EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 1

It’s ESC time again!And the focus is heart failureGiven the exponential increase in the patientspresenting with heart failure in recent years, a totalof 53 sessions have been dedicated to the topic ofheart failure. The sessions include clinical updatesand state-of-the-art lectures, but also the newest ondiagnosis and therapy will be presented. In theirwelcoming address, Kim Fox and Jeroen Baxhighlight some of the lures of this important andnotable event for cardiologists worldwide

1–5 September and the Viennavenue for the annual Congress ofthe European Society ofCardiology (ESC) will engrossabout 22,000 people, arrivingfrom all over the world to attendEurope’s biggest cardiologymeeting. 351 sessions areplanned to take place in 28rooms, and there will be manypresentations of originalscientific work.

Four named lectures – fourpresenters● The William Harvey Lecture

on Basic Science will bepresented by Professor PCarmeliet

● The Geoffrey Rose Lecture onPopulation Science byProfessor P Puska

● The Rene Laennec Lecture onClinical Cardiology byProfessor W McKenna

● The Andreas GruentzigLecture on InterventionalCardiology by Professor TLuescher.

The Focus sessionsThese consist of livetransmissions from Europeanlocations – Katowice, Berlin, BadNauheim, Bern and Vienna – todemonstrate practical skills inimaging and intervention.Clinical Practice sessions willencourage interactive discussionsbetween an expert panel andaudience. Two of the session willfocus on mild heart failure (HF)and end-stage HF.

Joint sessionsThe American Heart Associationand the American College ofCardiology, as well as societiesrepresenting subspecialties suchas hypertension, atherosclerosisand diabetes, etc. will presentjoint sessions.

12 main sessionsThese will be packed withimportant clinical topics, e.g. therelation between anaemia andheart failure, or the role of BNPin heart failure.

The safety of drug-elutingstents will be another hotlydiscussed subject, as will theincreasing role of non-invasiveimaging using differentmodalities, and the developmentof percutaneous valve therapy.

New ESC guidelinesFive new ESC guidelines are tobe released on acute coronarysyndromes without ST elevation,valve disease, cardiac pacing,hypertension and prevention ofcardiovascular disease. In

addition, the new UniversalDefinition of MyocardialInfarction (endorsed by the AHA,ACC and ESC) will be presented.

The EHSPLessons from the Euro HeartSurvey Programme – an extensivequestionnaire involving manyhospitals in ESC countries acrossEurope – will be the focus of fourother sessions.

Annual meetingsThe five ESC Associations willreport on their annual meetings orpresent their news in 90-minutesessions organised in theAssociation Corner. The fiveinclude subspecialisations –echocardiography, heart rhythm,prevention, percutaneous coronaryintervention, and heart failure.

Working lunch Participants can also fill theirlunch periods with attendance atnine practical sessions under thebanners Meet the Expert; Readwith the Expert, and How to.

Three Hotlines - Two ClinicalTrial Updates Late-breaking trials and the mostrecent updates on published trialswill be presented. These sessionsfrequently include large, random-ised clinical trials that have majorimpact on patient management.

Basic ScienceThe Council for BasicCardiovascular Science will presentsessions in a bench-to-bedsideformat, focusing on thetranslational aspect of basicscience, but also highly specificbasic science research will bepresented.

Abstracts and postersSubmitted abstracts: almost10,000. Reviewers to gradeabstracts: Acceptance rate: 37%.

New for 2007: the State-of-the-Art and Featured Research Track.Sessions will include a keynotelecture by an expert, combinedwith four oral presentations of thehighest ranked abstracts on aspecific top.

Kim Fox, President of theEuropean Society ofCardiology

Jeroen Bax, Chairman ofthe Congress ProgrammeCommittee

Professor Hamm: ‘As far as the visualisation of vessels and vessel periphery isconcerned, MRI has made other imaging modalities all but obsolete. Whole-bodyangiography, which is state-of-the-art MRI technology, for the first time offers thepossibility to visualise all vessels non-invasively. Patients who suffer from a stenosis– which in most cases is accompanied by arteriosclerosis – will particularly benefitfrom this new technology. Arteriosclerosis is a systemic condition, which quite oftenmeans you will find stenoses in different regions of the body that have not yetbecome clinically relevant. In such cases, whole-body angiography can significantlyinfluence therapy management: Imagine a patient who is diagnosed with a stenosisin the pelvic region but the whole-body angio shows a second stenosis, for examplein the carotid artery. Obviously, to prevent future intra-operative complications, wewill treat the latter first. This non-invasive method has many advantages – both forthe physician and patient.’What role does molecular imaging currently play in cardiology?‘In molecular imaging we – just like everyone else – are in the very early stages. Wedo basic research, so to speak. Research into the visualisation and differentiation ofstable and vulnerable plaque is very important for us. Vulnerable - that is inflamed -plaque can rupture at any moment and cause thromboses, which are often fatal. Atthis point we do not have a method do distinguish vulnerable from stable plaque.This is where molecular medicine comes in: The macrophages (cells that play acrucial role in the inflammation process of the plaque) bind well with magneticnano particles. In the Nano for Life Working Group, a research co-operation betweenSiemens and here at the Charité in Berlin, we work with ultra small iron particlesthat can make vulnerable plaque visible in MRI. Even more: we can determine thestatus of the inflammation, because the higher the inflammation activity the betterthe uptake of the iron markers. Based on the number and distribution of the markersin the body, we can then provide a very precise risk analysis for the patient. MRI isthe most sensitive procedure to visualise these markers.

‘There are also CT research projects that are important for cardiology – the non-invasive visualisation of the coronary vessels, for example. We are working with a64-slice CT which is able to visualise the coronary vessels very reliably.

‘In summary we expect immense progress in cardiological imaging in the nearfuture – progress which will enable us to diagnose diseases earlier and moreprecisely.’

MRI and the diagnosisof arteriosclerosis andplaque imaging

EUROPEAN HOSPITALThis special cardiology supplement is a EUROPEAN HOSPITAL publication

www.european-hospital.comCARDIOLOGY

The spatial-anatomic visualisation offered by MRIalready provides immense diagnostic possibilities forcardiology. However, as yet, the potential of thisimaging modality is far from exploited, according toProfessor Bernd Hamm (right), of the RadiologyDepartment at the Charité Hospital, Berlin. DanielaZimmermann of European Hospital, asked him why

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CARDIO 2 EUROPEAN HOSPITAL Vol 17 Issue 4/07

C A R D I O L O G Y

Hot Spots:NANOSCALE CONTRASTAGENT FOR IMAGINGCORONARY ARTERIES

VSOP particle with yellow molecules indicating the citrate bound to the iron oxide surface (grey).Functionalisation of the particle by specific peptides e.g. Annexin V

‘The tiny particles under investi-gation are less than sevennanometres across, with an ironcore that is highly responsive to the intense magnetism of anMR system. Most MR imaging of coronary arteries alreadyemploys contrast agents toimprove image quality. Coronaryarteries are small and due to themovement of the heart duringthe cardiac cycle, there is very lit-tle net imaging time, so you needa contrast agent to get a suffi-cient signal-to-noise ratio. Thesuper paramagnetic iron oxideparticles under developmenthave an optimal signal-enhancingeffect far above that of existingcontrast agents. An on goingphase II trial is measuring bloodflow through coronary arteries.The goal is to compare imagesmade with the nanocontrastagent to those made with tradi-tional X-ray angiography.

A second application for thehighly responsive nanoscale par-ticles is more speculative, butcould prove more valuable. Withassistance from Siemens, the con-sortium leader of Nano AG, Prof.Taupitz and colleagues at otherluminary academic sites are try-

ing to attach the tiny particles topeptides that bind to specificstructures in the body, whichcould turn the nanoparticles intodisease–hunters inside the body.

