European Perspectives in CardiologyEuropean Perspectives in Cardiology

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f61Circulation March 19, 2013

Creation of a Multicentre Database to Evaluatethe Use of Pacemakers and Defibrillators inPaediatric Patients with Congenital Heart DiseasesPeter A. Zartner, MD, FESC, paediatric cardiologist andmedical computer scientist, German Paediatric Heart Centre,Sankt Augustin, Germany, received €10 000 from theGerman Foundation for Heart Research (see www.dshf.de)in 2012 to evaluate the use of pacemakers and defibrillatorsin paediatric patients with congenital heart diseases.

Current use of pacemakers in infants and children hasbeen adapted from techniques and material used for adults,but paediatric patients require different and individualstrategies for in- and ex-plantation procedures, program-ming and tracing of the systems, adaptation to a variety ofanatomical malformations, and coordination with interven-tional or surgical procedures. Paediatric restrictions andchanges over time, such as vessel diameter and patient’sgrowth, must be considered. The levels of evidence in theAmerican Heart Association, American College ofCardiology, and Heart Rhythm Society guidelines fordevice-based therapy for patients with a congenital heartdisease are C, with an increasing number of B, whichreflects the necessity of an extended and comprehensivedata analysis in this patient group.

To address the lack of information, Dr Zartner’s projectaims to retrospectively analyse the use of electronic pacingsystems in paediatric patients over the past 20 years in amulticentre setting. An internet-based, relational database

Funding: German Foundation for HeartResearch (Deutsche Stiftung für Herzforschung)

is being created using patient data from the different cen-tres, especially concerning implanted material and implan-tation strategies (eg, epimyocardial vs transvenous) in rela-tion to a patient’s age, size, heart defects, and clinical prob-lems to determine which parameters provide informationon the quality of pacemaker therapy. Computer-based sta-tistical evaluation of this database isolates the most com-mon problems and complications. All parameters will beassessed to optimise the runtime of the implanted systemsand reduce the frequency of revisions. Dr Zartner says,“We hope to gain new insights into foreseeable problemswith implantable electronic devices in paediatric practiceto optimise strategies for pacemaker therapy in children.

On other pages...

Recipients of German Foundation for Heart Research (Deutsche Stiftung für Herzforschung) grants in 2012describe the funding and their research to Jennifer Taylor, BSc, MSc, MPhil.

Funding Patient-Oriented Cardiovascular Research

Dr Zartner in theatre. Photograph courtesy of Dr Zartner.

European Meetings Update, 1 to 29 May, 2013List of cardiovascular meetings in Europe taking place fromMay 1 to May 29, 2013.

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Awards: Women and HeartResearch PrizeA research prize of CHF 30 000awarded to researchers or researchgroups in Switzerland for projects thathave cardiovascular disease in womenas their main focus. Page f64

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We also want to gather a collection of bail-out proceduresin pacemaker therapy in children.”

Essential support in initiating and conducting the proj-ect has been provided by the Department of PaediatricCardiology, Friedrich-Alexander University of Erlangen-Nürnberg. The project is coordinated by the government-funded Kompetenznetz Angeborene Herzfehler (Compe -tence Network for Congenital Heart Defects) in Berlin,Germany. Departments of Paediatric Cardiology that haveagreed to participate so far are those based at Friedrich-Alexander University of Erlangen-Nürnberg; the HeartCentre of the University of Leipzig, Leipzig, Germany; theGerman Paediatric Heart Centre, Sankt Augustin,Germany; the West-German Heart Centre, University ofEssen, Essen, Germany; and the German Heart Centre,Berlin, Germany.

Before receiving the grant, Dr Zartner conducted clini-cal research on pacemaker therapy in children,1–3 newstrategies in coronary interventions in children, the use ofbiodegradable magnesium stents in newborns, the use ofstents in pulmonary arteries and arterial ducts in infants,and interventional closure of interatrial communicationswith different devices. He says, “Hopefully, receiving theGerman Cardiac Research Foundation 2012 research grantwill help us gain valuable information for treating ourpatients and boost future research grant applications.”

