Research

Competence Center Pediatric Cardiology

Team:

All residents and specialists of the Department of Pediatric Cardiology are involved in research projects as employees of the Medical University of Vienna in addition to their clinical work.

Brief description:

The Research Competence Center Pediatric Cardiology includes the scientific examination of questions from the clinical field as well as basic research in the field of pediatric cardiovascular diseases. Data collection and analysis, particularly in the assessment of the effects of new drugs, requires special care and the involvement of families, as is the case in pediatric research in general. The special requirements for studies in children are already taken into account when submitting applications for various projects and priority is given to non-invasive methods, in each case in consultation with the ethics committee of the Medical University of Vienna.

EU directives require extensive documentation and consideration of the special characteristics of the child's organism, in each case on the basis of good clinical practice.

Main focus:

• Non-invasive measurement of cardiac output
• Cardiac resynchronization for infantile cardiomyopathy
• Catheter interventional therapy
• Echocardiography of congenital valve diseases
• Genetics of congenital heart disease
• Pulmonary hypertension - electrocardiography and drug trials
• Electrophysiology in childhood
• Animal model of pulmonary hypertension

Research projects:

• Cardiac Resynchronization Therapy; Michel-Behnke, Pees Christiane
• (Refacto AF) in Children with Hemophilia A, A/KP/158/08; Michel-Behnke Ina, Male C.
• 7 Day Holter & PH; Michel-Behnke Ina
• Dabigatran etexilate; Michel-Behnke Ina
• Diag. Tech. for Central Venous Catheters; Michel-Behnke Ina
• Pediatric Cardiology; Michel-Behnke Ina
• Hemoph. Projects (continuation FA781Z0029); Michel-Behnke Ina, Male C.
• The AT1-receptor antagonist losartan for the prevention of excessive aortic root dilatation in children and adolescents with Marfan syndrome (A/KP/174/09); Michel-Behnke/Pees
• Non-invasive measurement of cardiac output using Innocor TM in patients with dual-chamber pacemakers-comparison of programming single-chamber mode (VVI) versus dual-chamber mode (DDD/VDD) with and without AV time optimization; Michel-Behnke/Pees
• Incidence of atrial fibrillation in patients with diabetes mellitus - screening by 7-day Holter ECG; Albinni Sulaima
• CO and PH in children - non-invasive measurement of cardiac output in children with pulmonary hypertension; Albinni Sulaima, Zervan Katarina, Glaser Verena, Marx Manfred
• Interventional cardiac catheterization in premature infants weighing less than 2000g; Kitzmüller Erwin
• Mutation analysis in congenital heart defects from myocardial samples; Greber-Platzer Susanne
• Perforated Helex device for shunt reduction in "fenestrated Fontan" circulation; Kitzmüller Erwin
• EPU retrospective cohort study; Marx Manfred
• Longitudinal follow-up of aortic root width in children and adolescents with genetically confirmed Marfan syndrome under beta-blocker therapy with regard to the respective specific mutation retrospective analysis in preparation for the Losartan study (A/KP/174/09); Pees Christiane
• Measurement of stiffness and distensibility of the aortic root in children and adolescents with native bicuspid aortic valves and in patients after Ross or arterial switch surgery in comparison with children and adolescents with normal tricuspid aortic valves; Pees Christiane
• Late recovery of the AV node in postoperative or congenital AV block in children with permanently implanted pacemakers with or without congenital heart defect - is explantation of the pacemaker system possible? Pees Christiane
• Developmental neurological evaluation of children with congenital heart defects; Salzer-Muhar Ulrike
• Register for recording patients with documented long QT syndrome in Austria - multicenter project of the Pediatric Cardiology Working Group of the ÖGKJ; Salzer-Muhar Ulrike
• A Phase II, Open-label, Multi-Center Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recepients Converted from a Prograf Based Immunosuppresive Regimen to a Tacrolimus Prolonged Release, Advagraf Based Immunosuppressive Regimen, Including a Long-Term Follow-Up; Salzer-Muhar Ulrike, Luckner Doris
• Cardiac Resynchronization Therapy (CRT) in Children with Congenital Heart Defects; Dr. Peer Hauck
• Evaluation of children with functional univentricular circulation using different echocardiographic methods; Dr. Peer Hauck
• Evaluation of different non-invasive methods to determine cardiac output in children with functional univentricular circulation; Dr. Peer Hauck
• Monochorial Gemini and heart defects, Dr. E.Mlczoch
• Developmental neurological follow-up in cardiac children, Dr. E. Mlczoch
• Lung volumes in fetal MRI in fetuses with heart defects, Dr. E.Mlczoch