To detect arterial plaque, thenanoscale iron oxide particlescould be attached to a factorthat would, in turn, attach tocompounds involved in apopto-sis. Programmed cell death in theartery wall is one sign of vulner-able plaque. A second tacticcould link to compounds associ-ated with angiogenesis, whichoften occurs in unstable plaque.In either case, the tiny particleswill enrich within the pathologicvessel walls and generate hotspots on a MR image.

Currently, physicians must relyon indirect methods to specifi-cally image diseased arteries. Itis a change in paradigm for vas-cular diagnosis. We may have tolook not so much at flow-limit-ing stenosis, or narrowing, but atthe composition of the plaquesand the change in the vesselwalls. Using a specific contrastmedium means to get functionalinformation and then to make aprediction of the risk of plaquerupture in the artery.‘

A next-generation diagnostic tool for cardiovasculardisease, using a nanoscale iron particle, is now underdevelopment at a unique industry-government-university named Nano AG. A report from Siemensdescribes the research and progress at the centre

A new blood pressure (BP) mea-suring device that provides,along with all the conventionalcardiovascular parameters, thecardiac stroke volume, peripher-al resistance and arterial aug-mentation, has been developedat the Austrian Research Centre(ARC), Vienna-Seibersdorf, havebeen working to develop a new,more powerful method to mea-sure blood pressure. The resultof seven years’ work byresearchers, the device, namedCardioMon, is now ready forsale.

The ARC refers to one study inparticular to underline the needfor their advanced measuringsystem. Conducted during aVienna Cardiovascular Eventsprogramme in 2005, within one

BP measuring deviceNEW

week the blood pressure of 7,018patients was measured. Of those,1,109 people were receivingtreatments. However, only 175were being correctly regulated,mainly because conventionalblood pressure measuring meth-ods could only indicate symp-toms, but not the cause of prob-lems. For those, invasive meth-ods, such as catheterisation, havebeen necessary. The ARC reportsthat its CardioMon will makesuch a difference to this, that itwill have supplanted all conven-tional blood pressure measuringtools in just a few years.

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For and againstBy Dirk Boese MD, with S SackMD and R Erbel MD, of the WestGerman Heart Centre in Essen,and Cardiology Department atthe University of Duisburg-Essen,Germany, have summarisesCoronary stents provide wall wrappingof dissection, prevent elastic recoil,and reduce restenosis afterpercutaneous transluminal coronaryangioplasty. In addition, drug elutingstents loaded with antiproliferativeagents inhibit intimal hyperplasia andoffer a further reduction of restenosis.But stents are foreign bodies (‘metaljackets’) that transform elastic vesselsinto rigid tubes, impair vasomotion,and, due to the potential risk of evenlate thrombosis, require long termantiplatelet treatment.

To overcome limitations of currentstent technology, a magnesium-basedabsorbable metal stent (AMS-stent)was developed in Berlin, by BiotronikGmbH & Co, and successfully tested inanimals and below the kneeinterventions. The magnesium stentprovides vessel scaffolding within thefirst weeks after implantation and iscompletely absorbed within eightweeks before long term complicationsmay occur.

The efficiency of absorbable metalstents in the treatment of coronary

Final angiographic result after implantation of a 3.0x15 mm AMS-stent in a proximal rightcoronary artery. Arrow indicates stented segment. Intravascular ultrasound examinationindicated a good stent expansion with complete stent apposition (Panel A). After four months,angiography revealed a good long term result, without significant restenosis. IVUS- controlproved a nearly complete absorption of the AMS-stent with only stent remnants (Panel B).

Absorbable metal stents

Absorbable metal stent (from Biotronik) after expansion (left panel) and in electron microscopymagnification (right panel)

stents (elastic recoil ~ 7%) and noMACE (Major Adverse Cardiac Events)were observed during hospital stay.After four months, the ischemic drivenrevascularisation rate was 23.8% andtherefore comparable to conventionalstainless steal stents. Intravascularultrasound (IVUS) examination duringfour months follow-up demonstratedan advanced absorption process withonly small ‘stent remnants’. In the 12month clinical follow-up period nostent thrombosis was observed.

This study is the proof of conceptthat biodegradable magnesium stents

artery stenosis was determined in thePROGRESS-AMS (Clinical Performanceand Angiographic Results of CoronaryStenting with Absorbable MetalStents) clinical trial. Seventy-onestents (3.0 - 3.5mm in diameter) weresuccessfully implanted in severecoronary stenosis of 63 patients(mean age 61.3 ± 9.5 years).Procedural success could be achievedin all patients and the diameterstenosis could be reduced from 61.5%(±13.1%) to 12.6% (± 5.6%). Duringimplantation, the stent characteristicswere comparable to stainless steal

Dr Dirk Boese, West German Heart Centre, Essen

can achieve an immediate resultsimilar to the result of other metalstents and be safely degraded afterfour months. Nevertheless, therestenosis rate remains high andmodifications of the stentcharacteristics, i.e. prolongeddegradation and/or drug elution areobjects of further developmentaddressing the problems of excessive

recoil and proliferation.Due to reduced radiolucency of the

used magnesium alloy, the AMS-stentcannot be visualized by X-ray andinduces no metallic artifacts duringassessment with computedtomography and magnetic resonance.This characteristic allows the non-invasive assessment, even of thestented segment, after implantation ofan AMS-stent and gives newopportunities in the follow-upexaminations after coronary arteryinterventions.Contact for references and furtherdetails: Dr Boese. +49-201-7234888e-mail: dirk.boese@uk-essen.de

EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 3

C A R D I O L O G Y

Cardiac resynchronisation therapy Worldwide clinical trial gets underway Switzerland – A clinical trial ofcardiac resynchronisation therapy(CRT) in patients with advancedheart failure and a narrow QRScomplex <120 ms, has been initiat-ed by Zurich University.

The clinical benefits of CRT, asan adjunct to drug therapies, inpatients with NYHA class III/IVheart failure (HF) have beenshown repeatedly in randomisedtrials and clinical practice. TheMiracle ICD trials [Young JB,Abraham WT, Smith AL, et al,.Combined cardiac resynchronisa-tion and implantable cardioversiondefibrillation in advanced chronicheart failure: The MIRACLE ICDTrial. JAMA. 2003;289:2685-2694], and Companion trials [Bris-tow MR, Saxon LA, Boehmer J etal. Cardiac-resynchronisation ther-apy with or without animplantable defibrillator inadvanced chronic heart failure. NEngl J Med 2004;350:2140-50]suggested that CRT, which pacesthe left as well as right ventriclessimultaneously, used in conjunc-tion with an implantable car-dioverter defibrillator (ICD)improved the quality of life, func-tional capacity and exercise testperformance in patients with HFwith a wide QRS (�120 ms) inter-val. Indeed current guidelines forthe selection of suitable patientsfor CRT based on the publishedevidence advise that optimal candi-dates to benefit from CRT haveQRS >120 ms. [Strickberger SA,Conti J, Daoud EG et al. Patientselection for cardiac resynchro-nization therapy: from the Councilon Clinical Cardiology Subcom-mittee on Electrocardiography andArrhythmias and the Quality ofCare and Outcomes ResearchInterdisciplinary Working Group,in collaboration with the HeartRhythm Society. Circulation2005;111:2146-50.]

This means that until now, themajority of HF patients, thosewith a narrow QRS complex, havebeen excluded from CRT, althoughsuffering from dyssynchrony. TheEchocardiography guided CardiacResynchronisation Therapy(EchoCRT) study aims to providethe necessary evidence base toexpand therapeutic options for thispopulation.

EchoCRT is the first prospective,randomised clinical trial to evalu-ate the impact of cardiac resyn-chronisation therapy in HFpatients (NYHA Class III) whoshow mechanical dyssynchrony asassessed directly by echocardiogra-phy. Echocardiogram (ultrasoundof the heart) will provide a directmeasure of ventricular dyssyn-chrony, which is not apparent onindirect assessment by ECGbecause of the narrow QRS. Morethan 1,000 patients with advancedHF (NYHA Class III) will be ran-domised into treatment groupswith CRT or no CRT. Both groupswill receive an ICD to protectagainst sudden cardiac death, butin only half of the patients will theCRT capacity be switched on.

