taxus-treated stenting is associated with high vs. 5% BxVelocity, p=.15) and target er prevalence of diabetes (44% in the 571, Drug eluting stenting in saphe - lesions vs. bare metal stents-treated restenosis rates in saphenous vein vessel revascularisation (34% Cypher SOS trial vs. 15% in the RRISC trial) nous vein graft angioplasty – DIVA) lesions (9% vs. 51% for both in-seg - graft lesions. The results of mostly vs. 38% BxVelocity, p=.74). and smoking (26% in the SOS trial may begin enrolment in 2009.

Drug-eluting stents compete against Cypher demonstrates bare metal for chronic total occlusions sustained benefits compared to DATA PUBLISHED in the lesions and less favourable diabetes vs. 4.7% with no February 2009 issue of JACC baseline characteristics com - diabetes; p=.002). bare metal stents at six years Cardiovascular Interventions pared to those treated in the The study also reported In the first six-year follow-up of a pivotal study of drug-eluting stents, the clinical showed that, when used for bare metal stent era. The rates of one-year clinical out - chronic total occlusions, characteristics included: dia - comes in the sirolimus-elut - benefits of Cypher compared to a bare metal stent were sustained, according to drug-eluting stents appear betes, 24.5%; prior infarction, ing stent group: 1% myocar - data presented at the Cardiovascular Revascularization Therapies conference, safer and result in substan - 33.5%; and stent length, dial infarction, 1% stent Washington, DC, USA, in March 2009. tial reductions in angio - 45.9mm median (quartile 1, thrombosis (defi - graphic restenosis compared 30.2mm; quartile 2, 62.1mm). nite/probable), 9.8% target NO DIFFERENCES were the six-year follow up. 6.4%, compared to 7% for the with bare metal stents. A total of 199 patients lesion revascularisation, observed between the Cypher Cypher demonstrated lower bare metal stent (p=.774). The findings of the (99.5%) were treated with 10.9% target vessel failure, sirolimus-eluting coronary rates of target lesion revascu - There was no significant dif - ACROSS/TOSCA-4 sirolimus-eluting stent, and 10.3% major adverse cardiac stent and the bare metal stent larisation and major adverse ference in the overall rate of (Approaches to chronic procedural success was 98%. events, and no deaths. in the safety measures of cardiac events, which include stent thrombosis between the occlusions with sirolimus- Kandzari told myocardial infarction, death myocardial infarction and Cypher and the bare metal eluting stents/total occlusion Cardiovascular News or stent thrombosis. death, compared to the bare stent, regardless of the defini - study of coronary arteries-4) International that he will At six-year follow-up, metal stent. Revascularisation tion of stent thrombosis study were presented at the have the three-year out - patients in the Cypher stent rate for Cypher was 11.9% vs. employed. The definitions International Chronic Total comes available this Autumn arm of the SIRIUS 27.9% for the bare metal stent include the original SIRIUS Occlusion Summit, 5 and expects to present the (Sirolimus-coated BX (p<.0001), and the major trial protocol definition and the February 2009, New York, data at the Transcatheter Velocity balloon-expandable events rate for Cypher was Academic Research USA. The research “Drug- Cardiovascular Therapeutics stent in treatment of patients 22.6% vs. 37.2% for the bare Consortium (ARC) definition. eluting stents for CTO revas - (TCT) 2009 meeting, in with de novo coronary artery metal device (p<.0001). These At six years, the protocol defi - cularization: Two steps for - September. lesions) trial experienced sig - six-year outcomes support the nition identified a rate of 1.2% ward, one step back?” was In his presentation at the nificantly lower rates of target previously reported results of stent thrombosis for Cypher led by David E Kandzari, David E Kandzari International Chronic Total vessel failure, the primary the trial and showed no signs vs. .8% for the bare metal stent Scripps Clinic, La Jolla, USA. Occlusion Summit, Kandzari endpoint of the trial, than of late “catch-up.” (p=.536). The defi - The study assessed 200 The sirolimus-eluting stent mentioned two other trials of those who received the bare There was no significant nite/probable ARC definition consecutive total chronic group had significantly less interest. PRISON III is cur - metal stent (26.1% vs. 39.9%, difference in the mortality or identified a stent thrombosis occlusion patients at 15 cen - angiographic restenosis at rently recruiting patients for p<.0001). Target vessel failure the myocardial infarction rates rate of 1.2% for Cypher vs. tres in North America for six months compared to the a randomised single-blinded was defined as a composite of between the Cypher and the 2.1% for the bare metal stent treatment with a sirolimus- bare metal stent group: study comparing Cypher cardiac death, myocardial bare metal stent at six-year (p=.304). There was no trend eluting stent. To allow for 22.6% vs. 55.2%. This gap (Cordis) with the infarction and target vessel follow-up. The mortality rate for an increase in ARC-defined comparison with a historical between the sirolimus-elut - zotarolimus-eluting stents revascularisation. was 8.9% for those receiving definite or probable very late bare metal stent cohort ing stent amounted to a 33% Endeavor and Resolute In the double-blinded, mul - the Cypher compared to 9.4% stent thrombosis rates between (n=202) from the TOSCA-1 absolute reduction and an (Medtronic), and PEPCAD- ticentre randomised trial, for those receiving bare metal one and six years (.8% in the study, the current trial used 85% adjusted relative reduc - CTO, a single-arm phase II patients were divided into stent (p=.974). The myocardial Cypher arm vs. 1% in the bare similar enrolment criteria tion in restenosis with the study in which patients with two treatment groups: 533 infarction rate for Cypher was metal stent arm). and trial methodology. The sirolimus-eluting stent. In the de novo chronic total occlu - patients received the Cypher primary endpoint was six- drug-eluting stent group, six- sions receive initial treat - and 525 patients received a month angiographic binary month in-segment resteno - ment with a paclitaxel-elut - bare metal stent. Of the origi - The trial restenosis within the treated sis was 12.4% and in-stent ing balloon followed by bare nal 1,058 participants, The SIRIUS trial, sponsored by Cordis, served as a pivotal segment. restenosis was 9.5%. Among metal stent implantation. approximately 50% (271 study for the American approval of the Cypher stent in Patients receiving the the risk factors, only dia - Results of PEPCAD-CTO patients receiving Cypher and 2003 and is the longest running USA-based study for a sirolimus-eluting stent pre - betes increased six-month should be available for the 255 patients receiving a bare drug-eluting stent. sented with more complex in-stent restenosis (22% with TCT meeting. metal stent) participated in

BIBA Publishing

20 Cardiovascular News International Issue 13 May 2009

Profile Christian Hamm

Cardiovascular News International talks to Professor Christian Hamm, Director of the Department of Cardiology, Kerckhoff Heart Centre, Bad Nauheim, Germany, about his influences, current areas of research, and the challenges facing cardiology.

When did you decide you wanted a career in medicine? lowship in Cape Town scientific thinking and writing papers – In my family there are many doctors, my father and my grand - something that was of great help when I returned to clinical father were general practitioners. However, I thought I had to cardiology. Before I became chief of a large department, I break this tradition and started studying German literature. My learnt from Professor Thomas Meinertz how you have to talk father accepted this only if I also signed up for medicine. It to the patient. The best knowledge of facts and skills in the soon turned out that medicine fascinated me much more and I cath lab are of less value if you cannot communicate with the switched over. A career was never on my schedule, first I patient. I am also proud to say that Professor Eugene wanted to become a well-trained doctor. Braunwald was an important mentor to me who early under - stood the value of troponins in acute coronary syndromes and supported me in making this heard. Why did you decide to specialise in internal medicine and cardiology? This was more by chance. I did not want to become a surgeon, What have been your proudest moments? but wanted to do something with my hands, not only ward If I exclude my private life highlights, maybe my first stand - rounds. I planned to become a gastroenterologist, but was not alone percutaneous transluminal coronary angiography in accepted, because I was considered not to be dedicated 1983. The daily positive feedbacks from satisfied patients enough. The gastroenterologists recommended cardiology to are always new proud moments. It is still always great me, because this was seen as an unimportant subspecialty at moments when a paper is completed and accepted by a high the end of the seventies. So, I was lucky that cardiology was a ranked journal. This gives me a kick and the motivation to specialty that progressed so rapidly. Particularly the rise of continue in periods when things are not running so well. interventional cardiology came at the right time for me. How has invasive cardiology evolved since you began Who have been your greatest influences? your career? Where do you see this field going in the next I have several teachers in my career that influenced me at dif - ten years? ferent phases. The late Professor Walter Bleifeld was my first I was so lucky to be involved in interventions since the early clinical teacher who supported me very early by letting me into eighties, which means that I have more than 25 years of expe - the cath lab. I could develop interventional skills at a young rience in manipulating the coronary arteries. The changes are age which I try to do today also with selected fellows in my enormous. The fellows of today have not the faintest idea what department. Professor Bleifeld was in addition somebody with can happen if you do not have stents. I am fascinated by the great visions, who early recognised that acute coronary syn - developments in coronary interventions but maintain great dromes is an important field of research and he taught me to respect of what can happen. The potential of catheter-based always strictly think in pathophysiologic terms. From interventions, like those in the valves, seems to be the next Professor Lionel Opie I learnt, during a wonderful research fel - wave of innovation in interventional cardiology.

“I see drug-eluting stents only as a transient phase. In the long term we will find ways not to leave metal behind. The next step will be bioabsorbable material.”