References1. Zartner PA, Toussaint-Goetz N, Photiadis J, Wiebe W, Schneider MB.

Telemonitoring with implantable electronic devices in young patientswith congenital heart diseases. Europace. 2012;14:1030–1037.

2. Zartner PA, Wiebe W, Toussaint-Goetz N, Schneider MB. Vascularinterventions in young patients undergoing transvenous pacemakerrevision. Catheter Cardiovasc Interv. 2011;78:920–925.

3. Zartner PA, Wiebe W, Toussaint-Goetz N, Schneider MB. Leadremoval in young patients in view of lifelong pacing. Europace.2010;12:714–718.

Investigating Stress and Responses to Stress inPatients with Transient Left Ventricular ApicalBallooning SyndromeSabrina Kastaun, Dipl Psych, psychologist, and MesutYeniguen, MD, neurologist, Heart and Brain ResearchGroup, Department of Neurology, Justus-Liebig-University Giessen, Giessen, Germany, and Kerckhoff

Clinic Bad Nauheim, Bad Nauheim, Germany, received aGerman Foundation for Heart Research grant of €60 000 in2012 over 21 months to investigate patients with stress(takotsubo) cardiomyopathy in terms of personality traits,stress management, and psychopathological predisposingfactors.

Stress-induced cardiomyopathy, also referred to as tran-sient left ventricular apical ballooning syndrome (TLVAB)is a recently described disease mimicking acute myocardialinfarction. It presents with acute chest pain and dyspnoea,accompanied by ST-segment elevation and/or T-waveinversion in the electrocardiogram, elevation of cardiacenzyme levels, and transient wall motion abnormalities inthe left ventricle mid-segments in the absence of obstruc-tive coronary disease.1 Its prevalence among patients withsuspected acute myocardial infarction varies between 0.7%and 2.5%. Although systolic dysfunction mostly recoverswithin a few weeks, the in-hospital mortality rate is 2%.2

The aetiology of TLVAB is not fully understood.Possible theories include ischaemia-mediated stunningcaused by multivessel epicardial or microvascular spasmand myocarditis. An elevated release of catecholaminesseems to play a key role. A theory of catecholamine-medi-ated myocardial stunning provoked by emotional or physi-ological stress is supported by increased plasma cate-cholamine measurements during the acute phase in >70%of patients.3 Interestingly, TLVAB predominantly occurs inpostmenopausal women, typically during an emotionally orphysiologically stressful event (eg, bereavement, argu-ments, surgery, severe pain). No stressful trigger isobserved in ≈one-third of patients.2

Psychological approaches to understanding the aetiologyof TLVAB have not yet been applied. However, with fund-ing from the German Foundation for Heart Research, MsKastaun and Dr Yeniguen will address this by investigatingthe relationship between TLVAB and premorbid psychi-atric disorders, certain personality traits, and/or an exces-sive susceptibility to stress. Their case-control study assessesthe presence of chronic stress, stressful life events, stressmanagement strategies, personality traits, locus of control(internal, external), and the presence and pattern of psychi-atric symptoms in female patients diagnosed with TLVABat Kerckhoff Clinic Bad Nauheim within the past 4 years.

Female patients with a previous history of non–ST-seg-ment elevation myocardial infarction serve as 1 controlgroup. A second control group of cardiac-healthy women isdrawn from the general population. Both control groups arematched for age, and the non–ST-segment elevationmyocardial infarction group is also matched for the indexevent date.

In a self-designed stress experiment, the researcherswill also measure salivary cortisol to determine patients’stress reaction pattern and the general vulnerability tostress for each group. Measurement of neuroendocrinemarkers, such as free cortisol in saliva, has proved usefulfor assessing functioning and reactivity of the hypothalamic–pituitary–adrenal axis in psychological stress tasks.4

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Sabrina Kastaun and Dr Yeniguen. Photo courtesy of Dr Yeniguen.

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Ms Kastaun says, “The study aims to determine the roleof personality traits, stress management, and psychopatho-logical predisposing factors in the pathogenesis of stresscardiomyopathy.”