The co-principal investigators inZurich are Dr Frank Ruschitzkaand Dr Johannes Holzmeister.

In an interview with DrRuschitzka, we asked why Zurichhas become the international cen-tre for this study and what therationale is behind the EchoCRTtrial.

‘This is a very large clinical trial

of a medical device and willinvolve 120 different centresworldwide, but it’s led by Zurichbecause of our wealth of experi-ence in clinical cardiology trials.’The trial is sponsored by Biotron-ik, which manufactures theimplanted devices but, DrRuschitzka pointed out,‘EchoCRT is an independent,investigator led trial overseen by

an international executive com-mittee.’

‘Many cardiologists feel, as Ido, that we are not treating manyHF patients who would benefitfrom CRT simply because thereare no scientifically evidence-based guidelines telling us to. Ihave used CRT successfully inpatients with narrow QSR, and sohave many others. The medicalliterature supporting this belief isincreasing with observational

studies and anecdotal cases of suc-cess in several thousands of thesepatients.

‘The ESC recently conducted apoll asking its members if theythought patients with a narrowQSR would benefit from CRT.The time is now right for a large-scale, international trial to providethe definitive answer. Recruitingwill begin in the first quarter of2008 and will probably last for upto two years. The trial itself will

probably run for a further two orthree years after recruiting is com-plete depending on when we reachthe numbers required statisticallyof primary end-point. It would bestopped immediately if it becameobvious that the benefits of CRTtherapy were statistically superior.The results are due in 2011.

‘I’m very confident that CRT isthe way to go with HF patientswith narrow QRS. These are verysick patients with a high morbidityand mortality. I am convinced thatit is unwise to withhold CRT fromthis population and that EchoCRTwill provide the necessary evidenceto support this treatment change.’

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Progenitor cell transferfor cardiac repair after myocardial infarction

By Stefan P Janssens,Professor ofMedicine at theCardiologyDepartment,GasthuisbergUniversity Hospital,KU-Leuven, Belgium

Progenitor cell transfer torepair the damaged hearthas emerged as aninnovative and promising

recent development incardiovascular medicine. Since thefirst reports that adult bonemarrow-derived stem cells werecapable of transdifferentiatinginto a cardiomyocyte phenotype,research in regenerative medicinehas advanced in an explosivemanner.

A variety of progenitor celltypes that reside in bone marrow,

The therapeuticpotential of adultstem cells in CVDsBy Professor Bodo-Eckehard Strauer MD, Head of the Department ofCardiology, Pneumology and Angiology at Dusseldorf University Hospital

Fig. 2: Test results from 50 patients with acute myocardial infarction –controlled studies. Before cell therapy i.e. on the 8–9th day after infarction, andthree months after cell therapy

cell transfer of variable magnitude(absolute increase ranging from1.2 to 2.5%). The latter wasassociated with a favourableeffect on myocardial perfusion(evaluated as coronary flowreserve), infarct remodelling witha greater reduction in infarct sizeand greater recovery of regionalLV function. Although we are stillin a preliminary phase of clinicaldevelopment, meta-analysis ofpublished randomised controlledtrials and cohort studies of bonemarrow cell transfer (including

Cardiac infarction ischaracterised by tissueischaemia with loss ofcontractile heart muscle. Theconsequence is cardiacinsufficiency and disturbanceto cardiac rhythm. About twothirds of all patients have nosymptoms before aninfarction; about two thirds ofall patients do not survivetheir cardiac infarction. Abouta third of surviving infarctionpatients experienceincreasingly worsening heartfunction in the first year afterthe infarction (remodelling).

The aim of therapy is to re-open the infarcted vessel usingacute procedures (balloondilatation and stentimplantation), though this ismerely the tip of the icebergand the destroyed heartmuscle usually remainsuseless. This is wheretreatment with stem cellscomes in as causal therapy,striving to regenerate heartmuscle by injecting stem cellsinto it.

Fig. 1: Method for intracoronary stem cell transplantation: Site of the primary vascularocclusion caused by infarction is dilated with a balloon catheter and bone marrow stem cellsare simultaneously and repeatedly injected into the ischaemic area or infarct. This isundertaken in the acute infarction stage (2–8 days after infarction) and in the chronic stage(up to 8 years subsequently). Injection total: 100 to 200 million bone marrow stem cells. Fourto six pressure insufflations. Length of PTCA time: approx. 3–4 minutes

Fig. 3: Ejection fraction over a period up to three years after stem cell transplantation.Maintained improvement can be seen in patients who received stem cell treatment (TX)

Fig. 4: Stem cell transplantation procedure inperipheral occlusive disease. Combined intra-arterial and intramuscular injection. For bettermigration, stem cells are injected after repeatedcompression using a cuff and ergometry loading

or circulate in the blood, arecapable of improving function ofthe infarcted heart in pre-clinicalmodels, but underlyingmechanisms remain incompletelyunderstood. Consequently, thetraditional view of the heart as aterminally differentiated organ hasbeen challenged by several groups,who have reported the isolation ofcardiac stem or progenitor cells -characterised by the absence oftraditional cardiomyocyte,endothelial, or smooth musclemarkers, and that have a slowturn-over rate, and mightconstitute an endogenous reservoirfor cell-based repair.

However, massive cell loss ofcardiomyocytes and theseprogenitors alike, such as afteracute myocardial infarction,precludes sufficient repair capacityof these endogenous progenitorsin the infarcted territory. Therefore,cell-based repair requires inventivestrategies to mobilise or deliversignificant numbers of progenitorcells to sites of injury and securetheir survival, or to stimulateneighbouring cardiac precursorcells to multiply, integrate, andcouple with spared myocardiumand enhance myocardial function.

While those strategies are veryappealing, a major question iswhether we have the knowledgeand tools to implement them atthis stage in clinical practice, at anequitable cost-benefit?

Initial trials of autologous bonemarrow cells focusedunderstandably on safety andfeasibility both in patients withacute myocardial infarction (AMI)and chronic ischemia and reportedenhanced recuperation of LVfunction. However, by virtue oftheir design, these studies werenot randomised, or lacked a propercontrol population undergoing theexact same interventions aspatients receiving cell transfer.Subsequent double-blind, placebo-controlled randomised trials ofautologous bone marrow celltransfer in myocardial infarctionpatients have shown augmentedrecovery of global LV function after

999 patients) confirmed anoverall benefit, above andbeyond state-of-the-art therapy.

While the absolute increase inglobal function recuperation mayseem modest at first glance, itrepresents an incrementalimprovement of almost equalmagnitude as the initialtherapeutic effects of primarycoronary revascularisation.Moreover, we now haveconvincing data from the largestrandomised double blind studythat a delayed strategy of celltransfer offers the greatestbenefit and that it is almostexclusively observed in patientswith a significant reduction inmyocardial function at baseline.

These insights will help tofacilitate strategies whereby cell-based treatment algorithms arereserved for patients sufferingthe largest infarcts and wherecell transfer can be establishedaccording to the highestscientific standards. Indeed,quality assurance of allstem/progenitor cell isolatesrequires significanthaematological expertise, andhas been shown to have a majorimpact on clinical results in earlyexploratory trials.

At this stage, while safety hasbeen uniformly reassuring, proofof clinical efficacy (improvedsurvival and reduction of heartfailure) awaits larger multi-centreoutcome trials that are presentlybeing designed. To implementstandardised, SOP-based cellisolation, and characterisationprotocols, haematological andcell culture expertise fromexperienced institutions,including central blood bank orRed Cross laboratories or bonemarrow transplant centres, willbe indispensable.

Finally, enabling suchtreatment at an affordable costwill require intense collaborationbetween translational scientists,physicians, healthcareadministrators, and private andpublic health insurancecompanies.

Before cell therapy After cell therapy P

n = 50Pat.