BIBA Publishing Cardiovascular News International Issue 13 May 2009 21

What do you think are the biggest challenges facing the management of acute coronary syndrome today? The treatment has reached such a high level of development. The Fact File challenge is more to get the best treatment to the patient and to make Christian Hamm it affordable. Education and training 1973–1976 University of Mainz, Germany How far do you think it is possible to go regarding advances 1976–1979 University of Hamburg, Germany in drug-eluting stents? 1980–1981 Research Fellow at Ischaemic Heart Research I see drug-eluting stents only as a transient phase. In the long Unit, University of Cape Town (Professor LH term we will find ways not to leave metal behind. The next step Opie), South Africa will be bioabsorbable material. 1981–1984 Department of Cardiology, University of Hamburg (Professor W Bleifeld) 1985–1987 Medical Clinic and Department of Radiology, What are your current areas of research? University of Hamburg My key areas of research are, of course, everything around acute 1988 Postgraduate qualification in internal medicine coronary syndromes and invasive cardiology. That means new and cardiology biomarkers, remodeling, and optimising the treatment. Here, we 1989–1998 Associate Professor in Internal Medicine & have a great number of ongoing experimental as well as clinical Cardiology, Department of Cardiology, studies. The preclinical phase is currently something that I focus University Hospital Hamburg on to improve in terms of diagnostic tools and therapy. I also have Since 1999 Full Professor of Cardiology, State of Hessen an active research group on cardiac magnetic resonance imaging and electrophysiology. In general, my interest is always to bring Editorial boards the basic science results to clinical practice. European Heart Journal, Circulation, Clinical Research in Cardiology, Education in HEART, Cardiology International, Emergency care, Current Cardiology Reviews, Outside of medicine, what other interests do International Journal of Cardiovascular Interventions, you have? Clinical Cardiology, EuroIntervention, Acute Cardiac Care, Literature has remained important to me, if I find the Cardiology in Review, Recent Patents on Cardiovascular time to read. Travelling with my family and seeing Drugs other parts of the world, without giving only lec - tures, helps me to understand that cardiology is only Fellowships a small part of what is going on in the world. 1991 Fellow of the European Society of Cardiology 1993 Fellow of the American College of Cardiology 1982 German Society of Cardiology 1988 German Society of Internal Medicine 1989 German Society of Intensive Care Major fields of research Cardiac biomarkers, acute coronary syndrome, invasive cardiology, cardiac magnetic resonance imaging and computed tomography Study steering committees/Principle Investigator GABI, CRUSADE, TRUST, STING, COBRA, PRIDE (Europe), German Cypher Registry, DaVinci, APEX-AMI, CHARISMA, IBIS-2, PEPCAD-III, CHAMPION, CRESCENDO, ON-TIME 2. Major publications 190 original peer-reviewed papers, 92 editorials and reviews, more than 600 abstracts, three books

BIBA Publishing 22 Cardiovascular News International Issue 13 May 2009

Lower risk of death Cypher shows better outcomes and heart attack with drug-eluting stents than Taxus at two years in HEART DISEASE PATIENTS AGED 65 and older who receive drug-eluting stents are more likely to survive and less likely to suffer a heart attack than people fitted with bare metal stents, diabetics according to a new study supported by the A study conducted by researchers from Health and Human Services’ Agency for Healthcare Research and Quality (AHRQ) and Seoul, South Korea, showed that, in the American College of Cardiology’s National diabetic patients, Cypher resulted in Cardiovascular Data Registry. better revascularisation rates at two The comparative effectiveness study of years than Taxus. The results appear in 262,700 Medicare patients who received stents is the largest ever to compare drug-eluting with the 3 March 2009 issue of the Journal bare metal ones. It was presented on 28 March of the American College of Cardiology . 2009 at the American College of Cardiology’s 58th Annual Scientific Session in Orlando, USA. “SIROLIMUS-ELUTING STENT [Cypher, A team of researchers from Duke University, Cordis] implantation significantly reduced AHRQ and Kaiser Permanente found that, com - two-year risks of target lesion revascularisa - pared with patients who received bare metal tion and major adverse cardiac events Seong-Wook Park Seung-Whan Lee stents, those fitted with drug-eluting stents had (death, myocardial infarction, and target an 18% better survival rate over the 30-month lesion revascularisation), compared with graphic restenosis and nine-month adverse group, occurred while the patients were on study period and were 16% less likely to suffer a paclitaxel [Taxus, Boston Scientific] implan - clinical outcomes. However, the long-term dual antiplatelet therapy. heart attack. tation in diabetic patients,” first author effectiveness of sirolimus over paclitaxel-elut - “Late stent thrombosis occurred only in one “The findings provide important new evidence Seung-Whan Lee, Asan Medical Center, and ing stent remains controversial. To compare patient (.25% of overall study population) for decision making by heart disease patients and colleagues, including Seong-Wook Park, the long-term effectiveness, Lee’s group evalu - during two-year follow up with prolonged use their physicians,” said AHRQ Director Carolyn wrote. “The use of sirolimus-eluting stent ated the two-year clinical outcomes, including of clopidogrel, which suggests that extended M Clancy. “These results should help resolve with a larger post-procedural minimal lumen stent thrombosis, target vessel revascularisa - use of clopidogrel after drug-eluting stent many lingering questions regarding the safety of diameter improved the two-year clinical out - tion, and major adverse cardiac events, of the implantation in diabetic patients may be bene - drug-eluting stents in recent years.” comes in diabetic patients. Late stent throm - patients included in the DES-DIABETES trial. ficial to reduce long-term adverse clinical out - The researchers in the AHRQ-funded study bosis occurred only in one patient (.25% of In the latest published report, Cypher sig - comes,” the authors wrote. found that 16.5% of the patients implanted with overall study population) during two-year nificantly reduced two-year rates of target At least two previous studies by different bare metal stents died within 30 months of follow-up with prolonged use of clopidogrel, vessel revascularisation (5.5% Cypher vs. researchers have been inconsistent with implantation, compared with 13.5% of those with which suggests that extended use of clopido - 12% Taxus, p=.014), target lesion revascular - respect to two-year results of sirolimus-elut - drug-eluting stents, after adjusting for population grel after drug-eluting implantation in dia - isation (3.5% vs. 11%, p=.006), and major ing stent and paclitaxel-eluting stent in dia - differences. They also found that 8.9% of the betic patients may be beneficial to reduce adverse cardiac events, with rates of death betics. According toLee and colleagues, one patients with bare metal stents suffered heart long-term adverse clinical outcomes.” (0% vs. 1.5%, p=.248), infarction (.5% vs. of the studies was not randomised and anoth - attacks during the period, compared with 7.5% of Previous studies found sirolimus-eluting 1%, p=.999), and stent thrombosis (1% vs. er was a subgroup analysis of a larger trial. those with drug-eluting stents – a 16% higher stents to have greater efficacy than paclitaxel- 0%, p=.499) equivalent between groups. “In contrast, our study, which was rate. The researchers further found that patients eluting stents in diabetic patients for limited Of the three deaths that occurred at two prospective, multicentre, randomised and fitted with drug-eluting stents in 2005 and 2006 follow-up duration. Lee’s group previously years, all were in the Taxus group (two car - dedicated to diabetic patients, demonstrated had a lower risk of death than those given the performed a randomised, multicentre, prospec - diac, one noncardiac). Both cardiac deaths that sirolimus-eluting stent maintained a stents in 2004. tive study, the DES-DIABETES (Drug-eluting were related to non-target-vessel myocardial reduction in target lesion revascularisation stent in patients with diabetes mellitus), show - infarction, and the noncardiac death was due and major adverse cardiac events at two “The findings provide ing that sirolimus-eluting stent was superior to to cancer. The two incidences of stent throm - years compared with paclitaxel-eluting paclitaxel-eluting stent in reducing angio - bosis, which were seen only in the Cypher sents,” Lee and colleagues wrote. important new evidence for decision making by heart disease patients and ATLANTA results positive for Catania stent their physicians.” TWELVE-MONTH DATA from the ATLANTA Carolyn M Clancy (Assessment of the latest non-thrombo - genic angioplasty stent) trial were pub - “Some previous studies have suggested that lished in the 2 March 2009 issue of the drug-eluting stents are associated with an excess Journal of the American College of long-term death rate, whereas others have not,” Cardiology: Cardiovascular Interventions . said the study’s lead author, Pamela S Douglas, According to the data, the Catania coronary Duke University. stent system with NanoThin Polyzene-F The researchers found no significant differ - offers sustained benefit in the treatment of ences in the percentages of drug-eluting and de novo coronary lesions and maximises bare metal stent patients who required a repeat endothelialisation, while reducing resteno - angioplasty or coronary artery bypass graft sur - sis, thrombogenicity, and the need for long- gery (roughly 23%) and in the percentages of term dual-antiplatelet therapy. The device patients who suffered strokes or major bleeding may be an alternative to both bare metal (about 3% and 3.5%, respectively). The results and drug-eluting stent. were not affected by age, gender, race, ethnicity The ATLANTA trial is a first-in-man, or other factors. prospective, single-centre study involving According to AHRQ’s Art Sedrakyan, coau - 55 patients treated with the Catania stent Corrado Tamburino thor of the study, the better outcomes found for for symptomatic ischemic heart disease patients with drug-eluting stents may be at least due to de novo , obstructive lesions of stent implantation and at 6-months. Analysis investigator in the ATLANTA trial. “The 12- partially explained because those patients are native coronary arteries. The trial was spon - of 19,028 struts using optimal coherence month ATLANTA data indicate that the required to take blood-thinning drugs, such as sored by CeloNova BioSciences, manufac - tomography in a subset of 15 randomly Catania stent with Polyzene-F is truly a new clopidogrel, for a long time after their procedure. turer of the Catania stent. selected patients revealed complete endothe - and promising class of stent.” Patients who receive bare metal stents are usually At 12 months, in an unusually complex FIM lialisation and 99.5% stent strut coverage. The rapid-exchange, cobalt-chromium prescribed blood-thinner medications for a short - patient population, the results showed zero “CeloNova has started a scientific revolu - Catania stent is currently available for sale er period of time and may take them less often. per cent stent thrombosis, death, myocardial tion involving the way physicians think in Europe in 60 sizes, in lengths from In addition, patients with drug-eluting stents may infarction, stroke, or coronary artery bypass about bare metal stents and drug-eluting 8–38mm and in diameters from 2–4mm. visit their doctors more often after hospital dis - graft. Target lesion revascularisation was stents. I can definitely assert that Polyzene- The Catania stent surface has a 35–40 charge and may receive prescriptions for drugs 10.9% (only 3.6% clinically driven), with a F is innovative, effective in several aspects, nanometer surface treatment of Polyzene-F, and therapies to lower their cholesterol levels and binary restenosis rate of 6.8%. All patients unique and striking. The polymer is, without an inorganic, biocompatible polymer that is manage other heart conditions more often than stopped dual antiplatelet therapy after 30 any doubt, the main reason for the great antithrombotic, anti-inflammatory, bacterial- patients who received bare metal stents. days. The procedural success rate was 100%. results we have obtained, which is why I resistant, lubricious, and essentially cloaks The authors call for longer follow-up studies to Independent laboratories analysed coro - chose the Catania stent to implant in my the device’s presence from the body to pro - further support the study's results and to confirm nary angiography and intravascular ultra - very best friend,” said Corrado Tamburino, mote healthy endothelial cell growth with - the possible effects of post-implantation treatment sound data for all patients immediately after Ferrarotto Hospital, Catania, Italy, and lead out stimulating platelet activation. with blood-thinning drugs such as clopidogrel.