The Heart and Brain Research Group is a joint venturebetween the Department of Neurology of the Justus-Liebig-University Giessen and the Departments ofCardiosurgery and Cardiology of the Kerckhoff Clinic inBad Nauheim. Since 2000, their work has focused on neu-rological and neuropsychological aspects of heart diseasesand cardiac surgery, including clinical and preclinicalapproaches. Dr Yeniguen concludes, “The interdisciplinaryphilosophy of our group will hopefully provide innovativescientific approaches that help us to understand the com-plex pathophysiology of stress-induced cardiomyopathy.”

References1. Nef HM, Moellman H, Akashi YJ, Hamm C. Mechanism of stress

(Tako-Tsubo) cardiomyopathy. Nat Rev Cardiol. 2010;7:187–193.2. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical

ballooning syndrome or Takotsubo cardiomyopathy: a systematicreview. Eur Heart J. 2006;27:1523–1529.

3. Pilgrim TM, Wyss TR. Takotsubo cardiomyopathy or transient left ven-tricular apical ballooning syndrome: A systematic review. Int J Cardiol.2008;124:283–292.

4. Kirschbaum C, Hellhammer DH. Salivary cortisol in psychoneuroen-docrine research: recent developments and applications. Psychoneuro -endocrinology. 1994;20:313–333.

Investigating Platelet Function in Patients withAcute Coronary Syndrome Treated with MildHypothermiaJan Kaufmann, MD, cardiologist, Department of InternalMedicine, Cardiology, German Heart Institute Berlin,Berlin, Germany, received €30 000 from the GermanFoundation for Heart Research in 2012 for 1.5 years toassess platelet function in patients with acute coronary syn-drome treated with mild hypothermia.

Therapeutic hypothermia has been demonstrated toimprove outcomes for patients with acute coronary syn-drome.1 The highest risk for stent thrombosis occurs with-in the first 48 hours after percutaneous coronary interven-tion, so quick and sufficient inhibition of platelet functionis crucial to avoid thrombembolic complications. However,previous data point to an interaction between hypothermiaand drug metabolisation, thus potentially impacting onplatelet function under antiplatelet therapy.2

Dr Kaufmann’s study involves close cooperationbetween the Deutsches Herzzentrum Berlin and theDepartment of Nephrology/Intensive Care Medicine,Charité University Hospital Berlin (Campus Virchow). Thestudy tutor at the Charité site is Christian Storm, MD.Following resuscitation and revascularisation by percuta-neous coronary intervention, patients with acute coronarysyndrome are subjected to mild hypothermia (33°C) inaccordance with current guidelines for 24 to 48 hours usinga noninvasive feedback surface cooling device. All patientsin the study receive routine thienopyridine treatment withclopidogrel.

Previous ex vivo analysis of platelet function suggestsincreased platelet reactivity in mild hypothermia compared

with normal body temperature, indicating an attenuatedclopidogrel response.3 Clopidogrel is a prodrug activatedby hepatic cytochrome P450. This involves an intermediateactivation step leading to the generation of 2-oxo-clopido-grel, followed by a final oxidative step resulting in theactive metabolite. Cytochrome P450 2C19 has been demon-strated to contribute up to 45% of the initial and 20% of thefinal clopidogrel prodrug activation. Alterations in bioen-zyme transformation in hypothermia may impact activedrug levels. Platelet function might also be affected byhypothermia, leading to a diminished antiplatelet effect.Thus, hypothermia may also influence action of morenovel P2Y12 ADP-receptor antagonists, such as prasugreland ticagrelor.

To discriminate a pharmacokinetic from a pharmacody-namic impact, platelet function is tested ex vivo under con-ditions of mild therapeutic hypothermia (33°C) and normalbody temperature. Different devices that highlight severalaspects of platelet aggregation are used to assess plateletfunction. The control group comprises patients with acutecoronary syndrome and percutaneous coronary interven-tion but not needing hypothermia. Clopidogrel metabolitesare measured, and patients are screened for genetic deter-minants of clopidogrel metabolisation.