LV-Ejection fraction, % 55±10 63±11 <0.01

Stroke volume inex ml/m2 48±18 53±17 0.05

EDV, ml 173±55 160±48 n.s.

EDV Index, ml/m2 87±30 85±25 n.s.

ESV, ml 80±34 61±29 <0.005

ESV Index, ml/m2 40±17 32±15 <0.005

Ejection fraction

Stem cell application

CARDIO 4 EUROPEAN HOSPITAL Vol 17 Issue 4/07

C A R D I O L O G Y

intraatriell

intramuscular

The body itself containsnaturally occurring, adultautologous stem cells, e.g. inthe bone marrow. They are anethical resource of cells that iscompletely safe. The idea wastherefore to regenerate heartmuscle clinically, bytransplanting naturallyoccurring bone marrow stemcells into the infarcted region.This process was developed inDusseldorf.

Bone marrow was removedand the cells prepared, then,after re-opening the infarctedvessel by balloon dilatation,they were injected into it underlow pressure, using a balloontechnique. The vessel was keptopen with a catheter (aprocedure lasting about 30minutes), during which timetwo to three ml of a suspensionof stem cells were injected intothe infarcted region, a processrepeated with four to sixinsufflations. The interventionwas carried out on consciouspatients with local anaesthesia,and at most produced mildpain at the site of injection.

Follow-up controls for threeyears and longer after theinfarction show that long-lasting improvement in cardiacfunction has been achieved,with an average increase incardiac function of 50% and areduction in the size of theinfarct of about 20%. At thesame time, blood supply to thecardiac muscle has beenconsiderably improved, as hasmetabolism, and physicalstrength has increased. As yet,no side effects have beenreported, so the procedureshould be considered anethically safe treatment ofmuscle loss after infarction, andcausal therapy that is reallybeneficial to the patient.

The Dusseldorf results havesince been confirmedworldwide. Work groups inFrankfurt, Hanover andRostock have been able toshow, even in larger studies,that regeneration of infarctedcardiac muscle can be achievedby transplanting autologousbone marrow stem cells. Whatis important is that thismyocardial regeneration,which, depending on studydesign, is between 4–16%, is ofan order of magnitude that is atleast as great as the sum of alltherapeutic improvements inventricular function achievedwith balloon dilatation or stentimplantation for cardiacinfarction. Consequently, addedimprovement in patients’ventricular function can thus beachieved, on top of surgical

Fig. 5: Long-term evolution of theankle/arm indexes before and after stemcell therapy. Improvement after six monthsaverages up to 30%

intervention and drug treatment.No complications from the stem cell

treatment have been reported so far.There is no malignant degeneration as thecells used occur naturally in the body. Nosigns of inflammation have beenobserved, nor have disturbances tocardiac rhythm, angina pectoris orrespiratory distress. Complications arisingfrom the procedure itself are much thesame as those that might occur inordinary heart catheterisation procedures,and are insignificant.

It should be mentioned that a similarprocedure is also effective in treatingperipheral arterial disease. In this case,treatment involves intra-arterial andintramuscular injection of autologous

bone marrow stem cells into the limbsaffected, the therapy first practised byBartsch et al. Ischaemic preconditioning,such as by compression induced with acuff, or even ergometry, greatly promotesmigration of stem cells into the muscles.

After three months there was markedimprovement in the length of stride, theankle/arm indexes, oxygen saturationand even venous occlusionplethysmography parameters.Consequently, autologous stem celltherapy can also be classed as asuccessful procedure for peripheralarterial occlusive disease, wheresymptoms are refractory to treatment,and in advanced stages of vasculardisease.

Ankle-arm index

EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 5

C A R D I O L O G Y

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CARDIO 6 EUROPEAN HOSPITAL Vol 17 Issue 4/07

C A R D I O L O G Y

The Lifebridge B2T (bridge-to-transport) is the first,fully portable emergency lifesupport system for patients

suffering cardiogenic shock, orthose showing signs of imminentcardiogenic shock. The machineensures circulation and sufficientblood oxygenation can berestored in just minutes, thuspreventing multi-organ failureleading to death. Whether inhospital or an ambulance, apatient can be connected to theLifebridge to replace externalcardiopulmonary reanimation.

First introduced in 2005 (seeEH 3/2005), this equipmentrecently received a CE markallowing sales across Europe. Itssmall size (61 x 45 x 37 cm), lowweight (17.5 kg) and power supplyvia integrated battery make itideal for ambulant use. The partly

Platinum chromium alloyenhances designBoston Scientific Corporation has commenced enrolment of a targeted1,500 patients for the Taxus Perseus clinical trials, planned to take placein 100 international centres. The aim is to evaluate the firm’s third-generation paclitaxel-eluting coronary stent - the Taxus Element Stent.This stent features the proprietary Platinum Chromium Alloy (designedspecifically for stents) which, combined with a new stent design, isdesigned to allow thinner struts, increased flexibility, and a lower profile,while improving radial strength, recoil, and radiopacity, Boston Scientificreports, adding that the stent’s platform incorporates new balloontechnology, intended to improve on the firm’s Maverick Balloon Cathetertechnology.

Dean J Kereiakes MD is principal investigator for the trials and MedicalDirector at The Christ Hospital Heart and Vascular Centre and The LindnerResearch Centre, in Cincinnati. Louis A Cannon MD, of the Cardiac andVascular Research Centre of Northern Michigan in Petoskey, is co-principal investigator.

Dr Kereiakes predicted: ‘This new platform, designed for improveddeliverability, should allow us to bring the long-term proven performanceof the Taxus Stent to even the most complex and challenging anatomy.’

The first of the two-part study, called Taxus Perseus Workhorse, willevaluate the safety and efficacy of the TAXUS Element Stent comparedwith Boston Scientific’s first generation drug-eluting stent (TaxusExpress2). 1,264 patients with ‘workhorse’ lesions from 2.75 to 4.0millimetres will be evaluated, with the primary endpoint of target lesionfailure (TLF) at 12 months; its secondary endpoint is in-segment percentdiameter stenosis at nine months.

The second part, the Taxus Perseus Small Vessel study, will comparethe Taxus Element Stent with a historic control (the Taxus V de novobare-metal Express Coronary Stent System). It will involve 224 patientswith lesions from 2.25 up to 2.75 millimetres. The primary endpoint ofthe small vessel study is in-stent late loss at nine months, and itssecondary endpoint is TLF at 12 months. Study success is dependent onboth endpoints, Boston Scientific explains.

Hank Kucheman, Senior Vice President and Group President,Interventional Cardiology, said: ‘The platinum chromium alloy and newballoon technologies in this system are also being developed in anEverolimus version and is intended to serve as foundational technologyin Boston Scientific’s dual-drug DES portfolio, including a drug-elutingbifurcation stent and next-generation Everolimus- and Paclitaxel-elutingstents.’

Ready for action: The 17.5The world’s firstportable, plug-and-play system toprovide hours ofemergencycardiopulmonarysupport is now onsale in Europe.EH correspondentHolger Zorn reports

guided, partly automated set-upmeans that in five minutes it isready for use by emergencydoctors or paramedics – withoutneeding a specialised technician.

To avoid air embolisms, sevensecurity steps guaranteemaximum patient protection.Access to the patient is either bypercutaneous puncture andinsertion of cannulae in vesselsin the groin or, afterthoracotomy, via insertion ofcentral cannulae into the rightatrium and rising aorta.Depending on the access, bloodcirculation of six litres perminute can be achieved, avolume that ensures adequategas exchange and sufficientperfusion of all importantorgans.

The German Heart Institute in Berlin tested the Lifebridge

during elective routineprocedures in bypass surgery.The objective of those trials wasto demonstrate the quality of thenew, portable system comparedwith a traditional heart-lung-machine. The Lifebridge ran forup to 103 minutes (average: 82 minutes). Under conditionstypically found in this kind ofheart surgery, with completecardiac arrest and no ventilation,the machine facilitated sufficientblood circulation to the organsand adequate gas exchange.Therefore, the Lifebridge alsocan be used pre-emptively duringrisky cardiac surgery (e.g. high-risk PCI).