BIBA Publishing

24 Cardiovascular News International Issue 13 May 2009

News in brief Relaxin promising results Two more efficient applications Corthera announced at the American College of Cardiology’s 58th Annual Scientific Session, Orlando, USA, in March that results from Pre- RELAX-AHF, the phase II portion of a phase II/III multicentre, randomised, double-blind, place - of biomarkers for heart failure bo-controlled international study, demonstrated Reports in the April issue of the European Journal of Heart Failure suggest two more efficient applications of biomarkers, promising efficacy and safety for relaxin, the and with them the promise of even earlier diagnosis and improved treatment of heart failure. company’s investigational drug for treatment of acute heart failure. ACCORDING TO RESULTS from a study in may enable a reduction in the number of up, and almost 17 times after five years. The data from 234 patients in eight countries Hull, UK, repeat measurement of the well- repeat echocardiograms. The study’s first author, Urban Alehagen, showed that when administered with standard- of-care therapy for acute heart failure, relaxin established biomarker N-terminal pro-B-type “We suggest that the main role of conven - Heart Centre of Linkoping University caused rapid, substantial and sustained relief natriuretic peptide (NT-proBNP) once treat - tional echocardiography should be to diag - Hospital, Sweden, said: “Because the major - from dyspnea. Relaxin also demonstrated con - ment has been optimised provides stronger nose and differentiate the principal causes of ity of patients with heart failure are elderly sistent trends in improvement of the hospital prognostic information than either the base - heart failure, with subsequent NT-proBNP and often affected by other organ symptoms, course of patients, prevention of heart failure line value, the change in NT-proBNP, or other monitoring used to identify worsening dis - including renal impairment, it is important worsening during hospitalisation, shortening of conventional methods of assessment. ease and trigger further echocardiographic to identify those at high risk, both for the in hospital stay and improved longer-term out - The finding emerged from a study of 354 assessment. Given the relatively high cost of provision of optimal treatment and the most comes following discharge when compared to patients with chronic heart failure treated in a echocardiography compared to NT-proBNP, effective use of health resources. The use of placebo. community-based heart failure programme. such a policy is likely to be cost effective.” a single blood test and the analysis of two Measurement of NT-proBNP was performed biomarkers is one way of identifying those Excess weight and inactivity A report published in at baseline and, in those surviving (318), Combined application patients where health resources are best Circulation , American once again between the fourth and sixth A study from Sweden suggests the combined focused. More and more clinicians are using Heart Association month of follow-up. During the study fol - application of two biomarkers gives better information from natriuretic peptides. (AHA), showed that low-up period (a median of 39 months) 125 prognostic information about the risk of car - However, it is now possible to expand the staying lean and fit patients died, and analysis showed that fol - diovascular mortality in heart failure patients use of these biomarkers in clinical practice, can lower the risk of low-up NT-proBNP measurement proved a than just one biomarker. This was a study of and our study proposes one such potent heart failure in men. better predictor of death than either baseline 464 elderly patients with the symptoms of combination.” In the Physicians’ NT-proBNP or change in NT-proBNP. heart failure followed up over a ten-year peri - The use of biomarkers for identifying Health Study, Indeed, say the authors, NT-proBNP “was od at Linkoping University Hospital. those at risk of cardiovascular mortality is researchers from the consistently the strongest independent prog - Throughout that time, serum measurements of now central to the management of patients Brigham and Women’s Hospital, nostic marker at predicting death or the biomarker cystatin C (a marker of renal with heart failure. Research now aims to find Boston, USA, fol - Satish Kenchaiah unplanned cardiovascular hospitalisations function) were taken, with results showing new, more sensitive markers and more effi - lowed 21,094 male after baseline or follow-up assessment”. that those with levels within the highest quar - cient use of existing markers. The ultimate physicians, 40 to 84 years old, for 20 years. First author Milos Kubanek, Castle Hill tile had almost three times the risk of cardio - aim, as this issue of the European Journal of Some of the findings: Hospital, Hull, added: “NT-proBNP monitor - vascular death than those with levels in the Heart Failure suggests, is to make earlier and
Lean and active men had the lowest risk for ing will enable the identification of patients first, second, or third quartiles. more accurate diagnosis possible, and there - heart failure and obese and inactive men had who are not responding well to treatment or However, when these measurements were by improve treatment and survival. the highest risk. help flag up those patients needing more combined with measurements of NT-proBNP, Karl Swedberg, editor-in-chief of the
Compared with men who rarely or never vig - aggressive management and monitoring. We the mortality risk assessment was even more European Journal of Heart Failure , said: “A orously exercised, men engaging in vigorous found NT-proBNP to be a much stronger pre - emphatic. For example, if those with high combination of biomarkers to improve diag - physical activity five to seven times a week had a 36% reduction in heart failure risk. dictor of mortality and cardiovascular hospi - concentrations of cystatin C also had a plas - nosis and prognosis – as suggested by
Compared with participants who were lean talisation than echocardiographic measure - ma concentration of NT-proBNP within the Alehagen and colleagues – now seems to be and active, the risk of heart failure increased ments of, for example, ejection fraction, and highest quartile, the risk of death increased to the basis of optimal management of patients 19% in the lean and inactive; 49% in the over - therefore repeat NT-proBNP measurement more than 13 times over ten years of follow- with heart failure.” weight and active; 78% in the overweight and inactive; 168% in the obese and active; and 293% in the obese and inactive. “Whereas previous studies have established Hormone no guide to heart failure that obese men have a higher likelihood of developing heart failure, the present investiga - tion has extended this knowledge by pointing outcomes in older patients out that even overweight or pre-obese men are not spared from this increased risk. On USING A MEASURE of the hormone N-ter - tive heart failure) study had an 18-month average, in men who are five feet ten inches minal brain natriuretic peptide (BNP) to follow-up. Patients were randomised to tall, for every seven pounds of excess body guide therapy for older patients with heart receive treatment to reduce symptoms of a weight, the risk of heart failure will go up by failure did not improve overall clinical or certain level of heart failure (symptom-guid - 11% over the next 20 years,” Satish quality of life outcomes compared to ed therapy) or treatment to reach BNP level Kenchaiah, lead author of the study, told an patients receiving conventional symptom- of two times or less the upper limit of nor - American Heart Association report. guided therapy, according to a study in the mal and reduce symptoms of a certain level 28 January issue of Journal of the of heart failure (BNP-guided therapy). Heart failure guidelines updated Updated guidelines on the diagnosis and man - American Medical Association . Compared with symptom-guided therapy, agement of heart failure will help physicians BNP is produced predominantly by the the BNP-guided strategy did not improve 18- incorporate the latest research findings into the heart muscle cells, and levels of the hor - month survival free of any hospitalisation Matthias Pfisterer treatment of patients with this complex and dis - mone are increased in patients with con - (41% for BNP-guided group vs. 40% for abling disease. gestive heart failure. Therapy for heart fail - symptom-guided group). Overall survival Commenting on behalf of the European The guidelines update was a joint effort of ure guided by N-terminal BNP has been rates did not differ significantly. Survival free Society of Cardiology, Kenneth Dickstein, the American College of Cardiology and the proposed to improve outcomes compared of hospitalisations for heart failure was Stavanger University Hospital, Norway, American Heart Association, and was accom - with conventional therapy in patients with improved with BNP-guided therapy (72% vs. emphasises the study’s difference in out - plished in collaboration with the International chronic heart failure in some studies. 62% for symptom-guided group). come between the under and over-75s. “The Society for Heart and Lung Transplantation. However, these studies were small, not All measures of quality of life improved older people in this study did not do as well The new document, a focused revision of guidelines released in 2005, was published conclusive, had limited follow-up and from the start of the trial to month 12 in as the younger and did not respond as well online on 26 March, 2009 in the focused on younger patients, according to both treatment groups and remained to therapy,” he says. “So we still need trials Journal of the and background information in the article. unchanged between month 12 and month properly powered to show the effect of BNP American College of Cardiology Circulation, journal of the American Heart Intensified N-terminal BNP-guided therapy 18. There were no significant differences in measurement as a marker in elderly patients Association. may be particularly beneficial for older the magnitude of these improvements who more closely reflect our everyday heart The new document includes several key patients who are less physically active and between the two treatment strategies. Heart failure populations today. So, while we saw a updates, including an entirely new section on in whom symptoms are less reliable. Heart failure therapy guided by BNP improved benefit of intensive therapy guided by BNP managing patients who are hospitalised with failure is the most common reason for hos - outcomes in patients age 60 to 75 years, levels in younger patients in this study, we acute heart failure, strengthened recommen - pitalisation in patients age 65 years or older. but not in those age 75 years or older. did not see it in the over-75s, who generally dations on two medications, hydralazine and Matthias Pfisterer, University Hospital “The findings of the TIME-CHF study sug - had more advanced disease, co-morbidity isosorbide dinitrate, streamlined information on the use of implantable cardioverter-defib - Basel, Switzerland, and colleagues com - gest that persistence in intensifying medical and higher BNP levels.” rillators and cardiac resynchronisation pared a N-terminal BNP-guided strategy to therapy seems to be the key for an optimal The study also showed that continual devices, and clarification of treatment goals in the standard symptom-guided therapy for clinical outcome in patients aged 60 to 74 monitoring of BNP levels (performed at patients with both heart failure and atrial fib - 499 patients age 60 years or older with years, whereas it may not be beneficial to one, three, six, 12 and 18 months in the rillation. chronic heart failure, who had prior hospi - push doses to the limits in patients aged 75 BNP group) as a guide to treatment was not talisation for heart failure within one year years or older,” the authors wrote. “Together associated with any improvement in out - and N-terminal BNP level of two or more with the main results of the TIME-CHF study, come: “A baseline measurement of BNP Read the full document with the updated times the upper limit of normal. The TIME- this study underscores the need for new tri - may be enough to initiate effective thera - guidelines on: CHF (Trial of intensified vs. standard med - als specifically addressing the large popula - py,” said Dickstein. “Serial measurements www.cardiovascularnews.com ical therapy in elderly patients with conges - tion of older heart failure patients.” do not appear to have added value.”

BIBA Publishing cx32-cardiovascularnews-issue11:Layout 2 17/4/09 15:59 Page 1 32 Years EUROPE’S LONGEST RUNNING AND LEADING VASCULAR SYMPOSIUM

VASCULAR & ENDOVASCULAR CHALLENGES UPDATE

Incorporating the Global Endovascular Forum New Technologies | New Techniques | New Horizons

IMPERIAL COLLEGE, LONDON, UK 10 - 13 April 2010 WWW.CXSYMPOSIUM.COM Additional CX events: CX Programme Chairman: CX Office-Based Vein Practice Course Roger M Greenhalgh CX Innovation Showcase CX 3D Imaging Course CX Vascular Ultrasound Course Best of ilegx @ CX CX Vascular Revision Course CX Endovascular Simulation Course email: [email protected] ISET @ CX Complex Case Review symposium hotline: +44 (0) 20 7736 8788 CX Learning Centres fax: +44 (0) 20 7736 8283 CX Training Village