Dr Kaufmann says, “This combination of clinical andbasic science will help to identify the impact of hypother-mia on platelet function and thus identify patients with anincreased risk for thrombembolic complications.” He adds,“The support of the German Foundation for HeartResearch enables independent project management andbecause the financial support is provided by a notable foun-dation, it has a positive impact on the career of all partici-pants. Furthermore, it facilitates cooperation projects andencourages continuing interdisciplinary research.”

References1. Storm C, Steffen I, Schefold JC, Krueger A, Oppert M, Jörres A, Hasper

D.. Mild therapeutic hypothermia shortens intensive care unit stay ofsurvivors after out-of-hospital cardiac arrest compared to historicalcontrols. Crit Care. 2008;12:R78.

2. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia ondrug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit CareMed. 2007;35:2196–2204.

3. Hogberg C, Erlinge D, Braun OO. Mild hypothermia does not attenu-ate platelet aggregation and may even increase ADP-stimulated plateletaggregation after clopidogrel treatment. Thromb J. 2009;7:2.

Jennifer Taylor is a freelance medical journalist.

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Dr Kaufmann (right) with Dr Storm in the lab. Photograph cour-tesy of Dr Kaufmann.

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To encourage cardiovascular research in women, theOlten Heart Foundation, a branch of the Swiss Heart

Foundation, decided to launch the research prize “Womenand Heart” in 2007.

Although clinically manifested disease develops 7 to10 years later in women than in men, cardiovascular dis-ease is the major cause of death in women >65 years ofage, yet women are underrepresented in research in manyimportant areas of cardiology. The mean percentage ofwomen enrolled in cardiovascular clinical trials since2006 has been 30%, and only 50% of trials report resultsby gender analysis. Less evidence-based preventive, diag-nostic, and therapeutic options for women with cardiovas-cular disease may lead to undertreatment and a lower qual-ity of care compared with men. Moreover, female-specificissues related to pregnancy and hormonal changes duringmenopause need more attention.1

The “Women and Heart” research prize of CHF 30 000is awarded to researchers or research groups inSwitzerland for research projects that have cardiovasculardisease in women as their main focus.

The scientific committee that decides the winner iscomposed of leading academic staff from 3 SwissUniversity Hospitals and Olten Heart Foundation board

members. Since the first call for applications, 5 distin-guished researchers have been awarded the prize. Eachyear, the award round is announced at Swiss universityhospitals and in the Swiss medical press. The deadline forsubmission of new projects for the 2013 prize is 27 May2013.

The 3 most recent winners of the “Women and Heart”research prize are Nicole Aebischer, MD, head, OutpatientCardiology Clinic, University Hospital Centre HospitalierUniversitaire Vaudois, Lausanne, Switzerland, in 2010 forher project titled “Menopausal Women with PeripheralArtery Disease and Cardiovascular Risk Factors:Prevalence of Coronary Artery Disease”; ProfessorElisabeth Zemp Stutz, MD, MPH, PhD, unit leaderSociety, Gender, and Health, Swiss Tropical and PublicHealth Institute, Basel, Switzerland, in 2011 for her proj-ect titled, “Project RACHEL (Reproductive History andCardiovascular Health)”; and Petra Stute, MD, PD, deputyhead, Department of Gynaecological Endocrinology andReproductive Medicine and head, Menopause Clinic,University Women’s Hospital Inselspital Bern, Bern,Switzerland, in 2012 for her research project, “Is There aWindow of Opportunity for Coronary Heart DiseasePrevention in Swiss Women?”

Awards: Women and Heart Research Prize

Jennifer Taylor, BSc, MSc, MPhil, describes the Swiss Women and Heart Research Prize, and 2012 winner,Petra Stute, MD, PD, deputy head, Department of Gynaecological Endocrinology and Reproductive Medicineand head, Menopause Clinic, University Women’s Hospital Inselspital Bern, Bern, Switzerland, describes herwork and her prize-winning project.