In an earlier experimental studyat the University of Cologne,cardiac surgery using theLifebridge was simulated usingpigs. The animals’ blood gaseswere kept constant during theentire length of the study. Theblood circulation remainedconstant even when the heightdifference between the machineand heart was changed. Injectionof up to 100ml of venous air alsodid not reduce blood flow, andeven the most disadvantageousconditions did not result in anarterial air embolism (source:Mehlhorn U et al., Ann ThoracSurg 2005; 80: 1887-92).Gap in supply of technology forthe treatment of cardiogenicshock can be filledAnnually, hundreds of thousandsof Europeans suffer heart attacks,

STENTING MONITORINGAt the launch a panel of experts discussed the merits of portability

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ATRIAL FIBRILLATION MONITORINGFIRST EUROPEAN AF PATIENTS RECEIVE LONG-TERM, CONTINUOUS MONITORING DEVICE

The Netherlands - The firstimplant of the Reveal XT, aninsertable cardiac monitor madeby US firm Medtronic, whichrecently received CE (ConformitéEuropéenne) Mark, was carriedout in June by Professor Karl-Heinz Kuck MD, at the AsklepiosKlinik St. Georg in Hamburg,Germany.

Medtronic reports that this isthe first insertable cardiacmonitor to offer long-term andcontinuous monitoring of atrialfibrillation (AF): ‘All othercurrent monitoring tools areeither for a limited period or onan intermittent basis. Long-term,continuous monitoring meansthat a clinician no longer needsto rely only on incomplete datato evaluate how AF may beprogressing or treatmenteffectiveness,’ the firm points out.

As is well known, treatment ofAF is difficult because episodesoften show no symptoms and cango unnoticed by patients. ‘Atrialfibrillation is the most frequentcardiac arrhythmia. It is oftenaccompanied by symptoms that

are very unpleasant for thepatient,’ said Prof Kuck.‘Additionally, atrial fibrillation islinked with increased mortalityand an increase in the incidenceof stroke, by a factor of two- toseven-fold. However, with thenew Reveal XT, atrial fibrillationcan now be scrutinised over aperiod of three years with asubcutaneous monitor. This givesus totally new possibilities formonitoring and adjusting thetreatment.’

During its three-year activity,the device is reported to monitorAF patients 24 hours a day.

Up till now there has been nomethod to gather detailed data,over an extended period, on theprogression of AF and the effectof treatment. Reveal XT isexpected to give new insight intopatients’ heart rhythms, whichmight help physicians to evaluatestroke risk and determineappropriate treatment andtherapy options for their patients,Medtronic suggests.

ImplantationThe Reveal XT is inserted justunder the skin, and there is noneed for wires or sticky pads tokeep it in place. The patient issaid to experience no restrictionsin daily activities and, becausecardiac data is recorded duringthe patient’s normal routines thereal-life information obtainedcould provide important insight

to this condition. The medical devices manu-

facturer Medtronic, Inc.(www.medtronic.com) is based inMinneapolis; its European officein the Netherlands.

New remote monitoringfeature for implantablecardioverter-defibrillators(ICDs)The company also recentlylaunched a remote monitoringfeature for ICDs, which haveproved effective (98% of casesreported) in patients sufferingrecurring ventricular arrhythmias.

These patients have needed tohave device check-up’s two tofour times annually, as well asunscheduled visits in criticalsituations, Medtronic points out,adding that its new CareLinkNetwork system will enablehome-monitoring, with internet-transmission of data fromimplanted cardiac devices. To dothis, the patient holds a smallantenna over the device andinformation on how their heartand ICD are working istransmitted to a secure physicianwebsite for a virtual checkup.

‘This technology,’ said PeterSteinmann, Medtronic’s Vice-President for Western Europe,Cardiac Rhythm DiseaseManagement, ‘opens up thepotential for more efficientchronic disease management andbetter outcomes.’

EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 7

C A R D I O L O G Y

More women than men die of cardio-vascular disease (CVD) every year, yetfemales receive only 33% of angio-plasties, stents and bypass surgeries;28% of implantable defibrillators, and36% of open heart surgeries.

Looking at this situation, Abbott,which produces the Xience VEverolimus Eluting Coronary StentSystem, is involved in a clinical trial -in Europe, Asia-Pacific, Canada andLatin America – to study the stent’ssafety and effectiveness in womenpatients who have untreated coronaryartery lesions.

The first patient to enrol in the trial,called Xience V Spirit Women, hasbeen operated on in Argentina, byLiliana Grinfeld MD, at the ItalianHospital in Buenos Aires, Argentina,who reported that the stent systemhad performed well, and that thepatient will be checked for up to fiveyears.

Abbott reports that the trial willfocus on ‘…specific aspects ofwomen’s health in relation to coronaryartery disease, such as general aware-ness about the disease, symptoms attime of presentation, referral patterns,and hormonal menopausal status.’

The trial’s principal investigator,Marie-Claude Morice MD, at theJaques Cartier Institute, in Massy,France, commented that it is ‘tragic’that women amount to just 25% ofparticipants in all heart-relatedresearch studies, and added that thetrial had the potential to enhanceaccess to CVD therapy by increasingtheir and their physicians’ awareness.

kg heart-lung machine

Trial to raiseawareness ofgender and CVD

caused by the occlusion ofcoronary vessels followingcoronary heart disease. To avoiddeath or lasting damage a patientideally needs to receive treatmentwithin ‘the golden hour’.However, according to datasupplied by MITRA, Germany’sheart attack register, in thatcountry alone, the time lapsebetween heart attacks and start oftreatment is on a continuousincrease. Between 60,000 and65,000 patients do not survivetheir heart attacks (source: MarkB et al., Dts Aerzteblatt 2006;103: A 1378). Cardiogenic shockkills around 20,000 people. ‘Upto 50% of those patients couldsurvive if they received fastmechanical, extracorporealcirculation support,’ points outProf Zerkowski of BaselUniversity, Switzerland.

Ideally, artificial circulatorysupport should begin duringtransfer to a specialised hospital,because vital vessels and organsneed sufficient blood supply toavoid irreversible damage causedby hypoperfusion. However,mobile emergency systems are notusually used during a transfer,because currently availableequipment does not meetrequirements for portability andquick, safe use. ‘Filling this gap inthe supply is of utmost urgency,’said Prof Ruediger Lange, directorof the Cardiovascular SurgeryDepartment, German HeartCentre, Munich, during asymposium held during a market

launch for Lifebridge. Inspecialist centres, heart-lungmachines used during cardiacsurgery must be set up and runby trained perfusionists. Theirsize and weight make themunsuitable for mobile use. Apatient in cardiogenic shock,according to Lange, needssupport for cardiovascularfunction by a lightweight, fast,easy to use machine, which can

be used anywhere. The situation for hospital

treatment is similar. Cardiogenicshock develops in 7 – 10% of allinfarctions, and it isunpredictable. In such anemergency, currently, doctorsmainly use intra-aortic balloonpump counterpulsation (IABP),left-ventricular assist systemsalong with conventional heart-lung machines (HLM). However,

the former can only be used if theheart muscle has remainingfunctionality. In the case of acute,complete cardiac arrest, theimmediate use of a heart-lungmachine is necessary.

Even ultra-modern,percutaneous heart-lungmachines, which are connected tothe patient’s circulation via theiliac vessels during externalcardiopulmonary reanimation,can only be used after 15–20minutes. In addition, because theydepend on manual operation, usererrors and air embolisms cannotbe eliminated.

Therefore, a fully-integrated

‘click’n’run’ heart-lung supportsystem is an urgent requirement,said Prof Zerkowski.

Lifebridge Medizintechnik AG(founded: 1999) has found amarket niche with LifebridgeB2T. With 22 employees, the firmis supported by Bavarianfinanciers and an investmentbank in the United ArabEmirates. It reports that therehas already been strong demandfrom hospitals for this portableheart-lung device, and ManfredSalat, Chairman of the Board,predicts that, as from next year,the Lifebridge should be able tofinance further growth internally.