Diplomarbeiten 2010:

• Electrophysiology and ablation - Outcome and complications in children 1993-2009, Diploma student: Azra Mujagic ,Supervisor: Prof. M. Marx and Dr. A. Hanslik
• Doppler echocardiographic measurements of the aortic flow volume-time integral (velocity time interval = VTI) for the determination of cardiac output in infants, children and adolescents - standardization of values ,Diploma student: Eva Glagau, Supervisors: Prof. Dr. I. Michel-Behnke and Dr. C. Pees
• Noninvasive measurement of cardiac output in children, Diploma student: Judith Kloiber Supervisor: Prof. Dr. I. Michel-Behnke

Hemostaseology department

Team: 

Dr.Katharina Thom, DKKS Eva Wissmann (study-nurse)

Brief description:

Clinical research projects related to the clinical care of children with thrombosis, stroke and children at increased risk of thrombosis as well as children with congenital and acquired bleeding disorders. Drug development in children in general.

Main focus:

• Diagnosis of venous thrombosis
• Primary thrombosis prophylaxis in children with cardiac diseases
• Development of new antithrombotic drugs for children
• Hemophilia and von Willebrand syndrome
• Pharmacokinetics in children

Research projects on the following topics:

Thromboses:

• KIDCAT study

Content: Recording the incidence of CVC-associated thrombosis, comparison of diagnostic methods and investigation of the influence of exogenous and endogenous risk factors. Publications: "Incidence and diagnosis of thrombosis in children with short-term central venous lines." Hanslik A et al, Pediatrics 2008;122;1284-91 and "No impact of prothrombotic conditions on the risk of central venous line-related thrombotic events in children: results of the KIDCAT Study." Thom K et al, (in preparation); further data analysis in progress.

• HEARTCAT Study

Project leader: Dr. Andreas Hanslik Content: Randomized controlled trial to compare a high-dose versus low-dose heparin regimen during cardiac catheterization in children; laboratory project to compare various parameters for monitoring heparin. Study completion: 2009; laboratory project ongoing. Publication: Interim analyses of laboratory data and clinical data (several abstracts). Report of the primary results at the annual meeting of the Ges. f. Thrombose & Hämostaseforschung, Feb 2010: Comparison of high-dose versus low-dose heparinization protocols for prophylaxis of thrombotic complications during cardiac catheterization in children (HEARTCAT study). Hanslik A, Kitzmüller E, Thom K, Haumer M, Salzer-Muhar U, Michel-Behnke I, Male C. Haemostaseologie 2010; 30: SY13-03; Manuscript submitted.

Industry-sponsored studies:

• Pilot Study for Assessing Diagnostic Techniques for Central Venous Catheters -related Venous Thromboembolism (AESOP Imaging). Multizentrisch; Principal investigator and Steering Committee chair: C. Male; Sponsor: Bristol-Myers-Squibb. Thema: Vergleich von Ultraschall und Magnetresonanztomographie zur Diagnose von katheter-assoziierten Thrombosen bei Kindern. Projektbeginn 2009, Rekrutierung laufend.
• Single-dose pilot study of oral rivaroxaban (BAY 59-7939) in pediatric subjects with venous thromboembolism. Multizentrisch; Member of Steering committee: C. Male; Sponsor: Bayer Healthcare. Thema: Phase I Studie zur Entwicklung eines neuen oralen Antikoagulans für Kinder. Projektbeginn: 2009; Rekrutierung laufend.
• Open-label safety and tolerability of dabigatran etexilate mesilate given for 3 days at the end of standard anticoagulant therapy in successive groups of children aged 2 years to less than 12 years, and 1 year to less than 2 years. Multizentrisch; Sponsor: Böhringer-Ingelheim. Thema: Phase I Studie zur Entwicklung eines neuen oralen Antikoagulans für Kinder. Projektbeginn: 2010; Rekrutierung laufend.

Hemophilia:

Academic studies

• Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component .Treated Patients (MBCTPs) when Exposed to plasma-derived von Willebrand Factor-Containing Factor VIII (VWF/FVIII) Concentrates and to Recombinant Factor VIII (rFVIII) Concentrates (SIPPET) ,Multizentrisch; Studienleitung: Prof. Dr. A. Gringeri, Mailand .Thema: Randomisiert kontrollierte Studie zum Vergleich plasmatischer versus rekombinanter FVIII Konzentrate bei bislang unbehandelten Kindern mit Hämophilie A bezüglich der Häufigkeit von Hemmkörpern. Projektbeginn: 2010; Rekrutierung laufend.
• Hemophilia Inhibitor Genetics Study (HIGS) .multizentrisch; Studienleitung: E. Bernthorp, Malmö, Schweden. Thema: Erfassung der genetischen Ursachen der Faktor-VIII-Inhibitorentstehung. Projekt: Rekrutierung laufend, Abschluss 2011 geplant
• EUHASS : European Haemophilia Safety Surveillance . multizentrisch; EU Grant; Studienleitung: Mike Makris Sheffield, United Kingdom. Thema: Internationales Surveillancedatabase zur Erfassung schwerer Nebenwirkungen der Behandlung von PatientInnen mit Hämophilie und anderen angeborenen Gerinnungsstörungen. Projekt: Beginn 2008, Rekrutierung laufend.