The Most Important Prize for Cardiovascular Gender Research in Switzerland

From left to right: Dr Aebischer, MD, winner of the Women and Heart prize in 2010; Professor Stutz, winner of the Women and Heart prizein 2011; Julia Dratva, MD, MPH, Professor Stutz’s scientific collaborator at the Swiss Tropical and Public Health Institute. Photographscourtesy of Dr Aebischer and Professor Stutz.

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2012 Winner: InvestigatingEffect of HormoneReplacement TherapyStarted Within 6 Years ofMenopause on Occurrenceand Severity of AcuteCoronary SyndromeBasic science and observationalstudies suggest that oestrogensprotect against coronary heart dis-ease. However, the Women’sHealth Initiative failed to provethis hypothesis.2 One explanationfor this lack of benefit and theincrease in coronary heart diseaserisk observed in the Women’sHealth Initiative may derive fromthe harmful effects of hormonereplacement therapy in olderwomen. In contrast, younger post-menopausal women seem to benefit from oestrogen therapy.A timing hypothesis has been postulated, with exogenousoestrogens having beneficial cardiovascular effects whenadministered soon after endogenous oestrogen deficiencybefore significant atherosclerosis has developed, but hav-ing no or deleterious effects when given later.

The aim of Dr Stute’s study is to test whether hormonereplacement therapy started within 6 years of menopausedelays a first acute coronary syndrome and/or decreases itsseverity. A total of 4827 women with a first acute coronarysyndrome event have been recorded in the database of theDepartment of Cardiology Inselspital Bern between 1995and 2010. These women will be contacted by mail, andthose who then volunteer for the study will be contactedfor a telephone interview. The interview will addressreproductive history, exogenous hormone exposure (hor-monal contraception, hormone replacement therapy), andpsychosocial stress factors preceding the acute coronarysyndrome event.

The goal is to recruit ≈1500 women. Information oncardiovascular risk factors will be extracted from medicalrecords. Risk parameters are likely to change due to treat-ment effects. Statistical analysis will therefore take intoaccount dynamic modelling of the hazard function.

During the project, Dr Stute will be assisted by 3 med-ical students to conduct the telephone interviews as part oftheir doctoral theses. In addition, she has 2 coworkers withstatistical expertise: Prisca Eser, PhD, research assistant,Department of Cardiovascular Prevention andRehabilitation, Inselspital Bern, and Winfried Stute, PhD,professor of statistics and theory of probability, Institute ofMathematics, Justus-Liebig University Giessen, Giessen,Germany.

Dr Stute, who is originally from Germany, moved toSwitzerland for her current position in 2009. She has sincecollaborated with the Department of CardiovascularPrevention and Rehabilitation, Inselspital Bern.

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Previously, Dr Stute’s scientific focus on themenopause and postmenopausal hormone replacementtherapy has mainly concerned its effect on the breast. Tohelp her make the transfer to cardiovascular research, shehas undergone postdoctoral research training at thePrimate Center, Department of Comparative Medicine,Wake Forest University School of Medicine in WinstonSalem, NC, a well-known research centre for cardiovascu-lar health with Professor Thomas B. Clarkson, DVM.

“The results of the study may justify hormone replace-ment therapy when prescribed correctly to prevent coro-nary heart disease if a delay in first acute coronary syn-drome event or a decrease in acute coronary syndromeseverity can be shown for a particular hormone replace-ment therapy group,” says Dr Stute.

“The potential long-term effect of this study mayinclude coronary heart disease mortality reduction inwomen. Thus, on the public health level, we are investi-gating whether hormone replacement therapy may reducethe economic burden in our healthcare system by decreas-ing the incidence of coronary heart disease and/or itsseverity with probably a reduction (oestrogen only thera-py) or null effect (oestrogen-progestogen therapy) onbreast cancer risk, respectively.”

References1. Maas AH, van der Schouw YT, Regitz-Zagrosek V, Swahn E,

Appelman YE, Pasterkamp G, Ten Cate H, Nilsson PM, Huisman MV,Stam HC, Eizema K, Stramba-Badiale M. Red alert for women’s heart:the urgent need for more research and knowledge on cardiovasculardisease in women: proceedings of the workshop held in Brussels ongender differences in cardiovascular disease, 29 September 2010. EurHeart J. 2011;32:1362–1368.