N E W S

Research Projectin Telemedicine

PARTNERSHIP FOR HEART

CARDIO 8 EUROPEAN HOSPITAL Vol 17 Issue 4/07

C A R D I O L O G Y

In Germany, approximately 1.5million people suffer from chron-ic cardiac insufficiency. Veryoften, the insidious symptoms arerecognised too late, leading tocomplications and hospitalisa-tion. ‘Partnership for the Heart‘is a joint project by science,industry and healthcare systemled by the Berlin Charité andaiming to develop a telemedicalearly warning system. The systemmonitors patients 7/24 at homeand a mini-computer records alltherapy-relevant vital parame-ters.

Body weight is an importantrisk indicator. A sudden increasein body weight for example mayindicate beginning water reten-tion in the body. Seca designedscales for this project based onthe floor scale seca 867. An inte-grated RS232 interface and a

A non-invasivemeasurement of

arterial wallatherosclerosis

By Thaddeus Chodakauskas BSRDMS and Steve Feinstein MD FACC

Non-invasive ultrasound imaging techniquescontinue to provide a major role in diagnosis andmanagement of patients with cardiovascular disease.The early presence of atherosclerosis predates majorclinical events such as myocardial infarction andstroke. Over the last 17 years, the ultrasound-basedmeasurement of carotid artery intima-mediathickness (c-IMT) has become a standard forassessing arteriosclerosis and is recommended by theAmerican Heart Association for the non-invasiveassessment of cardiovascular risk.

Carotid intima-media thickness is defined as thedistance between the lumen-intima interface and themedia-adventitia interface, which corresponds to theinner and outer echogenic lines seen on the B-modeultrasound image. (Fig.1). Measurement of c-IMT istraditionally performed with the image of the carotidartery in the longitudinal axis, revealing the commoncarotid artery, the carotid bifurcation, and theinternal and external carotid arteries. Although thesemeasurements have been performed for years,significant variability exists when measuring the nearwall due to technical and acoustic difficultiesencountered when imaging the c-IMT of the nearwall.

Due to those technical limitations, clinicalmeasurement of c-IMT using B-mode ultrasound isoften applied to the far (posterior) wall of thecommon carotid artery. With the development ofnon-invasive imaging technologies, ultrasoundmethods can be used to reliably measure intima-media thickness (IMT). This measurement serves anon-invasive marker of arterial wall atheroscleroticdisease. Studies have found that, on average, basedon gender and age, the intima-media thickness willincrease 0.01-0.03mm per year. (See tables onhistorical clinical studies of c-IMT).

Figure 2: 50-60 data points

Figure 3

Figure 5

Figure 6

Figure 1: Intima-media wall thickness

If the IMT measurement result is acceptable, select‘Transfer’ in the measurement Carotid folder. The resultswill be displayed in the worksheet and in the final report.

Performing IMT measurement on the Vivid 7 and Vivid i:• Select Measurement key on the keyboard.• Select from the measurement menu carotid folder, then

CCA IMT, to identify the right or left carotid artery,then CCA IMT Post, for posterior wall.

• Position the IMT cursor above the intimated wall, thenpress select key to anchor the first cursor. Repositionthe second cursor using the trackball then press selectkey to anchor the second cursor.

• Approximately 50-60 data points is an adequatesample when used to measure the intima-mediathickness.

Imaging common carotid artery

• Maximise the depth selection and optimise the gainsettings to visualise the posterior intima-media wall ofthe common carotid artery.

• Attempt to capture the common carotid artery withthe jugular vein to improve visualisation of theanterior and posterior carotid walls.

Measuring c-IMT

• Identify a single frame during the end-diastolic phasebetween the P and Q wave off the ECG trace.

The automated IMT package from Vivid 7/Vivid i: thebenefits• The measurement procedure is not operator dependent

and not as time intensive compared with manual IMTmeasurements.

• The semi-automated technique simplifies the time takento perform the measurement compared with manualmeasurement.

• The improved technology enhances c-IMT precisionmeasurements and increases consistency and reliabilityof the results.

• The methodology is robust, reproducible and buildsconfidence among radiographers and physicians.

Intima-mediaTo perform these studies, radiographers/clinicians usehigh frequency (7, 10 or 12) MHz linear arraytransducers with the Vivid 7 Dimension and the Vivid ito efficiently acquire multiple c-IMT measurementswithin seconds. The semi-automated measurement forintima-media wall is simple, easy and takes less thanfour steps. The physician receives immediate results,which consist of these parameters: maximum, mean,average and number of data points examined. Usingthe software application, the c-IMT measurement canbe exported directly to a worksheet and report pageand, subsequently, placed in the patient’s medicalrecord.

BlueTooth module allow smoothtransmission of the values to theCharité’s telemedical centres orthe Robert Bosch Hospital inStuttgart. Blood pressure andECG are determined in a similarway.

Specialist physicians monitorthe values around the clock andinitiate appropriate actions whenneeded – they inform the patientand the family physician or theemergency medical service.

Since the telemedical earlywarning system is considered aviable alternative to currentoptions it is being supported by the German Ministry ofEconomics. The government con-tributes 5 mio. EUR, the sameamount is made available by theindustry partners.Further information: www.partnership-for-the-heart.de

Tips: c-IMT measurements for the Vivid 7 Dimension/Vivid i

Intima-media

Media-adventitia

Jugularvein

Commoncarotidartery

BetweenP and Qwave

FRED® easyportis a Life-SaverCardiac infarction and cardiovascular failure are two of today’s most frequent emergencies.SCHILLER’s FRED® easyport® pocket is the onlypocket defibrillator in the world. It is so small(133x126x50 mm) and light (490 gr incl. battery)that for many doctors it is already standard equip-ment in their emergency bag. It is also suitable toaccompany risk patients and their relatives aroundthe clock.

This life-saver is always available to give doctors,paramedics and rescue technicians peace of mind inemergency situations.

For example during the World Cup 2006, para-medics on duty at the football stadiums carried outtheir duties with FRED easyport clipped to a beltaround their waist. In Switzerland an entire policedepartment has been equipped with this device tohelp fight against sudden cardiac death.

Patients at risk can easily carry this small defibrilla-tor with them, after they and their families have beeninstructed by their doctor. This dramatically reducesthe response time to treat ventricular fibrillation andtachycardias, giving the patient a much better chanceof survival.

For cardiologists this defibrillator can now also besupplied with a manual shock option, i.e. the doctorcan switch off the AED mode and decide the energylevel and exact moment of defibrillation.

Figure 4

EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 9

C A R D I O L O G Y

Finland - An increased TWA (T-wave alternans) is a significantindicator of all-cause andcardiovascular mortality, as wellas of sudden cardiac death inpatients with mostly normalejection fraction, according to arecently published study byresearchers led by Dr TuomoNieminen. Until now, this wasonly known as an indicator forthose patients suffering severeheart diseases predisposing tolife-threatening arrhythmias. Inan interview with Meike Lerner,of European Hospital, DrNieminen explained theadvantages of the TWAmeasurement, study results andthe consequences these have forfuture research.

‘The T-wave represents theelectric repolarisation of theheart, Dr Nieminen explained.Thus, alternans in the T-wave isa marker of an alternatingrepolarisation process, whichmight indicate cellulardisturbances duringrepolarisation. This is important,since pathological repolarisationphase predisposes to ventriculararrhythmias. In general, theTWA measurement could beused for arrhythmic riskstratification, but it is also one ofthe diagnostic criteria for longQT interval syndrome, anotherrepolarisation abnormality.

TWA can be measured with aregular electrocardiogram; noextra examinations are necessary.The possibility to measure the T-wave alternans is a specialfeature within normal ECGsoftware.