CX 2009 Major Sponsors: Cardiovascular News International Issue 13 May 2009 27

2005). “Philip was certainly one of the greatest and wisest human beings who has passed through the history of the Society,” said Alan Professor Poole-Wilson: Farewell J. Howard, CEO European Society of Cardiology (ESC). He was also Founding President of the British Society for Heart to a leading heart researcher Failure in 1998. Poole-Wilson was awarded the society’s highest award, the Mackenzie THE CARDIOLOGY FIELD has lost one of Independent , Dr John Bell describes that, as a Medal in 2007, and among his many achieve - its great British talents. Professor Philip scholar at Marlborough College, Poole-Wilson ments, honours, honorary degrees, visiting Poole-Wilson, an expert on heart failure and was an all-rounder. Excelling at games, espe - professorships and guest lectures, Poole- coronary heart disease prevention, died in cially rugby and cricket, he played for college Wilson was awarded Le Prix Europe by the London on 4 March, from a suspected infarc - teams. Poole-Wilson was an undergraduate at French Institute of Health Science in 2001. tion. The day before, Circulation published a Trinity College, Cambridge University, read - six-page article entitled: “Pioneer in ing Natural Sciences (chemistry, physics, Wisdom and enthusiasm Cardiology: Philip Poole-Wilson”. mathematics and physiology) before moving to “Philip Poole-Wilson put heart failure on the Poole-Wilson had retired from his position St Thomas’ Hospital Medical School. map in the UK and was a giant in the field in as Head of Cardiovascular Medicine at the “At Trinity he had many friends from differ - Europe and further afield. Philip directly and National Heart and Lung Institute and Imperial ent faculties and kept up his cricket and rugby. indirectly mentored a generation of doctors, sci - College London in October 2008, but was still At an early dinner in Hall, discussion revolved entists and nurses interested in heart failure. He working as a Senior Research Investigator at around the meaning of the college motto, filled us with his enthusiasm. We will miss him Imperial and continuing with many other proj - ‘semper eadem’. Confidently, Poole-Wilson greatly,” said Dr John McMurray, President of ects. He was 65 years old. explained that it meant ‘keep smiling’ – it actu - the Heart Failure Association of the ESC. “Philip gave a lifetime of major, innovative, ally translates as ‘always the same’. Both epi - “Professor Poole-Wilson was a brilliant lec - very substantial and sustained contributions to thets would describe his nature over the next turer, chairman, and debater at international the world of cardiology and cardiovascular 50 years,” Bell wrote. meetings. Whether presenting the results of his medicine,” wrote Nicholas Boon, President of own many landmark clinical studies, basic sci - the British Cardiovascular Society. Field engagement ence reviews or whether debating the presenta - Peter Weissberg, British Heart Foundation In 1973 Poole-Wilson was awarded a British- tions and data of others, he combined wisdom, Medical Director, said: “Professor Philip Philip Poole-Wilson American Travelling Fellowship supported by enthusiasm, a passion for scientific correctness Poole-Wilson was one of the world’s leading the British Heart Foundation and undertook yet with a deep understanding of human val - cardiologists and his untimely death will be “Keep smiling” research in Los Angeles. In 1976, he took up ues. He was a lifelong clinician and, his sin - felt far beyond London and the UK. His Poole-Wilson was born in London in 1943. His a senior post at the age of 32 at the National cere approach to patients, combined with a research has had a major impact on our under - father, Denis, a colonel in the Royal Army Heart Hospital. He was appointed as commanding understanding of the science of standing of heart failure and its treatment, and Medical Corps, shared a tent in Egypt during Professor of Cardiology at the University of cardiovascular medicine, made Philip a much he was responsible for raising the standard of the Second World War with Paul Wood, one of London in 1983 and has held numerous visit - respected clinical cardiologist,” wrote Boon. care for patients with heart disease through his the fathers of modern British cardiology who ing professor positions in the UK and USA. Poole-Wilson published over 500 papers, leadership of organisations such as the was later to be a cardiac physician at the He has been clinical director for cardiology, written many book chapters and edited leading European Society of Cardiology and the World Brompton. Denis Poole-Wilson went on to research director, a non-executive board textbooks (Diseases of the Heart 1996, Hurst’s Heart Federation. He was the perfect exemplar become an eminent urological surgeon in member at the Royal Brompton Hospital, and The Heart 2008) in his specialist interest area of a clinician scientist with interests spanning Manchester, establishing in the 1950s a pio - was Head of National Heart and Lung of heart failure, coronary heart disease and the the whole spectrum of medical science from neering screening for bladder cancer in dye Institute from 1997 to 2000. global prevention of heart disease and stroke. molecules to man, but always directed at workers. Poole-Wilson’s mother was part Poole-Wilson was president of the European Poole-Wilson is survived by his wife, Mary, resolving questions of direct relevance to French and a keen amateur racing driver. Society of Cardiology (1994-1996), and presi - two sons, William and Michael, and his daugh - patients with heart disease.” In an appreciation published in The dent of the World Heart Federation (2003- ter, Oenone.

BIBA Publishing 28 Cardiovascular News International Issue 13 May 2009

Drug for atrial New ideas at EuroPCR fibrillation one step THIS YEAR’S EUROPCR , which will take place from 19–22 May in the Barcelona International Convention Centre, will bring closer to approval new features to the more than 10,000 cardi - THE FDA’S CARDIOVASCULAR and Renal ologists, cardiac surgeons, vascular surgeons, Drugs Advisory Committee recommended on 18 angiologists, nurses, technicians, fellows, March the approval of dronedarone for the treat - practitioners, researchers, and industry part - ment of patients with atrial fibrillation or atrial ners expected to attend the international con - flutter for the reduction of the risk of cardiovas - ference in Barcelona, Spain. cular hospitalisation or death. With plenary sessions designed and struc - The FDA’s committee voted 10 to three in tured around a range of specific themes and favour of the approval of dronedarone (Multaq, topics addressing the entire cardiovascular Sanofi-Aventis). The efficacy of the new drug community, the course includes live case was assessed in ATHENA, a placebo-controlled, transmissions, late breaking trials, practical randomised, double-blind, parallel arm trial. The training, and a wide range of sessions. results of the study were published in the 12 In 2009, EuroPCR will once again place the February 2009 issue of the New England Journal patient at the centre of the debate by inviting of Medicine by Stefan H Hohnloser, JW Goethe the entire medical team to work together, with University, Germany, and principal investigator. the aim of finding a consensus on the best Data from ATHENA, a multicentre trial treatment option for each individual patient. involving 4,628 patients with moderate to high- Fifteen collaborating live centres worldwide risk paroxysmal or persistent atrial fibrillation, will transmit during EuroPCR 2009. this with how the case was actually treated. reality sessions, based on the use of simu - have shown 24% reduction in all-cause mortali -
Bifurcation management – Coronary bifur - lators, allow attendees to virtually practice ty and cardiovascular hospitalisations (primary Some of this year’s features: cation lesions will be covered by the coronary or peripheral angioplasties and endpoint), as well as a 29% reduction in risk of
Abstracts – This year for the first time forum approach, which includes an update closure techniques. cardiovascular death on top of standard therapy EuroPCR solicited abstracts, a total of 564 on the latest news on diagnosis and imag -
The last word – EuroPCR has created a ver - and a 45% reduction in the risk of arrhythmic high-quality papers were received, and ing, bifurcation management, outcomes sion of the famous Hyde Park Speaker’s death. Study investigators believe no other over 250 of these have been incorporated and techniques and specific issues in bifur - Corner, which will be located at the antiarrhythmic therapy has achieved such reduc - into 44 thematic sessions, including bifur - cation management. This theme will pro - entrance-hall end of the Rambla. Hyde Park tions. Importantly, the reduction was achieved cation lesions, transcatheter aortic valve vide experts with a combination of lec - Corner in London dates back to 1842, looks in patients who were in most cases receiving implantation, new devices, diabetes, inno - tures and case presentations, along with east to Piccadilly and was used to announce appropriate antithrombotic therapy. Both arms vations, coronary total occlusion, critical time for interactive discussions. the death of King George VI in 1952. At showed a similar rate of adverse effects. limb ischaemia and more.
Revascularisation – The Secondary EuroPCR 2009, speakers will be looking “The ATHENA trial is the first trial to show a
TAVI Forum – The transcatheter aortic Coronary Revascularisation sessions, in north-west towards the main arena, and reduction in the incidence of cardiovascular hos - valve implantation (TAVI) forum is built collaboration with the Hospital Clínico San attendees will use this “platform of expres - pitalisation or death in patients taking an antiar - around five themes – patient selection, Carlos, Madrid, Spain, and the sion” to address what they consider to be the rhythmic drug for atrial fibrillation,” commented vascular access and closure, valve size Thoraxcenter in Rotterdam, The most important issues in the world of car - Hohnloser. selection, cardiac and noncardiac compli - Netherlands, will introduce attendees to diovascular medicine today. Dronedarone is intended to be an alternative to cations and pitfalls in imaging techniques. specific secondary revascularisation issues. EuroPCR is the official meeting of the amiodarone (Cordarone), the treatment of choice
How Should I Treat? – These are new inter - EuroPCR aims to identify and understand European Association of Percutaneous for older patients with atrial fibrillation who have active sessions that bring two experts, an the problems associated with repeated Cardiovascular Interventions, a registered structural heart disease. interventionalist and a surgeon, together to coronary interventions and the benefits of a branch of the European Society of Cardiology, discuss the different treatment strategies multidisciplinary team approach. built in collaboration with the European Panel recommendation applicable to a particular case, and compare
Training – Practical training and virtual Association of Cardio-Thoracic Surgeons. According to Heart.org , several of the votes in favour of dronedarone’s approval were stated, unofficially, as “a cautious yes”. Some members of the FDA’s Cardiovascular and Renal Drugs Phase III data published Tips and tricks for chronic Advisory Committee expressed reservations about whether dronedarone had actually demonstrated on the effect of Tredaptive total occlusions adequate safety in the wide range of patients seen in clinical practice, as compared with the narrower RESULTS FROM a phase III clin - APPROXIMATELY UP groups in clinical trials or in the kind of long-term ical study published in the 30–40% of patients with coro - chronic use not examined in the trials. British Journal of Cardiology nary artery disease show at All those who voted yes were in favour of showed that patients with pri - angiography at least one occlud - excluding patients with severe systolic heart fail - mary hypercholesterolaemia or ed artery, but only 7–15% of ure from the indication, based in large part on the mixed dyslipidaemia, when chronic total occlusion (CTO) are ANDROMEDA (Antiarrhythmic trial with treated with 2g Tredaptive treated by percutaneous coronary dronedarone in moderate-to-severe congestive (nicotinic acid/laropiprant) intervention. Various studies have heart failure evaluating morbidity decrease) trial. coadministered with simvas - indicated that presence of CTO is In casting his vote supporting approval, Darren tatin (pooled across 20mg or the most important factor for select - McGuire, University of Texas Southwestern, 40mg doses) (n=609), experi - ing bypass as the choice of coronary Dallas, appreciated the “meaningful clinical-out - enced reduced LDL-C by nearly vascular revascularisation. comes evidence" provided by ATHENA. “I think 48%, increased HDL-C by near - Treatment of CTO lesions still rep - the outcomes data, as circumspect as some of ly 28%, and reduced triglyc - resents the last frontier for the inter - their features are, are a great step forward in atri - eride levels by approximately ventionalist. New guide wires, tech - al fibrillation management.” 33% following 12 weeks of niques and specific devices have led to higher procedural success One of the three panellists voting against treatment. rate, and nowdays recanalisation may be achieved in 70 –80% in recommending approval, appointed consumer The primary study endpoint Christie Ballantyne hands of expert operators. Even in this subset of lesions drug-elut - representative Sidney M Wolfe, Public Citizen, was change in LDL-C levels in ing stents significantly reduced the incidence of restenosis and reoc - Washington, DC, said he agrees with the cau - patients treated with 2g (n=585) reduced LDL-C by clusion, providing also to these complex procedures improved long- tion expressed in an FDA background docu - Tredaptive coadministered with 37%, increased HDL-C by 6%, term patency. ment accompanying the hearings, “That the simvastatin compared to those and reduced triglycerides by Considering all these dynamic changes, and difficulties of these safety of dronedarone presents a problem that treated with 2g of the drug nearly 15%. Comparative lipid procedures, Professor Alfredo R Galassi, Ferrarotto Hospital, the label alone may not be able to cover.” alone. Secondary endpoints efficacy results were measured University of Catania, Italy, is launching the comprehensive and That statement refers to dronedarone’s signifi - included change in LDL-C, HDL- as mean percent change from practical handbook Percutaneous Coronary Interventions for cant mortality risk in ANDROMEDA. “There C, and triglyceride levels in baseline for LDL-C and HDL-C, Chronic Total Occlusions – Galassi’s Tips & Tricks. is a continuum in patients with atrial fibrilla - patients treated with 2g of the and median percent change for “When I thought of this handbook my intention was to provide a tion/atrial flutter, they go in and out of conges - drug and simvastatin (pooled) triglycerides. meaningful and concise practical guide for the interventional cardi - tive heart failure,” the document said. So an compared to those treated with “The results in this study ologist, who has good overall experience in the field of coronary individual might more resemble simvastatin alone. suggest that nicotinic angioplasty, and is willing to improve his skilfulness in the field of ANDROMEDA’s population at one time but In the other treatment arms, acid/laropiprant, used with a revascularisation of CTO,” said Galassi. ATHENA’s at another. In the real world, Wolfe 2g Tredaptive alone (n=192) statin, could offer another The content underlines clinical treatment issues, operator differ - said, patients aren’t so narrowly defined that reduced LDL-C by 17%, approach to treat patients with ent techniques, and practical case-based scenarios for each of differ - they consistently fit the entry criteria of clini - increased HDL-C by approxi - dyslipidaemia,” said Christie M ent situations that an interventionalist may encounter during cal trials. mately 23%, and reduced Ballantyne, Baylor College of recanalisation of a chronic total occlusion. Dronedarone is under regulatory review by the triglycerides by nearly 22%; Medicine, Houston, USA, coau - The foreword has been written by Professor Corrado Tamburino, European Medicines Agency. The ATHENA trial and simvastatin alone (pooled) thor of the study. Ferrarotto Hospital, University of Catania. was sponsored by Sanofi-Aventis.