2. Rossouw JE, Manson JE, Kaunitz AM, Anderson GL. Lessons learnedfrom the women’s health initiative trials of menopausal hormone ther-apy. Obstet Gynecol. 2013;121:172–176.

Jennifer Taylor is a freelance medical journalist.

Dr Stute in the lab. Photo courtesy of Dr Stute.

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The opinions expressed in Circulation: European Perspectivesin Cardiology are not necessarily those of the editors or of the American Heart Association.

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Editor: Christoph Bode, MD, FESC, FACC, FAHAManaging Editor: Lindy van den Berghe, BMedSci, BM, BSWe welcome comments. E-mail: lindy@circulationjournal.org

European Meetings Update1 to 31 May, 2013

2 to 5 MayThe Heart and Beyond: Intercellular and InterorganCommunicationVarenna, Italy For further details, seehttp://www.escardio.org/communities/Working-Groups/myofunction/meetings/3 to 4 MayEuroValve Congress Ibiza, Spain For further details, seehttp://www.eurovalvecongress.com4 to 7 May21st Annual Congress of the Czech Society of Cardiology Brno, Czech Republic For further details, seehttp://www.cksonline.cz5 to 8 MayICNC 11, Nuclear Cardiology and Cardiac CT Berlin, Germany For further details, seehttp://www.escardio.org/congresses/ICNC116 to 6 MayESC Webinar on Diabetes and Heart Disease Online, France For further details, seehttp://www.escardio.org/education/eLearning/webinars/8 to 10 MayThe Role of Advanced Cardiac Imaging: Clinical DecisionMaking in Coronary Artery Disease Venice, Italy For further details, seehttp://www.escardio.org/communities/EACVI/congress-meetings/Pages/Role-Advanced-Cardiac-Imaging8 to 11 MayAnnual Meeting of the Hungarian Society of CardiologyBalatonfüred, Hungary For further details, seehttp://www.mkardio.hu16 to 18 MayThe International Cardiology Symposium—A GlobalAgenda (ICS-13), Dubai, United Arab Emirates For further details, seewww.ics2013.com 16 to 18 MayAnnual Meeting of the Danish Society of Cardiology 2013 Nyborg, Denmark For further details, seehttp://www.cardio.dk

17 to 18 May4th Georgian Congress of Cardiology Tbilisi, Georgia For further details, contactcardio@geosc.ge

20 to 24 MayHammersmith Echocardiology Conference 2013 London, United Kingdom For further details, seehttp://www.w12conferences.co.uk/w12-event-calendar21 to 24 MayEuroPCR 2013 Paris, France For further details, seehttp://www.escardio.org/congresses/EuroPCR22 to 25 MayAssociation for European Paediatric and CongenitalCardiology (AEPC 2013) London, United Kingdom For further details, seehttp://www.aepc-2013.org23 to 25 MayEuroCMR 2013 Florence, Italy For further details, seehttp://eurocmr2013.medconvent.at/23 to 25 MayCardiac Nuclear and CT Imaging in Clinical PracticeSophia Antipolis, France For further details, seehttp://www.escardio.org/education/live-events/courses/nuclear-cardiology23 to 25 MayCroEcho 2013 Dubrovnik, Croatia For further details, contactinfo@361events.hr24 to 24 MayNew Recommendations for ST-Elevation MyocardialInfarction Management Online, France For further details, seehttp://www.escardio.org/education/eLearning/webinars24 to 25 MayBrugada Symposium: 20 Years of Scientific Progress Brussels, Belgium For further details, seehttp://www.brugada-symposium.com/25 to 28 MayHeart Failure 2013 Lisbon, Portugal For further details, seehttp://www.escardio.org/congresses/hf201328 to 29 MayFirst International Symposium on Vascular TissueEngineering Leiden, The Netherlands For further details, seehttp://www.vasculartissueengineering.org

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