There are two methods forTWA assessment: time-domainmodified moving average(MMA) and spectral methods.Both methods seem to measurethe same phenomenom. For ourstudy, we used the GE Health-care software embedded with theMMA method, which can beapplied in routine exercise testprotocol without stabilising theheart rate to any specific level.’ Several studies have proved theeffectiveness of measuring TWAfor prognoses. What makes thisstudy different?‘Essentially all previous studiesincluded patients with an ejec-tion fraction of less than 50 per-cent, which is called abnormal.But in our population this onlyrefers to 13 percent of thepatients.

In 2001, we launched theFinnish Cardiovascular Study(FINCAVAS), in which we enrolall volunteering patientsperforming a clinical exercise testat Tampere University Hospital.We use the standard protocols ofthe bicycle ergometer test, withan increasing load every minute.This TWA analysis aimed to testwhether TWA predicts mortalityin our study population. Theresults of the study show that theTWA measurement providesprognostic value also in patientswith a normal ejection fraction.’ What consequences do thesefindings have for patients’treatment?‘Our results suggest that TWA

identifies patients prone to sud-den cardiac death at an earlierstage of cardiac disease thansupposed before. It is the firstbut naturally important step toshow that a certain marker isassociated with mortality.Another equally important stepwill be to test whether the

patients with such a patholog-ical marker will benefit fromtreatment options, such asanti-arrhythmogenic pharma-ceuticals, or an ICD implant.The results of our study didnot answer that latter part,which is a big question for thefuture - studies are being

TWA predicts mortality in patientswith normal ejection fraction

planned and conducted to reachthat goal.

We need to bear in mind thatestimating the aggregate risk forsudden cardiac death should bebased on several parameters.No single marker will suffice,but TWA seems to be a verygood candidate to be involved!’

Dr Tuomo Nieminen,Tampere University Hospital

CARDIO 10 EUROPEAN HOSPITAL Vol 17 Issue 4/07

C A R D I O L O G Y

MolecularmedicineA weapon to beat high-risk plaque

Paul Smit

The high riskplaque initiative THE BASIC STUDYThis will take place in twomobile units, located in a num-ber of large cities in the USA.The design of the study and theprotocol development is beingformulated in a close collabora-tion with BG Medicine, whichwill develop the blood-basedbiomarkers, and with leaders invulnerable plaque research fromleading Universities in the USA,Denmark and the Netherlands,as well as with partners Merckand Astra Zeneca.

The first patients will bescanned in the autumn of 2007,and the complete bio-imagingstudy will take about one year.While the compete set of imag-ing data will be ready in morethan a year - the study will takeabout four years.

It has only recently beendiscovered that very often itis not the size of the plaquein the coronary vessels but

its inflammation status thatdetermines the occurrence of acardiac infarction. Thisknowledge triggered newresearch approaches for its earlydiagnosis and treatment incardiology – for example theHigh-Risk Plaque Initiativejointly founded by PhilipsMedizin Systeme, AstraZeneca,Merck & Co, BG Medicine andHumana, which focuses on thepossibilities that molecularmedicine now offers. Theresearchers are trying to identifysuitable biomarkers that allowthe early diagnosis and targetedtherapy of inflamed, so-calledhigh-risk, plaque.

In molecular medicine, theHigh-Risk Plaque Initiative isone of the most importantprojects of Philips MedizinSysteme, as Paul Smit, in chargeof strategy and development in

the Dutch company, explained:‘Today, high-risk plaque isrecognised as the major cause ofcardiac infarction which killsabout 50 percent of the patients.This means, in many cases, deathis the first symptom of thedisease. Furthermore, thosepatients who survive the event are

chronically ill and requiremedical care for the rest oftheir lives. This disease is notonly dangerous for the patientsbut also presents an immensefinancial burden on thehealthcare system – a burdenthat will increase steadily overthe next few years. In short,

high-risk plaque is one of themost fatal and one of the mostexpensive diseases.’

In addition, coronary plaque isa highly unpredictable conditionbecause, depending on the degreeof inflammation, the plaquesuddenly ruptures and causes anembolism, which in turn leads to

A T R I A L F I B R I L L A T I O N

Robot moves steadilyin on catheter ablationSensei Robotic Catheter System installed in London

St Mary’s NHS Trust, which wasawarded a ‘good’ performance inthe 2006 NHS performance rat-ings, has 3,600 staff that providesspecialist care for women’shealth, cardiology, children’s ser-vices, infection and immunity androbotic surgery. The Trust reportsthat it has one of the lowest mor-tality rates in the UK, and a ‘richhistory of research, developmentand teaching thriving todaythrough the relationship withinternationally renowned univer-sity partner, Imperial CollegeLondon’.

Dr Wyn Davies set up the elec-trophysics department at StMary’s and also has been praisedby the British Medical Associationfor initiating a ‘day return’ cardiactreatment service in 2001. Withthis service, patients receivetreatment during a day and returnto their local hospital thatevening. This has shortened wait-ing times for beds to becomevacant for their potentially life-saving operations. In addition, hepointed out that returning totheir local hospitals mean rela-tives and friends can visit moreeasily.

The Sensei Robotic CatheterSystem, a first generation roboticplatform launched by HansenMedical at the USA’s HeartRhythm Society ScientificSessions in May this year, is in usein Europe. St Mary’s Hospital, inPaddington, central London,became the World’s first centre ofexcellence for training in anddevelopment of the system, underthe guidance of consultant cardi-ologist and electrophysiologistWyn Davies MD FRCP FHRS. Asof July, over 20 atrial fibrillationpatients had been operated on atSt Mary’s using this robotic surgi-cal aid controlled by the surgeonat a nearby workstation.

The Sensei system and Artisancatheter aim to enable physiciansto easily and accurately placemapping catheters in hard-to-reach anatomical locations withinthe heart with stability, during thediagnostic phase of complex car-diac arrhythmia treatment,Hansen reports.

‘The new robotic system allowsthe operator to perform EP proce-dures in a more consistent fash-ion, which I believe will lead tothe development of a standardapproach for complex diseases,’Wyn Davies observed.

Currently, the majority of clin-icians manually guide cathetersthrough the heart to detect andtreat a variety of cardiac arrhyth-mias. This technique requiresphysicians to perform a series ofcomplex manipulations at oneend of the catheter without assur-ance that the tip of the catheterwill respond as desired wheninside a patient’s heart. Achievingstable contact at anatomic siteswithin the heart, which is essen-tial for successful mapping proce-dures, can be difficult, Hansenpoints out. ‘As a result, insuffi-cient contact between the cathetertip and the inside of the heart wallcan lead to highly variable and

less than optimal procedureresults for the patient. HansenMedical believes its robotic plat-form overcomes these hurdles andwill enable physicians to performprocedures that historically have

been too difficult or time con-suming to accomplish routinelywith existing manual technique.’

The systemThe Sensei system is compatiblewith fluoroscopy, ultrasound, 3-D surface map and patient elec-trocardiogram data. The twomain components that comprisethe system are the Artisan con-trol catheter and an ergonomi-cally designed, remotely-placedworkstation where the physiciansits throughout the procedure. Inaddition to lessening operatorfatigue, the remote workstationcreates a virtual shield for physi-cians against harmful radiation,Hansen added. ’The openarchitecture provided by theSensei system, which allows theuse of pre-approved catheters from third-party manufacturers,requires a labelling additionfrom the FDA. The addition isintended to remind physiciansthat the safety and effectivenessof the system for use with cardiacablation catheters in the treat-ment of cardiac arrhythmias,including atrial fibrillation, havenot been established. The Senseisystem has received CE markapproval in Europe, and theArtisan Control Catheter is cur-rently pending CE markapproval.’

For many patients, a catheterablation is the most effective wayof treating AF; however a short-age of clinicians able to performthese complex procedures con-tributes to thousands living withthe condition and its associatedrisks. In the UK alone, over50,000 people develop AF annu-ally, yet fewer than 10% undergocatheter ablation.