BIBA Publishing

30 Cardiovascular News International Issue 13 May 2009 Product News

Voyager NC Abbott’s Voyager NC coronary balloon catheter launched

Abbott announced in March the launch of Voyager NC Coronary Dilatation Catheter, a high-pressure capability device designed to optimise the treatment of patients with coro - nary artery disease during angioplasty proce - dures. The device is now available in the USA, Europe and some countries in Asia and Latin America. The Voyager NC system can be used for both predilatation and postdilatation proce - dures. Physicians can use the device to navi - gate tortuous anatomy and open up lesions ication and revascularisation treatments.” intracardiac images. The system transmits before a stent is delivered, or expand a stent A study published in Heart found that neu - ViewMate II: high-frequency sound waves through a more precisely against the vessel wall after it is rostimulation was effective at reducing angina transducer on the tip of the catheter – the implanted. The device is available in a variety and the need for nitrate medications to treat Real-time views transducer converts electric energy into of diameters (2 –5mm) and lengths (6 –25mm). it. In the study, angina patients who used neu - sound energy, the sound waves then reflect “When choosing a dilatation catheter, one rostimulation several times a day had 86% inside the heart off structures inside the heart and the trans - of the key attributes interventional cardiolo - fewer episodes of angina and lowered their ducer converts them back into electric ener - gists look for is the ability to accurately deliv - nitrate use by 89% compared to periods in St Jude Medical has announced the first use gy to produce the anatomical images. er the balloon to the target lesion, particularly which they received placebo treatment. outside the United States of its ultrasound The intracardiac images created by the in challenging coronary anatomy,” said Dean “People living with chronic angina often imaging system that enables physicians to ViewMate II System help guide physicians in J Kereiakes, The Christ Hospital Heart and face a poor quality of life due to constant or view real-time images from inside the heart performing procedures such as radiofre - Vascular Center, Cincinnati, USA. “Voyager recurring physical pain and loss of social as they diagnose and treat conditions result - quency ablation to treat irregular heart NC delivers on its promise as a high perform - function,” said Clas Mannheimer, Östra ing from abnormal rhythms or structural rhythms, including atrial fibrillation, and in ance balloon dilatation catheter with high- Hospital, Gothenburg, Sweden. problems. By providing clear, accurate closing defects such as patent foramen pressure capability, frequently making diffi - “Neurostimulation provides a minimally-inva - images of the heart’s interior anatomy and ovale, a small hole or opening in the wall cult cases easier, even when treating the sive treatment option for managing this the position of devices, the system enables between the two atria. Clear views inside the most challenging lesions.” painful condition.” physicians to perform procedures with heart also help reduce the time that it takes Advancements that Abbott engineered into In addition to chronic angina, the Genesis increased control. The ViewMate II physicians to perform procedures, enabling the Voyager NC include a specialised tip with neurostimulation system is approved for Ultrasound System with the ViewFlex PLUS patients to recover more quickly and a smooth, rounded shape designed to deflect treating chronic neuropathic pain of the trunk Intracardiac Echocardiography Catheter was enhancing hospital productivity. off stent struts and enhance balloon delivery and limbs and pain from back surgeries that featured at the Boston Atrial Fibrillation The ViewMate II System with the ViewFlex through stents; flexible tungsten markers have failed. Patients can obtain more infor - Symposium, in January. PLUS Catheter recently received European CE designed to help physicians navigate through mation about neurostimulation pain therapies The ViewMate system uses ultrasound mark approval. The system received FDA clear - arteries and properly position the balloon at www.PowerOverYourPain.com. technology to produce high-resolution ance in January 2008. St Jude began market - within a treatment area; and bilayer balloon The Genesis neurostimulation system has material designed to make the balloon thin - not been approved in the USA for the treat - ner and more flexible, enabling controlled ment of chronic angina. balloon growth.

GE’s first portable electrocardiogram cleared in the USA

The FDA has cleared GE Healthcare’s latest electrocardiogram solution, the portable MAC 800, based on cell phone technology. GE’s new device targets physician’s offices and the pharmaceutical industry. Originally developed and introduced in China in 2008, the lightweight portable device combines the keypad of a phone with a full- size color display and world-class diagnostic software to help clinicians shape the future of healthcare in regions across the world. St Jude Medical’s Genesis MAC 800 has the features of a full size, 65- pound electrocardiogram device, engineered down to under seven pounds, battery includ - ed. The unit’s integrated carrying handle Neurostimulation enables clinicians to carry it like a briefcase, expanding access to care, regardless of patient system for chronic location. Its lithium ion battery keeps it running for roughly two hours and a quick, four-hour angina CE marked recharge ensures minimal downtime. MAC 800’s multiple communication St Jude Medical announced in March options fit the needs of most practices, European CE mark approval of its Genesis including LAN, modem, SD card and serial neurostimulation system for managing port to store and send electrocardiogram chronic angina. Approximately the size of a data from any location. Additionally, the stopwatch, this neurostimulation system device offers the option of a PDF or XML helps to control angina pain by sending mild output for universally recognised storing and pulses of electricity from a device implanted data sharing. MAC 800 also connects seam - in the torso via thin insulated wires called lessly to a variety of vendors’ EMR solutions leads to nerves located along the spinal cord. via Cardiosoft, GE’s cardiology information “While the stimulator will help mask the software system, creating a fully digital elec - pain of angina, studies have shown that neu - trocardiogram workflow. rostimulation will not mask the pain of a heart MAC 800 will launch to the American pri - attack,” said Mike JL DeJongste, University mary care market during the second quarter of Groningen, The Netherlands. “This therapy 2009. The device was showcased at the is designed to provide relief for those Scientific Sessions of the American College patients who suffer from chronic angina that of Cardiology, in Orlando, USA, in the end ViewMate with ViewFlex does not respond sufficiently to optimal med - of March.

BIBA Publishing Cardiovascular News International Issue 13 May 2009 31 Product News

ing and distributing the ViewMate following its percutaneous coronary interventions involve of the heart at the conclusion of an open-heart merger with EP MedSystems in July 2008. blood vessels with diameters of 2.5mm or less. surgical procedure to reduce the severity of Yaariv Khaykin and Atul Verma, Southlake BioMatrix was originally launched in Europe adhesions that form between the surface of Regional Health Centre in Newmarket, in April 2008, where its proprietary coating for - the heart and adjacent tissue surfaces follow - Canada, performed the first procedures using mulation consisting of an abluminal ing the surgical procedure. REPEL-CV is the ViewMate outside the USA. “The biodegradable polymer and the Biolimus A9 designed to provide the therapeutic benefit ViewMate System provides images of drug has been very well accepted. BioMatrix is and then degrade so that it is cleared from the improved contrast. Sharper, clearer images now available in many international markets surgical site. REPEL-CV represents the first in a are critical to accurate diagnoses and precise excluding China, the USA and Japan. series of anti-adhesion products under devel - treatments,” said Khaykin. Verma added, “The Biolimus A9 was designed specifically for opment that are based on the company's pro - ViewMate System enables me to obtain use in drug-eluting stent systems. In addition Boston Scientific’s iCross prietary polymer technology. images with greater depth, which in turn to effective immunosuppressive and anti- In a randomised, controlled clinical trial allows for more informed diagnoses and inflammatory properties, the drug has a high - conducted at 15 pediatric cardiac surgery treatment decisions.” er lipophilic and hydrophobic profile than Hospital Center. “The combination of the centres throughout the United States, over The ViewFlex PLUS catheter’s one-hand other limus analogs, enabling rapid absorp - iCross’ outstanding image quality and excel - 70% of the REPEL-CV treated patients were control frees physicians to simultaneously tion of the drug into the targeted tissue and lent deliverability should help physicians bet - completely free of clinically-significant adhe - position other devices with the other hand. reduced systemic exposure. Precision auto - ter identify lesion characteristics.” sions, the most severe grade of adhesions Its tip features a 64-element, linear-phased mated coating ensures the PLA and drug The iCross Catheter features a Bioslide measured, as compared to less than 30% in array transducer capable of detailed, high- combination is applied only to the abluminal Hydrophilic Coating that has been shown in the control patients. In the primary clinical resolution imaging. The tip itself has a bidi - (outer) surface of the stent. The PLA fully bench tests to provide a 28% improvement endpoint assessment, the mean extent of rectional curve and a deflection angle of up degrades into water and carbon dioxide as in pushability in challenging anatomy. clinically-significant adhesions in the control to 120 degrees, allowing it to capture images the drug elutes, ultimately leaving in place a patients was 2.5 times greater than in the across broad areas of the heart. The biocompatible stent surface. REPEL-CV treated patients. catheter’s 9 French size allows physicians to create a smaller opening through which to FDA approves insert the catheter into a vessel, yet its design provides stability and control over Boston Scientific REPEL-CV for Medtronic’s viewing angles and positioning. launches iCross paediatric surgery Endeavor is imaging catheter SyntheMed has announced that the FDA has approved in Japan CE mark for granted the premarket approval application Boston Scientific has announced the launch for REPEL-CV Adhesion Barrier for use in pae - Medtronic has announced approval of its smaller-diameter of its iCross coronary imaging catheter, a diatric cardiac surgery patients. REPEL-CV is a Endeavor drug-eluting coronary stent by the product designed to improve the deliverabili - bioresorbable film designed to be placed over Japanese Ministry of Health, Labor and BioMatrix stent ty of the company’s market-leading intravas - the surface of the heart at the conclusion of Welfare. Medtronic plans to launch the cular ultrasound (IVUS) technology, the iLab an open-heart surgical procedure to reduce Endeavor immediately following the authori - Biosensors International Group has received Ultrasound Imaging System. The company the formation of postoperative adhesions. sation of reimbursement, which is expected CE mark approval for a 2.25mm diameter ver - said the iCross catheter would be available REPEL-CV has CE mark approval for use in on 1 May. sion of its BioMatrix drug-eluting stent sys - immediately in the USA. all cardiac surgical patients and is currently The Endeavor clinical program has demon - tem, further expanding the currently available “Boston Scientific’s iCross coronary imag - marketed through a network of independent strated that the stent is associated with low range of 2.5mm to 4mm stent diameters. ing catheter is a powerful tool for visualising distributors in the European Union and in rates of stent thrombosis, myocardial infarction This new addition to the BioMatrix portfolio coronary intravascular pathology, especially several Southeast Asian countries. and cardiac death, as well as low rates of clini - offers a major opportunity to increase market in patients with complex coronary artery dis - REPEL-CV is a bioresorbable adhesion barri - cally-driven target lesion revascularisation, out penetration, as an estimated 12% to 15% of all ease,” said Augusto Pichard, Washington er film designed to be placed over the surface to as long as five years of patient follow-up.