Austrian Hemophilia Registry

Multi-center, cooperation of all Austrian haemophilia centers; study director: Prof. I. Pabinger . Topic: epidemiological recording of all Austrian hemophilia patients, quality control of care, various study projects; project start 2008, ongoing annual recording of all patient data. Publications:

Austrian Hemophilia Registry: design, development and set of variables. Reitter S, Streif W, Schabetsberger T, Wozak F, Hartl H, Male C, Muntean W, Pabinger I. Wien Klin Wochenschr. 2009;121(5-6):196-201.

Austrian haemophilia registry: update 2008. Reitter S, Sturn R, Streif W, Schabetsberger T, Wozak F, Male C, Muntean W, Pabinger I. Haemostaseologie. 2009 Oct;29 Suppl 1:S13-5.

Spectrum of causative mutations in patients with haemophilia A in Austria. Reitter S, Sturn R, Horvath B, Freitag R, Male C, Muntean W, Streif W, Pabinger I, Mannhalter C; the Austrian Molecular Haemophilia Study Group. Thromb Haemost. 2010 Apr 29;104(1).

International Study on etiology of inhibitors in patients with a moderate or mild form of hemophilia A (INSIGHT study). multicenter, principal investigator: K. Fijnvandraat, Amsterdam, NL. Topic: Incidence and risk factors for the occurrence of FVIII inhibitors in patients with moderate and mild hemophilia A. Project start 2009, recruitment until 12/2010.

Effect of a hemostatic aptamer on ex vivo blood coagulation of patients with acquired or hereditary coagulation defects. Study director B. Jilma, Clinical Pharmacology, together with Department of Internal Medicine I, Division of Hemoseology, MUW. Topic: Testing the effect of an innovative hemostatic aptamer on ex-vivo plasma samples from patients with congenital coagulation defects. Project start: 2009, recruitment ongoing.

Industry-sponsored studies

• Prospective clinical study in children with severe haemophilia A to investigate clinical efficacy, immunogenicity, pharmacokinetics, and safety of Human-cl rhFVIII (GENA). Multizentrisch; Sponsor: Octapharma. Thema: Klinische Entwicklung eines neuen rekombinanten FVIII Konzentrates aus einer humanen Zelllinie. Studienbeginn: 2010; Rekrutierung laufend.
• Open-label study to evaluate prophylaxis treatment and to characterize the efficacy and safety and pharmakokinetics of B-domain deleted recombinant factor VIII albumin free (Refacto AF) in children with hemophilia A. multizentrisch; Sponsor: Wyeth/Pfizer. Thema: Randomisiert kontrollierte Studie zum Vergleich verschiedener Prophylaxeregimes und der Bedarfsbehandlung mit einem neuen FVIII Konzentrat (Phase II/III); Projekt: Beginn 2008, Abschluss geplant 2011.
• A Postauthorisation Safety Surveillance Study of Patients Switching to RefactoAF from Refacto or other Factor VIII Products in Usual Care Settings. multizentrisch; Sponsor: Wyeth/Pfizer. Beginn 2009, Rekrutierung offen.
• An Open-Label Study of the Safety and Efficacy of RefactoAF in Previously Untreated Patients in Usual Care Settings. multizentrisch; Sponsor: Wyeth/Pfizer. Beginn 2009; Rekrutierung bis voraussichtlich 2014.
• Österreichische Anwendungsbeobachtung von Faktor VIII Konzentraten bei Kindern mit Hämophilie multizentrisch; Studienleitung: M. Muntean, Graz; Sponsor: CSL Behring. Thema: Longitudinale Anwendungsbeobachtung zur Wirksamkeit und Behandlungssicherheit von Faktor VIII-Konzentraten; Projekt: Beginn 1996, Rekrutierung offen. Publikation: „Sixteen years of treatment with pasteurized human clotting factor concentrates in children and adolescents: a pharmacosurveilance investigation comprising 727 patient years." Muntean W et al, Sem Thromb Hemost 2002; 28 S1:64-73.