St Mary’s, which runs one ofthe UK’s busiest cardiac centres,is now one of only four hospitalsglobally that are using the Senseirobot. Wyn Davies said it has

Czech Republic – During ameeting of cardiologists inPrague earlier this year toexchange experiences with newmethods and treatments tocontrol atrial fibrillation, DrJosef Kautzner, Head ofCardiology Department atIKEM (Institute of Clinical andExperimental Medicine) pointedout that numbers of patientswith AF will more than doubleduring the next 20 years. In theCzech Republic alone, there areabout 120 thousand peoplediagnosed with AF. All thesepatients have worsened qualityof life, twice the mortality dueto cardiac failure, and a fivetimes greater risk of cerebralvascular accident (CVA) whencompared with the normalpopulation of the same age. AFalso causes about a fourth of allCVAs, which means around fivethousand people are afflicted bythis disease.

The annual treatment of onepatient is 40 thousand CZK, i.e.almost 5 billion CZK (178.5million EUR). Figures for the

UK, according to theNICE guidance, indicatethat, in July 2006, therewere more than 1.4million UK patients withAF (source: NICE costimpact report) consumingsubstantial part of

healthcare financialbudget.

The main goals ofAF treatment arewidely recognised– to renew normalcardiac rhythm,and to ensure thatAF doesn’t occuragain.

Therapeuticmodalities are

wide, apart fromanti-arrhythmics, modern mini-invasive methods are recently onthe rise – cardiostimulators andcardioverters and defibrillators,electric cardioversion andparticularly catheter ablation.

In the Czech Republic, the firstpatient with an implantedcardiostimulator was seen atIKEM back in 1962, and the firstdigital cardiostimulator wasimplanted in 2003 in Prague’s NaHomolce Hospital. Catheterablation as an AF treatment hasbeen in use for quite some time.

With new medical technologyachievements, three-dimensionalimaging has arrived in this scene.New diagnostic approaches allow3-D views inside of the heart, socardiologists can combine thatimaging technique with a cardiacCT scan, and navigate thecatheter through the heart with afull stereometric view.

One of the pioneers in the fieldof even more advanced medicaltechniques is London’s St. Mary’sHospital (see robot feature onthis page).Report: Rostislav Kuklik

Electrophysicist Wyn Davies at the Senseiworkstation

Cardiologistsmeet to sumup progress

EUROPEAN HOSPITAL Vol 17 Issue 4/07 CARDIO 11

C A R D I O L O G Y

a cardiac infarction, or a stroke.This sudden rupture of inflamedplaque in a coronary arteryexplains why 70–75% of cardiacinfarctions occur without priorsymptoms.

‘Hitherto physicians wereunable to determine when theplaque has reached a dangerousstage. Today, molecularmedicine offers the possibility toidentify indicators of theinflammation. The first task ofthe High-Risk Plaque Initiative isto develop a broad patientscreening concept, which wehope will show early indicatorsin patients with infarcts that arenot present in the control group.If we know these earlyindicators, or biomarkers, whichpredict an inflammation, thanksto modern imaging methods wewill be able to locate the high-risk plaque and determine itsvolume,’ Paul Smit pointed out.

The collected data can becombined with statistical valuesand thus provide valuable

information on the patient’scurrent and future risk.Currently, Philips and the othermembers of the High-Risk PlaqueInitiative are developing a testthat will be applied to more than6,000 patients in coming years.

Early diagnosis of high-riskplaque is no doubt a major stepforward. However, it has to leadto targeted therapies for theaffected coronary vessels. Today,physicians are rather powerlesswhen it comes to the treatment ofplaque, since there are novalidated tests to determine theeffectiveness of drugs. However,it appears to be proven that

regular monitoring and ahealthy lifestyle often improve apatient’s condition.

Molecular medicine offerspromising approaches for otherdiseases as well - cancer, forexample. Currently, methods arebeing researched that useultrasound to transportmedication through the vesselsright to the affected bodyregion. The medication isdocked onto micro-bubbles, or acontrast agent, and injected into the body. With the help ofultrasound signals the physiciancan trace the bubbles’ route tothe target region. As soon as the

bubbles reach the affected tissuea certain ultrasound frequencycauses them to burst and theactive agent is released. Becausethe medication is administered ina very targeted way, a muchlower dose than in a systemictherapy is required – whichincreases the therapeutic successand significantly reduces sideeffects. The principle has alreadybeen tested in pre-clinical trialsand is now being developed forclinical use in a joint effort withthe pharmaceutical industry. ThePhilips research team has alreadygone one step further and isworking on finding out whether

this innovative method can beused for cardiac diseases.

‘We are still in the early stageof research into validatedbiomarkers and it will take aboutfour more years before we will beable to identify high-risk plaquewith the help of biomarkers.However,’ Paul Smit concludedoptimistically, ‘thesedevelopments will open entirelynew possibilities from which boththe patients and the healthcaresystem will profit: Early diagnosiscan significantly reduce treatmentand follow-up costs of manydiseases.’Report: Meike Lerner

‘enormous potential to helpdeliver difficult catheter ablationprocedures’. Pointing to theshortage of expertise in the UK,which means there are too fewcentres where highly complexcases can be carried out, headded: ‘With further develop-ment that we are alreadyembarking on, this robot willenable complex procedures to becarried out almost automatically,increasing the opportunities totreat more patients and ultimate-ly reducing clinical risk. Therobot allows accuracy and con-trol of catheter movement whichcannot currently be achievedwithout a skill level that usuallytakes considerable time toacquire. We are thrilled that StMary’s cardiology unit has beenable to pioneer this excitingadvance. With the other surgicalrobotic programmes alreadyestablished at the hospital, St.Mary’s is a world leader in robot-ic medicine.’

Although capable of use in allforms of ablation procedures,Hansen reports that the robotwill predominately be used forcomplex ablation procedures totreat atrial fibrillation.

The Czech Republic andGermany Another chosen centre of excel-lence is the Cleveland ClinicFoundation in Ohio, where thesystem is being used under theguidance of Andrea Natale MD,who is director for the Centre forAtrial Fibrillation, director of theElectrophysiology Laboratoriesand head of the Section of Pacingand Electrophysiology there. Shehad used the Sensei system dur-ing clinical evaluation on 25patients in the Czech Republicand Germany. ‘The stability ofthe Artisan catheter allowed usto perform catheter mappingprocedures more efficiently andeffectively,’ Dr Natale said. ‘Theincorporation of the Sensei sys-tem and catheter did not addtime to the procedures, nor did itrequire increased radiation time,as would normally be expectedwith new technology. As a result,I’d expect this new system tobecome the medical standard forperforming complex EP proce-dures, which are currently limit-ed to those individuals with thehighest level of skill.’Report: Brenda Marsh

© 2007 Cardiac Science Corporation

ELECTROCARDIOGRAPHS

Burdick Atria™ ECGs offer cutting-edge technology, combining the convenienceof a traditional ECG with the flexibility of digital communications.

The Atria product family truly offers the best of both worlds. • Flexible connectivity options including wired Ethernet and wireless 802.11• Advanced encryption tools ensure the highest level of data security• Ideal for device for EMR integration.• Transmit test results via XML, E-mail colleagues test results• ECG reports attach to the patient’s EMR, keeping all data in one place• E-mail colleagues diagnostic-quality test results• FAA Compliant

For information contact your local representative

Atria 6100 – Hospital grade performance at a physician’s office price point• Large, full color preview screen• Continuous waveform viewing• Interpretation based on five criteria

Atria 3100 – Compact, simple to use• 3-, 4- or 6-channel, 12-lead ECG tracings• Easy-to-use keyboard, menu driven interface• Most popular ECG in the physicians’ office

Proven performance meets state-of-the-art EMR connectivity

www.medica.de

Düsseldorf, Germany

14–17 November 2007

39th World Forum for MedicineInternational Trade Fair with Congress

Messe Düsseldorf GmbH Postfach 1010 0640001 DüsseldorfGermanyTel. +49(0)211/45 60-0 1Fax +49(0)211/45 60-6 68www.messe-duesseldorf.de