BIBA Publishing GET BREAKING NEWS FAST! Sign up at www.cardiovascularnews.com

NEWS & VIEWS for cardiovascular specialists Cardiovascular News International Issue 13 May 2009 33 Product News Cypher Select Plus approved for diabetic patients

Biotronik’s The Cordis’ Cypher Select Plus Sirolimus- PRO-Kinetic eluting Coronary Stent has received CE mark - stent ing within the European Union for treatment of patients with diabetes. The expanded indi - cation for the stent is based on numerous New PRO-Kinetic clinical studies, both randomised and nonran - domised clinical trials that have been pre - Energy Stent sented at major medical meetings and/or appeared in international peer reviewed pub - System launched lications, supporting the safety and efficacy of the device in patients with diabetes. Biotronik has announced the launch of its In addition to diabetes, Cypher has recently new generation PRO-Kinetic (PK) Energy received CE marking for chronic total occlu - Stent System with Probio silicon carbide sion, multivessel disease and bifurcations. In coating. The company is launching this prod - August 2008, the stent received CE marking uct immediately in all countries accepting CE for treatment of acute myocardial infarction. mark approval. Cypher Select Plus Stent was previously indi - The new PK Energy Stent System makes cated for de novo lesions, in-stent restenosis use of the company’s Pantera balloon tech - and small vessels. The device has a total of nology to improve the deliverability of the eight different indications. stent. The Pantera balloon catheter was Cypher launched in mid-2008 and has received posi - tive reviews as an exceptional balloon for ous anatomies and difficult lesions. larisation rate of 4.9% and a .75 mm late loss crossing difficult to treat lesions. The new PK Energy continues to have the that is close to some drug-eluting stents seen New Carpentier- The Pantera balloon makes use of more Probio silicon carbide coating. This ultra on the market,” said Johannes B Dahm, Heart flexible and thinner materials. Additional thin, passive layer prevents allergenic ions & Vascular Center Neu-Bethlehem, Göttingen, Edwards mitral improvements of the PK Energy include from being released from the stent surface. Germany, on his publication in minor adjustments to stent design to opti - By eliminating this process, stents coated EuroIntervention on the PRO Heal Registry. valve repair ring mise the overall tension distribution and a with Probio have a dramatic reduction in This positive effect is also reflected in the new thermal crimping technology. thrombus formation and greater haemocom - interim results from the company’s Multi Edwards Lifesciences launched the The PK Energy Stent was designed with a patibility. BENE study, a prospective, multicentre trial Carpentier-Edwards Physio II mitral valve double helical shape that gives it high flexibil - “Through accelerating rapid endothelialisa - looking at the safety and efficacy of the PRO- repair ring at the 45 th annual meeting of the ity and a smooth crimp profile, while the tion to an earlier functional layer, Probio coat - Kinetic, that have shown very low major Society of Thoracic Surgeons in San cobalt chromium material allows for some of ing on ultra-thin cobalt chromium stents adverse cardiac events (8.1%) and target Francisco, USA. the thinnest struts on the market today leads to less recurrent restenosis after stent lesion revascularisation (8.1%) rates at six “Since the creation of the original (60 m/.0024”). The new delivery system with placement without increased occurrence of months. The full six-month results of the Carpentier-Edwards Physio ring, scientific newµ balloon material ensures greater flexibili - stent thrombosis. In our latest publication, we Multi BENE study are scheduled to be pre - knowledge about mitral valve anatomy ty for added deliverability for the most tortu - have found a very low target lesion revascu - sented in the second quarter 2009. and pathology has expanded significant -
34

BIBA Publishing 34 Cardiovascular News International Issue 13 May 2009 Product News

33
ly, and these new learnings have been that implantation of the CryoValve SG applied in the design of the new Carpentier- Carillon Mitral Contour System reduces the risk of inducing HLA class I and CrossBoss and Edwards Physio II ring,” said Alain F class II alloantibodies, based on panel reac - Carpentier, Hôpital Europeen Georges tive antibody (PRA) measured at up to one Stingray: First Pompidou, Paris, France, the inventor of the year, compared to the standard- processed original Carpentier-Edwards Physio ring. pulmonary human heart valve. The effect of case in the USA Carpentier, the foremost pioneer in the field reduced alloantibodies, however, on the long- of heart valve repair for more than 40 years, term durability, or long-term resistance to BridgePoint Medical has completed the first and David H Adams, one of the leading mitral rejection by the patient, of the CryoValve SG human clinical case in the United States repair authorities in the world, are the coin - has not yet been clinically proven. The com - using its CrossBoss CTO Catheter and ventors of the next-generation ring. pany has documented the implantation of Stingray CTO Re-Entry System. CrossBoss The Carpentier-Edwards Physio II ring is a more than 1,800 CryoValve SG pulmonary and Stingray are under clinical investigation novel mitral valve repair solution. It is the only human heart valves. to demonstrate safety and effectiveness in annuloplasty ring offering “shape optimisa - The CryoValve SG pulmonary human heart the treatment of chronic total occlusions tion,” which matches the geometry of the ring valve is indicated for the replacement of dis - (CTO). The FAST-CTOs (Facilitated antegrade to the characteristics of the patient's diseased eased, damaged, malformed or malfunction - steering technique for chronic total occlu - mitral valve, and does not ing native or prosthetic pulmonary valves. sions) trial was conditionally approved in limit repair options based The valve can be used in conjunction with January 2009 by the FDA. on etiology, or cause, of right ventricular outflow tract reconstruction The first clinical case was completed by the mitral valve disease. procedures, commonly performed in children William Lombardi, North Cascade Cardiology Several new features, sinus/great cardiac vein to reshape the annu - with congenital heart defects. In addition, the in Bellingham, Washington, USA. The patient such as a unique sewing lus around the mitral valve, thereby reducing valve can be used for pulmonary valve was a 61-year-old woman with a chronic total cuff, provide surgeons with a mitral regurgitation. Preclinical and early clin - replacement during the Ross Procedure, an occlusion of her right coronary artery, chest device that is also easier to implant. ical data have suggested both a reduction in operation in which a patient’s defective aortic pain (characterised as level three angina) and Edwards received 510(k) clearance from mitral regurgitation and improvements in valve is removed and replaced with his or her a positive stress test. The patient was the FDA to market the Carpentier-Edwards other key parameters including NYHA class, own pulmonary valve. The CryoValve SG is referred to Lombardi for inclusion in Physio II ring. It will also be available in six-minute walk distances and quality of life. then surgically implanted in place of the BridgePoint Medical’s FAST-CTOs clinical trial Europe, as the company has also received CE removed native pulmonary valve. after a failed treatment attempt to cross the mark approval. A PRA screen is used to identify allosensi - lesion by a referring physician. tized patients prior to organ transplantation. Procedural completion took 35 minutes, FDA clears An elevated PRA level, indicating pretrans - resulting in the opening of the completely plant alloantibodies, increases the risk of blocked vessel and return of normal blood Carillon Mitral new claim for organ transplant rejection and patient mor - flow to the patient’s heart. “The BridgePoint tality. In addition, high and prolonged PRA Medical System allowed me to open this chal - Contour System CryoValve SG levels may prevent or delay transplantation lenging total occlusion”, stated Lombardi. until a suitable crossmatch-compatible donor “BridgePoint Medical’s clinical trial is designed receives CE mark CryoLife has announced that is identified. to demonstrate the CrossBoss CTO Catheter the FDA has cleared a new and the Stingray Re-Entry System are broadly Cardiac Dimensions (Kirkland, Washington, claim for the CryoValve SG effective in re-establishing blood flow across USA) has announced that it has received the pulmonary human heart completely blocked arteries and these devices CE mark approval for its Carillon Mitral valve. The new labeling Second-generation will hopefully provide improved options for Contour System from KEMA Quality BV – a claim relates to reducing patient care.” The patient was released from European Union Notified Body from The a component of the small vessel and the hospital the day after the procedure. Netherlands. The Carillon system is a percu - immune response in taneous treatment for functional mitral regur - recipients of the long lesion stents gitation. The CE mark approval is an impor - CryoValve SG. tant milestone for Cardiac Dimensions, CryoValve SG pul - Boston Scientific has announced that it has Maquet Cardiohelp allowing the company to market the product monary human heart valve is processed with submitted to the FDA the final modules of in countries that accept CE marking. the company’s proprietary SynerGraft tech - the company’s premarket approval applica - wins design The Carillon system combines a propri - nology, which is designed to remove allo - tions for both its Taxus Liberte Atom etary implantable device and delivery sys - geneic donor cells and cellular remnants from Paclitaxel-Eluting Coronary Stent System and awards tem. The implant consists of a shaping ribbon the valve without compromising the integrity its Taxus Liberte Long Paclitaxel-Eluting between distal and proximal anchors. It is of the underlying collagen matrix. Coronary Stent System. If approved, the The Design Zentrum Nordrhein-Westfalen has delivered percutaneously via jugular vein The new claim relates to the fact that data Taxus Liberte Atom Stent will become the bestowed the red dot design award on the access under fluoroscopic guidance. The from three company-sponsored clinical stud - company’s second 2.25mm diameter drug- world’s smallest cardiopulmonary support implant is designed to be positioned, adjust - ies and a comprehensive review of the scien - eluting stent (DES) available in the USA. It system Cardiohelp. Before that, the Maquet ed and gently anchored in the coronary tific literature on allograft heart valves show will then likely succeed the Taxus Express innovation had already received the iF prod - Atom Stent, which is the company’s first uct design award. approved small stent and the only DES cur - The red dot award is globally recognised as rently approved by the FDA to treat small a hallmark of design excellence. Cardiohelp vessels. The Taxus Liberte Long Stent is was one of the winning entries in the product designed to be the first 38mm drug-eluting category Life Science and Medicine. A whole stent available in the USA. range of criteria is used to assess the prod - These premarket approval submissions ucts: innovation, functionality, quality of form, include clinical data from the global, multi - ergonomics, symbolic and emotional content, centre Taxus ATLAS Small Vessel and Long product periphery, degree of self-explanation, Lesion studies, designed to compare the and environmental compatibility. performance of the Taxus Liberte Atom and This year 3,231 products from a total of 49 Taxus Liberte Long Stents with Taxus nations were entered for a red Express. dot product design 2009 award. While the second-generation Taxus The international panels of Liberte stent uses identical drug dose, poly - experts bestowed a red dot on 683 mer and release kinetics as the Taxus products, with the best 49 receiving Express, it features thinner struts and a uni - the additional tag: best of the best. form architecture specifically designed for drug delivery. One-year results from the Taxus ATLAS SV and LL studies were published in the December 2008 issue of the Journal of American College of Cardiology . The studies both met their primary endpoint of non-infe - rior, nine-month, in-segment diameter stenosis versus the Taxus Express Stent control group. They reported a significant reduction in small vessel in-stent restenosis and major adverse coronary events in patients treated with the Taxus Liberte Atom Stent, and a significantly reduced rate of myocardial infarction in patients with long lesions treated with the Taxus Liberte Taxus Taxus Liberte Long Stent. Cardiohelp

BIBA Publishing

36 Cardiovascular News International Issue 13 May 2009 Clinical News

enrolment by October. This should enable American and Japanese launches of Promus vProtect Luminal Element, consistent with the expiration of the company’s existing Promus supply agree - Shield stabilises ment in mid-2012. The European launch is planned to occur in the fourth quarter of 2009. vulnerable plaque PLATINUM will evaluate the safety and effi - cacy of the Promus Element in three studies. The first patient receiving focal preventive The first, Promus Platinum Workhorse, will treatment for vulnerable plaque underwent a evaluate the safety and efficacy of the six-month follow-up examination that Promus Element compared to Promus. This revealed successful stabilisation of the target 1:1 randomised study will evaluate 1,532 plaque, it was announced in January. The patients from 160 global sites with de novo interventional cardiology team led by Patrick “workhorse” lesions from 2.5 to 4.25mm in W Serruys, Erasmus University, Rotterdam, diameter and less than 24mm in length. The The Netherlands, placed a vProtect Luminal primary endpoint of the workhorse study is Shield (Prescient Medical) in the left anterior target lesion failure at 12 months, with clini - descending coronary artery of the patient in cal follow-up scheduled out to five years. June 2008. The 64-year-old man is enrolled in Two additional parallel studies will evalu - SECRITT I, a pilot study designed to evaluate ate the Promus Element in small vessels and vProtect. long lesions. The small vessel study will By January, the treated artery demonstrat - examine lesions from 2.25 to 2.5mm in diam - ed excellent blood flow and healing. The eter and less than or equal to 28mm in shield is now covered by a thin layer of tis - length, while the long lesion study will exam - sue, incorporating it into the arterial wall. ine lesions from 2.5 to 4.25mm in diameter This is a hallmark of a successful implant and and 24 to 34mm in length. The primary end - demonstrated that the shield performed Medtronic’s Endeavor point of both studies is target lesion failure at much better than would be expected for tra - 12 months. ditional bare metal stents and comparable to the first generation of drug-eluting stents. demonstrated that the Endeavor stent is Patients enrolled in SECRITT I have been PROTECT trial associated with low rates of stent thrombo - referred to the cath lab for treatment of clini - sis, infarction and cardiac death, as well as Terumo completes cally significant coronary lesions, which are enrolment is low rates of clinically-driven target lesion treated according to current standards of care. revascularisation and target vessel revascu - enrolment in Using a combination of ultrasound and optical completed larisation, out to as long as five years of imaging techniques, the investigators examine patient follow-up. The program has enrolled NOBORI 2 the coronary arteries for signs of additional, Medtronic announced in February the com - more than 21,000 subjects to date. nonflow-limiting vulnerable plaques, for which pletion of enrolment in PROTECT, the compa - Terumo has announced that the enrolment of patients would not generally receive treat - ny’s global study comparing its Endeavor to 3,000 patients was completed in the NOBORI ment. Patients with vulnerable plaques under - Cordis’s Cypher in the treatment of coronary 2 clinical trial. NOBORI 2 is a prospective, go follow-up diagnostic catheterisations six artery disease. Boston Scientific multicentre, real-life study to validate the months post-treatment, at which time investi - PROTECT will yield contemporary data on safety and effectiveness of the Nobori stent gators determine the shield’s impact. stent thrombosis rates and other clinically rel - begins enrolment in patients enrolled in routine daily practice in “We are very good at opening arteries that evant endpoints for these two drug-eluting 129 centres across more than 20 countries. are blocked, but we have not succeeded in stents (DES), including the role of antiplatelet for new stent The primary endpoint is a device-oriented preventing heart attacks related to plaque therapy after their implantation. The trial suc - composite of cardiac death, myocardial rupture. The vProtect Luminal Shield has cessfully randomised 8,800 patients in 18 Boston Scientific announced in February the infarction and target lesion revascularisation demonstrated that it can be safely placed months. The trial steering committee beginning of patient enrolment in the PLAT - at 12 months post-procedure. over a vulnerable lesion without rupturing the includes William Wijns, Cardiovascular INUM clinical trial, which is designed to eval - “The data collected from the 3,000 plaque, and the results at six months are Center in Aalst, Belgium, Philippe Gabriel uate the Promus Element everolimus-eluting patients, treated with Nobori in the large extremely promising. The shield performed Steg, Hôpital Bichat-Claude Bernard in Paris, coronary stent. The first American patient scale NOBORI 2 study will allow us to exactly as intended, allowing us to prevent France, and Edoardo Camenzind, University was enrolled at the Medical Center of the increase understanding about the efficacy plaque rupture and an acute event, rather Hospital Geneva in Switzerland. Rockies in Loveland by Thomas Downes. The and long-term safety of this most innovative than trying to repair the damage after the PROTECT is powered to detect a clinically first Japanese patient was also enrolled in the drug-eluting stent, in a truly representative fact,” said Serruys. significant difference in rates of stent throm - end of January. patients population,” said Gian Battista bosis between the two devices. The PLATINUM clinical program will enroll Danzi, Ospedale Maggiore Policlinico, Milan, “With the Endeavor DES, the rate of VLST 1,728 patients at 160 sites worldwide. The Italy, the principal investigator of NOBORI 2 [very late stent thrombosis] appears to be trial will compare the Promus Element to the study. “Particularly appealing is the expected Infarction treated remarkably and sustainably low – a reassur - Promus. Boston Scientific plans to develop quality of data from this trial with anticipated ing record,” said steering committee member additional variations of the Element stent 100% online monitoring, on-site monitoring with Stentys William O’Neill, University of Miami School of platform, including next generations of a bare for the first 1,000 patients and 30% of addi - Medicine, USA. “While the Endeavor DES metal stent and a paclitaxel-eluting Taxus tional 2,000 patients, and all serious adverse extended system has demonstrated durable efficacy to four Element stent. events”, added Danzi. years of patient follow-up in comparison to The Element platform features a propri - The efficacy and safety of Nobori have Stentys has announced that it has extended other DES, its long-term safety profile resem - etary Platinum Chromium Alloy, designed for been established in clinical trials including its self-expanding and disconnectable stent bles that of a bare-metal stent, the bench - coronary stents. This alloy, coupled with new NOBORI 1, NOBORI CORE and NOBORI technology platform to include a second mark for stent safety. PROTECT puts this con - stent architecture, is designed to enable thin - Pharmacokinetics study. Compared with major indication – acute myocardial infarc - tention to the test in a large randomised ner struts, increased flexibility and a lower Taxus Express and Taxus Liberté, Nobori stent tion. Two patients were successfully treated clinical trial.” profile while improving radial strength, recoil proved its noninferiority and even superiority during infarction procedures in March by Drs Very late stent thrombosis emerged as a and visibility. In addition, the Promus Element in efficacy endpoints such as in-stent late Stefan Verheye, Antwerp, Belgium, and K E safety concern with the first generation of incorporates the new Apex Dilatation loss, with low frequency of adverse cardiac Hauptmann, Trier, Germany. drug-eluting stents in 2006, when clinical tri - Catheter technology, designed to enhance events and no stent thrombosis. In NOBORI The self-expanding feature ensures optimal als conducted to support the regulatory deliverability to complex lesions. CORE, a comparative study versus Cypher, apposition in the critical initial hours and approvals of these devices revealed a numer - The global principal investigator for the Nobori showed excellent performance with days after the procedure by being constantly ical increase in the rate of VLST compared to trial is Gregg W Stone, Columbia University very low rate of adverse cardiac events. The applied to the vessel surface during throm - bare metal stents controls. Medical Center and the Cardiovascular overall restenosis rate in all NOBORI trials was bus and vessel spasm relief, therefore avoid - The trials that supported the regulatory Research Foundation in New York, USA. The as low as .5% and no late stent thrombosis ing malapposition. The disconnectability fea - approvals of the Endeavor have shown no American coprincipal investigator is Paul was recorded in any of the trials. ture is designed to treat lesions close to a increase in the rate of VLST compared with Teirstein, Scripps Green Hospital in La Jolla, Nobori utilises Biolimus A9, an analogue of bifurcation, by ensuring safe main branch its bare metal stent control and no new and the international coprincipal investigator sirolimus which is expected to reduce tissue provisional stenting and optimal side branch events after two years through four years of is Ian Meredith, Monash Medical Centre, proliferation and which is eluted from a biore - access when needed. The Stentys platform is follow-up. These observations served as the Melbourne, Australia. sorbable polymer, polylactic acid. The stent implanted by usual stenting techniques rationale for PROTECT. “The new alloy and stent design of the delivery system applies Terumo’s proprietary requiring no additional training. The trial’s primary endpoint is overall stent Promus Element Stent promise to offer hydrophilic coating which enhances deliver - “The Stentys device was simple to implant, thrombosis at three years; secondary end - improved deliverability and visibility, even in ability and reduces arterial wall damage. conformed snugly to the treated vessel, and points include death and non-fatal myocardial patients with complex and challenging anato - created minimal vessel injury since no high- infarction, target lesion revascularisation and my,” said Stone. “I am enthusiastic about the The NOBORI 2 trial will involve pressure inflation was required,” said Verheye. target vessel revascularisation. Three-year possibility of having both everolimus and “When comparing immediate and five days data are expected to be available in 2012. paclitaxel versions of this innovative stent sys - 3,000 patients enrolled in129 post-procedure results using IVUS [intravascu - Involving more than 200 medical centres tem available, allowing for the tailored treat - centres in more than 20 lar ultrasound], the coronary vessel expanded worldwide, PROTECT constitutes a large part ment of patients with coronary artery disease.” countries. slightly, and Stentys followed intimately the of the Endeavor clinical program, which has Boston Scientific expects to complete vessel remodeling with perfect apposition.”

BIBA Publishing

38 Cardiovascular News International Issue 13 May 2009 Industry News

Image by Nico Avelardi raised the company’s rating outlook to posi - Cordis celebrates tive from negative, while affirming the com - Sorin acquires pany’s corporate credit rating at BB+. 50 years The Standard and Poor’s upgrade followed Datascope’s the Moody’s actions of 12 March when it Founded in a garage in Miami, USA, Cordis raised the company’s outlook to stable from Clearglide line celebrated its 50th anniversary in April. The negative. company has grown into a global organisa - Standard and Poor’s said the revised rating Sorin Group has announced that it has tion with well over half of its US$3.1 billion in outlook reflects: the company’s ongoing debt acquired the Clearglide endoscopic vessel 2008 sales coming from outside the USA, pay down over the past several years; main - harvesting product line of Datascope. and its products now touch an estimated one tenance of its leading market share in the Endoscopic vessel harvesting devices enable million patients every year. drug-eluting stent market in the face of less-invasive harvesting of vessels for use in Cordis was founded in 1957 by William P increasing competition; and prospects for (at coronary artery bypass grafting. The proce - Murphy, Jr, the son of a Nobel laureate. The a minimum) modest growth in cardiac dures replace traditional open vessel har - company, originally named Medical rhythm management devices given recent, vesting, and avoid significant pain and dis - Development Corporation, rapidly gained new product launches. comfort for patients. In addition, the large recognition as a pioneer in innovative prod - incision that is required in an open vessel ucts for interventional vascular medicine. In harvesting procedure is associated with a 1959, Murphy changed the company’s name high rate of wound complications including to Cordis (“of the heart”), indicating its pri - Medtronic dehiscence, hematoma and infection. The mary therapeutic focus. endoscopic approach is associated with During the 1960s, Cordis became involved in acquires CoreValve fewer wound complications than the tradi - the relatively new field of cardiac pacing and tional open method. also introduced the first full line of “pre-shaped” Cordis’ anniversary was celebrated at and Ventor Judkins catheters, a preformed catheter used in the CX Symposium, London, UK, in April certain angioplasty procedures. Medtronic has announced the completion of In the early 1970s, Cordis introduced the in the USA – was approved by the FDA for its acquisition of CoreValve, developer of Medrad revenues first sheath introducers with hemostasis coronary artery applications. percutaneous, catheter-based transfemoral valves, which were designed to minimise In 2003, the FDA approved the Cypher aortic valve replacement products. The grow 10% in 2008 blood loss during an angioplasty procedure. sirolimus-eluting coronary stent, the first definitive agreement called for an initial pay - By then, Cordis also ranked second only to combination drug-device product intended to ment of US$700 million, plus additional pay - Medrad’s revenues grew to over US$600 mil - Medtronic among America’s leading pace - help reduce restenosis of a treated coronary ments contingent upon the achievement of lion in 2008, an increase of more than 10% maker manufacturers. artery. The American Heart Association agreed milestones. over the previous year. Last year’s business In the 1980s, Cordis launched a full line of named the Cypher stent one of the top 10 The company has also announced its highlights include the acquisition of Possis percutaneous transluminal coronary angio - medical advancements of that year. acquisition of Ventor Technologies (Netanya, Medical, award-winning product innovations plasty guiding catheters. In the early 1990s, By early 2006, two million patients world - Israel), a developer of transcatheter heart and LEED certification for two new buildings. the company introduced the first angioplasty wide had received the Cypher stent and, in valve technologies for the treatment of aortic Medrad acquired Possis Medical in April balloon utilising nylon balloon material. 2008, the three-million-patient mark was valve disease. Medtronic will acquire Ventor 2008, pairing Possis’ leadership position in In 1996, Cordis merged with Johnson & reached, a milestone unmatched by any for a payment of US$325 million. the thrombectomy market with Medrad’s Johnson Intervention Systems to form Cordis other drug-eluting stent at that time. The Ventor acquisition adds two technolo - cardiovascular products and worldwide Corporation, with, at the time, 3,500 employ - gies to Medtronic’s transcatheter valve port - infrastructure. ees. In 1997, Cordis expanded into the field of folio: a minimally-invasive, surgical transapi - The company’s AngioJet product is a electrophysiology through the acquisition of cal technology and a next-generation world’s leading mechanical thrombectomy Biosense, which merged with Webster Boston Scientific’s percutaneous, transfemoral, technology. system, with FDA approval to remove large Laboratories in 1998 to form Biosense Webster. According to the company, these comple - and small clots from coronary arteries, coro - The 1990s also saw the launch of the com - rating outlook mentary technologies offer compelling clini - nary bypass grafts, and peripheral arteries pany’s biggest breakthrough yet – coronary cal benefit to distinctly different subsets of and veins. This segment of Medrad’s busi - stents. In 1994, the Palmaz-Schatz balloon- Boston Scientific has announced that patients with aortic stenosis who are at high ness is now known as Medrad expandable stent – the first bare-metal stent Standard and Poor’s Ratings Services has or prohibitive risk for surgery. Interventional/Possis.

Calendar Cardiovascular News International 6–9 May Tel: +1 (202) 464 3400 Westin St Francis Hotel 17–19 June Fax: +44 (0)1922 455 238 Editor: th SCA&I (The Society for Email: [email protected] Tel: +1 (978) 927 8330 8 International Congress on Email: wheldonevents@ Dr Kevin Fox Cardiovascular Angiography Web: www.hrsonline.org/sessions Fax: +1 (978) 524 8890 Complications during btconnect.com nd Publisher: and Interventions) 32 Email: [email protected] Coronary Interventions: Web: www.heartuk.org.uk Stephen Greenhalgh Annual Scientific Sessions 19–22 May Web: www.ismics.org Management and Prevention Las Vegas, USA EuroPCR 2009 Lausanne, Switzerland 27–30 June Managing Editor: Caesars Palace Barcelona, Spain 10–12 June Tel: +43 1 867 49 44-0 Joint Meeting of the Society Marcio Brito, Tel: (800) 992 7224 Forum CCIB Convention XXXI SOLACI-SBHCI Fax: +43 1 867 49 44-9 for Heart Valve Disease & [email protected] Fax: (202) 689 7224 Center Congress – Latin-American Email: [email protected] Heart Valve Society of Editorial contribution: Email: [email protected] Email: europcr@ Interventional Cardiology Web: www.coronary America Walter Alexander Web: www.scai.org europa-organisation.com Society complications.org Berlin, Germany Advertising: Web: www.europcr.com Rio de Janeiro, Brazil Ritz Carlton Hotel Sanna Eronen, 6–9 May RioCentro 18–20 June Tel: +49 (0) 6106 84 4410 th [email protected] EuroPRevent 2009 30 May–2 June Tel: +55 11 5571 7742 18 Interventional Cardiology Fax: +49 (0) 6106 84 4444 Stockholm, Sweden Heart Failure 2009 Email: [email protected] Symposium Email: [email protected] Design: Stockholmsmaessan Nice, France Web: www.solaci-sbhci2009.org Montreal, Canada Web: www.shvd.org/sections/ David Reekie Tel: +33 (0)4 9294 7600 Palais Acropolis Tel: +1 514 287 1070 2009_Biennial_Meetin/index.html Layout: Fax: +33 (0)4 9294 7601 Tel: +33 (0)4 9294 7600 11–13 June Fax: +1 514 287 1248 Matt Hadfield www.escardio.org/congresses/ Web: www.escardio.org/ 2009 AMA-MSS (American Email: [email protected] 9–11 July europrevent-2009 congresss/HF2009 Medical Association) Annual Web: www.mhi.interv.org Congenital & Structural Meeting Interventions 2009 – 12th Cardiovascular News 10–13 May 1–3 June Chicago, USA 21–24 June International Congress International is published by ICNC9 – Nuclear Cardiology British Cardiovascular Hyatt Regency Chicago Europace 2009 Frankfurt, Germany BIBA Publishing, a division of th and Cardiac CT Society 87 Annual Email: [email protected] Berlin, Germany Congress Center Frankfurt BIBA Medical Ltd. Barcelona, Spain Conference and Exhibition Web: www.ama-assn.org ICC Berlin Phone: +49 (0) 6078 9316877 Head Office: Palau de Congressos de London, UK Tel: +33 (0)4 9294 7600 Fax: +49 (0) 6078 9316879 BIBA Publishing Ltd, Barcelona ExCeL 12–14 June Fax: +33 (0)4 9294 7601 Email: [email protected] 44 Burlington Road, Tel: +33 (0)4 9294 7600 Tel: +44 (0)20 7383 3887 Rhythm 2009 – Arrhythmias Web: www.escardio.org/ Web: www.csi-congress.org Fulham, London SW6 4NX, UK Fax: +33 (0)4 9294 7601 Email: [email protected] & Heart Failure: Future congresses/europace2009 Tel: +44 (0) 20 7736 8788 Email: [email protected] Web: www.bcs.com Technologies & 29 August–2 September Fax: +44 (0) 20 7736 8283 Web: www.icnc9.org Investigational Directions 24–26 June ESC Congress 2009 3–6 June Cannes, France Heart UK – The Cholesterol Barcelona, Spain rd 13–16 May 09 ISMICS (International Martinez Hotel Charity 23 Annual Fira de Barcelona Copyright ©: BIBA Medical Ltd. All rights reserved. No part of this publication may be Heart Rhythm 2009 Society for Minimally Tel: +33 (0) 491 097053 Conference Tel: +33 (0)4 9294 7600 reproduced, stored in a retrieval system, Boston, USA Invasive Cardiothoracic Email: vbereron@ Liverpool, UK Fax: +33 (0)4 9294 7601 transmitted in any form or by any other Boston Convention & Surgery) rhythmcongress.com Liverpool Hope University Web:www.escardio.org/ means, electronic, mechanical, photocopy - Exhibition Center San Francisco, USA Web: www.rhythmcongress.com Tel: +44 (0)1922 457 984 congresses/esc-2009 ing, recording or otherwise without prior per - mission in writing of the editor.

BIBA Publishing